ID ADK_HUMAN STANDARD; PRT; 362 AA. AC P55263; O00741; O00742; Q16710; Q9BTN2; DT 01-OCT-1996 (Rel. 34, Created) DT 30-MAY-2000 (Rel. 39, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Adenosine kinase (EC 2.7.1.20) (AK) (Adenosine 5'-phosphotransferase). GN ADK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND SEQUENCE OF 94-133; 175-200 AND 272-289. RC TISSUE=Liver; RX MEDLINE=96165550; PubMed=8577746; RA Spychala J., Datta N.S., Takabayashi K., Datta M., Fox I.H., RA Gribbin T., Mitchell B.S.; RT "Cloning of human adenosine kinase cDNA: sequence similarity to RT microbial ribokinases and fructokinases."; RL Proc. Natl. Acad. Sci. U.S.A. 93:1232-1237(1996). RN [2] RP SEQUENCE FROM N.A., AND CHARACTERIZATION. RX MEDLINE=97075030; PubMed=8917457; RA Singh B., Hao W., Wu Z.-C., Eigl B., Gupta R.S.; RT "Cloning and characterization of cDNA for adenosine kinase from RT mammalian (Chinese hamster, mouse, human and rat) species. High RT frequency mutants of Chinese hamster ovary cells involve structural RT alterations in the gene."; RL Eur. J. Biochem. 241:564-571(1996). RN [3] RP SEQUENCE FROM N.A., AND ALTERNATIVE SPLICING. RX MEDLINE=97224402; PubMed=9070863; RA McNally T., Helfrich R.J., Cowart M., Dorwin S.A., Meuth J.L., RA Idler K.B., Klute K.A., Simmer R.L., Kowaluk E.A., Halbert D.N.; RT "Cloning and expression of the adenosine kinase gene from rat and RT human tissues."; RL Biochem. Biophys. Res. Commun. 231:645-650(1997). RN [4] RP SEQUENCE FROM N.A. (ISOFORM SHORT). RC TISSUE=Skin; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF SHORT ISOFORM. RX MEDLINE=99060037; PubMed=9843365; RA Mathews I.I., Erion M.D., Ealick S.E.; RT "Structure of human adenosine kinase at 1.5-A resolution."; RL Biochemistry 37:15607-15620(1998). RN [6] RP PHOSPHORYLATION OF TYR-77. RX MEDLINE=22107313; PubMed=12112843; RA Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G., RA Fitzgerald D.J.; RT "Identification of the phosphotyrosine proteome from thrombin RT activated platelets."; RL Proteomics 2:642-648(2002). CC -!- FUNCTION: ATP dependent phosphorylation of adenosine and other CC related nucleoside analogs to monophosphate derivatives. Serves as CC a potential regulator of concentrations of extracellular adenosine CC and intracellular adenine nucleotides. CC -!- CATALYTIC ACTIVITY: ATP + adenosine = ADP + AMP. CC -!- COFACTOR: Magnesium. CC -!- PATHWAY: Purine salvage. CC -!- SUBUNIT: Monomer. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P55263-1; Sequence=Displayed; CC Name=Short; CC IsoId=P55263-2; Sequence=VSP_004668; CC -!- TISSUE SPECIFICITY: Widely expressed. Highest level in placenta, CC liver, muscle and kidney. CC -!- SIMILARITY: Belongs to the carbohydrate kinase pfkB family. CC -!- CAUTION: Ref.2 sequence differs from that shown due to a CC frameshift in position 17. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U50196; AAA97893.1; -. DR EMBL; U33936; AAB01689.1; ALT_FRAME. DR EMBL; U90338; AAB50234.1; -. DR EMBL; U90339; AAB50235.1; -. DR EMBL; BC003568; AAH03568.1; -. DR PIR; JC5363; JC5363. DR PIR; JC5364; JC5364. DR PDB; 1BX4; 13-OCT-99. DR Genew; HGNC:257; ADK. DR GK; P55263; -. DR MIM; 102750; -. DR GO; GO:0004001; F:adenosine kinase activity; TAS. DR GO; GO:0009156; P:ribonucleoside monophosphate biosynthesis; TAS. DR InterPro; IPR001805; Adenokinase. DR InterPro; IPR002173; PfkB. DR Pfam; PF00294; pfkB; 1. DR PRINTS; PR00989; ADENOKINASE. DR PROSITE; PS00583; PFKB_KINASES_1; FALSE_NEG. DR PROSITE; PS00584; PFKB_KINASES_2; 1. KW Transferase; Kinase; Purine salvage; Magnesium; Alternative splicing; KW Phosphorylation; 3D-structure. FT ACT_SITE 317 317 FT MOD_RES 77 77 PHOSPHORYLATION. FT VARSPLIC 1 21 MAAAEEEPKPKKLKVEAPQAL -> MTSV (in isoform FT Short). FT /FTId=VSP_004668. FT CONFLICT 21 21 L -> V (in Ref. 2). FT CONFLICT 98 98 H -> A (IN REF. 1; AA SEQUENCE). FT CONFLICT 133 133 N -> D (in Ref. 2). FT CONFLICT 171 171 K -> R (in Ref. 2). FT CONFLICT 190 190 T -> H (in Ref. 1). FT CONFLICT 219 219 I -> F (in Ref. 4). FT CONFLICT 273 273 S -> V (IN REF. 1; AA SEQUENCE). FT CONFLICT 289 289 I -> N (IN REF. 1; AA SEQUENCE). FT CONFLICT 307 307 K -> R (in Ref. 2). FT TURN 23 24 FT STRAND 26 29 FT STRAND 33 39 FT HELIX 42 47 FT TURN 48 49 FT STRAND 54 57 FT HELIX 60 62 FT HELIX 63 72 FT STRAND 76 80 FT HELIX 82 94 FT TURN 98 99 FT STRAND 101 108 FT HELIX 111 122 FT TURN 123 124 FT STRAND 126 132 FT STRAND 139 145 FT TURN 146 147 FT STRAND 148 154 FT HELIX 156 160 FT HELIX 163 165 FT TURN 166 168 FT HELIX 170 178 FT STRAND 181 185 FT HELIX 186 190 FT TURN 191 191 FT HELIX 193 205 FT TURN 206 207 FT STRAND 209 213 FT HELIX 217 222 FT TURN 223 223 FT HELIX 224 230 FT HELIX 231 233 FT STRAND 236 240 FT HELIX 241 250 FT TURN 251 252 FT HELIX 258 266 FT TURN 267 267 FT TURN 273 274 FT STRAND 278 283 FT TURN 284 285 FT STRAND 286 291 FT STRAND 296 299 FT TURN 307 308 FT HELIX 312 327 FT TURN 328 330 FT HELIX 333 347 FT TURN 348 349 SQ SEQUENCE 362 AA; 40545 MW; 48AA4925865BFE70 CRC64; MAAAEEEPKP KKLKVEAPQA LRENILFGMG NPLLDISAVV DKDFLDKYSL KPNDQILAED KHKELFDELV KKFKVEYHAG GSTQNSIKVA QWMIQQPHKA ATFFGCIGID KFGEILKRKA AEAHVDAHYY EQNEQPTGTC AACITGDNRS LIANLAAANC YKKEKHLDLE KNWMLVEKAR VCYIAGFFLT VSPESVLKVA HHASENNRIF TLNLSAPFIS QFYKESLMKV MPYVDILFGN ETEAATFARE QGFETKDIKE IAKKTQALPK MNSKRQRIVI FTQGRDDTIM ATESEVTAFA VLDQDQKEII DTNGAGDAFV GGFLSQLVSD KPLTECIRAG HYAASIIIRR TGCTFPEKPD FH // ID ATM_HUMAN STANDARD; PRT; 3056 AA. AC Q13315; O15429; Q12758; Q16551; Q93007; Q9NP02; Q9UCX7; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Serine-protein kinase ATM (EC 2.7.1.37) (Ataxia telangiectasia DE mutated) (A-T, mutated). GN ATM. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=96154672; PubMed=8589678; RA Savitsky K., Sfez S., Tagle D.A., Ziv Y., Sartiel A., Collins F.S., RA Shiloh Y., Rotman G.; RT "The complete sequence of the coding region of the ATM gene reveals RT similarity to cell cycle regulators in different species."; RL Hum. Mol. Genet. 4:2025-2032(1995). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=97343327; PubMed=9199932; RA Platzer M., Rotman G., Bauer D., Uziel T., Savitsky K., Bar-Shira A., RA Gilad S., Shiloh Y., Rosenthal A.; RT "Ataxia-telangiectasia locus: sequence analysis of 184 kb of human RT genomic DNA containing the entire ATM gene."; RL Genome Res. 7:592-605(1997). RN [3] RP SEQUENCE OF 1-24 FROM N.A. RX MEDLINE=97263790; PubMed=9108147; RA Savitsky K., Platzer M., Uziel T., Gilad S., Sartiel A., Rosenthal A., RA Elroy-Stein O., Shiloh Y., Rotman G.; RT "Ataxia-telangiectasia: structural diversity of untranslated sequences RT suggests complex post-transcriptional regulation of ATM gene RT expression."; RL Nucleic Acids Res. 25:1678-1684(1997). RN [4] RP SEQUENCE OF 1-1369 FROM N.A., AND VARIANT AT 2546-SER--ILE-2548 DEL. RX MEDLINE=96381439; PubMed=8789452; RA Byrd P.J., McConville C.M., Cooper P., Parkhill J., Stankovic T., RA McGuire G.M., Thick J.A., Taylor A.M.R.; RT "Mutations revealed by sequencing the 5' half of the gene for ataxia RT telangiectasia."; RL Hum. Mol. Genet. 5:145-149(1996). RN [5] RP SEQUENCE OF 1-2756 FROM N.A., AND VARIANT MCL LYS-750. RA Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W., RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP SEQUENCE OF 1349-3056 FROM N.A., AND VARIANT ASN-3003. RX MEDLINE=96105020; PubMed=8521392; RA Rasio D., Negrini M., Croce C.M.; RT "Genomic organization of the ATM locus involved in ataxia- RT telangiectasia."; RL Cancer Res. 55:6053-6057(1995). RN [7] RP SEQUENCE OF 1349-3056 FROM N.A., AND VARIANTS AT 2427-LEU-ARG-2428 RP DEL; 2546-SER--ILE-2548 DEL AND SER-2860 DEL. RC TISSUE=Fibroblast; RX MEDLINE=95312868; PubMed=7792600; RA Savitsky K., Bar-Shira A., Gilad S., Rotman G., Ziv Y., Vanagaite L., RA Tagle D.A., Smith S., Uziel T., Sfez S., Ashkenazi M., Pecker I., RA Frydman M., Harnik R., Patanjali S.R., Simmons A., Clines G.A., RA Sartiel A., Gatti R.A., Chessa L., Sanal O., Lavin M.F., RA Jaspers N.G.J., Taylor A.M.R., Arlett C.F., Miki T., Weissman S.M., RA Lovett M., Collins F.S., Shiloh Y.; RT "A single ataxia telangiectasia gene with a product similar to PI-3 RT kinase."; RL Science 268:1749-1753(1995). RN [8] RP PARTIAL SEQUENCE FROM N.A., AND VARIANTS CYS-49; ARG-1054; PHE-1420; RP ILE-2079 AND ALA-2287. RX MEDLINE=96275738; PubMed=8665503; RA Vorechovsky I., Rasio D., Luo L., Monaco C., Hammarstroem L., RA Webster A.D.B., Zaloudik J., Barbanti-Brodano G., James M.R., RA Russo G., Croce C.M., Negrini M.; RT "The ATM gene and susceptibility to breast cancer: analysis of 38 RT breast tumors reveals no evidence for mutation."; RL Cancer Res. 56:2726-2732(1996). RN [9] RP PHOSPHORYLATION. RX MEDLINE=97126018; PubMed=8969240; RA Chen G., Lee E.Y.-H.P.; RT "The product of the ATM gene is a 370-kDa nuclear phosphoprotein."; RL J. Biol. Chem. 271:33693-33697(1996). RN [10] RP SUBCELLULAR LOCATION. RX MEDLINE=97203148; PubMed=9050866; RA Brown K.D., Ziv Y., Sadanandan S.N., Chessa L., Collins F.S., RA Shiloh Y., Tagle D.A.; RT "The ataxia-telangiectasia gene product, a constitutively expressed RT nuclear protein that is not up-regulated following genome damage."; RL Proc. Natl. Acad. Sci. U.S.A. 94:1840-1845(1997). RN [11] RP SUBCELLULAR LOCATION, AND VARIANTS AT 2546-SER--ILE-2548 DEL AND RP TYR-2824. RX MEDLINE=97294602; PubMed=9150358; RA Watters D., Khanna K.K., Beamish H., Birrell G., Spring K., Kedar P., RA Gatei M., Stenzel D., Hobson K., Kozlov S., Zhang N., Farrell A., RA Ramsay J., Gatti R.A., Lavin M.F.; RT "Cellular localisation of the ataxia-telangiectasia (ATM) gene product RT and discrimination between mutated and normal forms."; RL Oncogene 14:1911-1921(1997). RN [12] RP KINASE ACTIVITY. RX MEDLINE=97141775; PubMed=8988033; RA Jung M., Kondratyev A., Lee S.A., Dimtchev A., Dritschilo A.; RT "ATM gene product phosphorylates I kappa B-alpha."; RL Cancer Res. 57:24-27(1997). RN [13] RP C-ABL BINDING. RX MEDLINE=97311400; PubMed=9168117; RA Shafman T., Khanna K.K., Kedar P., Spring K., Kozlov S., Yen T., RA Hobson K., Gatei M., Zhang N., Watters D., Egerton M., Shiloh Y., RA Kharbanda S., Kufe D., Lavin M.F.; RT "Interaction between ATM protein and c-Abl in response to DNA RT damage."; RL Nature 387:520-523(1997). RN [14] RP P53 BINDING, AND KINASE ACTIVITY. RX MEDLINE=99057351; PubMed=9843217; RA Khanna K.K., Keating K.E., Kozlov S., Scott S., Gatei M., Hobson K., RA Taya Y., Gabrielli B., Chan D., Lees-Miller S.P., Lavin M.F.; RT "ATM associates with and phosphorylates p53: mapping the region of RT interaction."; RL Nat. Genet. 20:398-400(1998). RN [15] RP BETA-ADAPTIN BINDING. RX MEDLINE=98374320; PubMed=9707615; RA Lim D.-S., Kirsch D.G., Canman C.E., Ahn J.-H., Ziv Y., Newman L.S., RA Darnell R.B., Shiloh Y., Kastan M.B.; RT "ATM binds to beta-adaptin in cytoplasmic vesicles."; RL Proc. Natl. Acad. Sci. U.S.A. 95:10146-10151(1998). RN [16] RP PHOSPHORYLATION OF P53. RX MEDLINE=98404273; PubMed=9733514; RA Banin S., Moyal L., Shieh S.-Y., Taya Y., Anderson C.W., Chessa L., RA Smorodinsky N.I., Prives C., Reiss Y., Shiloh Y., Ziv Y.; RT "Enhanced phosphorylation of p53 by ATM in response to DNA damage."; RL Science 281:1674-1677(1998). RN [17] RP PHOSPHORYLATION OF P53, AND MUTAGENESIS OF ASP-2870 AND ASN-2875. RX MEDLINE=98404274; PubMed=9733515; RA Canman C.E., Lim D.-S., Cimprich K.A., Taya Y., Tamai K., RA Sakaguchi K., Appella E., Kastan M.B., Siliciano J.D.; RT "Activation of the ATM kinase by ionizing radiation and RT phosphorylation of p53."; RL Science 281:1677-1679(1998). RN [18] RP DNA BINDING. RX MEDLINE=99432198; PubMed=10500142; RA Smith G.C.M., Cary R.B., Lakin N.D., Hann B.C., Teo S.-H., Chen D.J., RA Jackson S.P.; RT "Purification and DNA binding properties of the ataxia-telangiectasia RT gene product ATM."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11134-11139(1999). RN [19] RP PHOSPHORYLATION OF BRCA1. RX MEDLINE=20018333; PubMed=10550055; RA Cortez D., Wang Y., Qin J., Elledge S.J.; RT "Requirement of ATM-dependent phosphorylation of brca1 in the DNA RT damage response to double-strand breaks."; RL Science 286:1162-1166(1999). RN [20] RP IDENTIFICATION OF ATM AS MEMBER OF BASC. RX MEDLINE=20245492; PubMed=10783165; RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.; RT "BASC, a super complex of BRCA1-associated proteins involved in the RT recognition and repair of aberrant DNA structures."; RL Genes Dev. 14:927-939(2000). RN [21] RP PHOSPHORYLATION OF NIBRIN. RX MEDLINE=20227312; PubMed=10766245; RA Lim D.-S., Kim S.-T., Xu B., Maser R.S., Lin J., Petrini J.H.J., RA Kastan M.B.; RT "ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway."; RL Nature 404:613-617(2000). RN [22] RP PHOSPHORYLATION OF NIBRIN. RX MEDLINE=20296355; PubMed=10839545; RA Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N., RA O'Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G., RA Livingston D.M., Weaver D.T.; RT "ATM phosphorylation of Nijmegen breakage syndrome protein is required RT in a DNA damage response."; RL Nature 405:477-482(2000). RN [23] RP PHOSPHORYLATION OF NIBRIN. RX MEDLINE=20264381; PubMed=10802669; RA Gatei M., Young D., Cerosaletti K.M., Desai-Mehta A., Spring K., RA Kozlov S., Lavin M.F., Gatti R.A., Concannon P., Khanna K.K.; RT "ATM-dependent phosphorylation of nibrin in response to radiation RT exposure."; RL Nat. Genet. 25:115-119(2000). RN [24] RP PHOSPHORYLATION OF CTIP. RX MEDLINE=20365735; PubMed=10910365; RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., RA Lee E.Y.-H.P., Lee W.-H.; RT "Functional link of BRCA1 and ataxia telangiectasia gene product in RT DNA damage response."; RL Nature 406:210-215(2000). RN [25] RP PHOSPHORYLATION OF TERF1. RX MEDLINE=21369915; PubMed=11375976; RA Kishi S., Zhou X.Z., Ziv Y., Khoo C., Hill D.E., Shiloh Y., Lu K.P.; RT "Telomeric protein Pin2/TRF1 as an important ATM target in response to RT double strand DNA breaks."; RL J. Biol. Chem. 276:29282-29291(2001). RN [26] RP PHOSPHORYLATION BY ARK5. RX MEDLINE=22393479; PubMed=12409306; RA Suzuki A., Kusakai G.-I., Kishimoto A., Lu J., Ogura T., Lavin M.F., RA Esumi H.; RT "Identification of a novel protein kinase mediating Akt survival RT signaling to the ATM protein."; RL J. Biol. Chem. 278:48-53(2003). RN [27] RP VARIANTS AT GLY-2424; 2546-SER--ILE-2548 DEL AND CYS-2827. RX MEDLINE=96335701; PubMed=8755918; RA McConville C.M., Stankovic T., Byrd P.J., McGuire G.M., Yao Q.-Y., RA Lennox G.G., Taylor A.M.R.; RT "Mutations associated with variant phenotypes in RT ataxia-telangiectasia."; RL Am. J. Hum. Genet. 59:320-330(1996). RN [28] RP VARIANT AT 2546-SER--ILE-2548 DEL, AND VARIANT ILE-2438. RX MEDLINE=96404417; PubMed=8808599; RA Wright J., Teraoka S., Onengut S., Tolun A., Gatti R.A., Ochs H.D., RA Concannon P.; RT "A high frequency of distinct ATM gene mutations in ataxia- RT telangiectasia."; RL Am. J. Hum. Genet. 59:839-846(1996). RN [29] RP VARIANTS AT 705-PHE--PRO-707 AND 2546-SER--ILE-2548 DEL, AND RP VARIANTS CYS-49; LEU-858; ARG-1054; PHE-1420 AND ARG-1691. RX MEDLINE=96390593; PubMed=8797579; RA Vorechovsky I., Luo L., Lindblom A., Negrini M., Webster A.D.B., RA Croce C.M., Hammarstroem L.; RT "ATM mutations in cancer families."; RL Cancer Res. 56:4130-4133(1996). RN [30] RP VARIANT AT 705-PHE--PRO-707, AND VARIANTS LEU-858 AND ARG-1054. RX MEDLINE=97196780; PubMed=9043869; RA Vorechovsky I., Luo L., Prudente S., Chessa L., Russo G., Kanariou M., RA James M.R., Negrini M., Webster A.D.B., Hammarstroem L.; RT "Exon-scanning mutation analysis of the ATM gene in patients with RT ataxia-telangiectasia."; RL Eur. J. Hum. Genet. 4:352-355(1996). RN [31] RP VARIANT AT ARG-2867. RX MEDLINE=96305462; PubMed=8698354; RA Baumer A., Bernthaler U., Wolz W., Hoehn H., Schindler D.; RT "New mutations in the ataxia telangiectasia gene."; RL Hum. Genet. 98:246-249(1996). RN [32] RP VARIANTS AT 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; SER-2860 RP DEL AND GLY-2904. RX MEDLINE=96254972; PubMed=8845835; RA Gilad S., Khosravi R., Shkedy D., Uziel T., Ziv Y., Savitsky K., RA Rotman G., Smith S., Chessa L., Jorgensen T.J., Harnik R., Frydman M., RA Sanal O., Portnoi S., Goldwicz Z., Jaspers N.G.J., Gatti R.A., RA Lenoir G., Lavin M.F., Tatsumi K., Wegner R.-D., Shiloh Y., RA Bar-Shira A.; RT "Predominance of null mutations in ataxia-telangiectasia."; RL Hum. Mol. Genet. 5:433-439(1996). RN [33] RP VARIANTS TPLL THR-1407; HIS-1682; HIS-1910; LYS-2164; SER-2396; RP GLY-2424; PRO-2442; 2546-SER--ILE-2548 DEL; ALA-2695; ARG-2722; RP VAL-2725; LEU-2732; LYS-2810 DEL; 2871-ARG-HIS-2872 DELINS SER RP AND VAL-2890, AND VARIANTS BNHL VAL-1040; SER-1463 AND CYS-2832. RX MEDLINE=97434220; PubMed=9288106; RA Vorechovsky I., Luo L., Dyer M.J.S., Catovsky D., Amlot P.L., RA Yaxley J.C., Foroni L., Hammarstroem L., Webster A.D.B., RA Yuille M.A.R.; RT "Clustering of missense mutations in the ataxia-telangiectasia gene in RT a sporadic T-cell leukaemia."; RL Nat. Genet. 17:96-99(1997). RN [34] RP VARIANTS TPLL GLY-2725; PRO-3006 AND CYS-3008. RX MEDLINE=97475207; PubMed=9334731; RA Stilgenbauer S., Schaffner C., Litterst A., Liebisch P., Gilad S., RA Bar-Shira A., James M.R., Lichter P., Doehner H.; RT "Biallelic mutations in the ATM gene in T-prolymphocytic leukemia."; RL Nat. Med. 3:1155-1159(1997). RN [35] RP VARIANT AT CYS-2832. RX MEDLINE=98107941; PubMed=9443866; RA Telatar M., Teraoka S., Wang Z., Chun H.H., Liang T., RA Castellvi-Bel S., Udar N., Borresen-Dale A.-L., Chessa L., RA Bernatowska-Matuszkiewicz E., Porras O., Watanabe M., Junker A., RA Concannon P., Gatti R.A.; RT "Ataxia-telangiectasia: identification and detection of founder-effect RT mutations in the ATM gene in ethnic populations."; RL Am. J. Hum. Genet. 62:86-97(1998). RN [36] RP VARIANTS AT LEU-292; ASP-768; GLN-1001; ARG-1691; ILE-1743; GLY-2424; RP 2427-LEU-ARG-2428 DEL; 2546-SER--ILE-2548 DEL; ASP-2554; GLY-2668 RP AND CYS-2827. RX MEDLINE=98130536; PubMed=9463314; RA Stankovic T., Kidd A.M.J., Sutcliffe A., McGuire G.M., Robinson P., RA Weber P., Bedenham T., Bradwell A.R., Easton D.F., Lennox G.G., RA Haites N., Byrd P.J., Taylor A.M.R.; RT "ATM mutations and phenotypes in ataxia-telangiectasia families in the RT British Isles: expression of mutant ATM and the risk of leukemia, RT lymphoma, and breast cancer."; RL Am. J. Hum. Genet. 62:334-345(1998). RN [37] RP VARIANT AT 1812-ALA-PHE-1813 DELINS VAL. RX MEDLINE=98163439; PubMed=9497252; RA Gilad S., Chessa L., Khosravi R., Russell P., Galanty Y., Piane M., RA Gatti R.A., Jorgensen T.J., Shiloh Y., Bar-Shira A.; RT "Genotype-phenotype relationships in ataxia-telangiectasia and RT variants."; RL Am. J. Hum. Genet. 62:551-561(1998). RN [38] RP VARIANT AT PRO-2656. RX MEDLINE=98111350; PubMed=9450874; RA Toyoshima M., Hara T., Zhang H., Yamamoto T., Akaboshi S., Nanba E., RA Ohno K., Hori N., Sato K., Takeshita K.; RT "Ataxia-telangiectasia without immunodeficiency: novel point mutations RT within and adjacent to the phosphatidylinositol 3-kinase-like RT domain."; RL Am. J. Med. Genet. 75:141-144(1998). RN [39] RP VARIANT TPLL GLY-2486. RX MEDLINE=98241437; PubMed=9573030; RA Stoppa-Lyonnet D., Soulier J., Lauge A., Dastot H., Garand R., RA Sigaux F., Stern M.-H.; RT "Inactivation of the ATM gene in T-cell prolymphocytic leukemias."; RL Blood 91:3920-3926(1998). RN [40] RP VARIANTS AT 2855-ARG-ILE-2856 AND CYS-3008, AND VARIANT VAL-1853. RX MEDLINE=99091900; PubMed=9872980; RA Hacia J.G., Sun B., Hunt N., Edgemon K., Mosbrook D., Robbins C., RA Fodor S.P.A., Tagle D.A., Collins F.S.; RT "Strategies for mutational analysis of the large multiexon ATM gene RT using high-density oligonucleotide arrays."; RL Genome Res. 8:1245-1258(1998). RN [41] RP VARIANT AT 2625-GLU-PRO-2626. RX MEDLINE=98180886; PubMed=9521587; RA van Belzen M.J., Hiel J.A.P., Weemaes C.M.R., Gabreeels F.J.M., RA van Engelen B.G.M., Smeets D.F.C.M., van den Heuvel L.P.W.J.; RT "A double missense mutation in the ATM gene of a Dutch family with RT ataxia telangiectasia."; RL Hum. Genet. 102:187-191(1998). RN [42] RP VARIANT AT LEU-2829, AND VARIANTS GLU-126; ASP-514 AND ASN-1853. RX MEDLINE=98375694; PubMed=9711876; RA Sasaki T., Tian H., Kukita Y., Inazuka M., Tahira T., Imai T., RA Yamauchi M., Saito T., Hori T., Hashimoto-Tamaoki T., Komatsu K., RA Nikaido O., Hayashi K.; RT "ATM mutations in patients with ataxia telangiectasia screened by a RT hierarchical strategy."; RL Hum. Mutat. 12:186-195(1998). RN [43] RP VARIANTS AT ASP-1091 AND ARG-1566, AND VARIANTS LEU-858 AND ARG-1054. RX MEDLINE=99006895; PubMed=9792409; RA Broeks A., de Klein A., Floore A.N., Muijtjens M., Kleijer W.J., RA Jaspers N.G.J., van 't Veer L.J.; RT "ATM germline mutations in classical ataxia-telangiectasia patients in RT the Dutch population."; RL Hum. Mutat. 12:330-337(1998). RN [44] RP VARIANTS AT ARG-2491 AND GLY-2909. RX MEDLINE=99006896; PubMed=9792410; RA Fukao T., Song X.-Q., Yoshida T., Tashita H., Kaneko H., Teramoto T., RA Inoue R., Katamura K., Mayumi M., Hiratani M., Taniguchi N., Arai J., RA Wakiguchi H., Bar-Shira A., Shiloh Y., Kondo N.; RT "Ataxia-telangiectasia in the Japanese population: identification of RT R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two RT being relatively common mutations."; RL Hum. Mutat. 12:338-343(1998). RN [45] RP VARIANTS TPLL GLY-2139; VAL-2890 AND CYS-3008. RX MEDLINE=98147367; PubMed=9488043; RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., RA Matutes E., Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., RA Catovsky D.; RT "ATM is usually rearranged in T-cell prolymphocytic leukaemia."; RL Oncogene 16:789-796(1998). RN [46] RP ERRATUM. RA Yuille M.A.R., Coignet L.J.A., Abraham S.M., Yaqub F., Luo L., RA Matutes E., Brito-Babapulle V., Vorechovsky I., Dyer M.J.S., RA Catovsky D.; RL Oncogene 16:2955-2955(1998). RN [47] RP VARIANTS BCLL VAL-1853; ARG-1953; PRO-2420; HIS-3008 AND ASN-3018, RP VARIANTS MCL LYS-2418 INS AND GLY-2423, AND VARIANT ASN-1853. RX MEDLINE=99326327; PubMed=10397742; RA Schaffner C., Stilgenbauer S., Rappold G.A., Doehner H., Lichter P.; RT "Somatic ATM mutations indicate a pathogenic role of ATM in B-cell RT chronic lymphocytic leukemia."; RL Blood 94:748-753(1999). RN [48] RP VARIANTS BCLL CYS-332; ARG-1691 AND GLY-2424. RX MEDLINE=99107196; PubMed=9892178; RA Bullrich F., Rasio D., Kitada S., Starostik P., Kipps T., Keating M., RA Albitar M., Reed J.C., Croce C.M.; RT "ATM mutations in B-cell chronic lymphocytic leukemia."; RL Cancer Res. 59:24-27(1999). RN [49] RP VARIANT AT PRO-1465. RX MEDLINE=99250766; PubMed=10234507; RA Izatt L., Vessey C., Hodgson S.V., Solomon E.; RT "Rapid and efficient ATM mutation detection by fluorescent chemical RT cleavage of mismatch: identification of four novel mutations."; RL Eur. J. Hum. Genet. 7:310-320(1999). RN [50] RP VARIANTS CYS-49; LEU-182; PRO-707; LEU-858; PHE-1420; ALA-1570; RP ASN-1853 AND SER-2765. RX MEDLINE=20005806; PubMed=10534763; RA Izatt L., Greenman J., Hodgson S.V., Ellis D., Watts S., Scott G., RA Jacobs C., Liebmann R., Zvelebil M.J., Mathew C., Solomon E.; RT "Identification of germline missense mutations and rare allelic RT variants in the ATM gene in early-onset breast cancer."; RL Genes Chromosomes Cancer 26:286-294(1999). RN [51] RP VARIANTS AT SER-570; CYS-785; GLY-1913; GLY-2016; ASP-2067; CYS-2227; RP ASP-2470; VAL-2662 DEL; PRO-2849 AND ARG-2867, AND VARIANTS CYS-49; RP LEU-858; ARG-1054; ASN-1853 AND VAL-1853. RX MEDLINE=99105918; PubMed=9887333; RA Sandoval N., Platzer M., Rosenthal A., Doerk T., Bendix R., RA Skawran B., Stuhrmann M., Wegner R.-D., Sperling K., Banin S., RA Shiloh Y., Baumer A., Bernthaler U., Sennefelder H., Brohm M., RA Weber B.H.F., Schindler D.; RT "Characterization of ATM gene mutations in 66 ataxia telangiectasia RT families."; RL Hum. Mol. Genet. 8:69-79(1999). RN [52] RP VARIANTS AT, AND VARIANTS ASN-1454 AND ASN-1853. RX MEDLINE=99355715; PubMed=10425038; RA Castellvi-Bel S., Sheikhavandi S., Telatar M., Tai L.-Q., Hwang M.J., RA Wang Z., Yang Z., Cheng R., Gatti R.A.; RT "New mutations, polymorphisms, and rare variants in the ATM gene RT detected by a novel SSCP strategy."; RL Hum. Mutat. 14:156-162(1999). RN [53] RP VARIANTS BCLL THR-350; THR-352; ARG-1054; LYS-2274 AND ALA-2695, AND RP VARIANT ASN-3003. RX MEDLINE=99146552; PubMed=10023947; RA Stankovic T., Weber P., Stewart G., Bedenham T., Murray J., Byrd P.J., RA Moss P.A.H., Taylor A.M.R.; RT "Inactivation of ataxia telangiectasia mutated gene in B-cell chronic RT lymphocytic leukaemia."; RL Lancet 353:26-29(1999). RN [54] RP VARIANT ARG-1054. RX MEDLINE=99231468; PubMed=10217116; RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.; RT "Missense mutations at ATM gene and cancer risk."; RL Lancet 353:1276-1276(1999). RN [55] RP ERRATUM. RA Vorechovsky I., Luo L., Ortmann E., Steinmann D., Doerk T.; RL Lancet 354:780-780(1999). RN [56] RP VARIANTS AT GLU-224; VAL-323; PRO-1420; CYS-2218; 2546-SER--ILE-2548 RP DEL; GLN-2625; CYS-2832; 2855-ARG-ILE-2856 AND CYS-3008, AND VARIANTS RP VAL-1853 AND ILE-2438. RX MEDLINE=20275351; PubMed=10817650; RA Li A., Swift M.; RT "Mutations at the ataxia-telangiectasia locus and clinical phenotypes RT of A-T patients."; RL Am. J. Med. Genet. 92:170-177(2000). RN [57] RP VARIANTS AT. RX MEDLINE=20334897; PubMed=10873394; RA Becker-Catania S.G., Chen G., Hwang M.J., Wang Z., Sun X., Sanal O., RA Bernatowska-Matuszkiewicz E., Chessa L., Lee E.Y.-H.P., Gatti R.A.; RT "Ataxia-telangiectasia: phenotype/genotype studies of ATM protein RT expression, mutations, and radiosensitivity."; RL Mol. Genet. Metab. 70:122-133(2000). RN [58] RP VARIANTS MCL LYS-750; LYS-2418 INS; GLY-2423 AND CYS-3008. RX MEDLINE=20183964; PubMed=10706620; RA Schaffner C., Idler I., Stilgenbauer S., Doehner H., Lichter P.; RT "Mantle cell lymphoma is characterized by inactivation of the ATM RT gene."; RL Proc. Natl. Acad. Sci. U.S.A. 97:2773-2778(2000). CC -!- FUNCTION: Involved in signal transduction, cell cycle control and CC DNA repair. May function as a tumor suppressor. Necessary for CC activation of ABL1 and SAPK. Phosphorylates p53, NFKBIA, BRCA1, CC CTIP, NIBRIN (NBS1), TERF1, and RAD9. May play a role in vesicle CC and/or protein transport. Inhibited by wortmaninn. Could play a CC role in T-cell development, gonad and neurological function. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Exists in monomeric and tetrameric state. Binds DNA ends, CC P53, ABL1, BRCA1, NIBRIN (NBS1) and TERF1. Part of the BRCA1- CC associated genome surveillance complex (BASC), which contains CC BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 CC protein complex. This association could be a dynamic process CC changing throughout the cell cycle and within subnuclear domains. CC -!- SUBCELLULAR LOCATION: Primarily nuclear. Found also in endocytic CC vesicles in association with beta-adaptin. CC -!- TISSUE SPECIFICITY: Found in pancreas, kidney, skeletal muscle, CC liver, lung, placenta, brain, heart, spleen, thymus, testis, CC ovary, small intestine, colon and leukocytes. CC -!- INDUCTION: By ionizing radiation. CC -!- PTM: Phosphorylated by ARK5. CC -!- DISEASE: Defects in ATM are the cause of ataxia talangiectasia CC (AT) [MIM:208900]; also known as Louis-Bar syndrome, which CC includes four complementation groups: A, C, D and E. This rare CC recessive disorder is characterized by progressive cerebellar CC ataxia, dilation of the blood vessels in the conjunctiva and CC eyeballs, immunodeficiency, growth retardation and sexual CC immaturity. AT patients have a strong predisposition to cancer; CC about 30% of patients develop tumors, particularly lymphomas and CC leukemias. Cells from affected individuals are highly sensitive to CC damage by ionizing radiation and resistant to inhibition of DNA CC synthesis following irradiation. CC -!- DISEASE: Defects in ATM contribute to T-cell acute lymphoblastic CC leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is CC characterized by a high white blood cell count, with a CC predominance of prolymphocytes, marked splenomegaly, CC lymphadenopathy, skin lesions and serous effusion. The clinical CC course is highly aggressive, with poor response to chemoterapy and CC short survival time. TPLL occurs both in adults as a sporadic CC disease and in younger AT patients. CC -!- DISEASE: Defects in ATM contribute to B-cell non-Hodgkin's CC lymphomas (BNHL), including mantle cell lymphoma (MCL). CC -!- DISEASE: Defects in ATM contribute to B-cell chronic lymphocytic CC leukemia (BCLL). BCLL is the commonest form of leukemia in the CC elderly. It is characterized by the accumulation of mature CD5+ B CC lymphocytes, lymphadenopathy, immunodeficiency and bone marrow CC failure. CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. CC -!- DATABASE: NAME=Ataxia talangiectasia mutation db; CC WWW="http://www.vmresearch.org/atm.htm". CC -!- DATABASE: NAME=Atlas Genet. Cytogenet. Oncol. Haematol.; CC WWW="http://www.infobiogen.fr/services/chromcancer/Genes/ATM123.html". CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U33841; AAC50289.1; -. DR EMBL; U82828; AAB65827.1; -. DR EMBL; U67092; AAC51298.1; -. DR EMBL; AY220758; AAO26044.1; -. DR EMBL; U55757; AAB38309.1; -. DR EMBL; U55704; AAB38309.1; JOINED. DR EMBL; U55705; AAB38309.1; JOINED. DR EMBL; U55707; AAB38309.1; JOINED. DR EMBL; U55708; AAB38309.1; JOINED. DR EMBL; U55709; AAB38309.1; JOINED. DR EMBL; U55710; AAB38309.1; JOINED. DR EMBL; U55711; AAB38309.1; JOINED. DR EMBL; U55712; AAB38309.1; JOINED. DR EMBL; U55713; AAB38309.1; JOINED. DR EMBL; U55714; AAB38309.1; JOINED. DR EMBL; U55715; AAB38309.1; JOINED. DR EMBL; U55716; AAB38309.1; JOINED. DR EMBL; U55717; AAB38309.1; JOINED. DR EMBL; U55718; AAB38309.1; JOINED. DR EMBL; U55719; AAB38309.1; JOINED. DR EMBL; U55720; AAB38309.1; JOINED. DR EMBL; U55721; AAB38309.1; JOINED. DR EMBL; U55722; AAB38309.1; JOINED. DR EMBL; U55723; AAB38309.1; JOINED. DR EMBL; U55724; AAB38309.1; JOINED. DR EMBL; U55725; AAB38309.1; JOINED. DR EMBL; U55726; AAB38309.1; JOINED. DR EMBL; U55727; AAB38309.1; JOINED. DR EMBL; U55728; AAB38309.1; JOINED. DR EMBL; U55729; AAB38309.1; JOINED. DR EMBL; U55730; AAB38309.1; JOINED. DR EMBL; U55731; AAB38309.1; JOINED. DR EMBL; U55732; AAB38309.1; JOINED. DR EMBL; U55733; AAB38309.1; JOINED. DR EMBL; U55734; AAB38309.1; JOINED. DR EMBL; U55735; AAB38309.1; JOINED. DR EMBL; U55736; AAB38309.1; JOINED. DR EMBL; U55737; AAB38309.1; JOINED. DR EMBL; U55738; AAB38309.1; JOINED. DR EMBL; U55739; AAB38309.1; JOINED. DR EMBL; U55740; AAB38309.1; JOINED. DR EMBL; U55741; AAB38309.1; JOINED. DR EMBL; U55742; AAB38309.1; JOINED. DR EMBL; U55743; AAB38309.1; JOINED. DR EMBL; U55744; AAB38309.1; JOINED. DR EMBL; U55745; AAB38309.1; JOINED. DR EMBL; U55746; AAB38309.1; JOINED. DR EMBL; U55747; AAB38309.1; JOINED. DR EMBL; U55748; AAB38309.1; JOINED. DR EMBL; U55749; AAB38309.1; JOINED. DR EMBL; U55750; AAB38309.1; JOINED. DR EMBL; U55751; AAB38309.1; JOINED. DR EMBL; U55752; AAB38309.1; JOINED. DR EMBL; U55753; AAB38309.1; JOINED. DR EMBL; U55754; AAB38309.1; JOINED. DR EMBL; U55755; AAB38309.1; JOINED. DR EMBL; U55756; AAB38309.1; JOINED. DR EMBL; U55757; AAB38310.1; -. DR EMBL; U55726; AAB38310.1; JOINED. DR EMBL; U55727; AAB38310.1; JOINED. DR EMBL; U55728; AAB38310.1; JOINED. DR EMBL; U55729; AAB38310.1; JOINED. DR EMBL; U55730; AAB38310.1; JOINED. DR EMBL; U55731; AAB38310.1; JOINED. DR EMBL; U55732; AAB38310.1; JOINED. DR EMBL; U55733; AAB38310.1; JOINED. DR EMBL; U55734; AAB38310.1; JOINED. DR EMBL; U55735; AAB38310.1; JOINED. DR EMBL; U55736; AAB38310.1; JOINED. DR EMBL; U55737; AAB38310.1; JOINED. DR EMBL; U55738; AAB38310.1; JOINED. DR EMBL; U55739; AAB38310.1; JOINED. DR EMBL; U55740; AAB38310.1; JOINED. DR EMBL; U55741; AAB38310.1; JOINED. DR EMBL; U55742; AAB38310.1; JOINED. DR EMBL; U55743; AAB38310.1; JOINED. DR EMBL; U55744; AAB38310.1; JOINED. DR EMBL; U55745; AAB38310.1; JOINED. DR EMBL; U55746; AAB38310.1; JOINED. DR EMBL; U55747; AAB38310.1; JOINED. DR EMBL; U55748; AAB38310.1; JOINED. DR EMBL; U55749; AAB38310.1; JOINED. DR EMBL; U55750; AAB38310.1; JOINED. DR EMBL; U55751; AAB38310.1; JOINED. DR EMBL; U55752; AAB38310.1; JOINED. DR EMBL; U55753; AAB38310.1; JOINED. DR EMBL; U55754; AAB38310.1; JOINED. DR EMBL; U55755; AAB38310.1; JOINED. DR EMBL; U55756; AAB38310.1; JOINED. DR EMBL; U26455; AAA86520.1; -. DR EMBL; X91196; CAA62603.1; -. DR PIR; A43100; A43100. DR Genew; HGNC:795; ATM. DR GK; Q13315; -. DR MIM; 607585; -. DR MIM; 208900; -. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS. DR GO; GO:0006281; P:DNA repair; TAS. DR GO; GO:0007131; P:meiotic recombination; TAS. DR GO; GO:0000074; P:regulation of cell cycle; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR003151; FAT. DR InterPro; IPR003152; FATC. DR InterPro; IPR000403; PI3_PI4_kinase. DR Pfam; PF02259; FAT; 1. DR Pfam; PF02260; FATC; 1. DR Pfam; PF00454; PI3_PI4_kinase; 1. DR SMART; SM00146; PI3Kc; 1. DR PROSITE; PS00915; PI3_4_KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. KW Transferase; Kinase; Nuclear protein; Cell cycle; DNA repair; KW DNA-binding; Phosphorylation; Polymorphism; Disease mutation; KW Anti-oncogene. FT DOMAIN 1373 1382 C-ABL-BINDING. FT DOMAIN 1966 2566 FAT. FT DOMAIN 2712 3056 PI3K/PI4K. FT VARIANT 49 49 S -> C (in dbSNP:1800054). FT /FTId=VAR_010798. FT VARIANT 126 126 D -> E. FT /FTId=VAR_010799. FT VARIANT 182 182 V -> L. FT /FTId=VAR_010800. FT VARIANT 224 224 K -> E (in AT). FT /FTId=VAR_010801. FT VARIANT 292 292 P -> L (in AT; associated with lymphoma). FT /FTId=VAR_010802. FT VARIANT 323 323 I -> V (in AT). FT /FTId=VAR_010803. FT VARIANT 332 332 Y -> C (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010804. FT VARIANT 350 350 A -> T (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010805. FT VARIANT 352 352 I -> T (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010806. FT VARIANT 514 514 G -> D. FT /FTId=VAR_010807. FT VARIANT 570 570 F -> S (in AT). FT /FTId=VAR_010808. FT VARIANT 705 707 YSS -> FIP (in AT; might be associated FT with susceptibility to cancer). FT /FTId=VAR_010809. FT VARIANT 707 707 S -> P. FT /FTId=VAR_010810. FT VARIANT 750 750 N -> K (in mantle cell lymphoma). FT /FTId=VAR_010811. FT VARIANT 768 768 N -> D (in AT). FT /FTId=VAR_010812. FT VARIANT 785 785 R -> C (in AT). FT /FTId=VAR_010813. FT VARIANT 858 858 F -> L (rare polymorphism; FT dbSNP:1800056). FT /FTId=VAR_010814. FT VARIANT 950 950 L -> R (in AT). FT /FTId=VAR_010815. FT VARIANT 1001 1001 L -> Q (in AT; associated with T-cell FT acute lymphoblastic leukemia). FT /FTId=VAR_010816. FT VARIANT 1040 1040 M -> V (in B-cell non-Hodgkin's FT lymphoma). FT /FTId=VAR_010817. FT VARIANT 1054 1054 P -> R (in dbSNP:1800057). FT /FTId=VAR_010818. FT VARIANT 1082 1082 H -> L (in AT). FT /FTId=VAR_010819. FT VARIANT 1091 1091 E -> D (in AT). FT /FTId=VAR_010820. FT VARIANT 1407 1407 I -> T (in T-prolymphocytic leukemia). FT /FTId=VAR_010821. FT VARIANT 1420 1420 L -> F (rare polymorphism; FT dbSNP:1800058). FT /FTId=VAR_010822. FT VARIANT 1420 1420 L -> P (in AT). FT /FTId=VAR_010823. FT VARIANT 1454 1454 K -> N. FT /FTId=VAR_010824. FT VARIANT 1463 1463 F -> S (in B-cell non-Hodgkin's FT lymphoma). FT /FTId=VAR_010825. FT VARIANT 1465 1465 L -> P (in AT). FT /FTId=VAR_010826. FT VARIANT 1566 1566 P -> R (in AT). FT /FTId=VAR_010827. FT VARIANT 1570 1570 V -> A. FT /FTId=VAR_010828. FT VARIANT 1682 1682 D -> H (in T-prolymphocytic leukemia). FT /FTId=VAR_010829. FT VARIANT 1691 1691 S -> R (in AT and B-cell chronic FT lymphocytic leukemia; could be a rare FT polymorphism; dbSNP:1800059). FT /FTId=VAR_010830. FT VARIANT 1743 1743 T -> I (in AT; associated with FT preleukemic T-cell proliferation). FT /FTId=VAR_010831. FT VARIANT 1812 1813 AF -> V (in AT). FT /FTId=VAR_010832. FT VARIANT 1853 1853 D -> N (common polymorphism; FT dbSNP:1801516). FT /FTId=VAR_010833. FT VARIANT 1853 1853 D -> V (might contribute to B-cell FT chronic lymphocytic leukemia; FT dbSNP:1801673). FT /FTId=VAR_010834. FT VARIANT 1910 1910 L -> H (in T-prolymphocytic leukemia). FT /FTId=VAR_010835. FT VARIANT 1913 1913 V -> G (in AT). FT /FTId=VAR_010836. FT VARIANT 1953 1953 T -> R (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010837. FT VARIANT 2016 2016 D -> G (in AT). FT /FTId=VAR_010838. FT VARIANT 2063 2063 G -> E (in AT). FT /FTId=VAR_010839. FT VARIANT 2067 2067 A -> D (in AT). FT /FTId=VAR_010840. FT VARIANT 2079 2079 V -> I (in dbSNP:1800060). FT /FTId=VAR_010841. FT VARIANT 2139 2139 E -> G (in T-prolymphocytic leukemia; FT somatic mutation). FT /FTId=VAR_010842. FT VARIANT 2164 2164 E -> K (in T-prolymphocytic leukemia). FT /FTId=VAR_010843. FT VARIANT 2218 2218 S -> C (in AT). FT /FTId=VAR_010844. FT VARIANT 2224 2227 MALR -> IS (in AT). FT /FTId=VAR_010845. FT VARIANT 2227 2227 R -> C (in AT). FT /FTId=VAR_010846. FT VARIANT 2246 2252 CIKDILT -> H (in AT). FT /FTId=VAR_010847. FT VARIANT 2274 2274 A -> K (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010848. FT VARIANT 2287 2287 G -> A (in dbSNP:1800061). FT /FTId=VAR_010849. FT VARIANT 2396 2396 T -> S (in T-prolymphocytic leukemia). FT /FTId=VAR_010850. FT VARIANT 2418 2418 K -> KK (in mantle cell lymphoma). FT /FTId=VAR_010851. FT VARIANT 2420 2420 A -> P (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010852. FT VARIANT 2423 2423 E -> G (in mantle cell lymphoma). FT /FTId=VAR_010853. FT VARIANT 2424 2424 V -> G (in AT, B-cell chronic lymphocytic FT leukemia and T-prolymphocytic leukemia; FT associated with increased risk for breast FT cancer). FT /FTId=VAR_010854. FT VARIANT 2427 2428 Missing (in AT; associated with T- FT prolymphocytic leukemia). FT /FTId=VAR_010855. FT VARIANT 2438 2438 T -> I. FT /FTId=VAR_010856. FT VARIANT 2442 2442 Q -> P (in T-prolymphocytic leukemia). FT /FTId=VAR_010857. FT VARIANT 2470 2470 Y -> D (in AT). FT /FTId=VAR_010858. FT VARIANT 2486 2486 R -> G (in T-prolymphocytic leukemia). FT /FTId=VAR_010859. FT VARIANT 2491 2491 W -> R (in AT). FT /FTId=VAR_010860. FT VARIANT 2546 2548 Missing (in AT, T-prolymphocytic leukemia FT and T-cell acute lymphoblastic leukemia). FT /FTId=VAR_010861. FT VARIANT 2554 2554 H -> D (in AT). FT /FTId=VAR_010862. FT VARIANT 2625 2625 D -> Q (in AT; requires 2 nucleotide FT substitutions). FT /FTId=VAR_010863. FT VARIANT 2625 2626 DA -> EP (in AT). FT /FTId=VAR_010864. FT VARIANT 2656 2656 L -> P (in AT; partial functional loss). FT /FTId=VAR_010865. FT VARIANT 2662 2662 Missing (in AT). FT /FTId=VAR_010866. FT VARIANT 2663 2663 Missing (in AT). FT /FTId=VAR_010867. FT VARIANT 2668 2668 E -> G (in AT). FT /FTId=VAR_010868. FT VARIANT 2695 2695 G -> A (in T-prolymphocytic leukemia and FT B-cell chronic lymphocytic leukemia). FT /FTId=VAR_010869. FT VARIANT 2702 2702 I -> R (in AT). FT /FTId=VAR_010870. FT VARIANT 2722 2722 L -> R (in T-prolymphocytic leukemia). FT /FTId=VAR_010871. FT VARIANT 2725 2725 D -> G (in T-prolymphocytic leukemia). FT /FTId=VAR_010872. FT VARIANT 2725 2725 D -> V (in T-prolymphocytic leukemia). FT /FTId=VAR_010873. FT VARIANT 2726 2726 A -> V (in AT). FT /FTId=VAR_010874. FT VARIANT 2732 2732 F -> L (in T-prolymphocytic leukemia). FT /FTId=VAR_010875. FT VARIANT 2765 2765 G -> S (may contribute to breast cancer). FT /FTId=VAR_010876. FT VARIANT 2810 2810 Missing (in T-prolymphocytic leukemia). FT /FTId=VAR_010877. FT VARIANT 2824 2824 C -> Y (in AT). FT /FTId=VAR_010878. FT VARIANT 2827 2827 F -> C (in AT; mild). FT /FTId=VAR_010879. FT VARIANT 2829 2829 P -> L (in AT). FT /FTId=VAR_010880. FT VARIANT 2832 2832 R -> C (in AT and B-cell non-Hodgkin's FT lymphoma). FT /FTId=VAR_010881. FT VARIANT 2849 2849 R -> P (in AT). FT /FTId=VAR_010882. FT VARIANT 2855 2855 S -> R (in AT). FT /FTId=VAR_010883. FT VARIANT 2855 2856 SV -> RI (in AT). FT /FTId=VAR_010884. FT VARIANT 2860 2860 Missing (in AT). FT /FTId=VAR_010885. FT VARIANT 2867 2867 G -> R (in AT). FT /FTId=VAR_010886. FT VARIANT 2871 2872 RH -> S (in T-prolymphocytic leukemia). FT /FTId=VAR_010887. FT VARIANT 2890 2890 L -> V (in T-prolymphocytic leukemia). FT /FTId=VAR_010888. FT VARIANT 2904 2904 E -> G (in AT). FT /FTId=VAR_010889. FT VARIANT 2909 2909 R -> G (in AT). FT /FTId=VAR_010890. FT VARIANT 3003 3003 D -> N. FT /FTId=VAR_010891. FT VARIANT 3006 3006 A -> P (in T-prolymphocytic leukemia). FT /FTId=VAR_010892. FT VARIANT 3008 3008 R -> C (in AT, T-prolymphocytic leukemia FT and mantle cell lymphoma). FT /FTId=VAR_010893. FT VARIANT 3008 3008 R -> H (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010894. FT VARIANT 3018 3018 K -> N (in B-cell chronic lymphocytic FT leukemia). FT /FTId=VAR_010895. FT MUTAGEN 2870 2870 D->A: LOSS OF KINASE ACTIVITY. FT MUTAGEN 2875 2875 N->K: LOSS OF KINASE ACTIVITY. FT CONFLICT 46 46 H -> N (in Ref. 4). FT CONFLICT 56 56 N -> I (in Ref. 4). FT CONFLICT 313 313 Y -> N (in Ref. 4). FT CONFLICT 488 488 W -> G (in Ref. 4). FT CONFLICT 554 554 A -> T (IN REF. 2, 4, 5 AND 8). FT CONFLICT 754 754 Q -> K (in Ref. 4). FT CONFLICT 887 887 E -> G (in Ref. 4). FT CONFLICT 1003 1003 Q -> L (in Ref. 4). FT CONFLICT 1049 1049 L -> W (in Ref. 4). FT CONFLICT 1089 1089 A -> V (in Ref. 4). SQ SEQUENCE 3056 AA; 350641 MW; 9AB9F31BBD58B08D CRC64; MSLVLNDLLI CCRQLEHDRA TERKKEVEKF KRLIRDPETI KHLDRHSDSK QGKYLNWDAV FRFLQKYIQK ETECLRIAKP NVSASTQASR QKKMQEISSL VKYFIKCANR RAPRLKCQEL LNYIMDTVKD SSNGAIYGAD CSNILLKDIL SVRKYWCEIS QQQWLELFSV YFRLYLKPSQ DVHRVLVARI IHAVTKGCCS QTDGLNSKFL DFFSKAIQCA RQEKSSSGLN HILAALTIFL KTLAVNFRIR VCELGDEILP TLLYIWTQHR LNDSLKEVII ELFQLQIYIH HPKGAKTQEK GAYESTKWRS ILYNLYDLLV NEISHIGSRG KYSSGFRNIA VKENLIELMA DICHQVFNED TRSLEISQSY TTTQRESSDY SVPCKRKKIE LGWEVIKDHL QKSQNDFDLV PWLQIATQLI SKYPASLPNC ELSPLLMILS QLLPQQRHGE RTPYVLRCLT EVALCQDKRS NLESSQKSDL LKLWNKIWCI TFRGISSEQI QAENFGLLGA IIQGSLVEVD REFWKLFTGS ACRPSCPAVC CLTLALTTSI VPGAVKMGIE QNMCEVNRSF SLKESIMKWL LFYQLEGDLE NSTEVPPILH SNFPHLVLEK ILVSLTMKNC KAAMNFFQSV PECEHHQKDK EELSFSEVEE LFLQTTFDKM DFLTIVRECG IEKHQSSIGF SVHQNLKESL DRCLLGLSEQ LLNNYSSEIT NSETLVRCSR LLVGVLGCYC YMGVIAEEEA YKSELFQKAN SLMQCAGESI TLFKNKTNEE FRIGSLRNMM QLCTRCLSNC TKKSPNKIAS GFFLRLLTSK LMNDIADICK SLASFIKKPF DRGEVESMED DTNGNLMEVE DQSSMNLFND YPDSSVSDAN EPGESQSTIG AINPLAEEYL SKQDLLFLDM LKFLCLCVTT AQTNTVSFRA ADIRRKLLML IDSSTLEPTK SLHLHMYLML LKELPGEEYP LPMEDVLELL KPLSNVCSLY RRDQDVCKTI LNHVLHVVKN LGQSNMDSEN TRDAQGQFLT VIGAFWHLTK ERKYIFSVRM ALVNCLKTLL EADPYSKWAI LNVMGKDFPV NEVFTQFLAD NHHQVRMLAA ESINRLFQDT KGDSSRLLKA LPLKLQQTAF ENAYLKAQEG MREMSHSAEN PETLDEIYNR KSVLLTLIAV VLSCSPICEK QALFALCKSV KENGLEPHLV KKVLEKVSET FGYRRLEDFM ASHLDYLVLE WLNLQDTEYN LSSFPFILLN YTNIEDFYRS CYKVLIPHLV IRSHFDEVKS IANQIQEDWK SLLTDCFPKI LVNILPYFAY EGTRDSGMAQ QRETATKVYD MLKSENLLGK QIDHLFISNL PEIVVELLMT LHEPANSSAS QSTDLCDFSG DLDPAPNPPH FPSHVIKATF AYISNCHKTK LKSILEILSK SPDSYQKILL AICEQAAETN NVYKKHRILK IYHLFVSLLL KDIKSGLGGA WAFVLRDVIY TLIHYINQRP SCIMDVSLRS FSLCCDLLSQ VCQTAVTYCK DALENHLHVI VGTLIPLVYE QVEVQKQVLD LLKYLVIDNK DNENLYITIK LLDPFPDHVV FKDLRITQQK IKYSRGPFSL LEEINHFLSV SVYDALPLTR LEGLKDLRRQ LELHKDQMVD IMRASQDNPQ DGIMVKLVVN LLQLSKMAIN HTGEKEVLEA VGSCLGEVGP IDFSTIAIQH SKDASYTKAL KLFEDKELQW TFIMLTYLNN TLVEDCVKVR SAAVTCLKNI LATKTGHSFW EIYKMTTDPM LAYLQPFRTS RKKFLEVPRF DKENPFEGLD DINLWIPLSE NHDIWIKTLT CAFLDSGGTK CEILQLLKPM CEVKTDFCQT VLPYLIHDIL LQDTNESWRN LLSTHVQGFF TSCLRHFSQT SRSTTPANLD SESEHFFRCC LDKKSQRTML AVVDYMRRQK RPSSGTIFND AFWLDLNYLE VAKVAQSCAA HFTALLYAEI YADKKSMDDQ EKRSLAFEEG SQSTTISSLS EKSKEETGIS LQDLLLEIYR SIGEPDSLYG CGGGKMLQPI TRLRTYEHEA MWGKALVTYD LETAIPSSTR QAGIIQALQN LGLCHILSVY LKGLDYENKD WCPELEELHY QAAWRNMQWD HCTSVSKEVE GTSYHESLYN ALQSLRDREF STFYESLKYA RVKEVEEMCK RSLESVYSLY PTLSRLQAIG ELESIGELFS RSVTHRQLSE VYIKWQKHSQ LLKDSDFSFQ EPIMALRTVI LEILMEKEMD NSQRECIKDI LTKHLVELSI LARTFKNTQL PERAIFQIKQ YNSVSCGVSE WQLEEAQVFW AKKEQSLALS ILKQMIKKLD ASCAANNPSL KLTYTECLRV CGNWLAETCL ENPAVIMQTY LEKAVEVAGN YDGESSDELR NGKMKAFLSL ARFSDTQYQR IENYMKSSEF ENKQALLKRA KEEVGLLREH KIQTNRYTVK VQRELELDEL ALRALKEDRK RFLCKAVENY INCLLSGEEH DMWVFRLCSL WLENSGVSEV NGMMKRDGMK IPTYKFLPLM YQLAARMGTK MMGGLGFHEV LNNLISRISM DHPHHTLFII LALANANRDE FLTKPEVARR SRITKNVPKQ SSQLDEDRTE AANRIICTIR SRRPQMVRSV EALCDAYIIL ANLDATQWKT QRKGINIPAD QPITKLKNLE DVVVPTMEIK VDHTGEYGNL VTIQSFKAEF RLAGGVNLPK IIDCVGSDGK ERRQLVKGRD DLRQDAVMQQ VFQMCNTLLQ RNTETRKRKL TICTYKVVPL SQRSGVLEWC TGTVPIGEFL VNNEDGAHKR YRPNDFSAFQ CQKKMMEVQK KSFEEKYEVF MDVCQNFQPV FRYFCMEKFL DPAIWFEKRL AYTRSVATSS IVGYILGLGD RHVQNILINE QSAELVHIDL GVAFEQGKIL PTPETVPFRL TRDIVDGMGI TGVEGVFRRC CEKTMEVMRN SQETLLTIVE VLLYDPLFDW TMNPLKALYL QQRPEDETEL HPTLNADDQE CKRNLSDIDQ SFDKVAERVL MRLQEKLKGV EEGTVLSVGG QVNLLIQQAI DPKNLSRLFP GWKAWV // ID BCKD_HUMAN STANDARD; PRT; 412 AA. AC O14874; Q96IN5; DT 15-JUL-1998 (Rel. 36, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, DE mitochondrial precursor (EC 2.7.1.115) (Branched-chain alpha-ketoacid DE dehydrogenase kinase) (BCKDHKIN) (BCKD-kinase). GN BCKDK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RA Chuang J.C., Cox R.P., Chuang D.T.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Placenta; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Catalyzes the phosphorylation and inactivation of the CC branched-chain alpha-ketoacid dehydrogenase complex, the key CC regulatory enzyme of the valine, leucine and isoleucine catabolic CC pathways. Key enzyme that regulate the activity state of the BCKD CC complex (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + [3-methyl-2-oxobutanoate dehydrogenase CC (lipoamide)] = ADP + [3-methyl-2-oxobutanoate dehydrogenase CC (lipoamide)] phosphate. CC -!- SUBUNIT: Monomer (By similarity). CC -!- SUBCELLULAR LOCATION: Mitochondrial matrix. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- PTM: Autophosphorylated (By similarity). CC -!- SIMILARITY: Belongs to the PDK/BCKDK protein kinase family. CC -!- SIMILARITY: Contains 1 histidine kinase domain. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF026548; AAB82714.1; -. DR EMBL; BC007363; AAH07363.1; -. DR InterPro; IPR003594; ATPbind_ATPase. DR InterPro; IPR004358; Bact_sens_pr_C. DR InterPro; IPR005467; His_kinase. DR Pfam; PF02518; HATPase_c; 1. DR PRINTS; PR00344; BCTRLSENSOR. DR SMART; SM00387; HATPase_c; 1. DR PROSITE; PS50109; HIS_KIN; 1. KW Kinase; Transferase; Transit peptide; Mitochondrion; Phosphorylation. FT TRANSIT 1 30 Mitochondrion (By similarity). FT CHAIN 31 412 [3-METHYL-2-OXOBUTANOATE DEHYDROGENASE FT [LIPOAMIDE]] KINASE. FT DOMAIN 159 404 HISTIDINE KINASE. FT MOD_RES 52 52 PHOSPHORYLATION (AUTO-) (BY SIMILARITY). FT CONFLICT 218 218 V -> F (in Ref. 1). SQ SEQUENCE 412 AA; 46360 MW; AC97CF5D151FEFB4 CRC64; MILASVLRSG PGGGLPLRPL LGPALALRAR STSATDTHHV EMARERSKTV TSFYNQSAID AAAEKPSVRL TPTMMLYAGR SQDGSHLLKS ARYLQQELPV RIAHRIKGFR CLPFIIGCNP TILHVHELYI RAFQKLTDFP PIKDQADEAQ YCQLVRQLLD DHKDVVTLLA EGLRESRKHI EDEKLVRYFL DKTLTSRLGI RMLATHHLAL HEDKPDFVGI ICTRLSPKKI IEKWVDFARR LCEHKYGNAP RVRINGHVAA RFPFIPMPLD YILPELLKNA MRATMESHLD TPYNVPDVVI TIANNDVDLI IRISDRGGGI AHKDLDRVMD YHFTTAEAST QDPRISPLFG HLDMHSGAQS GPMHGFGFGL PTSRAYAEYL GGSLQLQSLQ GIGTDVYLRL RHIDGREESF RI // ID C43B_HUMAN STANDARD; PRT; 624 AA. AC Q9Y5P4; Q96Q85; Q96Q88; Q9H2S7; Q9H2S8; DT 28-FEB-2003 (Rel. 41, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Goodpasture antigen-binding protein (EC 2.7.1.37) (GPBP) (Collagen DE type IV alpha 3 binding protein) (StAR-related lipid transfer protein DE 11) (StARD11) (START domain-containing protein 11). GN COL4A3BP OR STARD11. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1), AND CHARACTERIZATION. RX MEDLINE=99230287; PubMed=10212244; RA Raya A., Revert F., Navarro S., Saus J.; RT "Characterization of a novel type of Serine/Threonine kinase that RT specifically phosphorylates the human goodpasture antigen."; RL J. Biol. Chem. 274:12642-12649(1999). RN [2] RP SEQUENCE FROM N.A. (ISOFORMS 1 AND 2). RX MEDLINE=20568301; PubMed=11007769; RA Raya A., Revert-Ros F., Martinez-Martinez P., Navarro S., Rosello E., RA Vieites B., Granero F., Forteza J., Saus J.; RT "Goodpasture antigen-binding protein, the kinase that phosphorylates RT the Goodpasture antigen, is an alternatively spliced variant RT implicated in autoimmune pathogenesis."; RL J. Biol. Chem. 275:40392-40399(2000). RN [3] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Placenta; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE OF 1-77 FROM N.A. RA Ogi T., Yamamoto Y., Ohmori H.; RT "Homo sapiens genomic sequence, containing DINB1 & GPBP gene."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Phosphorylates on Ser and Thr residues the Goodpasture CC autoantigen (in vitro). Isoform 2 seems to be less active. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with COL4A3. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y5P4-1; Sequence=Displayed; CC Name=2; Synonyms=Delta26, GPBPD26; CC IsoId=Q9Y5P4-2; Sequence=VSP_006276; CC -!- TISSUE SPECIFICITY: Widely expressed. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 START domain. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF136450; AAD30288.1; -. DR EMBL; AF232930; AAG42046.1; -. DR EMBL; AF232935; AAG42051.1; -. DR EMBL; BC000102; AAH00102.1; -. DR EMBL; AB036934; BAB58974.1; -. DR EMBL; AB036936; BAB58977.1; -. DR Genew; HGNC:2205; COL4A3BP. DR MIM; 604677; -. DR GO; GO:0004672; F:protein kinase activity; TAS. DR GO; GO:0006955; P:immune response; NAS. DR GO; GO:0006468; P:protein amino acid phosphorylation; TAS. DR InterPro; IPR001849; PH. DR InterPro; IPR002913; START. DR Pfam; PF00169; PH; 1. DR Pfam; PF01852; START; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00234; START; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50848; START; 1. KW Transferase; Kinase; Serine/threonine-protein kinase; Coiled coil; KW Alternative splicing. FT DOMAIN 23 117 PH. FT DOMAIN 263 303 COILED COIL (POTENTIAL). FT DOMAIN 389 618 START. FT VARSPLIC 371 396 Missing (in isoform 2). FT /FTId=VSP_006276. SQ SEQUENCE 624 AA; 70834 MW; A125162492AC5A0E CRC64; MSDNQSWNSS GSEEDPETES GPPVERCGVL SKWTNYIHGW QDRWVVLKNN ALSYYKSEDE TEYGCRGSIC LSKAVITPHD FDECRFDISV NDSVWYLRAQ DPDHRQQWID AIEQHKTESG YGSESSLRRH GSMVSLVSGA SGYSATSTSS FKKGHSLREK LAEMETFRDI LCRQVDTLQK YFDACADAVS KDELQRDKVV EDDEDDFPTT RSDGDFLHST NGNKEKLFPH VTPKGINGID FKGEAITFKA TTAGILATLS HCIELMVKRE DSWQKRLDKE TEKKRRTEEA YKNAMTELKK KSHFGGPDYE EGPNSLINEE EFFDAVEAAL DRQDKIEEQS QSEKVRLHWP TSLPSGDAFS SVGTHRFVQK PYSRSSSMSS IDLVSASDDV HRFSSQVEEM VQNHMTYSLQ DVGGDANWQL VVEEGEMKVY RREVEENGIV LDPLKATHAV KGVTGHEVCN YFWNVDVRND WETTIENFHV VETLADNAII IYQTHKRVWP ASQRDVLYLS VIRKIPALTE NDPETWIVCN FSVDHDSAPL NNRCVRAKIN VAMICQTLVS PPEGNQEISR DNILCKITYV ANVNPGGWAP ASVLRAVAKR EYPKFLKRFT SYVQEKTAGK PILF // ID CARL_HUMAN STANDARD; PRT; 478 AA. AC Q9UHJ6; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 16-OCT-2001 (Rel. 40, Last annotation update) DE Carbohydrate kinase-like protein (EC 2.7.1.-). GN CARKL. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Fetal kidney; RX MEDLINE=20138496; PubMed=10673275; RA Touchman J.W., Anikster Y., Dietrich N.L., Maduro V.V., McDowell G., RA Shotelersuk V., Bouffard G.G., Beckstrom-Sternberg S.M., Gahl W.A., RA Green E.D.; RT "The genomic region encompassing the nephropathic cystinosis gene RT (CTNS): complete sequencing of a 200-kb segment and discovery of a RT novel gene within the common cystinosis-causing deletion."; RL Genome Res. 10:165-173(2000). CC -!- SUBCELLULAR LOCATION: Cytoplasmic (Potential). CC -!- TISSUE SPECIFICITY: Strongly expressed in liver, kidney and CC pancreas. Expressed at lower levels in placenta and heart. Very CC weakly expressed in lung and brain. CC -!- SIMILARITY: Belongs to the fucokinase / gluconokinase / CC glycerokinase / xylulokinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF163573; AAF24936.1; -. DR EMBL; AF168787; AAF43103.1; -. DR Genew; HGNC:1492; CARKL. DR MIM; 605060; -. DR GO; GO:0005975; P:carbohydrate metabolism; TAS. DR InterPro; IPR000577; FGGY_kin. DR Pfam; PF00370; FGGY; 1. DR PROSITE; PS00933; FGGY_KINASES_1; FALSE_NEG. DR PROSITE; PS00445; FGGY_KINASES_2; FALSE_NEG. KW Transferase; Kinase. SQ SEQUENCE 478 AA; 51503 MW; 3A7D0B3FBE86AC1C CRC64; MAARPITLGI DLGTTSVKAA LLRAAPDDPS GFAVLASCAR AARAEAAVES AVAGPQGREQ DVSRILQALH ECLAALPRPQ LRSVVGIGVS GQMHGVVFWK TGQGCEWTEG GITPVFEPRA VSHLVTWQDG RCSSEFLASL PQPKSHLSVA TGFGCATIFW LLKYRPEFLK SYDAAGTIHD YVVAMLCGLP RPLMSDQNAA SWGYFNTQSQ SWNVKTLRSS GFPVHLLPDI AEPGSVAGRT SHMWFEIPKG TQVGVALGDL QASVYSCMAQ RTDAVLNIST SVQLAASMPS GFQPAQTPDP TAPVAYFPYF NRTYLGVAAS LNGGNVLATF VHMLVQWMAD LGLEVEESTV YSRMIQAAVQ QRDTHLTITP TVLGERHLPD QLASVTRISS SDLSLGHVTR ALCRGIVQNL HSMLPIQQLQ EWGVERVMGS GSALSRNDVL KQEVQRAFPL PMSFGQDVDA AVGAALVMLR RHLNQKES // ID CEK1_HUMAN STANDARD; PRT; 537 AA. AC Q8TCT0; Q9BYB3; Q9UGE5; DT 10-OCT-2003 (Rel. 42, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Ceramide kinase (EC 2.7.1.138) (Acylsphingosine kinase) (hCERK) (Lipid DE kinase 4) (LK4). GN CERK OR KIAA1646. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND CHARACTERIZATION. RC TISSUE=Leukemia; RX MEDLINE=22075121; PubMed=11956206; RA Sugiura M., Kono K., Liu H., Shimizugawa T., Minekura H., Spiegel S., RA Kohama T.; RT "Ceramide kinase, a novel lipid kinase. Molecular cloning and RT functional characterization."; RL J. Biol. Chem. 277:23294-23300(2002). RN [2] RP SEQUENCE FROM N.A. RA Van Veldhoven P.P.; RT "A search for lipid kinases."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. RX MEDLINE=20057165; PubMed=10591208; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., RA Khan A.S., Lane L., Tilahun Y., Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [4] RP SEQUENCE OF 57-537 FROM N.A. RC TISSUE=Brain; RX MEDLINE=21156230; PubMed=11258795; RA Hirosawa M., Nagase T., Murahashi Y., Kikuno R., Ohara O.; RT "Identification of novel transcribed sequences on human chromosome 22 RT by expressed sequence tag mapping."; RL DNA Res. 8:1-9(2001). CC -!- FUNCTION: Catalyzes specifically the phosphorylation of ceramide CC to form ceramide 1-phosphate. Acts efficiently on natural and CC analog ceramides (C6, C8, C16 ceramides, and C8-dihydroceramide), CC to a lesser extent on C2-ceramide and C6-dihydroceramide, but not CC on other lipids, such as various sphingosines. CC -!- CATALYTIC ACTIVITY: ATP + ceramide = ADP + ceramide 1-phosphate. CC -!- COFACTOR: Calcium and magnesium. CC -!- SUBCELLULAR LOCATION: Cytoplasmic and membrane-associated. CC -!- TISSUE SPECIFICITY: High level expression in heart, brain, CC skeletal muscle, kidney and liver; moderate in peripheral blood CC leukocytes and thymus; very low in spleen, small intestine, CC placenta and lung. CC -!- MISCELLANEOUS: Optimal pH is 6.0-7.5. CC -!- SIMILARITY: Contains 1 DAGKc domain. CC -!- CAUTION: Ref.3 sequence differs from that shown due to CC erroneous gene model prediction. An additional exon may exist CC between amino acid positions 168 and 169. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AB079066; BAC01154.1; -. DR EMBL; AJ457828; CAD29884.1; -. DR EMBL; AL096766; CAB62977.1; ALT_SEQ. DR EMBL; AL118516; -; NOT_ANNOTATED_CDS. DR EMBL; AB051433; BAB33316.1; -. DR Genew; HGNC:19256; CERK. DR GO; GO:0000299; C:integral to membrane of membrane fraction; IDA. DR GO; GO:0004685; F:calcium/calmodulin-dependent protein kinase...; IDA. DR GO; GO:0001729; F:ceramide kinase activity; IDA. DR GO; GO:0000287; F:magnesium ion binding; IDA. DR GO; GO:0006672; P:ceramide metabolism; TAS. DR InterPro; IPR001206; DAGKc. DR Pfam; PF00781; DAGKc; 1. DR ProDom; PD005043; DAGKc; 1. KW Transferase; Kinase; Calcium; Magnesium. FT DOMAIN 132 278 DAGKC. SQ SEQUENCE 537 AA; 59977 MW; 3DBFC0ED8D679F7F CRC64; MGATGAAEPL QSVLWVKQQR CAVSLEPARA LLRWWRSPGP GAGAPGADAC SVPVSEIIAV EETDVHGKHQ GSGKWQKMEK PYAFTVHCVK RARRHRWKWA QVTFWCPEEQ LCHLWLQTLR EMLEKLTSRP KHLLVFINPF GGKGQGKRIY ERKVAPLFTL ASITTDIIVT EHANQAKETL YEINIDKYDG IVCVGGDGMF SEVLHGLIGR TQRSAGVDQN HPRAVLVPSS LRIGIIPAGS TDCVCYSTVG TSDAETSALH IVVGDSLAMD VSSVHHNSTL LRYSVSLLGY GFYGDIIKDS EKKRWLGLAR YDFSGLKTFL SHHCYEGTVS FLPAQHTVGS PRDRKPCRAG CFVCRQSKQQ LEEEQKKALY GLEAAEDVEE WQVVCGKFLA INATNMSCAC RRSPRGLSPA AHLGDGSSDL ILIRKCSRFN FLRFLIRHTN QQDQFDFTFV EVYRVKKFQF TSKHMEDEDS DLKEGGKKRF GHICSSHPSC CCTVSNSSWN CDGEVLHSPA IEVRVHCQLV RLFARGIEEN PKPDSHS // ID COAS_HUMAN STANDARD; PRT; 564 AA. AC Q13057; Q8NBM7; Q8NEW1; Q8WXD4; Q9NRM3; DT 01-NOV-1997 (Rel. 35, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Bifunctional coenzyme A synthase (CoA synthase) (NBP) (POV-2) DE [Includes: Phosphopantetheine adenylyltransferase (EC 2.7.7.3) DE (Pantetheine-phosphate adenylyltransferase) (PPAT) (Dephospho-CoA DE pyrophosphorylase); Dephospho-CoA kinase (EC 2.7.1.24) (DPCK) DE (Dephosphocoenzyme A kinase) (DPCOAK)]. GN COASY. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., FUNCTION, AND TISSUE SPECIFICITY. RX MEDLINE=22050577; PubMed=11923312; RA Daugherty M., Polanuyer B., Farrell M., Scholle M., Lykidis A., RA de Crecy-Lagard V., Osterman A.; RT "Complete reconstitution of the human coenzyme A biosynthetic pathway RT via comparative genomics."; RL J. Biol. Chem. 277:21431-21439(2002). RN [2] RP SEQUENCE FROM N.A., AND SUBUNIT. RX MEDLINE=22067063; PubMed=11994049; RA Aghajanian S., Worrall D.M.; RT "Identification and characterization of the gene encoding the human RT phosphopantetheine adenylyltransferase and dephospho-CoA kinase RT bifunctional enzyme (CoA synthase)."; RL Biochem. J. 365:13-18(2002). RN [3] RP SEQUENCE FROM N.A. RA Ota T., Nishikawa T., Suzuki Y., Kawai-Hio Y., Hayashi K., Ishii S., RA Saito K., Yamamoto J., Wakamatsu A., Nagai T., Nakamura Y., RA Nagahari K., Sugano S., Isogai T.; RT "HRI human cDNA sequencing project."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE OF 165-564 FROM N.A. RA Zhu Y.-B., Han Y.; RT "Molecular cloning of a NBP gene cDNA."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP SEQUENCE OF 332-564 FROM N.A. RC TISSUE=Ovary; RX MEDLINE=96070985; PubMed=8529999; RA Montagna M., Serova O., Sylla B.S., Feunteun J., Lenoir G.M.; RT "A 100-kb physical and transcriptional map around the EDH17B2 gene: RT identification of three novel genes and a pseudogene of a human RT homologue of the rat PRL-1 tyrosine phosphatase."; RL Hum. Genet. 96:532-538(1995). RN [6] RP SEQUENCE OF 340-564 FROM N.A. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP SEQUENCE OF 93-564 FROM N.A. RC TISSUE=Colon, and Muscle; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Bifunctional enzyme that catalyzes the fourth and fifth CC sequential steps of CoA biosynthetic pathway. The fourth reaction CC is catalyzed by the phosphopantetheine adenylyltransferase, coded CC by the coaD domain; the fifth reaction is catalyzed by the CC dephospho-CoA kinase, coded by the coaE domain. May act as a point CC of CoA biosynthesis regulation. CC -!- CATALYTIC ACTIVITY: ATP + pantetheine 4'-phosphate = diphosphate + CC 3'-dephospho-CoA. CC -!- CATALYTIC ACTIVITY: ATP + dephospho-CoA = ADP + CoA. CC -!- PATHWAY: Coenzyme A (CoA) biosynthesis; fourth step. CC -!- PATHWAY: Coenzyme A (CoA) biosynthesis; fifth (last) step. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Cytoplasmic (By similarity). CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined including CC brain, heart, skeletal muscle, colon, thymus, spleen, kidney, CC liver, small intestine, placenta, lung and peripheral blood CC leukocyte. Lowest expression in peripheral blood leukocytes and CC highest in kidney and liver. CC -!- MISCELLANEOUS: For the PPAT reaction, the Km for 4'- CC phoshopantetheine and ATP are 7.6 +/-1.3 and 145 +/-29.8 mM, CC respectively. For the DPCK reaction, the Km for dephospho-CoA and CC ATP are 16.7 +/-1.92 and 34.4 +/-6.6 mM, respectively. CC -!- SIMILARITY: In the central section; belongs to the eukaryotic CC coaD family. CC -!- SIMILARITY: In the C-terminal section; belongs to the coaE family. CC -!- CAUTION: Ref.3 sequence differs from that shown due to a CC frameshift in position 315. CC -!- CAUTION: Ref.5 sequence differs from that shown due to a CC frameshift in position 535. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF453478; AAL50813.1; -. DR EMBL; AY094602; AAM19996.1; -. DR EMBL; AK075415; BAC11605.1; ALT_FRAME. DR EMBL; AF208536; AAF87955.1; ALT_INIT. DR EMBL; U18919; AAA69699.1; ALT_FRAME. DR EMBL; BT007168; AAP35832.1; -. DR EMBL; BC006354; AAH06354.1; ALT_INIT. DR EMBL; BC020985; AAH20985.1; ALT_INIT. DR GO; GO:0000166; F:nucleotide binding; NAS. DR InterPro; IPR004820; Cytidylyltransf. DR InterPro; IPR004821; Cyt_tran_rel. DR InterPro; IPR001977; Depp_CoAkinase. DR Pfam; PF01121; CoaE; 1. DR Pfam; PF01467; CTP_transf_2; 1. DR ProDom; PD003329; Depp_CoAkinase; 1. DR TIGRFAMs; TIGR00125; cyt_tran_rel; 1. DR TIGRFAMs; TIGR00152; TIGR00152; 1. DR PROSITE; PS01294; COAE; 1. KW Coenzyme A biosynthesis; Multifunctional enzyme; Transferase; Kinase; KW Nucleotidyltransferase; ATP-binding. FT DOMAIN 180 358 PHOSPHOPANTETHEINE ADENYLYLTRANSFERASE. FT DOMAIN 359 564 DEPHOSPHO-COA KINASE. FT NP_BIND 365 372 ATP (Potential). FT CONFLICT 55 55 S -> Y (in Ref. 1 and 3). SQ SEQUENCE 564 AA; 62328 MW; 7DC9E93B356C5DB7 CRC64; MAVFRSGLLV LTTPLASLAP RLASILTSAA RLVNHTLYVH LQPGMSLEGP AQPQSSPVQA TFEVLDFITH LYAGADVHRH LDVRILLTNI RTKSTFLPPL PTSVQNLAHP PEVVLTDFQT LDGSQYNPVK QQLVRYATSC YSCCPRLASV LLYSDYGIGE VPVEPLDVPL PSTIRPASPV AGSPKQPVRG YYRGAVGGTF DRLHNAHKVL LSVACILAQE QLVVGVADKD LLKSKLLPEL LQPYTERVEH LSEFLVDIKP SLTFDVIPLL DPYGPAGSDP SLEFLVVSEE TYRGGMAINR FRLENDLEEL ALYQIQLLKD LRHTENEEDK VSSSSFRQRM LGNLLRPPYE RPELPTCLYV IGLTGISGSG KSSIAQRLKG LGAFVIDSDH LGHRAYAPGG PAYQPVVEAF GTDILHKDGI INRKVLGSRV FGNKKQLKIL TDIMWPIIAK LAREEMDRAV AEGKRVCVID AAVLLEAGWQ NLVHEVWTAV IPETEAVRRI VERDGLSEAA AQSRLQSQMS GQQLVEQSHV VLSTLWEPHI TQRQVEKAWA LLQKRIPKTH QALD // ID DCK_HUMAN STANDARD; PRT; 260 AA. AC P27707; DT 01-AUG-1992 (Rel. 23, Created) DT 01-AUG-1992 (Rel. 23, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Deoxycytidine kinase (EC 2.7.1.74) (dCK). GN DCK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND SEQUENCE OF 58-70; 119-127 AND 189-192. RX MEDLINE=91142207; PubMed=1996353; RA Chottiner E.G., Shewach D.S., Datta N.S., Ashcraft E., Gribbin D., RA Ginsburg D., Fox I.H., Mitchell B.S.; RT "Cloning and expression of human deoxycytidine kinase cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 88:1531-1535(1991). RN [2] RP PARTIAL SEQUENCE, AND CHARACTERIZATION. RX MEDLINE=91192170; PubMed=2013338; RA Eriksson S., Cederlund E., Bergman T., Joernvall H., Bohman C.; RT "Characterization of human deoxycytidine kinase. Correlation with RT cDNA sequences."; RL FEBS Lett. 280:363-366(1991). RN [3] RP SUBCELLULAR LOCATION. RX MEDLINE=98004502; PubMed=9342341; RA Johansson M., Brismar S., Karlsson A.; RT "Human deoxycytidine kinase is located in the cell nucleus."; RL Proc. Natl. Acad. Sci. U.S.A. 94:11941-11945(1997). CC -!- FUNCTION: Required for the phosphorylation of several CC deoxyribonucleosides and certain nucleoside analogs widely CC employed as antiviral and chemotherapeutic agents. CC -!- CATALYTIC ACTIVITY: NTP + deoxycytidine = NDP + dCMP. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Nuclear. CC -!- SIMILARITY: Belongs to the DCK/DGK family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M60527; AAA35752.1; -. DR PIR; A38585; A38585. DR PDB; 1P5Z; 01-JUL-03. DR Genew; HGNC:2704; DCK. DR GK; P27707; -. DR MIM; 125450; -. DR GO; GO:0004137; F:deoxycytidine kinase activity; TAS. DR GO; GO:0006220; P:pyrimidine nucleotide metabolism; TAS. DR InterPro; IPR002624; dNK. DR Pfam; PF01712; dNK; 1. KW Transferase; Kinase; ATP-binding; Nuclear protein; 3D-structure. FT NP_BIND 28 35 ATP (Probable). SQ SEQUENCE 260 AA; 30518 MW; 626B9D2D6BED8DBC CRC64; MATPPKRSCP SFSASSEGTR IKKISIEGNI AAGKSTFVNI LKQLCEDWEV VPEPVARWCN VQSTQDEFEE LTMSQKNGGN VLQMMYEKPE RWSFTFQTYA CLSRIRAQLA SLNGKLKDAE KPVLFFERSV YSDRYIFASN LYESECMNET EWTIYQDWHD WMNNQFGQSL ELDGIIYLQA TPETCLHRIY LRGRNEEQGI PLEYLEKLHY KHESWLLHRT LKTNFDYLQE VPILTLDVNE DFKDKYESLV EKVKEFLSTL // ID DGK_HUMAN STANDARD; PRT; 277 AA. AC Q16854; P78532; Q16759; Q96BC1; DT 01-NOV-1997 (Rel. 35, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Deoxyguanosine kinase, mitochondrial precursor (EC 2.7.1.113) (dGK). GN DGUOK OR DGK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=96293511; PubMed=8692979; RA Johansson M., Karlsson A.; RT "Cloning and expression of human deoxyguanosine kinase cDNA."; RL Proc. Natl. Acad. Sci. U.S.A. 93:7258-7262(1996). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=B-cell; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP SEQUENCE OF 18-277 FROM N.A. RC TISSUE=Brain; RX MEDLINE=96314545; PubMed=8706825; RA Wang L., Hellman U., Eriksson S.; RT "Cloning and expression of human mitochondrial deoxyguanosine kinase RT cDNA."; RL FEBS Lett. 390:39-43(1996). RN [4] RP SEQUENCE OF 1-47 FROM N.A. RA Stegmann A.P.A., Mitchell B.S.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Required for the phosphorylation of several CC deoxyribonucleosides and certain nucleoside analogs widely CC employed as antiviral and chemotherapeutic agents. CC -!- CATALYTIC ACTIVITY: ATP + deoxyguanosine = ADP + dGMP. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Mitochondrial. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q16854-1; Sequence=Displayed; CC Name=2; CC IsoId=Q16854-2; Sequence=VSP_003025; CC Name=3; CC IsoId=Q16854-3; Sequence=VSP_003024; CC Name=4; CC IsoId=Q16854-4; Sequence=VSP_003024, VSP_003025; CC Name=5; CC IsoId=Q16854-5; Sequence=VSP_003024, VSP_003026; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest expression in muscle, CC brain, liver and lymphoid tissues. CC -!- SIMILARITY: Belongs to the DCK/DGK family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U41668; AAC50624.1; -. DR EMBL; BC015757; AAH15757.1; -. DR EMBL; X97386; CAA66054.1; -. DR EMBL; U81499; AAB39858.1; -. DR PIR; JC6142; JC6142. DR PIR; S71315; S71315. DR PDB; 1JAG; 05-DEC-01. DR Genew; HGNC:2858; DGUOK. DR GK; Q16854; -. DR MIM; 601465; -. DR GO; GO:0005739; C:mitochondrion; TAS. DR GO; GO:0004138; F:deoxyguanosine kinase activity; TAS. DR GO; GO:0008617; P:guanosine metabolism; TAS. DR InterPro; IPR002624; dNK. DR Pfam; PF01712; dNK; 1. KW Transferase; Kinase; ATP-binding; Mitochondrion; Transit peptide; KW Alternative splicing; 3D-structure. FT TRANSIT 1 39 Mitochondrion (Potential). FT CHAIN 40 277 DEOXYGUANOSINE KINASE. FT NP_BIND 45 52 ATP (Potential). FT VARSPLIC 48 85 Missing (in isoform 3, isoform 4 and FT isoform 5). FT /FTId=VSP_003024. FT VARSPLIC 149 236 Missing (in isoform 2 and isoform 4). FT /FTId=VSP_003025. FT VARSPLIC 47 47 I -> IGNILKQIRGRAPIQET (in isoform 5). FT /FTId=VSP_003026. FT CONFLICT 83 83 T -> N (in Ref. 1). FT CONFLICT 159 159 G -> D (in Ref. 3). FT CONFLICT 212 212 K -> E (in Ref. 3). FT STRAND 39 45 FT TURN 47 48 FT HELIX 51 61 FT TURN 63 64 FT STRAND 66 68 FT HELIX 72 74 FT TURN 75 75 FT HELIX 95 101 FT HELIX 103 123 FT HELIX 128 131 FT STRAND 137 141 FT HELIX 144 149 FT TURN 150 150 FT HELIX 151 157 FT TURN 158 159 FT HELIX 163 179 FT HELIX 181 184 FT STRAND 188 193 FT HELIX 196 205 FT TURN 209 213 FT HELIX 216 230 FT TURN 231 231 FT TURN 240 241 FT HELIX 242 244 FT STRAND 247 251 FT TURN 256 258 FT HELIX 260 275 FT TURN 276 277 SQ SEQUENCE 277 AA; 32056 MW; 53E4514BFC2CB5E5 CRC64; MAAGRLFLSR LRAPFSSMAK SPLEGVSSSR GLHAGRGPRR LSIEGNIAVG KSTFVKLLTK TYPEWHVATE PVATWQNIQA AGTQKACTAQ SLGNLLDMMY REPARWSYTF QTFSFLSRLK VQLEPFPEKL LQARKPVQIF ERSVYSDRYI FAKNLFENGS LSDIEWHIYQ DWHSFLLWEF ASRITLHGFI YLQASPQVCL KRLYQRAREE EKGIELAYLE QLHGQHEAWL IHKTTKLHFE ALMNIPVLVL DVNDDFSEEV TKQEDLMREV NTFVKNL // ID E2K1_HUMAN STANDARD; PRT; 630 AA. AC Q9BQI3; Q8NBW3; Q9HC02; Q9NYE0; Q9P0V6; Q9P1J5; Q9P2H8; Q9UHG4; DT 16-OCT-2001 (Rel. 40, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Eukaryotic translation initiation factor 2 alpha kinase 1 DE (EC 2.7.1.37) (Heme-regulated eukaryotic initiation factor eIF-2-alpha DE kinase) (Heme-regulated inhibitor) (Heme-controlled repressor) DE (HCR) (Hemin-sensitive initiation factor-2 alpha kinase) (PRO1362). GN EIF2AK1 OR HRI OR KIAA1369. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Dermal papilla; RX MEDLINE=20550853; PubMed=11101152; RA Hwang S.-Y., Kim M.-K., Kim J.-C.; RT "Cloning of hHRI, human heme-regulated eukaryotic initiation factor RT 2alpha kinase: down-regulated in epithelial ovarian cancers."; RL Mol. Cells 10:584-591(2000). RN [2] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Skin; RA Cannon G., Naik S.M., Boss J.M., Caughman S.W.; RT "Cloning of the human heme-regulated eukaryotic initiation factor 2- RT alpha kinase from TNF-alpha stimulated dermal microvascular RT endothelial cells."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Brain; RX MEDLINE=20181126; PubMed=10718198; RA Nagase T., Kikuno R., Ishikawa K.-I., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. RT The complete sequences of 150 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [4] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Hypothalamus; RX MEDLINE=20402571; PubMed=10931946; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal RT axis and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [5] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Amygdala; RX MEDLINE=21154917; PubMed=11230166; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [6] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Bone marrow; RX MEDLINE=22279635; PubMed=12391722; RA Omasa T., Chen Y.-G., Mantalaris A., Tsai Y.C., Wu J.H.; RT "Molecular cloning and sequencing of the human heme-regulated RT eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase from bone RT marrow culture."; RL DNA Seq. 13:133-137(2002). RN [7] RP SEQUENCE FROM N.A. (ISOFORM 1), AND VARIANT ARG-558. RC TISSUE=Placenta; RA Isogai T., Ota T., Nishikawa T., Hayashi K., Otsuki T., Sugiyama T., RA Suzuki Y., Nagai K., Sugano S., Ishii S., Kawai-Hio Y., Saito K., RA Yamamoto J., Wakamatsu A., Nakamura Y., Kojima S., Nagahari K., RA Masuho Y., Ono T., Okano K., Yoshikawa Y., Aotsuka S., Sasaki N., RA Hattori A., Okumura K., Iwayanagi T., Ninomiya K.; RT "NEDO human cDNA sequencing project."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Amygdala; RA Ottenwaelder B., Obermaier B., Mewes H.-W., Gassenhuber J., RA Wiemann S.; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [9] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Ovary; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [10] RP SEQUENCE OF 450-630 FROM N.A., AND VARIANT ARG-558. RC TISSUE=Liver; RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J., RA Liu M., He F.; RT "Functional prediction of the coding sequences of 121 new genes RT deduced by analysis of cDNA clones from human fetal liver."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [11] RP INTERACTION WITH CDC37 AND THE HSP90 COMPLEX. RX MEDLINE=20576356; PubMed=11036079; RA Shao J., Grammatikakis N., Scroggins B.T., Uma S., Huang W., RA Chen J.-J., Hartson S.D., Matts R.L.; RT "Hsp90 regulates p50(cdc37) function during the biogenesis of the RT active conformation of the heme-regulated eIF2 alpha kinase."; RL J. Biol. Chem. 276:206-214(2001). CC -!- FUNCTION: Mediates down-regulation of protein synthesis in CC response to various stress conditions by the phosphorylation of CC EIF2S1 at Ser-48 and Ser-51. Protein synthesis is inhibited at the CC level of initiation (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- ENZYME REGULATION: Hemin inactivates EIF2AK1 by promoting the CC formation of a disulfide-linked homodimer. Binding of nitric oxide CC (NO) to the heme iron in the N-terminal heme-binding domain CC activates the kinase activity, while binding of carbon monoxide CC (CO) suppresses kinase activity (By similarity). CC -!- SUBUNIT: Synthesized in an inactive form that binds to the N- CC terminal domain of CDC37. Has to be associated with a multiprotein CC complex containing Hsp90, CDC37 and PPP5C for maturation and CC activation by autophosporylation. The phosphatase PPP5C modulates CC this activation. Homodimer; non-covalently bound in the absence of CC hemin. Converted to an inactive disulfide linked homodimer in the CC presence of hemin (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BQI3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BQI3-2; Sequence=VSP_007589; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Detected in heart, brain, placenta, lung, CC liver, skeletal muscle, pancreas, kidney, spleen, muscle and CC stomach. CC -!- PTM: Activated by autophosphorylation; phosphorylated CC predominantly on serine and threonine residues, but also on CC tyrosine residues (By similarity). CC -!- MISCELLANEOUS: Can bind 2 molecules of heme per polypeptide chain CC (By similarity). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. GCN2 CC subfamily. CC -!- SIMILARITY: Contains 2 heme regulatory motif (HRM) repeats. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF255050; AAF70289.1; -. DR EMBL; AF181071; AAF18391.1; -. DR EMBL; AB037790; BAA92607.1; ALT_INIT. DR EMBL; AF183414; AAG09683.1; -. DR EMBL; AL136563; CAB66498.1; -. DR EMBL; AF147094; AAF66736.1; -. DR EMBL; AK075192; BAC11461.1; -. DR EMBL; AL834494; CAD39152.1; -. DR EMBL; BC006524; AAH06524.1; -. DR EMBL; AF116634; AAF71057.1; ALT_INIT. DR GO; GO:0004694; F:eukaryotic translation initiation factor 2a...; IDA. DR GO; GO:0020037; F:heme binding; ISS. DR GO; GO:0042803; F:protein homodimerization activity; ISS. DR GO; GO:0046777; P:autophosphorylation; ISS. DR GO; GO:0046986; P:negative regulation of hemoglobin biosynthesis; ISS. DR GO; GO:0045993; P:negative regulation of translational initia...; NAS. DR GO; GO:0009605; P:response to external stimulus; IEP. DR GO; GO:0006950; P:response to stress; IEP. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00069; pkinase; 1. DR ProDom; PD000001; Prot_kinase; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. KW Transferase; Kinase; Serine/threonine-protein kinase; KW Protein synthesis inhibitor; ATP-binding; Repeat; Phosphorylation; KW Alternative splicing; Polymorphism. FT DOMAIN 167 582 PROTEIN KINASE. FT NP_BIND 173 181 ATP (By similarity). FT BINDING 196 196 ATP (By similarity). FT ACT_SITE 441 441 By similarity. FT MOD_RES 487 487 PHOSPHORYLATION (AUTO-) (BY SIMILARITY). FT REPEAT 409 414 HRM 1. FT REPEAT 551 556 HRM 2. FT VARSPLIC 244 244 Missing (in isoform 2). FT /FTId=VSP_007589. FT VARIANT 558 558 K -> R (in dbSNP:2640). FT /FTId=VAR_015732. FT CONFLICT 2 2 Q -> L (in Ref. 2). FT CONFLICT 24 32 PPAIDFPAE -> RRHRLSRR (in Ref. 1). FT CONFLICT 137 137 Q -> R (in Ref. 1). FT CONFLICT 171 171 A -> V (in Ref. 2). FT CONFLICT 206 206 T -> P (in Ref. 6). SQ SEQUENCE 630 AA; 71106 MW; D63021651806620B CRC64; MQGGNSGVRK REEEGDGAGA VAAPPAIDFP AEGPDPEYDE SDVPAEIQVL KEPLQQPTFP FAVANQLLLV SLLEHLSHVH EPNPLRSRQV FKLLCQTFIK MGLLSSFTCS DEFSSLRLHH NRAITHLMRS AKERVRQDPC EDISRIQKIR SREVALEAQT SRYLNEFEEL AILGKGGYGR VYKVRNKLDG QYYAIKKILI KGATKTVCMK VLREVKVLAG LQHPNIVGYH TAWIEHVHVI QPRADRAAIE LPSLEVLSDQ EEDREQCGVK NDESSSSSII FAEPTPEKEK RFGESDTENQ NNKSVKYTTN LVIRESGELE STLELQENGL AGLSASSIVE QQLPLRRNSH LEESFTSTEE SSEENVNFLG QTEAQYHLML HIQMQLCELS LWDWIVERNK RGREYVDESA CPYVMANVAT KIFQELVEGV FYIHNMGIVH RDLKPRNIFL HGPDQQVKIG DFGLACTDIL QKNTDWTNRN GKRTPTHTSR VGTCLYASPE QLEGSEYDAK SDMYSLGVVL LELFQPFGTE MERAEVLTGL RTGQLPESLR KRCPVQAKYI QHLTRRNSSQ RPSAIQLLQS ELFQNSGNVN LTLQMKIIEQ EKEIAELKKQ LNLLSQDKGV RDDGKDGGVG // ID EKI1_HUMAN STANDARD; PRT; 452 AA. AC Q9HBU6; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Ethanolamine kinase (EC 2.7.1.82) (EKI). GN EKI1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=21125782; PubMed=11044454; RA Lykidis A., Wang J., Karim M.A., Jackowski S.; RT "Overexpression of a mammalian ethanolamine-specific kinase RT accelerates the CDP-ethanolamine pathway."; RL J. Biol. Chem. 276:2174-2179(2001). RN [2] RP SEQUENCE OF 10-258 FROM N.A. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Highly specific for ethanolamine phosphorylation. May be CC a rate-controlling step in phosphatidylethanolamine biosynthesis. CC -!- CATALYTIC ACTIVITY: ATP + ethanolamine = ADP + O- CC phosphoethanolamine. CC -!- PATHWAY: Phosphatidylethanolamine biosynthesis. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- TISSUE SPECIFICITY: Expressed in kidney, liver, placenta, heart, CC leukocyte, ovary and testis. CC -!- SIMILARITY: Belongs to the choline/ethanolamine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF207600; AAF71220.2; -. DR EMBL; BC006111; AAH06111.1; ALT_INIT. DR GO; GO:0005737; C:cytoplasm; NAS. DR GO; GO:0004305; F:ethanolamine kinase activity; IDA. DR GO; GO:0006646; P:phosphatidylethanolamine biosynthesis; IDA. DR InterPro; IPR002573; Choline_kinase. DR Pfam; PF01633; Choline_kinase; 1. KW Transferase; Kinase. FT ACT_SITE 308 308 By similarity. FT DOMAIN 73 83 POLY-VAL. FT CONFLICT 228 258 RLIARQLAKIHAIHAHNGWIPKSNLWLKMGK -> SLSSLT FT LCKGKTTRCFGLTGCRGSRLLLSFF (in Ref. 2). SQ SEQUENCE 452 AA; 50968 MW; 9AF29EAC556ED91F CRC64; MLCGRPRSSS DNRNFLRERA GLSSAAVQTR IGNSAASRRS PAARPPVPAP PALPRGRPGT EGSTSLSAPA VLVVAVAVVV VVVSAVAWAM ANYIHVPPGS PEVPKLNVTV QDQEEHRCRE GALSLLQHLR PHWDPQEVTL QLFTDGITNK LIGCYVGNTM EDVVLVRIYG NKTELLVDRD EEVKSFRVLQ AHGCAPQLYC TFNNGLCYEF IQGEALDPKH VCNPAIFRLI ARQLAKIHAI HAHNGWIPKS NLWLKMGKYF SLIPTGFADE DINKRFLSDI PSSQILQEEM TWMKEILSNL GSPVVLCHND LLCKNIIYNE KQGDVQFIDY EYSGYNYLAY DIGNHFNEFA GVSDVDYSLY PDRELQSQWL RAYLEAYKEF KGFGTEVTEK EVEILFIQVN QFALASHFFW GLWALIQAKY STIEFDFLGY AIVRFNQYFK MKPEVTALKV PE // ID EKI2_HUMAN STANDARD; PRT; 394 AA. AC Q9NVF9; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Ethanolamine kinase-like protein EKI2 (FLJ10761). GN EKI2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RA Isogai T., Ota T., Hayashi K., Sugiyama T., Otsuki T., Suzuki Y., RA Nishikawa T., Nagai K., Sugano S., Ishibashi T., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Ishii S., Kawai Y., RA Saito K., Yamamoto J., Wakamatsu A., Nakamura Y., Nagahari K., RA Masuho Y., Kanehori K.; RT "NEDO human cDNA sequencing project."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP TISSUE SPECIFICITY. RX MEDLINE=21125782; PubMed=11044454; RA Lykidis A., Wang J., Karim M.A., Jackowski S.; RT "Overexpression of a mammalian ethanolamine-specific kinase RT accelerates the CDP-ethanolamine pathway."; RL J. Biol. Chem. 276:2174-2179(2001). CC -!- SIMILARITY: Belongs to the choline/ethanolamine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AK001623; BAA91793.1; -. DR GO; GO:0004103; F:choline kinase activity; NAS. DR InterPro; IPR002573; Choline_kinase. DR Pfam; PF01633; Choline_kinase; 1. KW Transferase; Kinase. FT ACT_SITE 247 247 By similarity. SQ SEQUENCE 394 AA; 44871 MW; 5B0D2C035622A81B CRC64; MAVPPSAPQQ RASFHLRRHT PCPQCSWGME EKAAASASCR EPPGPPRAAA VAYFGISVDP DDILPGALRL IQELRPHWKP EQVRTKRFTD GITNKLVACY VEEDMQDCVL VRVYGERTEL LVDRENEVRN FQLLRAHSCA PKLYCTFQNG LCYEYMQGVA LEPEHIREPR LFRLIALEMA KIHTIHANGS LPKPILWHKM HNYFTLVKNE INPSLSADVP KVEVLERELA WLKEHLSQLE SPVVFCHNDL LCKNIIYDSI KGHVRFIDYE YAGYNYQAFD IGNHFNEFAG VNEVDYCLYP ARETQLQWLH YYLQAQKGMA VTPREVQRLY VQVNKFALGP SCVSSTMTAS LQCCRVGNRH GEIARLTLSG LFPGVSLLLG SLGPHPEPVL HHRL // ID F261_HUMAN STANDARD; PRT; 471 AA. AC P16118; Q99951; DT 01-APR-1990 (Rel. 14, Created) DT 01-NOV-1997 (Rel. 35, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 (6PF-2-K/Fru- DE 2,6-P2ASE liver isozyme) [Includes: 6-phosphofructo-2-kinase DE (EC 2.7.1.105); Fructose-2,6-bisphosphatase (EC 3.1.3.46)]. GN PFKFB1 OR PFRX OR F6PK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=90301497; PubMed=2163524; RA Lange A.J., Pilkis S.J.; RT "Sequence of human liver 6-phosphofructo-2-kinase/fructose-2,6- RT bisphosphatase."; RL Nucleic Acids Res. 18:3652-3652(1990). RN [2] RP SEQUENCE OF 94-471 FROM N.A. RC TISSUE=Liver; RX MEDLINE=88240421; PubMed=2837207; RA Algaier J., Uyeda K.; RT "Molecular cloning, sequence analysis, and expression of a human liver RT cDNA coding for fructose-6-P,2-kinase:fructose-2,6-bisphosphatase."; RL Biochem. Biophys. Res. Commun. 153:328-333(1988). RN [3] RP SEQUENCE OF 1-409 FROM N.A. RA Isherwood J.; RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: D-fructose 2,6-bisphosphate + H(2)O = D- CC fructose 6-phosphate + phosphate. CC -!- ENZYME REGULATION: Phosphorylation results in inhibition of the CC kinase activity. CC -!- SUBUNIT: Homodimer. CC -!- TISSUE SPECIFICITY: Liver. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC phosphoglycerate mutase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X52638; CAA36861.1; -. DR EMBL; M19938; AAA35818.1; -. DR EMBL; Z83821; -; NOT_ANNOTATED_CDS. DR PIR; S12732; S12732. DR PDB; 1K6M; 11-DEC-02. DR Genew; HGNC:8872; PFKFB1. DR GK; P16118; -. DR MIM; 311790; -. DR InterPro; IPR003094; 6Pfruct_kin. DR InterPro; IPR001345; PG/BPGM_mutase. DR Pfam; PF01591; 6PF2K; 1. DR Pfam; PF00300; PGAM; 1. DR PRINTS; PR00991; 6PFRUCTKNASE. DR ProDom; PD002665; 6Pfruct_kin; 1. DR PROSITE; PS00175; PG_MUTASE; 1. KW Multifunctional enzyme; Transferase; Kinase; Hydrolase; ATP-binding; KW Phosphorylation; Multigene family; 3D-structure. FT DOMAIN 1 250 6-PHOSPHOFRUCTO-2-KINASE. FT DOMAIN 251 471 FRUCTOSE-2,6-BISPHOSPHATASE. FT MOD_RES 33 33 PHOSPHORYLATION (BY PKA) (BY SIMILARITY). FT NP_BIND 49 56 ATP (Potential). FT BINDING 105 105 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT ACT_SITE 131 131 Potential. FT ACT_SITE 161 161 Potential. FT BINDING 196 196 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT ACT_SITE 259 259 TELE-PHOSPHOHISTIDINE INTERMEDIATE FT (BY SIMILARITY). FT ACT_SITE 328 328 Potential. FT ACT_SITE 393 393 PROTON DONOR (BY SIMILARITY). FT CONFLICT 305 305 H -> R (in Ref. 1). FT CONFLICT 359 359 R -> H (in Ref. 2). FT CONFLICT 397 398 MR -> HA (in Ref. 2). FT STRAND 43 48 FT TURN 51 52 FT HELIX 55 68 FT TURN 69 70 FT STRAND 73 77 FT HELIX 78 83 FT TURN 84 84 FT HELIX 91 94 FT TURN 96 97 FT HELIX 99 121 FT TURN 122 122 FT STRAND 127 131 FT HELIX 137 150 FT TURN 151 151 FT STRAND 153 160 FT HELIX 164 175 FT TURN 176 177 FT TURN 180 181 FT HELIX 187 202 FT TURN 203 203 FT TURN 209 214 FT STRAND 217 221 FT TURN 222 225 FT STRAND 226 230 FT HELIX 235 244 FT TURN 245 246 FT STRAND 254 258 FT STRAND 262 262 FT HELIX 263 266 FT TURN 267 268 FT STRAND 269 269 FT STRAND 276 276 FT HELIX 278 294 FT TURN 295 295 FT STRAND 300 303 FT HELIX 307 314 FT TURN 315 316 FT STRAND 321 322 FT HELIX 324 326 FT HELIX 332 334 FT TURN 335 336 FT STRAND 338 338 FT HELIX 339 345 FT HELIX 347 355 FT TURN 357 359 FT TURN 363 364 FT HELIX 368 384 FT STRAND 388 392 FT HELIX 394 405 FT TURN 406 406 FT TURN 409 411 FT HELIX 412 414 FT TURN 419 420 FT STRAND 421 427 FT STRAND 432 438 FT TURN 456 457 FT HELIX 460 464 FT TURN 465 466 SQ SEQUENCE 471 AA; 54681 MW; C4FF081A295FB7D3 CRC64; MSPEMGELTQ TRLQKIWIPH SSGSSRLQRR RGSSIPQFTN SPTMVIMVGL PARGKTYIST KLTRYLNWIG TPTKVFNLGQ YRREAVSYKN YEFFLPDNME ALQIRKQCAL AALKDVHNYL SHEEGHVAVF DATNTTRERR SLILQFAKEH GYKVFFIESI CNDPGIIAEN IRQVKLGSPD YIDCDREKVL EDFLKRIECY EVNYQPLDEE LDSHLSYIKI FDVGTRYMVN RVQDHIQSRT VYYLMNIHVT PRSIYLCRHG ESELNIRGRI GGDSGLSVRG KQYAYALANF IQSQGISSLK VWTSHMKRTI QTAEALGVPY EQWKALNEID AGVCEEMTYE EIQEHYPEEF ALRDQDKYRY RYPKGESYED LVQRLEPVIM ELERQENVLV ICHQAVMRCL LAYFLDKSSD ELPYLKCPLH TVLKLTPVAY GCKVESIYLN VEAVNTHREK PENVDITREP EEALDTVPAH Y // ID F262_HUMAN STANDARD; PRT; 505 AA. AC O60825; O60824; Q9H3P1; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (6PF-2-K/Fru- DE 2,6-P2ASE heart-type isozyme) (PFK-2/FBPase-2) [Includes: 6- DE phosphofructo-2-kinase (EC 2.7.1.105); Fructose-2,6-bisphosphatase DE (EC 3.1.3.46)]. GN PFKFB2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RX MEDLINE=98314509; PubMed=9652401; RA Heine-Suner D., Diaz-Guillen M.A., Lange A.J., RA Rodriguez de Cordoba S.; RT "Sequence and structure of the human 6-phosphofructo-2- RT kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2)."; RL Eur. J. Biochem. 254:103-110(1998). RN [2] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Heart; RX MEDLINE=21269186; PubMed=11374908; RA Soejima H., Kawamoto S., Akai J., Miyoshi O., Arai Y., Morohka T., RA Matsuo S., Niikawa N., Kimura A., Okubo K., Mukai T.; RT "Isolation of novel heart-specific genes using the BodyMap database."; RL Genomics 74:115-120(2001). RN [3] RP SEQUENCE FROM N.A. (ISOFORM 2). RA Matsutani A.; RT "Human insulinoma PFK2/F26DPase."; RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: D-fructose 2,6-bisphosphate + H(2)O = D- CC fructose 6-phosphate + phosphate. CC -!- ENZYME REGULATION: Phosphorylation results in the activation of CC the kinase activity. CC -!- SUBUNIT: Homodimer (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O60825-1; Sequence=Displayed; CC Name=2; CC IsoId=O60825-2; Sequence=VSP_004675; CC -!- TISSUE SPECIFICITY: Heart. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC phosphoglycerate mutase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AJ005577; CAA06605.1; -. DR EMBL; AJ005578; CAA06606.1; -. DR EMBL; AB044805; BAB19681.1; -. DR EMBL; AF470623; AAL99386.1; -. DR HSSP; P07953; 1TIP. DR Genew; HGNC:8873; PFKFB2. DR GK; O60825; -. DR MIM; 171835; -. DR GO; GO:0003873; F:6-phosphofructo-2-kinase activity; TAS. DR GO; GO:0006000; P:fructose metabolism; TAS. DR InterPro; IPR003094; 6Pfruct_kin. DR InterPro; IPR001345; PG/BPGM_mutase. DR Pfam; PF01591; 6PF2K; 1. DR Pfam; PF00300; PGAM; 1. DR PRINTS; PR00991; 6PFRUCTKNASE. DR ProDom; PD002665; 6Pfruct_kin; 1. DR PROSITE; PS00175; PG_MUTASE; 1. KW Multifunctional enzyme; Transferase; Kinase; Hydrolase; ATP-binding; KW Phosphorylation; Alternative splicing; Multigene family. FT DOMAIN 1 248 6-PHOSPHOFRUCTO-2-KINASE. FT DOMAIN 249 505 FRUCTOSE-2,6-BISPHOSPHATASE. FT MOD_RES 29 29 PHOSPHORYLATION (BY PKA) (BY SIMILARITY). FT NP_BIND 45 52 ATP (Potential). FT BINDING 102 102 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT BINDING 193 193 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT ACT_SITE 128 128 Potential. FT ACT_SITE 158 158 Potential. FT ACT_SITE 257 257 TELE-PHOSPHOHISTIDINE INTERMEDIATE FT (BY SIMILARITY). FT ACT_SITE 326 326 Potential. FT ACT_SITE 391 391 PROTON DONOR (BY SIMILARITY). FT MOD_RES 466 466 PHOSPHORYLATION (BY PKA) (BY SIMILARITY). FT MOD_RES 475 475 PHOSPHORYLATION (BY PKC) (BY SIMILARITY). FT VARSPLIC 451 505 NNFPKNQTPVRMRRNSFTPLSSSNTIRRPRNYSVGSRPLKP FT LSPLRAQDMQEGAD -> AAETTLAVRRRPSAASLMLPC FT (in isoform 2). FT /FTId=VSP_004675. FT CONFLICT 28 28 Missing (IN REF. 1; CAA06605). FT CONFLICT 303 304 QL -> HV (IN REF. 1; CAA06606). FT CONFLICT 372 372 R -> L (IN REF. 1; CAA06606). FT CONFLICT 396 396 R -> H (IN REF. 1; CAA06606). FT CONFLICT 406 406 G -> D (IN REF. 1; CAA06606). FT CONFLICT 427 427 A -> T (IN REF. 1; CAA06606). SQ SEQUENCE 505 AA; 58476 MW; 5CD6A933A7EBF604 CRC64; MSGASSSEQN NNSYETKTPN LRMSEKKCSW ASYMTNSPTL IVMIGLPARG KTYVSKKLTR YLNWIGVPTK VFNLGVYRRE AVKSYKSYDF FRHDNEEAMK IRKQCALVAL EDVKAYLTEE NGQIAVFDAT NTTRERRDMI LNFAEQNSFK VFFVESVCDD PDVIAANILE VKVSSPDYPE RNRENVMEDF LKRIECYKVT YRPLDPDNYD KDLSFIKVIN VGQRFLVNRV QDYIQSKIVY YLMNIHVQPR TIYLCRHGES EFNLLGKIGG DSGLSVRGKQ FAQALRKFLE EQEITDLKVW TSQLKRTIQT AESLGVPYEQ WKILNEIDAG VCEEMTYAEI EKRYPEEFAL RDQEKYLYRY PGGESYQDLV QRLEPVIMEL ERQGNVLVIS HQAVMRCLLA YFLDKGADEL PYLRCPLHTI FKLTPVAYGC KVETIKLNVE AVNTHRDKPT NNFPKNQTPV RMRRNSFTPL SSSNTIRRPR NYSVGSRPLK PLSPLRAQDM QEGAD // ID F263_HUMAN STANDARD; PRT; 520 AA. AC Q16875; O43622; O75902; DT 15-JUL-1998 (Rel. 36, Created) DT 15-JUL-1998 (Rel. 36, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (6PF-2-K/Fru- DE 2,6-P2ASE brain/placenta-type isozyme) (iPFK-2) [Includes: 6- DE phosphofructo-2-kinase (EC 2.7.1.105); Fructose-2,6-bisphosphatase DE (EC 3.1.3.46)]. GN PFKFB3. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Placenta; RX MEDLINE=96271013; PubMed=8830046; RA Sakai A., Kato M., Fukasawa M., Ishiguro M., Furuya E., Sakakibara R.; RT "Cloning of cDNA encoding for a novel isozyme of fructose RT 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human RT placenta."; RL J. Biochem. 119:506-511(1996). RN [2] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Brain; RX MEDLINE=99172090; PubMed=10072580; RA Manzano A., Rosa J.L., Ventura F., Perez J.X., Nadal M., Estivill X., RA Ambrosio S., Gil J., Bartrons R.; RT "Molecular cloning, expression, and chromosomal localization of a RT ubiquitously expressed human 6-phosphofructo-2-kinase/ fructose-2, RT 6-bisphosphatase gene (PFKFB3)."; RL Cytogenet. Cell Genet. 83:214-217(1998). RN [3] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Brain; RA El-Maghrabi M.R.; RT "Human brain 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase."; RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Skeletal muscle; RX MEDLINE=99179012; PubMed=10077634; RA Chesney J., Mitchell R.A., Benigni F., Bacher M., Spiegel L., RA Al-Abed Y., Han J.H., Metz C., Bucala R.; RT "An inducible gene product for 6-phosphofructo-2-kinase with an AU- RT rich instability element: role in tumor cell glycolysis and the RT Warburg effect."; RL Proc. Natl. Acad. Sci. U.S.A. 96:3047-3052(1999). RN [5] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Testis; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: D-fructose 2,6-bisphosphate + H(2)O = D- CC fructose 6-phosphate + phosphate. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q16875-1; Sequence=Displayed; CC Name=2; CC IsoId=Q16875-2; Sequence=VSP_004680; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC phosphoglycerate mutase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; D49817; BAA08624.1; -. DR EMBL; AF109735; AAD08818.1; -. DR EMBL; AF041831; AAB99795.1; -. DR EMBL; AF041823; AAB99795.1; JOINED. DR EMBL; AF041824; AAB99795.1; JOINED. DR EMBL; AF041825; AAB99795.1; JOINED. DR EMBL; AF041826; AAB99795.1; JOINED. DR EMBL; AF041827; AAB99795.1; JOINED. DR EMBL; AF041828; AAB99795.1; JOINED. DR EMBL; AF041829; AAB99795.1; JOINED. DR EMBL; AF041830; AAB99795.1; JOINED. DR EMBL; AF056320; AAC62000.1; -. DR EMBL; BC040482; AAH40482.1; -. DR PIR; JC4626; JC4626. DR HSSP; P07953; 1FBT. DR Genew; HGNC:8874; PFKFB3. DR GK; Q16875; -. DR MIM; 605319; -. DR GO; GO:0003873; F:6-phosphofructo-2-kinase activity; NAS. DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolism; NAS. DR InterPro; IPR003094; 6Pfruct_kin. DR InterPro; IPR001345; PG/BPGM_mutase. DR Pfam; PF01591; 6PF2K; 1. DR Pfam; PF00300; PGAM; 1. DR PRINTS; PR00991; 6PFRUCTKNASE. DR ProDom; PD002665; 6Pfruct_kin; 1. DR PROSITE; PS00175; PG_MUTASE; 1. KW Multifunctional enzyme; Transferase; Kinase; Hydrolase; ATP-binding; KW Phosphorylation; Multigene family; Alternative splicing. FT DOMAIN 1 245 6-PHOSPHOFRUCTO-2-KINASE. FT DOMAIN 246 520 FRUCTOSE-2,6-BISPHOSPHATASE. FT NP_BIND 42 49 ATP (By similarity). FT BINDING 99 99 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT BINDING 190 190 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT ACT_SITE 125 125 Potential. FT ACT_SITE 155 155 Potential. FT ACT_SITE 254 254 TELE-PHOSPHOHISTIDINE INTERMEDIATE FT (BY SIMILARITY). FT ACT_SITE 323 323 Potential. FT ACT_SITE 388 388 PROTON DONOR (BY SIMILARITY). FT MOD_RES 461 461 PHOSPHORYLATION (BY PKA) (BY SIMILARITY). FT MOD_RES 471 471 PHOSPHORYLATION (BY PKC) (BY SIMILARITY). FT VARSPLIC 506 520 NMKGSRSSADSSRKH -> PLLGQACLT (in isoform FT 2). FT /FTId=VSP_004680. FT CONFLICT 136 136 M -> V (in Ref. 3). FT CONFLICT 141 141 A -> G (in Ref. 4). SQ SEQUENCE 520 AA; 59609 MW; A7675A4ADC376879 CRC64; MPLELTQSRV QKIWVPVDHR PSLPRSCGPK LTNSPTVIVM VGLPARGKTY ISKKLTRYLN WIGVPTKVFN VGEYRREAVK QYSSYNFFRP DNEEAMKVRK QCALAALRDV KSYLAKEGGQ IAVFDATNTT RERRHMILHF AKENDFKAFF IESVCDDPTV VASNIMEVKI SSPDYKDCNS AEAMDDFMKR ISCYEASYQP LDPDKCDRDL SLIKVIDVGR RFLVNRVQDH IQSRIVYYLM NIHVQPRTIY LCRHGENEHN LQGRIGGDSG LSSRGKKFAS ALSKFVEEQN LKDLRVWTSQ LKSTIQTAEA LRLPYEQWKA LNEIDAGVCE ELTYEEIRDT YPEEYALREQ DKYYYRYPTG ESYQDLVQRL EPVIMELERQ ENVLVICHQA VLRCLLAYFL DKSAEEMPYL KCPLHTVLKL TPVAYGCRVE SIYLNVESVC THRERSEDAK KGPNPLMRRN SVTPLASPEP TKKPRINSFE EHVASTSAAL PSCLPPEVPT QLPGQNMKGS RSSADSSRKH // ID F264_HUMAN STANDARD; PRT; 468 AA. AC Q16877; DT 15-JUL-1998 (Rel. 36, Created) DT 30-MAY-2000 (Rel. 39, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (6PF-2-K/Fru- DE 2,6-P2ASE testis-type isozyme) [Includes: 6-phosphofructo-2-kinase DE (EC 2.7.1.105); Fructose-2,6-bisphosphatase (EC 3.1.3.46)]. GN PFKFB4. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RA Sakakibara R.; RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=99196986; PubMed=10095107; RA Manzano A., Perez J.X., Nadal M., Estivill X., Lange A., Bartrons R.; RT "Cloning, expression and chromosomal localization of a human testis RT 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene."; RL Gene 229:83-89(1999). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Placenta; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE OF 356-468 FROM N.A. RC TISSUE=Placenta; RX MEDLINE=96271013; PubMed=8830046; RA Sakai A., Kato M., Fukasawa M., Ishiguro M., Furuya E., Sakakibara R.; RT "Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, RT 2-kinase/fructose 2,6-bisphosphatase from human placenta."; RL J. Biochem. 119:506-511(1996). CC -!- FUNCTION: Synthesis and degradation of fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 2,6-bisphosphate. CC -!- CATALYTIC ACTIVITY: D-fructose 2,6-bisphosphate + H(2)O = D- CC fructose 6-phosphate + phosphate. CC -!- ENZYME REGULATION: The most important regulatory mechanism of CC these opposing activities is by phosphorylation and CC dephosphorylation of the enzyme (By similarity). CC -!- SUBUNIT: Homodimer (By similarity). CC -!- SIMILARITY: In the C-terminal section; belongs to the CC phosphoglycerate mutase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; D49818; BAA18921.1; -. DR EMBL; AF108765; AAD09427.1; -. DR EMBL; BC010269; AAH10269.1; -. DR Genew; HGNC:8875; PFKFB4. DR GK; Q16877; -. DR MIM; 605320; -. DR GO; GO:0003873; F:6-phosphofructo-2-kinase activity; NAS. DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolism; NAS. DR InterPro; IPR003094; 6Pfruct_kin. DR InterPro; IPR001345; PG/BPGM_mutase. DR Pfam; PF01591; 6PF2K; 1. DR Pfam; PF00300; PGAM; 1. DR PRINTS; PR00991; 6PFRUCTKNASE. DR ProDom; PD002665; 6Pfruct_kin; 1. DR PROSITE; PS00175; PG_MUTASE; 1. KW Multifunctional enzyme; Transferase; Kinase; Hydrolase; ATP-binding; KW Phosphorylation; Multigene family. FT INIT_MET 0 0 By similarity. FT DOMAIN 1 248 6-PHOSPHOFRUCTO-2-KINASE. FT DOMAIN 249 468 FRUCTOSE-2,6-BISPHOSPHATASE. FT NP_BIND 45 52 ATP (By similarity). FT BINDING 102 102 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT BINDING 193 193 FRUCTOSE-6-PHOSPHATE (BY SIMILARITY). FT ACT_SITE 128 128 Potential. FT ACT_SITE 158 158 Potential. FT ACT_SITE 256 256 TELE-PHOSPHOHISTIDINE INTERMEDIATE FT (BY SIMILARITY). FT ACT_SITE 325 325 Potential. FT ACT_SITE 390 390 PROTON DONOR (BY SIMILARITY). FT MOD_RES 443 443 PHOSPHORYLATION (BY PKC) (POTENTIAL). SQ SEQUENCE 468 AA; 53908 MW; DB96CD59913BDCCB CRC64; ASPRELTQNP LKKIWMPYSN GRPALHACQR GVCMTNCPTL IVMVGLPARG KTYISKKLTR YLNWIGVPTR EFNVGQYRRD VVKTYKSFEF FLPDNEEGLK IRKQCALAAL RDVRRFLSEE GGHVAVFDAT NTTRERRATI FNFGEQNGYK TFFVESICVD PEVIAANIVQ VKLGSPDYVN RDSDEATEDF MRRIECYENS YESLDEDLDR DLSYIKIMDV GQSYVVNRVA DHIQSRIVYY LMNIHVTPRS IYLCRHGESE LNLKGRIGGD PGLSPRGREF AKSLAQFISD QNIKDLKVWT SQMKRTIQTA EALGVPYEQW KVLNEIDAGV CEEMTYEEIQ DNYPLEFALR DQDKYRYRYP KGESYEDLVQ RLEPVIMELE RQENVLVICH QAVMRCLLAY FLDKAAEQLP YLKCPLHTVL KLTPVAYGCK VESIFLNVAA VNTHRDRPQN VDISRPPEEA LVTVPAHQ // ID FN3K_HUMAN STANDARD; PRT; 309 AA. AC Q9H479; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Fructosamine-3-kinase (EC 2.7.1.-). GN FN3K. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., PARTIAL SEQUENCE, ACETYLATION, AND RP CHARACTERIZATION. RC TISSUE=Kidney; RX MEDLINE=20468660; PubMed=11016445; RA Delpierre G., Rider M.H., Collard F., Stroobant V., Vanstapel F., RA Santos H., Van Schaftingen E.; RT "Identification, cloning, and heterologous expression of a mammalian RT fructosamine-3-kinase."; RL Diabetes 49:1627-1634(2000). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: May initiate a process leading to the deglycation of CC fructoselysine and of glycated proteins. May play a role in the CC phosphorylation of 1-deoxy-1-morpholinofructose (DMF), CC fructoselysine, fructoseglycine, fructose and glycated lysozyme. CC -!- SUBUNIT: Monomer (Probable). CC -!- TISSUE SPECIFICITY: Expressed in erythrocytes. CC -!- SIMILARITY: Belongs to the fructosamine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AJ404615; CAC16393.1; -. DR EMBL; BC042680; AAH42680.1; -. DR GO; GO:0030387; F:fructosamine-3-kinase activity; NAS. DR GO; GO:0030393; P:fructoselysine metabolism; NAS. DR InterPro; IPR005581; Fructosamin_kin. DR Pfam; PF03881; Fructosamin_kin; 1. KW Transferase; Kinase; Acetylation. FT MOD_RES 1 1 ACETYLATION. SQ SEQUENCE 309 AA; 35171 MW; BA886A86655DE28F CRC64; MEQLLRAELR TATLRAFGGP GAGCISEGRA YDTDAGPVFV KVNRRTQARQ MFEGEVASLE ALRSTGLVRV PRPMKVIDLP GGGAAFVMEH LKMKSLSSQA SKLGEQMADL HLYNQKLREK LKEEENTVGR RGEGAEPQYV DKFGFHTVTC CGFIPQVNEW QDDWPTFFAR HRLQAQLDLI EKDYADREAR ELWSRLQVKI PDLFCGLEIV PALLHGDLWS GNVAEDDVGP IIYDPASFYG HSEFELAIAL MFGGFPRSFF TAYHRKIPKA PGFDQRLLLY QLFNYLNHWN HFGREYRSPS LGTMRRLLK // ID FN3X_HUMAN STANDARD; PRT; 309 AA. AC Q9HA64; Q9H0U7; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Hypothetical fructosamine kinase-like protein FLJ12171/DKFZp564D202. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Mammary gland; RA Isogai T., Ota T., Hayashi K., Sugiyama T., Otsuki T., Suzuki Y., RA Nishikawa T., Nagai K., Sugano S., Shiratori A., Sudo H., RA Wagatsuma M., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Chiba Y., Ishida S., Murakawa K., Ono Y., Takiguchi S., RA Watanabe S., Kimura K., Murakami K., Ishii S., Kawai Y., Saito K., RA Yamamoto J., Wakamatsu A., Nakamura Y., Nagahari K., Masuho Y., RA Ninomiya K., Iwayanagi T.; RT "NEDO human cDNA sequencing project."; RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE OF 1-197 FROM N.A. RC TISSUE=Brain; RX MEDLINE=21154917; PubMed=11230166; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [3] RP SEQUENCE OF 136-309 FROM N.A. RC TISSUE=Placenta; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- SIMILARITY: Belongs to the fructosamine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AK022233; BAB13992.1; -. DR EMBL; AL136631; CAB66566.1; -. DR EMBL; BC001458; AAH01458.1; -. DR InterPro; IPR005581; Fructosamin_kin. DR Pfam; PF03881; Fructosamin_kin; 1. KW Hypothetical protein; Transferase; Kinase. FT CONFLICT 129 129 G -> W (in Ref. 2). FT CONFLICT 136 138 ERP -> HEA (in Ref. 3). FT CONFLICT 265 265 G -> C (in Ref. 3). FT CONFLICT 278 278 R -> Q (in Ref. 3). SQ SEQUENCE 309 AA; 34440 MW; C34ED1C5BB2A7FF0 CRC64; MEELLRRELG CSSVRATGHS GGGCISQGRS YDTDQGRVFV KVNPKAEARR MFEGEMASLT AILKTNTVKV PKPIKVLDAP GGGSVLVMEH MDMRHLSSHA AKLGAQLADL HLDNKKLGEM RLKEAGTVGR GGGQEERPFV ARFGFDVVTC CGYLPQVNDW QEDWVVFYAR QRIQPQMDMV EKESGDREAL QLWSALQLKI PDLFRDLEII PALLHGDLWG GNVAEDSSGP VIFDPASFYG HSEYELAIAG MFGGFSSSFY SAYHGKIPKA PGFEKRLRLY QLFHYLNHWN HFGSGYRGSS LNIMRNLVK // ID FRAP_HUMAN STANDARD; PRT; 2549 AA. AC P42345; Q9Y4I3; DT 01-NOV-1995 (Rel. 32, Created) DT 01-NOV-1995 (Rel. 32, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE FKBP-rapamycin associated protein (FRAP) (Rapamycin target protein). GN FRAP1 OR FRAP OR FRAP2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=94277209; PubMed=8008069; RA Brown E.J., Albers M.W., Shin T.B., Ichikawa K., Keith C.T., RA Lane W.S., Schreiber S.L.; RT "A mammalian protein targeted by G1-arresting rapamycin-receptor RT complex."; RL Nature 369:756-758(1994). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=98317532; PubMed=9653645; RA Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A.; RT "Molecular cloning and expression analysis of five novel genes in RT chromosome 1p36."; RL Genomics 50:187-198(1998). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2018-2112. RX MEDLINE=96279639; PubMed=8662507; RA Choi J., Chen J., Schreiber S.L., Clardy J.; RT "Structure of the FKBP12-rapamycin complex interacting with the RT binding domain of human FRAP."; RL Science 273:239-242(1996). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2018-2112. RX MEDLINE=99190960; PubMed=10089303; RA Liang J., Choi J., Clardy J.; RT "Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 RT A resolution."; RL Acta Crystallogr. D 55:736-744(1999). CC -!- FUNCTION: ACTS AS THE TARGET FOR THE CELL-CYCLE ARREST AND CC IMMUNOSUPPRESSIVE EFFECTS OF THE FKBP12-RAPAMYCIN COMPLEX. CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. CC -!- SIMILARITY: Contains 8 HEAT repeats. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; L34075; AAA58486.1; -. DR EMBL; U88966; AAC39933.1; -. DR PIR; S45340; S45340. DR PDB; 1AUE; 18-NOV-98. DR PDB; 1FAP; 23-JUL-97. DR PDB; 1NSG; 18-MAR-98. DR PDB; 2FAP; 09-AUG-99. DR PDB; 3FAP; 13-SEP-00. DR PDB; 4FAP; 13-SEP-00. DR Genew; HGNC:3942; FRAP1. DR MIM; 601231; -. DR GO; GO:0000074; P:regulation of cell cycle; TAS. DR InterPro; IPR008938; ARM. DR InterPro; IPR003151; FAT. DR InterPro; IPR003152; FATC. DR InterPro; IPR000357; HEAT. DR InterPro; IPR000403; PI3_PI4_kinase. DR InterPro; IPR008940; Prenyl_trans. DR Pfam; PF02259; FAT; 1. DR Pfam; PF02260; FATC; 1. DR Pfam; PF00454; PI3_PI4_kinase; 1. DR SMART; SM00146; PI3Kc; 1. DR PROSITE; PS50077; HEAT_REPEAT; FALSE_NEG. DR PROSITE; PS00915; PI3_4_KINASE_1; 1. DR PROSITE; PS00916; PI3_4_KINASE_2; 1. DR PROSITE; PS50290; PI3_4_KINASE_3; 1. KW Transferase; Kinase; Repeat; 3D-structure. FT REPEAT 16 53 HEAT 1. FT REPEAT 650 688 HEAT 2. FT REPEAT 859 897 HEAT 3. FT REPEAT 988 1025 HEAT 4. FT REPEAT 1069 1106 HEAT 5. FT REPEAT 1109 1148 HEAT 6. FT REPEAT 1150 1186 HEAT 7. FT DOMAIN 1382 1982 FAT. FT REPEAT 1933 1970 HEAT 8. FT DOMAIN 2182 2549 PI3K/PI4K. FT CONFLICT 353 353 K -> N (in Ref. 2). FT CONFLICT 359 359 S -> N (in Ref. 2). FT CONFLICT 364 364 D -> N (in Ref. 2). FT CONFLICT 390 390 M -> L (in Ref. 2). FT CONFLICT 430 430 R -> L (in Ref. 2). FT CONFLICT 455 457 VLD -> GVE (in Ref. 2). FT CONFLICT 461 461 A -> G (in Ref. 2). FT CONFLICT 482 484 VFT -> FFN (in Ref. 2). FT CONFLICT 489 489 L -> V (in Ref. 2). FT CONFLICT 513 513 L -> I (in Ref. 2). FT CONFLICT 539 539 L -> V (in Ref. 2). FT CONFLICT 553 553 R -> C (in Ref. 2). FT CONFLICT 956 999 MRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPT FT FLN -> ADLPRPVTLSSSHHGCPGHHLHLQVPGTQMCAVP FT APGHAHVPY (in Ref. 2). FT CONFLICT 1075 1075 I -> S (in Ref. 2). FT HELIX 2023 2039 FT TURN 2040 2041 FT HELIX 2044 2060 FT HELIX 2065 2091 FT HELIX 2094 2111 SQ SEQUENCE 2549 AA; 288888 MW; 7D9AD6E784882AB4 CRC64; MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS PAKSTLVESR CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV ETGPMKKLHV STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE SEAESTENSP TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD VPTQVELLIK QATSHENLCQ CYIGWCPFW // ID FUK_HUMAN STANDARD; PRT; 990 AA. AC Q8N0W3; DT 28-FEB-2003 (Rel. 41, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE L-fucose kinase (EC 2.7.1.52) (Fucokinase). GN FUK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=22052376; PubMed=12056818; RA Hinderlich S., Berger M., Blume A., Chen H., Ghaderi D., Bauer C.; RT "Identification of human L-fucose kinase amino acid sequence."; RL Biochem. Biophys. Res. Commun. 294:650-654(2002). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Uterus; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Takes part in the salvage pathway for reutilization of CC fucose from the degradation of oligosaccharides. CC -!- CATALYTIC ACTIVITY: ATP + 6-deoxy-L-galactose = ADP + 6-deoxy-L- CC galactose 1-phosphate. CC -!- SIMILARITY: BELONGS TO THE GHMP KINASE FAMILY. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AJ441184; CAD29647.1; -. DR EMBL; BC032542; AAH32542.1; -. DR InterPro; IPR001174; Galkinase. DR InterPro; IPR006204; GHMP_kinase. DR InterPro; IPR006203; GHMPknse_ATP. DR InterPro; IPR006206; Mev_galkinase. DR Pfam; PF00288; GHMP_kinases; 1. DR PRINTS; PR00960; LMBPPROTEIN. DR PRINTS; PR00959; MEVGALKINASE. DR PROSITE; PS00627; GHMP_KINASES_ATP; FALSE_NEG. KW Kinase; Transferase; ATP-binding. FT NP_BIND 740 751 ATP (Potential). SQ SEQUENCE 990 AA; 107276 MW; EA97E05A26C51B89 CRC64; MGRDFPFDDC GRAFTCLPVE NPEAPVEALV CNLDCLLDIM TYRLGPGSPP GVWVCSTDML LSVPANPGIS WDSFRGARVI ALPGSPAYAQ NHGVYLTDPQ GLVLDIYYQG TEAEIQRCVR PDGRVPLVSG VVFFSVETAE RLLATHVSPP LDACTYLGLD SGARPVQLSL FFDILHCMAE NVTREDFLVG RPPELGQGDA DVAGYLQSAR AQLWRELRDQ PLTMAYVSSG SYSYMTSSAS EFLLSLTLPG APGAQIVHSQ VEEQQLLAAG SSVVSCLLEG PVQLGPGSVL QHCHLQGPIH IGAGCLVTGL DTAHSKALHG RELRDLVLQG HHTRLHGSPG HAFTLVGRLD SWERQGAGTY LNVPWSEFFK RTGVRAWDLW DPETLPAEYC LPSARLFPVL HPSRELGPQD LLWMLDHQED GGEALRAWRA SWRLSWEQLQ PCLDRAATLA SRRDLFFRQA LHKARHVLEA RQDLSLRPLI WAAVREGCPG PLLATLDQVA AGAGDPGVAA RALACVADVL GCMAEGRGGL RSGPAANPEW MRPFSYLECG DLAAGVEALA QERDKWLSRP ALLVRAARHY EGAGQILIRQ AVMSAQHFVS TEQVELPGPG QWVVAECPAR VDFSGGWSDT PPLAYELGGA VLGLAVRVDG RRPIGARARR IPEPELWLAV GPRQDEMTVK IVCRCLADLR DYCQPHAPGA LLKAAFICAG IVHVHSELQL SEQLLRTFGG GFELHTWSEL PHGSGLGTSS ILAGTALAAL QRAAGRVVGT EALIHAVLHL EQVLTTGGGW QDQVGGLMPG IKVGRSRAQL PLKVEVEEVT VPEGFVQKLN DHLLLVYTGK TRLARNLLQD VLRSWYARLP AVVQNAHSLV RQTEECAEGF RQGSLPLLGQ CLTSYWEQKK LMAPGCEPLT VRRMMDVLAP HVHGQSLAGA GGGGFLYLLT KEPQQKEALE AVLAKTEGLG NYSIHLVEVD TQGLSLKLLG TEASTCCPFP // ID FYV1_HUMAN STANDARD; PRT; 578 AA. AC Q9Y2I7; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE FYVE finger-containing phosphoinositide kinase (EC 2.7.1.68) (1- DE phosphatidylinositol-4-phosphate 5-kinase) (PIP5K) (PtdIns(4)P-5- DE kinase) (p235) (Fragment). GN PIP5K3 OR PIKFYVE OR KIAA0981. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=99246063; PubMed=10231032; RA Nagase T., Ishikawa K.-I., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 6:63-70(1999). CC -!- FUNCTION: SUPPORTS THE INTRACELLULAR PIP POOL AND TO A LESSER CC EXTENT, THE PI 4,5-P(2) POOL. IT GENERATES PIP FROM PI AND, TO A CC LESSER EXTENT, PI 4,5-P(2) FROM PI 4-P. THERE ARE INDICATIONS THAT CC IT PHOSPHORYLATES THE D-5 RATHER THAN THE D-4 POSITION. HAS A ROLE CC IN ENDOSOME-RELATED MEMBRANE TRAFFICKING (BY SIMILARITY). CC -!- CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol 4- CC phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. CC -!- COFACTOR: Binds 2.2 zinc equivalents per molecule (By similarity). CC -!- SIMILARITY: Belongs to the PtdIns(4)P-5-kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AB023198; BAA76825.1; -. DR Genew; HGNC:23785; PIP5K3. DR InterPro; IPR002498; PIP5K. DR Pfam; PF01504; PIP5K; 1. DR SMART; SM00330; PIPKc; 1. KW Transferase; Kinase. FT NON_TER 1 1 SQ SEQUENCE 578 AA; 64554 MW; FCBE9CA1F3AAFC22 CRC64; PSVPPSPGRL RQGEESKISA MDASPRNISP GLQNGEKEDR FLTTLSSQSS TSSTHLQLPT PPEVMSEQSV GGPPELDTAS SSEDVFDGHL LGSTDSQVKE KSTMKAIFAN LLPGNSYNPI PFPFDPDKHY LMYEHERVPI AVCEKEPSSI IAFALSCKEY RNALEELSKA TQWNSAEEGL PTNSTSDSRP KSSSPIRLPE MSGGQTNRTT ETEPQPTKKA SGMLSFFRGT AGKSPDLSSQ KRETLRGADS AYYQVGQTGK EGTENQGVEP QDEVDGGDTQ KKQLINPHVE LQFSDANAKF YCRLYYAGEF HKMREVILDS SEEDFIRSLS HSSPWQARGG KSGAAFYATE DDRFILKQMP RLEVQSFLDF APHYFNYITN AVQQKRPTAL AKILGVYRIG YKNSQNNTEK KLDLLVMENL FYGRKMAQVF DLKGSLRNRN VKTDTGKESC DVVLLDENLL KMVRDNPLYI RSHSKAVLRT SIHSDSHFLS SHLIIDYSLL VGRDDTSNEL VVGIIDYIRT FTWDKKLEMV VKSTGILGGQ GKMPTVVSPE LYRTRFCEAM DKYFLMVPDH WTGLGLNC // ID GAL1_HUMAN STANDARD; PRT; 392 AA. AC P51570; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Galactokinase (EC 2.7.1.6) (Galactose kinase). GN GALK1 OR GALK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND VARIANT GALACTOSEMIA MET-32. RX MEDLINE=95400298; PubMed=7670469; RA Stambolian D., Ai Y., Sidjanin D., Nesburn K., Sathe G., Rosenberg M., RA Bergsma D.J.; RT "Cloning of the galactokinase cDNA and identification of mutations in RT two families with cataracts."; RL Nat. Genet. 10:307-312(1995). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=97064967; PubMed=8908517; RA Bergsma D.J., Ai Y., Skach W.R., Nesburn K., Anoia E., RA van Horn S., Stambolian D.; RT "Fine structure of the human galactokinase GALK1 gene."; RL Genome Res. 6:980-985(1996). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP CHARACTERIZATION. RX MEDLINE=95352063; PubMed=7542884; RA Ai Y., Basu M., Bergsma D.J., Stambolian D.; RT "Comparison of the enzymatic activities of human galactokinase GALK1 RT and a related human galactokinase protein GK2."; RL Biochem. Biophys. Res. Commun. 212:687-691(1995). RN [5] RP VARIANT GALACTOSEMIA THR-28. RX MEDLINE=99452591; PubMed=10521295; RA Kalaydjieva L., Perez-Lezaun A., Angelicheva D., Onengut S., Dye D., RA Bosshard N.U., Jordanova A., Savov A., Yanakiev P., Kremensky I., RA Radeva B., Hallmayer J., Markov A., Nedkova V., Tournev I., Aneva L., RA Gitzelmann R.; RT "A founder mutation in the GK1 gene is responsible for galactokinase RT deficiency in Roma (Gypsies)."; RL Am. J. Hum. Genet. 65:1299-1307(1999). RN [6] RP VARIANT GALACTOSEMIA VAL-198. RX MEDLINE=21152290; PubMed=11231902; RA Okano Y., Asada M., Fujimoto A., Ohtake A., Murayama K., Hsiao K.-J., RA Choeh K., Yang Y., Cao Q., Reichardt J.K.V., Niihira S., Imamura T., RA Yamano T.; RT "A genetic factor for age-related cataract: identification and RT characterization of a novel galactokinase variant, 'Osaka,' in RT Asians."; RL Am. J. Hum. Genet. 68:1036-1042(2001). CC -!- FUNCTION: Major enzyme for galactose metabolism. CC -!- CATALYTIC ACTIVITY: ATP + D-galactose = ADP + D-galactose 1- CC phosphate. CC -!- PATHWAY: Galactose metabolism; first step. CC -!- DISEASE: Defects in GALK1 are the cause of galactosemia II CC [MIM:230200], an autosomal recessive deficiency characterized by CC congenital cataracts during infancy and presenile cataracts in the CC adult population. The cataracts are secondary to accumulation of CC galactitol in the lenses. CC -!- SIMILARITY: Belongs to the GHMP kinase family. GalK subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U26401; AAA96147.1; -. DR EMBL; L76927; AAB51607.1; -. DR EMBL; BC001166; AAH01166.1; -. DR Genew; HGNC:4118; GALK1. DR GK; P51570; -. DR MIM; 604313; -. DR MIM; 230200; -. DR GO; GO:0005737; C:cytoplasm; TAS. DR GO; GO:0004335; F:galactokinase activity; TAS. DR GO; GO:0006012; P:galactose metabolism; TAS. DR InterPro; IPR000705; Galactokinase. DR InterPro; IPR001174; Galkinase. DR InterPro; IPR006204; GHMP_kinase. DR InterPro; IPR006203; GHMPknse_ATP. DR InterPro; IPR006206; Mev_galkinase. DR Pfam; PF00288; GHMP_kinases; 1. DR PRINTS; PR00473; GALCTOKINASE. DR PRINTS; PR00960; LMBPPROTEIN. DR PRINTS; PR00959; MEVGALKINASE. DR TIGRFAMs; TIGR00131; gal_kin; 1. DR PROSITE; PS00106; GALACTOKINASE; 1. DR PROSITE; PS00627; GHMP_KINASES_ATP; 1. KW Transferase; Kinase; Galactose metabolism; ATP-binding; KW Disease mutation. FT NP_BIND 134 144 ATP (Potential). FT VARIANT 28 28 P -> T (in galactosemia II). FT /FTId=VAR_008514. FT VARIANT 32 32 V -> M (in galactosemia II). FT /FTId=VAR_002547. FT VARIANT 198 198 A -> V (in galactosemia II; mild FT deficiency; Osaka). FT /FTId=VAR_015746. SQ SEQUENCE 392 AA; 42272 MW; 8D7CFF8FDB0E4718 CRC64; MAALRQPQVA ELLAEARRAF REEFGAEPEL AVSAPGRVNL IGEHTDYNQG LVLPMALELM TVLVGSPRKD GLVSLLTTSE GADEPQRLQF PLPTAQRSLE PGTPRWANYV KGVIQYYPAA PLPGFSAVVV SSVPLGGGLS SSASLEVATY TFLQQLCPDS GTIAARAQVC QQAEHSFAGM PCGIMDQFIS LMGQKGHALL IDCRSLETSL VPLSDPKLAV LITNSNVRHS LASSEYPVRR RQCEEVARAL GKESLREVQL EELEAARDLV SKEGFRRARH VVGEIRRTAQ AAAALRRGDY RAFGRLMVES HRSLRDDYEV SCPELDQLVE AALAVPGVYG SRMTGGGFGG CTVTLLEASA APHAMRHIQE HYGGTATFYL SQAADGAKVL CL // ID GAL2_HUMAN STANDARD; PRT; 458 AA. AC Q01415; DT 01-JUL-1993 (Rel. 26, Created) DT 01-JUL-1993 (Rel. 26, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE N-acetylgalactosamine kinase (EC 2.7.1.-) (GalNAc kinase) DE (Galactokinase 2). GN GALK2 OR GK2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=93066348; PubMed=1438294; RA Lee R.T., Peterson C.L., Calman A.F., Herskowitz I., O'Donnell J.J.; RT "Cloning of a human galactokinase gene (GK2) on chromosome 15 by RT complementation in yeast."; RL Proc. Natl. Acad. Sci. U.S.A. 89:10887-10891(1992). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Placenta; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP CHARACTERIZATION. RX MEDLINE=95352063; PubMed=7542884; RA Ai Y., Basu M., Bergsma D.J., Stambolian D.; RT "Comparison of the enzymatic activities of human galactokinase GALK1 RT and a related human galactokinase protein GK2."; RL Biochem. Biophys. Res. Commun. 212:687-691(1995). RN [4] RP POSSIBLE FUNCTION. RX MEDLINE=96394479; PubMed=8798585; RA Pastuszak I., O'Donnell J., Elbein A.D.; RT "Identification of the GalNAc kinase amino acid sequence."; RL J. Biol. Chem. 271:23653-23656(1996). CC -!- FUNCTION: Acts on GalNac. Also acts as a galactokinase when CC galactose is present at high concentrations. CC -!- CATALYTIC ACTIVITY: ATP + N-acetyl-D-galactosamine = ADP + N- CC acetyl-D-galactosamine 1-phosphate. CC -!- SIMILARITY: Belongs to the GHMP kinase family. GalK subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M84443; AAA58612.1; -. DR EMBL; BC005141; AAH05141.1; -. DR PIR; A46366; A46366. DR Genew; HGNC:4119; GALK2. DR MIM; 137028; -. DR GO; GO:0004335; F:galactokinase activity; TAS. DR GO; GO:0005975; P:carbohydrate metabolism; TAS. DR InterPro; IPR000705; Galactokinase. DR InterPro; IPR006204; GHMP_kinase. DR InterPro; IPR006203; GHMPknse_ATP. DR InterPro; IPR006206; Mev_galkinase. DR Pfam; PF00288; GHMP_kinases; 1. DR PRINTS; PR00473; GALCTOKINASE. DR PRINTS; PR00959; MEVGALKINASE. DR TIGRFAMs; TIGR00131; gal_kin; 1. DR PROSITE; PS00106; GALACTOKINASE; 1. DR PROSITE; PS00627; GHMP_KINASES_ATP; 1. KW Transferase; Kinase; ATP-binding. FT NP_BIND 139 149 ATP (Potential). SQ SEQUENCE 458 AA; 50378 MW; 192B774938F32947 CRC64; MATESPATRR VQVAEHPRLL KLKEMFNSKF GSIPKFYVRA PGRVNIIGEH IDYCGYSVLP MAVEQDVLIA VEPVKTYALQ LANTNPLYPD FSTSANNIQI DKTKPLWHNY FLCGLKGIQE HFGLSNLTGM NCLVDGNIPP SSGLSSSSAL VCCAGLVTLT VLGRNLSKVE LAEICAKSER YIGTEGGGMD QSISFLAEEG TAKLIEFSPL RATDVKLPSG AVFVIANSCV EMNKAATSHF NIRVMECRLA AKLLAKYKSL QWDKVLRLEE VQAKLGISLE EMLLVTEDAL HPEPYNPEEI CRCLGISLEE LRTQILSPNT QDVLIFKLYQ RAKHVYSEAA RVLQFKKICE EAPENMVQLL GELMNQSHMS CRDMYECSCP ELDQLVDICR KFGAQGSRLT GAGWGGCTVS MVPADKLPSF LANVHKAYYQ RSDGSLAPEK QSLFATKPGG GALVLLEA // ID GCVK_HCMVA STANDARD; PRT; 707 AA. AC P16788; DT 01-AUG-1990 (Rel. 15, Created) DT 01-AUG-1990 (Rel. 15, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Ganciclovir kinase (EC 2.7.1.-) (HSRF3 protein). GN UL97. OS Human cytomegalovirus (strain AD169). OC Viruses; dsDNA viruses, no RNA stage; Herpesviridae; OC Betaherpesvirinae; Cytomegalovirus. OX NCBI_TaxID=10360; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=90269039; PubMed=2161319; RA Chee M.S., Bankier A.T., Beck S., Bohni R., Brown C.M., Cerny R., RA Horsnell T., Hutchison C.A. III, Kouzarides T., Martignetti J.A., RA Preddie E., Satchwell S.C., Tomlinson P., Weston K.M., Barrell B.G.; RT "Analysis of the protein-coding content of the sequence of human RT cytomegalovirus strain AD169."; RL Curr. Top. Microbiol. Immunol. 154:125-169(1990). RN [2] RP FUNCTION. RX MEDLINE=92310592; PubMed=1319559; RA Littler E., Stuart A.D., Chee M.S.; RT "Human cytomegalovirus UL97 open reading frame encodes a protein that RT phosphorylates the antiviral nucleoside analogue ganciclovir."; RL Nature 358:160-162(1992). RN [3] RP FUNCTION. RX MEDLINE=92310593; PubMed=1319560; RA Sullivan V., Talarico C.L., Stanat S.C., Davis M., Coen D.M., RA Biron K.K.; RT "A protein kinase homologue controls phosphorylation of ganciclovir RT in human cytomegalovirus-infected cells."; RL Nature 358:162-164(1992). RN [4] RP ERRATUM. RX MEDLINE=92396223; PubMed=1326083; RA Sullivan V., Talarico C.L., Stanat S.C., Davis M., Coen D.M., RA Biron K.K.; RL Nature 359:85-85(1992). RN [5] RP ERRATUM. RA Sullivan V., Talarico C.L., Stanat S.C., Davis M., Coen D.M., RA Biron K.K.; RL Nature 366:756-756(1993). CC -!- FUNCTION: Phosphorylates the antiviral nucleoside analog CC ganciclovir. CC -!- SIMILARITY: Belongs to the Tyr family of protein kinases. HCMV CC ganciclovir subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X17403; CAA35333.1; -. DR PIR; S09862; QQBEJ5. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR ProDom; PD000001; Prot_kinase; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; FALSE_NEG. KW Transferase; Kinase; ATP-binding. FT DOMAIN 41 63 ALA-RICH. FT NP_BIND 337 345 ATP (By similarity). FT BINDING 359 359 ATP (By similarity). FT ACT_SITE 456 456 By similarity. SQ SEQUENCE 707 AA; 78232 MW; 74914183E5A5E03A CRC64; MSSALRSRAR SASLGTTTQG WDPPPLRRPS RARRRQWMRE AAQAAAQAAV QAAQAAAAQV AQAHVDENEV VDLMADEAGG GVTTLTTLSS VSTTTVLGHA TFSACVRSDV MRDGEKEDAA SDKENLRRPV VPSTSSRGSA ASGDGYHGLR CRETSAMWSF EYDRDGDVTS VRRALFTGGS DPSDSVSGVR GGRKRPLRPP LVSLARTPLC RRRVGGVDAV LEENDVELRA ESQDSAVASG PGRIPQPLSG SSGEESATAV EADSTSHDDV HCTCSNDQII TTSIRGLTCD PRMFLRLTHP ELCELSISYL LVYVPKEDDF CHKICYAVDM SDESYRLGQG SFGEVWPLDR YRVVKVARKH SETVLTVWMS GLIRTRAAGE QQQPPSLVGT GVHRGLLTAT GCCLLHNVTV HRRFHTDMFH HDQWKLACID SYRRAFCTLA DAIKFLNHQC RVCHFDITPM NVLIDVNPHN PSEIVRAALC DYSLSEPYPD YNERCVAVFQ ETGTARRIPN CSHRLRECYH PAFRPMPLQK LLICDPHARF PVAGLRRYCM SELSALGNVL GFCLMRLLDR RGLDEVRMGT EALLFKHAGA ACRALENGKL THCSDACLLI LAAQMSYGAC LLGEHGAALV SHTLRFVEAK MSSCRVRAFR RFYHECSQTM LHEYVRKNVE RLLATSDGLY LYNAFRRTTS IICEEDLDGD CRQLFPE // ID GCVK_HSV6U STANDARD; PRT; 562 AA. AC P24446; DT 01-MAR-1992 (Rel. 21, Created) DT 01-MAR-1992 (Rel. 21, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Possible ganciclovir kinase (EC 2.7.1.-). GN U69 OR 15R. OS Human herpesvirus (type 6 / strain Uganda-1102) (HHV6). OC Viruses; dsDNA viruses, no RNA stage; Herpesviridae; OC Betaherpesvirinae; Roseolovirus. OX NCBI_TaxID=10370; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=90080132; PubMed=2152817; RA Lawrence G.L., Chee M., Craxton M.A., Gompels U.A., Honess R.W., RA Barrell B.G.; RT "Human herpesvirus 6 is closely related to human cytomegalovirus."; RL J. Virol. 64:287-299(1990). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=95266321; PubMed=7747482; RA Gompels U.A., Nicholas J., Lawrence G., Jones M., Thomson B.J., RA Martin M.E., Efstathiou S., Craxton M., Macaulay H.A.; RT "The DNA sequence of human herpesvirus-6: structure, coding content, RT and genome evolution."; RL Virology 209:29-51(1995). CC -!- FUNCTION: Phosphorylates the antiviral nucleoside analog CC ganciclovir (By similarity). CC -!- SIMILARITY: Belongs to the Tyr family of protein kinases. HCMV CC ganciclovir subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M68963; AAA65577.1; -. DR EMBL; X83413; CAA58361.1; -. DR PIR; E36769; QQBEH5. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR ProDom; PD000001; Prot_kinase; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; FALSE_NEG. KW Transferase; Kinase; ATP-binding; Early protein. FT NP_BIND 201 209 ATP (By similarity). FT BINDING 218 218 ATP (By similarity). FT ACT_SITE 313 313 By similarity. SQ SEQUENCE 562 AA; 63717 MW; 09111202754CC071 CRC64; MDNGVETPQG QKTQPINLPP VRKKLRKHEG LGKGVKRKLF AEDSSPLKKQ ISACSDMETL SSPVKSECES RSASLDESFG KCKHEIACDC SAIEELLCHE SLLDSPMKLS NAHTIFSSNK WKLELEKIIA SKQIFLDMSE NAELAAYGET LCNLRIFEKI SSPFLFDVQS EERSYSVVYV PHNKELCGQF CQPEKTMARV LGVGAYGKVF DLDKVAIKTA NEDESVISAF IAGVIRAKSG ADLLSHECVI NNLLISNSVC MSHKVSLSRT YDIDLHKFED WDVRNVMNYY SVFCKLADAV RFLNLKCRIN HFDISPMNIF LNHKKEIIFD AVLADYSLSE MHPNYNGTCA IAKEYDKNLQ LVPISRNKFC DMFNPGFRPL VANAMILVNV CGAFDGENNP LRHCNLDLCA FAQVVLSCVL RMTDKRGCRE AQLYYEKRLF ALANEACRLN PLKYPFAYRD ACCKVLAEHV VLLGLLFYRD VVEIYEKLYD FLDERGEFGS RDLFEATFLN NSKLTRRQPI REGLASLQSS EYGEKLLHDL RELFLINSTA DLDKDTSSLF HM // ID GCVK_HSV6Z STANDARD; PRT; 563 AA. AC P52446; Q9IBR7; DT 01-OCT-1996 (Rel. 34, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Possible ganciclovir kinase (EC 2.7.1.-). GN U69 OR CH2R. OS Human herpesvirus (type 6 / strain Z29) (HHV6). OC Viruses; dsDNA viruses, no RNA stage; Herpesviridae; OC Betaherpesvirinae; Roseolovirus. OX NCBI_TaxID=36351; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=99412318; PubMed=10482553; RA Dominguez G., Dambaugh T.R., Stamey F.R., Dewhurst S., Inoue N., RA Pellett P.E.; RT "Human herpesvirus 6B genome sequence: coding content and comparison RT with human herpesvirus 6A."; RL J. Virol. 73:8040-8052(1999). RN [2] RP SEQUENCE OF 284-563 FROM N.A. RX MEDLINE=96195263; PubMed=8634027; RA Lindquester G.J., Inoue N., Allen R.D., Castelli J.W., Stamey F.R., RA Dambaugh T.R., O'Brian J.J., Danovich R.M., Frenkel N., Pellett P.E.; RT "Restriction endonuclease mapping and molecular cloning of the human RT herpesvirus 6 variant B strain Z29 genome."; RL Arch. Virol. 141:367-379(1996). CC -!- FUNCTION: Phosphorylates the antiviral nucleoside analog CC ganciclovir (By similarity). CC -!- SIMILARITY: Belongs to the Tyr family of protein kinases. HCMV CC ganciclovir subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF157706; AAD49670.1; -. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; FALSE_NEG. KW Transferase; Kinase; ATP-binding. FT NP_BIND 202 210 ATP (By similarity). FT BINDING 219 219 ATP (By similarity). FT ACT_SITE 314 314 By similarity. SQ SEQUENCE 563 AA; 63883 MW; 22C6F87A346432C2 CRC64; MDNGVETPQG QKTQPINLPP DRKRLRKHDG LGKGVKRKLF AEDSSPLKKQ IPACSDMETL SSPVKFGCKS RSASALDESF GKCKHETACD CSAIEELLCH ESLLDSPMKL SNAHTIFSSD KWKLELEKII ASKQIFLDMS ENVELVAYGE TLCNLRIFEK ISSPFLFDVQ SEERSYSVVY VPHNKELCGQ FCQPEKTMAR VLGVGAYGKV FDLDKVAIKT ANEDESVISA FIAGVIRAKS GADLLSHDCV INNLLISNSV CMDHKVSLSR TYDVDLYKFE DWDVRNVMNY YSVFCKLADA VRFLNLKCRI NHFDISPMNI FINHKKEIIF DAVLADYSLS EIHPEYNGTC AIAKEYDRNL QLVPISRNKF CDMFNPGFRP LVANAMILVN VCEAFDGENN PLRHCNLDLC AFAQVVLLCV LRMTDKRGCR EAQLYYEKRL FALANEACRL NPLRYPFAYR DACCKVLAEH VVLLGLLFYR DVVDIYEKIY DFLDERGEFG LRDLFEATFL NNSKLTRRQP IRGGLASLQS SEYGEKLLHD LRALFLITSS ADLDKDTSSL FQM // ID GCVK_HSV7J STANDARD; PRT; 546 AA. AC P52344; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Possible ganciclovir kinase (EC 2.7.1.-). GN U69. OS Human herpesvirus (type 7 / strain JI) (HHV7). OC Viruses; dsDNA viruses, no RNA stage; Herpesviridae; OC Alphaherpesvirinae; Simplexvirus. OX NCBI_TaxID=57278; RN [1] RP SEQUENCE FROM N.A. RA Nicholas J.; RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Phosphorylates the antiviral nucleoside analog CC ganciclovir (By similarity). CC -!- SIMILARITY: Belongs to the Tyr family of protein kinases. HCMV CC ganciclovir subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U43400; AAC54730.1; -. DR PIR; T41970; T41970. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR ProDom; PD000001; Prot_kinase; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; FALSE_NEG. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. KW Transferase; Kinase; ATP-binding; Early protein. FT NP_BIND 185 193 ATP (By similarity). FT BINDING 202 202 ATP (By similarity). FT ACT_SITE 297 297 By similarity. SQ SEQUENCE 546 AA; 62853 MW; 4D75A01FE4695528 CRC64; MEQLKTPQNQ KTRPRNMLPK KKGKELKKRP CKVKRKLFGS ENIRPNKKIP LASDVDNELE KKRGSMIRKR SETDLCPDPS VTDLLCHESL TVSPKFERDG LSACTEFENF MDTRKIVLSR NEKSVTDLSA HYPVLCNLGI FERIHSPFLF SIHIDTQSFS VVYVPHKESS CSQFCEPEKN MARILGSGSY GMVYDLNNVA IKASDDLESC ISSYVSGVVR AKAGAQLTSR ECVFKSLLIC NSVCLNHKIS LSKTYDTDLY KFTDWKLENV ENYYSIFCNL AEAVRFLNMV CKINHCDISL ANILIHHKEG IILEAVLADY SLAEVHPQYN GKCGILRQFD HRIQIVPKSY NKLCDMFNPG FRPMIAHKII LVEVYAEFDG KGNPVRHCNL DLCALAQVFL LCVIRMLDER GCREAQKYYE NRLFTYSNEA CTLNPIKYPL EYKDACCKVL AEHLVLFGIL FYREVVDMFE NLYDFLHASG DLSVRDLLEE TYVNDSRDVR RQPIRYRHAQ LQRHEIGQIL LNDLQQLLSI ITISDLEKDP YSVFRV // ID GKP2_HUMAN STANDARD; PRT; 553 AA. AC Q14410; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Glycerol kinase, testis specific 2 (EC 2.7.1.30) (ATP:glycerol 3- DE phosphotransferase) (Glycerokinase) (GK). GN GK2 OR GKP2 OR GKTA. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=95078834; PubMed=7987308; RA Sargent C.A., Young C., Marsh S., Ferguson-Smith M.A., Affara N.A.; RT "The glycerol kinase gene family: structure of the Xp gene, and RT related intronless retroposons."; RL Hum. Mol. Genet. 3:1317-1324(1994). CC -!- FUNCTION: Key enzyme in the regulation of glycerol uptake and CC metabolism. CC -!- CATALYTIC ACTIVITY: ATP + glycerol = ADP + glycerol 3-phosphate. CC -!- PATHWAY: Glycerol utilization; rate-limiting step. CC -!- SUBCELLULAR LOCATION: BOUND TO THE MITOCHONDRIAL SURFACE OR CC CYTOPLASMIC. IN SPERM, THE MAJORITY OF THE ENZYME IS BOUND TO CC MITOCHONDRIA (BY SIMILARITY). CC -!- SIMILARITY: Belongs to the fucokinase / gluconokinase / CC glycerokinase / xylulokinase family. CC -!- CAUTION: This could be the product of a pseudogene. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X78712; CAA55365.1; -. DR PIR; I37417; I37417. DR HSSP; P08859; 1GLJ. DR Genew; HGNC:4291; GK2. DR MIM; 600148; -. DR GO; GO:0005737; C:cytoplasm; NAS. DR GO; GO:0005741; C:mitochondrial outer membrane; NAS. DR GO; GO:0004370; F:glycerol kinase activity; NAS. DR GO; GO:0006071; P:glycerol metabolism; NAS. DR InterPro; IPR000577; FGGY_kin. DR InterPro; IPR005999; Glycerol_kin. DR Pfam; PF00370; FGGY; 1. DR Pfam; PF02782; FGGY_C; 1. DR TIGRFAMs; TIGR01311; glycerol_kin; 1. DR PROSITE; PS00445; FGGY_KINASES_2; 1. DR PROSITE; PS00933; FGGY_KINASES_1; 1. KW Glycerol metabolism; Transferase; Kinase; ATP-binding. FT NP_BIND 167 179 ATP (Probable). SQ SEQUENCE 553 AA; 60609 MW; 8CF53B1686BC4AD6 CRC64; MAAPKTAAVG PLVGAVVQGT NSTRFLVFNS KTAELLSHHK VELTQEFPKE GWVEQDPKEI LQSVYECIAR TCEKLDELNI DISNIKAVGV SNQRETTVIW DKLTGEPLYN AVVWLDLRTQ TTVEDLSKKI PGNSNFVKSK TGLPLSTYFS AVKLRWMLDN VRNVQKAVEE GRALFGTIDS WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKELC DFFEIPMDLL PNVFSSSEIY GLIKTGALEG VPISGCLGDQ CAALVGQMCF QEGQAKNTYG TGCFLLCNTG RKCVFSEHGL LTTVAYKLGR EKPAYYALEG SVAIAGAVIR WLRDNLGIIE TSGDIERLAK EVGTSYGCYF VPAFSGLYAP YWEPSARGIL CGLTQFTNKC HIAFAALEAV CFQTREILEA MNRDCGIPLR HLQVDGGMTN NKVLMQLQAD ILHIPVIKPF MPETTALGAA MAAGAAEGVS VWSLEPQALS VLRMERFEPQ IQATESEIRY ATWKKAVMKS MGWVTSQSPE GGDPSIFCSL PLGFFIVSSM VMLIGARYIS GVP // ID GKP3_HUMAN STANDARD; PRT; 553 AA. AC Q14409; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Glycerol kinase, testis specific 1 (EC 2.7.1.30) (ATP:glycerol 3- DE phosphotransferase) (Glycerokinase) (GK). GN GKP3 OR GKTB. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=95078834; PubMed=7987308; RA Sargent C.A., Young C., Marsh S., Ferguson-Smith M.A., Affara N.A.; RT "The glycerol kinase gene family: structure of the Xp gene, and RT related intronless retroposons."; RL Hum. Mol. Genet. 3:1317-1324(1994). CC -!- FUNCTION: Key enzyme in the regulation of glycerol uptake and CC metabolism. CC -!- CATALYTIC ACTIVITY: ATP + glycerol = ADP + glycerol 3-phosphate. CC -!- PATHWAY: Glycerol utilization; rate-limiting step. CC -!- SUBCELLULAR LOCATION: BOUND TO THE MITOCHONDRIAL SURFACE OR CC CYTOPLASMIC. IN SPERM, THE MAJORITY OF THE ENZYME IS BOUND TO CC MITOCHONDRIA (BY SIMILARITY). CC -!- SIMILARITY: Belongs to the fucokinase / gluconokinase / CC glycerokinase / xylulokinase family. CC -!- CAUTION: This could be the product of a pseudogene. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X78711; CAA55364.1; -. DR HSSP; P08859; 1GLJ. DR Genew; HGNC:4292; GKP3. DR MIM; 600149; -. DR GO; GO:0005737; C:cytoplasm; NAS. DR GO; GO:0005741; C:mitochondrial outer membrane; NAS. DR GO; GO:0004370; F:glycerol kinase activity; NAS. DR GO; GO:0006071; P:glycerol metabolism; NAS. DR InterPro; IPR000577; FGGY_kin. DR InterPro; IPR005999; Glycerol_kin. DR Pfam; PF00370; FGGY; 1. DR Pfam; PF02782; FGGY_C; 1. DR TIGRFAMs; TIGR01311; glycerol_kin; 1. DR PROSITE; PS00445; FGGY_KINASES_2; 1. DR PROSITE; PS00933; FGGY_KINASES_1; 1. KW Glycerol metabolism; Transferase; Kinase; ATP-binding. FT NP_BIND 167 179 ATP (Probable). SQ SEQUENCE 553 AA; 60569 MW; A49F57BF5E7E7D01 CRC64; MAASKKAVLG PLVGAVDQGT SSTRFLVFNS RTAELLSHHQ VEIKQEFPRE GWVEQDPKEI LHSVYECIEK TCEKLGQLNI GISNIKAIGV SNQRETTVAW DKITGEPLYN AVVWLDLRTQ STVESLSKRI PGNNNFVKSK TGLPLSTYFS AVKLRWLLDN VRKVQKAVEE KRALFGTIDS WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKQLC EFFGIPMEIL PHVRSSSEIY GLMKAGALEG VPISGCLGDQ SAALVGQMCF QIGQAKNTYG TGCFLLCNTG HKCVFSDHGL LTTVAYKLGR DKPVYYALEG SVAIAGAVIR WLRDNLGIIK TSEEIEKLAK EVGTSYGCYF VPAFSGLYAP YWEPSARGII CGLTQFTNKC HIAFAALEAV CFQTREILDA MNRDCGIPLS HLQVDGGMTS NKILMQLQAD ILYIPVVKPL MPETTALGAA MAAGAAEGVD VWSLEPEDLS AVTMERFEPQ INAEESEIRY STWKKAVMKS MGWVTTQSPE GGDPSVFCSL PLGFFIVSSM AMLIGARYIS GIP // ID GLPK_HUMAN STANDARD; PRT; 524 AA. AC P32189; Q9UMP0; Q9UMP1; DT 01-OCT-1993 (Rel. 27, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Glycerol kinase (EC 2.7.1.30) (ATP:glycerol 3-phosphotransferase) DE (Glycerokinase) (GK). GN GK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Liver; RX MEDLINE=94004964; PubMed=8401584; RA Guo W., Worley K.C., Adams V., Mason J., Sylvester-Jackson D.E., RA Zhang Y.-H., Towbin J.A., Fogt D.D., Madu S., Wheeler D.A., RA McCabe E.R.B.; RT "Genomic scanning for expressed sequences in Xp21 identifies the RT glycerol kinase gene."; RL Nat. Genet. 4:367-372(1993). RN [2] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Fetal brain; RX MEDLINE=95078834; PubMed=7987308; RA Sargent C.A., Young C., Marsh S., Ferguson-Smith M.A., Affara N.A.; RT "The glycerol kinase gene family: structure of the Xp gene, and RT related intronless retroposons."; RL Hum. Mol. Genet. 3:1317-1324(1994). RN [3] RP SEQUENCE FROM N.A. (ISOFORM 3). RA Sargent C.A., Kidd A., Moore S., Dean J., Besley G.T.N., Affara N.A.; RT "Five cases of isolated glycerol kinase deficiency, including two RT families: failure to find genotype: phenotype correlations."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Blood; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP SEQUENCE OF 77-524 FROM N.A. (ISOFORM 3). RC TISSUE=Fetal brain; RX MEDLINE=93271973; PubMed=8499912; RA Sargent C.A., Affara N.A., Bentley E., Pelmear A., Bailey D.M.D., RA Davey P., Dow D., Leversha M., Aplin H., Besley G.T.N., RA Ferguson-Smith M.A.; RT "Cloning of the X-linked glycerol kinase deficiency gene and its RT identification by sequence comparison to the Bacillus subtilis RT homologue."; RL Hum. Mol. Genet. 2:97-106(1993). RN [6] RP SEQUENCE OF 130-524 FROM N.A. (ISOFORM 1). RC TISSUE=Fetal liver; RX MEDLINE=93271953; PubMed=8499898; RA Walker A.P., Muscatelli F., Monaco A.P.; RT "Isolation of the human Xp21 glycerol kinase gene by positional RT cloning."; RL Hum. Mol. Genet. 2:107-114(1993). RN [7] RP VARIANT GKD VAL-440. RX MEDLINE=96213755; PubMed=8651297; RA Walker A.P., Muscatelli F., Stafford A.N., Chelly J., Dahl N., RA Blomquist H.K., Delanghe J., Willems P.J., Steinmann B., Monaco A.P.; RT "Mutations and phenotype in isolated glycerol kinase deficiency."; RL Am. J. Hum. Genet. 58:1205-1211(1996). RN [8] RP VARIANT GKD ARG-503. RX MEDLINE=98383876; PubMed=9719371; RA Sjarif D.R., Sinke R.J., Duran M., Beemer F.A., Kleijer W.J., RA Ploos van Amstel J.K., Poll-The B.T.; RT "Clinical heterogeneity and novel mutations in the glycerol kinase RT gene in three families with isolated glycerol kinase deficiency."; RL J. Med. Genet. 35:650-656(1998). RN [9] RP VARIANT GKD ASP-288. RX MEDLINE=20311538; PubMed=10736265; RA Gaudet D., Arsenault S., Perusse L., Vohl M.C., St-Pierre J., RA Bergeron J., Despres J.P., Dewar K., Daly M.J., Hudson T., Rioux J.D.; RT "Glycerol as a correlate of impaired glucose tolerance: dissection of RT a complex system by use of a simple genetic trait."; RL Am. J. Hum. Genet. 66:1558-1568(2000). CC -!- FUNCTION: Key enzyme in the regulation of glycerol uptake and CC metabolism. CC -!- CATALYTIC ACTIVITY: ATP + glycerol = ADP + glycerol 3-phosphate. CC -!- PATHWAY: Glycerol utilization; rate-limiting step. CC -!- SUBCELLULAR LOCATION: BOUND TO THE MITOCHONDRIAL SURFACE OR CC CYTOPLASMIC. IN SPERM AND FETAL TISSUES, THE MAJORITY OF THE CC ENZYME IS BOUND TO MITOCHONDRIA, BUT IN ADULT TISSUES, SUCH AS CC LIVER FOUND IN THE CYTOPLASM. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P32189-1; Sequence=Displayed; CC Name=2; CC IsoId=P32189-2; Sequence=VSP_000771; CC Name=3; CC IsoId=P32189-3; Sequence=VSP_000770, VSP_000771; CC -!- TISSUE SPECIFICITY: HIGHLY EXPRESSED IN THE LIVER, KIDNEY AND CC TESTIS. ISOFORMS 2 AND 3 ARE EXPRESSED SPECIFICALLY IN TESTIS AND CC FETAL LIVER, BUT NOT IN THE ADULT LIVER. CC -!- DISEASE: Defects in GK are the cause of GK deficiency (GKD) CC [MIM:307030]. This disease can be either symptomatic with episodic CC metabolic and CNS decompensation or asymptomatic with CC hyperglycerolemia and hyperglyceroluria only. CC -!- SIMILARITY: Belongs to the fucokinase / gluconokinase / CC glycerokinase / xylulokinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; L13943; AAA52576.1; -. DR EMBL; X78211; -; NOT_ANNOTATED_CDS. DR EMBL; AJ252550; CAB54859.1; -. DR EMBL; AJ252551; CAB54859.1; JOINED. DR EMBL; AJ252552; CAB54859.1; JOINED. DR EMBL; AJ252553; CAB54859.1; JOINED. DR EMBL; AJ252554; CAB54859.1; JOINED. DR EMBL; AJ252555; CAB54859.1; JOINED. DR EMBL; AJ252556; CAB54859.1; JOINED. DR EMBL; AJ252557; CAB54859.1; JOINED. DR EMBL; AJ252558; CAB54859.1; JOINED. DR EMBL; AJ252559; CAB54859.1; JOINED. DR EMBL; AJ252560; CAB54859.1; JOINED. DR EMBL; AJ252561; CAB54859.1; JOINED. DR EMBL; AJ252562; CAB54859.1; JOINED. DR EMBL; AJ252563; CAB54859.1; JOINED. DR EMBL; AJ252564; CAB54859.1; JOINED. DR EMBL; AJ252565; CAB54859.1; JOINED. DR EMBL; AJ252566; CAB54859.1; JOINED. DR EMBL; AJ252567; CAB54859.1; JOINED. DR EMBL; AJ252568; CAB54859.1; JOINED. DR EMBL; AJ252569; CAB54859.1; JOINED. DR EMBL; AJ252570; CAB54859.1; JOINED. DR EMBL; AJ252550; CAB54858.1; -. DR EMBL; AJ252551; CAB54858.1; JOINED. DR EMBL; AJ252552; CAB54858.1; JOINED. DR EMBL; AJ252553; CAB54858.1; JOINED. DR EMBL; AJ252554; CAB54858.1; JOINED. DR EMBL; AJ252555; CAB54858.1; JOINED. DR EMBL; AJ252556; CAB54858.1; JOINED. DR EMBL; AJ252557; CAB54858.1; JOINED. DR EMBL; AJ252559; CAB54858.1; JOINED. DR EMBL; AJ252560; CAB54858.1; JOINED. DR EMBL; AJ252561; CAB54858.1; JOINED. DR EMBL; AJ252562; CAB54858.1; JOINED. DR EMBL; AJ252563; CAB54858.1; JOINED. DR EMBL; AJ252564; CAB54858.1; JOINED. DR EMBL; AJ252565; CAB54858.1; JOINED. DR EMBL; AJ252566; CAB54858.1; JOINED. DR EMBL; AJ252567; CAB54858.1; JOINED. DR EMBL; AJ252568; CAB54858.1; JOINED. DR EMBL; AJ252569; CAB54858.1; JOINED. DR EMBL; AJ252570; CAB54858.1; JOINED. DR EMBL; AJ252550; CAB54857.1; -. DR EMBL; AJ252551; CAB54857.1; JOINED. DR EMBL; AJ252552; CAB54857.1; JOINED. DR EMBL; AJ252553; CAB54857.1; JOINED. DR EMBL; AJ252554; CAB54857.1; JOINED. DR EMBL; AJ252555; CAB54857.1; JOINED. DR EMBL; AJ252556; CAB54857.1; JOINED. DR EMBL; AJ252557; CAB54857.1; JOINED. DR EMBL; AJ252559; CAB54857.1; JOINED. DR EMBL; AJ252560; CAB54857.1; JOINED. DR EMBL; AJ252561; CAB54857.1; JOINED. DR EMBL; AJ252562; CAB54857.1; JOINED. DR EMBL; AJ252563; CAB54857.1; JOINED. DR EMBL; AJ252564; CAB54857.1; JOINED. DR EMBL; AJ252565; CAB54857.1; JOINED. DR EMBL; AJ252566; CAB54857.1; JOINED. DR EMBL; AJ252567; CAB54857.1; JOINED. DR EMBL; AJ252568; CAB54857.1; JOINED. DR EMBL; AJ252570; CAB54857.1; JOINED. DR EMBL; BC037549; AAH37549.1; -. DR EMBL; X68285; CAA48346.1; -. DR EMBL; X69886; CAA49512.1; -. DR PIR; I37427; S36175. DR HSSP; P08859; 1GLJ. DR Genew; HGNC:4289; GK. DR GK; P32189; -. DR MIM; 307030; -. DR GO; GO:0005737; C:cytoplasm; NAS. DR GO; GO:0005741; C:mitochondrial outer membrane; NAS. DR GO; GO:0004370; F:glycerol kinase activity; NAS. DR GO; GO:0006071; P:glycerol metabolism; NAS. DR InterPro; IPR000577; FGGY_kin. DR InterPro; IPR005999; Glycerol_kin. DR Pfam; PF00370; FGGY; 1. DR Pfam; PF02782; FGGY_C; 1. DR TIGRFAMs; TIGR01311; glycerol_kin; 1. DR PROSITE; PS00445; FGGY_KINASES_2; 1. DR PROSITE; PS00933; FGGY_KINASES_1; 1. KW Glycerol metabolism; Transferase; Kinase; ATP-binding; Polymorphism; KW Disease mutation; Alternative splicing. FT NP_BIND 167 179 ATP (Probable). FT VARSPLIC 244 244 K -> KISHSVK (in isoform 3). FT /FTId=VSP_000770. FT VARSPLIC 523 524 IP -> DPSIFCSLPLGFFIVSSMVMLIGARYISGIP (in FT isoform 2 and isoform 3). FT /FTId=VSP_000771. FT VARIANT 185 185 S -> N. FT /FTId=VAR_001374. FT VARIANT 232 232 N -> H. FT /FTId=VAR_001375. FT VARIANT 288 288 N -> D (in GKD). FT /FTId=VAR_015433. FT VARIANT 376 376 A -> T. FT /FTId=VAR_001376. FT VARIANT 440 440 D -> V (in GKD). FT /FTId=VAR_001377. FT VARIANT 503 503 W -> R (in GKD). FT /FTId=VAR_010138. FT CONFLICT 201 210 NASRTMLFNI -> MQVGLCFSTC (in Ref. 5). FT CONFLICT 459 524 AAMAAGAAEGVGVWSLEPEDLSAVTMERFEPQINAEESEIR FT YSTWKKAVMKSMGWVTTQSPESGIP -> RLWRQGLQKESA FT YGVSNPRICLPSRWSGLNLRLMRRKVKFVILHGRKL (IN FT REF. 5). SQ SEQUENCE 524 AA; 57489 MW; 0FAA29ADC6054154 CRC64; MAASKKAVLG PLVGAVDQGT SSTRFLVFNS KTAELLSHHQ VEIKQEFPRE GWVEQDPKEI LHSVYECIEK TCEKLGQLNI DISNIKAIGV SNQRETTVVW DKITGEPLYN AVVWLDLRTQ STVESLSKRI PGNNNFVKSK TGLPLSTYFS AVKLRWLLDN VRKVQKAVEE KRALFGTIDS WLIWSLTGGV NGGVHCTDVT NASRTMLFNI HSLEWDKQLC EFFGIPMEIL PNVRSSSEIY GLMKAGALEG VPISGCLGDQ SAALVGQMCF QIGQAKNTYG TGCFLLCNTG HKCVFSDHGL LTTVAYKLGR DKPVYYALEG SVAIAGAVIR WLRDNLGIIK TSEEIEKLAK EVGTSYGCYF VPAFSGLYAP YWEPSARGII CGLTQFTNKC HIAFAALEAV CFQTREILDA MNRDCGIPLS HLQVDGGMTS NKILMQLQAD ILYIPVVKPS MPETTALGAA MAAGAAEGVG VWSLEPEDLS AVTMERFEPQ INAEESEIRY STWKKAVMKS MGWVTTQSPE SGIP // ID HXK1_HUMAN STANDARD; PRT; 917 AA. AC P19367; O43443; O43444; O75574; Q96HC8; Q9NNZ4; Q9NNZ5; DT 01-NOV-1990 (Rel. 16, Created) DT 01-NOV-1990 (Rel. 16, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Hexokinase, type I (EC 2.7.1.1) (HK I) (Brain form hexokinase). GN HK1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RX MEDLINE=89087485; PubMed=3207429; RA Nishi S., Seino S., Bell G.I.; RT "Human hexokinase: sequences of amino- and carboxyl-terminal halves RT are homologous."; RL Biochem. Biophys. Res. Commun. 157:937-943(1988). RN [2] RP SEQUENCE FROM N.A., AND ALTERNATIVE SPLICING. RX MEDLINE=98198402; PubMed=9531504; RA Ruzzo A., Andreoni F., Magnani M.; RT "Structure of the human hexokinase type I gene and nucleotide sequence RT of the 5' flanking region."; RL Biochem. J. 331:607-613(1998). RN [3] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE OF 287-917 FROM N.A. RC TISSUE=Placenta; RX MEDLINE=92344570; PubMed=1637300; RA Magnani M., Bianchi M., Casabianca A., Stocchi V., Daniele A., RA Altruda F., Ferrone M., Silengo L.; RT "A recombinant human 'mini'-hexokinase is catalytically active and RT regulated by hexose 6-phosphates."; RL Biochem. J. 285:193-199(1992). RN [5] RP SEQUENCE OF 11-31 AND 103-120. RC TISSUE=Placenta; RX MEDLINE=91093173; PubMed=1985912; RA Magnani M., Serafini G., Bianchi M., Casabianca A., Stocchi V.; RT "Human hexokinase type I microheterogeneity is due to different RT amino-terminal sequences."; RL J. Biol. Chem. 266:502-505(1991). RN [6] RP SEQUENCE OF 1-20 FROM N.A. (ISOFORM 2). RA Murakami K., Piomelli S.; RT "The erythrocyte-specific hexokinase isozyme (HKR) and the common RT hexokinase isozyme (HKI) are produced from a single gene by alternate RT promoters."; RL Blood 90:272-272(1998). RN [7] RP ALTERNATIVE SPLICING. RX MEDLINE=97180129; PubMed=9028305; RA Murakami K., Piomelli S.; RT "Identification of the cDNA for human red blood cell-specific RT hexokinase isozyme."; RL Blood 89:762-766(1997). RN [8] RP ALTERNATIVE SPLICING. RX MEDLINE=20435276; PubMed=10978502; RA Andreoni F., Ruzzo A., Magnani M.; RT "Structure of the 5' region of the human hexokinase type I (HKI) gene RT and identification of an additional testis-specific HKI mRNA."; RL Biochim. Biophys. Acta 1493:19-26(2000). RN [9] RP CRYSTALLIZATION. RX MEDLINE=96326597; PubMed=8706938; RA Aleshin A.E., Zeng C., Fromm H.J., Honatko R.B.; RT "Crystallization and preliminary X-ray analysis of human brain RT hexokinase."; RL FEBS Lett. 391:9-10(1996). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 16-914. RX MEDLINE=98154317; PubMed=9493266; RA Aleshin A.E., Zeng C., Bourenkov G.P., Bartunik H.D., Fromm H.J., RA Honzatko R.B.; RT "The mechanism of regulation of hexokinase: new insights from the RT crystal structure of recombinant human brain hexokinase complexed RT with glucose and glucose-6-phosphate."; RL Structure 6:39-50(1998). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 16-914. RX MEDLINE=98407979; PubMed=9735292; RA Aleshin A.E., Zeng C., Bartunik H.D., Fromm H.J., Honzatko R.B.; RT "Regulation of hexokinase I: crystal structure of recombinant human RT brain hexokinase complexed with glucose and phosphate."; RL J. Mol. Biol. 282:345-357(1998). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS). RX MEDLINE=20045192; PubMed=10574795; RA Rosano C., Sabini E., Rizzi M., Deriu D., Murshudov G., Bianchi M., RA Serafini G., Magnani M., Bolognesi M.; RT "Binding of non-catalytic ATP to human hexokinase I highlights the RT structural components for enzyme-membrane association control."; RL Structure 7:1427-1437(1999). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS). RX MEDLINE=20223513; PubMed=10686099; RA Aleshin A.E., Kirby C., Liu X., Bourenkov G.P., Bartunik H.D., RA Fromm H.J., Honzatko R.B.; RT "Crystal structures of mutant monomeric hexokinase I reveal multiple RT ADP binding sites and conformational changes relevant to allosteric RT regulation."; RL J. Mol. Biol. 296:1001-1015(2000). RN [14] RP VARIANT ANEMIA SER-529. RX MEDLINE=95384597; PubMed=7655856; RA Bianchi M., Magnani M.; RT "Hexokinase mutations that produce nonspherocytic hemolytic anemia."; RL Blood Cells Mol. Dis. 21:2-8(1995). CC -!- CATALYTIC ACTIVITY: ATP + D-hexose = ADP + D-hexose 6-phosphate. CC -!- ENZYME REGULATION: Hexokinase is an allosteric enzyme inhibited by CC its product Glc-6-P. CC -!- PATHWAY: First step of several metabolic pathways. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Bound to the outer mitochondrial membrane. CC Its hydrophobic N-terminal sequence may be involved in membrane CC binding. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Common; CC IsoId=P19367-1; Sequence=Displayed; CC Name=2; Synonyms=Erythrocyte, R; CC IsoId=P19367-2; Sequence=VSP_002071; CC Name=3; Synonyms=TA, TB; CC IsoId=P19367-3; Sequence=VSP_002072; CC Name=4; Synonyms=TD; CC IsoId=P19367-4; Sequence=VSP_002073; CC -!- TISSUE SPECIFICITY: Isoform 2 is erythrocyte specific; isoforms 3 CC and 4 are testis-specific. CC -!- DOMAIN: The N- and C-terminal halves of this hexokinase show CC extensive sequence similarity to each other. The catalytic CC activity is associated with the C-terminus while regulatory CC function is associated with the N-terminus. CC -!- MISCELLANEOUS: In vertebrates there are four major glucose- CC phosphorylating isoenzymes, designated hexokinase I, II, III and CC IV (glucokinase). CC -!- SIMILARITY: Belongs to the hexokinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M75126; AAA52646.1; -. DR EMBL; AF016365; AAC15862.1; -. DR EMBL; AF016349; AAC15862.1; JOINED. DR EMBL; AF016351; AAC15862.1; JOINED. DR EMBL; AF016352; AAC15862.1; JOINED. DR EMBL; AF016353; AAC15862.1; JOINED. DR EMBL; AF016354; AAC15862.1; JOINED. DR EMBL; AF016355; AAC15862.1; JOINED. DR EMBL; AF016356; AAC15862.1; JOINED. DR EMBL; AF016357; AAC15862.1; JOINED. DR EMBL; AF016358; AAC15862.1; JOINED. DR EMBL; AF016359; AAC15862.1; JOINED. DR EMBL; AF016360; AAC15862.1; JOINED. DR EMBL; AF016361; AAC15862.1; JOINED. DR EMBL; AF016362; AAC15862.1; JOINED. DR EMBL; AF016363; AAC15862.1; JOINED. DR EMBL; AF016364; AAC15862.1; JOINED. DR EMBL; AF016365; AAC15863.1; -. DR EMBL; AF016349; AAC15863.1; JOINED. DR EMBL; AF016351; AAC15863.1; JOINED. DR EMBL; AF016352; AAC15863.1; JOINED. DR EMBL; AF016353; AAC15863.1; JOINED. DR EMBL; AF016354; AAC15863.1; JOINED. DR EMBL; AF016355; AAC15863.1; JOINED. DR EMBL; AF016356; AAC15863.1; JOINED. DR EMBL; AF016357; AAC15863.1; JOINED. DR EMBL; AF016358; AAC15863.1; JOINED. DR EMBL; AF016359; AAC15863.1; JOINED. DR EMBL; AF016360; AAC15863.1; JOINED. DR EMBL; AF016361; AAC15863.1; JOINED. DR EMBL; AF016362; AAC15863.1; JOINED. DR EMBL; AF016363; AAC15863.1; JOINED. DR EMBL; AF016364; AAC15863.1; JOINED. DR EMBL; AF016365; AAF82319.1; -. DR EMBL; AF163910; AAF82319.1; JOINED. DR EMBL; AF163911; AAF82319.1; JOINED. DR EMBL; AF016351; AAF82319.1; JOINED. DR EMBL; AF016352; AAF82319.1; JOINED. DR EMBL; AF016353; AAF82319.1; JOINED. DR EMBL; AF016354; AAF82319.1; JOINED. DR EMBL; AF016355; AAF82319.1; JOINED. DR EMBL; AF016356; AAF82319.1; JOINED. DR EMBL; AF016357; AAF82319.1; JOINED. DR EMBL; AF016358; AAF82319.1; JOINED. DR EMBL; AF016359; AAF82319.1; JOINED. DR EMBL; AF016360; AAF82319.1; JOINED. DR EMBL; AF016361; AAF82319.1; JOINED. DR EMBL; AF016362; AAF82319.1; JOINED. DR EMBL; AF016363; AAF82319.1; JOINED. DR EMBL; AF016364; AAF82319.1; JOINED. DR EMBL; AF016365; AAF82320.1; -. DR EMBL; AF163912; AAF82320.1; JOINED. DR EMBL; AF016351; AAF82320.1; JOINED. DR EMBL; AF016352; AAF82320.1; JOINED. DR EMBL; AF016353; AAF82320.1; JOINED. DR EMBL; AF016354; AAF82320.1; JOINED. DR EMBL; AF016355; AAF82320.1; JOINED. DR EMBL; AF016356; AAF82320.1; JOINED. DR EMBL; AF016357; AAF82320.1; JOINED. DR EMBL; AF016358; AAF82320.1; JOINED. DR EMBL; AF016359; AAF82320.1; JOINED. DR EMBL; AF016360; AAF82320.1; JOINED. DR EMBL; AF016361; AAF82320.1; JOINED. DR EMBL; AF016362; AAF82320.1; JOINED. DR EMBL; AF016363; AAF82320.1; JOINED. DR EMBL; AF016364; AAF82320.1; JOINED. DR EMBL; BC008730; AAH08730.1; -. DR EMBL; AF029306; AAC00172.1; -. DR EMBL; X66957; CAA47379.1; -. DR EMBL; AF073786; AAC25424.1; -. DR PIR; A31869; A31869. DR PDB; 1DGK; 08-MAR-00. DR PDB; 1HKB; 03-JUN-98. DR PDB; 1HKC; 11-NOV-98. DR PDB; 1QHA; 10-NOV-99. DR PDB; 1CZA; 06-MAR-00. DR GK; P19367; -. DR Genew; HGNC:4922; HK1. DR MIM; 142600; -. DR MIM; 235700; -. DR GO; GO:0004396; F:hexokinase activity; TAS. DR GO; GO:0006096; P:glycolysis; TAS. DR InterPro; IPR001312; Hexokinase. DR Pfam; PF03727; hexokinase2; 2. DR Pfam; PF00349; hexokinase; 2. DR PRINTS; PR00475; HEXOKINASE. DR ProDom; PD001109; Hexokinase; 2. DR PROSITE; PS00378; HEXOKINASES; 2. KW Transferase; Kinase; Glycolysis; Allosteric enzyme; Repeat; KW ATP-binding; Membrane; Polymorphism; Alternative splicing; KW 3D-structure. FT DOMAIN 1 12 HYDROPHOBIC. FT DOMAIN 13 475 REGULATORY. FT DOMAIN 476 917 CATALYTIC. FT DOMAIN 149 175 GLUCOSE-BINDING (POTENTIAL). FT DOMAIN 597 623 GLUCOSE-BINDING (POTENTIAL). FT NP_BIND 84 89 ATP (Potential). FT NP_BIND 532 537 ATP (Potential). FT BINDING 558 558 ATP (Potential). FT VARSPLIC 1 21 MIAAQLLAYYFTELKDDQVKK -> MDCEHSLSLPCRGAEA FT WEIG (in isoform 2). FT /FTId=VSP_002071. FT VARSPLIC 1 21 MIAAQLLAYYFTELKDDQVKK -> MGQICQRESATAAEKP FT KLHLLAESE (in isoform 3). FT /FTId=VSP_002072. FT VARSPLIC 1 21 MIAAQLLAYYFTELKDDQVKK -> MAKRALRDF (in FT isoform 4). FT /FTId=VSP_002073. FT VARIANT 529 529 L -> S (in anemia). FT /FTId=VAR_009878. FT CONFLICT 730 730 N -> D (in Ref. 2 and 3). FT CONFLICT 776 776 M -> L (in Ref. 2 and 3). FT HELIX 18 25 FT TURN 26 26 FT HELIX 27 29 FT HELIX 33 51 FT TURN 53 58 FT STRAND 64 65 FT STRAND 78 85 FT STRAND 90 97 FT STRAND 106 112 FT HELIX 116 119 FT TURN 120 120 FT STRAND 122 122 FT HELIX 123 140 FT TURN 141 142 FT TURN 144 145 FT STRAND 149 154 FT STRAND 158 159 FT TURN 163 164 FT STRAND 167 168 FT TURN 173 174 FT STRAND 178 178 FT TURN 179 182 FT STRAND 184 184 FT HELIX 185 195 FT TURN 197 198 FT STRAND 202 207 FT HELIX 209 220 FT TURN 222 223 FT STRAND 224 230 FT STRAND 234 241 FT HELIX 242 244 FT TURN 246 247 FT STRAND 254 258 FT HELIX 261 263 FT TURN 264 267 FT TURN 269 273 FT HELIX 276 283 FT TURN 284 284 FT TURN 288 289 FT TURN 292 293 FT HELIX 294 297 FT HELIX 299 315 FT TURN 316 317 FT HELIX 320 322 FT TURN 326 329 FT TURN 331 332 FT HELIX 336 342 FT TURN 343 343 FT TURN 345 347 FT HELIX 348 358 FT TURN 359 360 FT HELIX 365 401 FT TURN 402 402 FT STRAND 406 413 FT HELIX 415 419 FT HELIX 423 434 FT TURN 436 437 FT STRAND 438 444 FT TURN 446 449 FT HELIX 450 474 FT HELIX 475 477 FT HELIX 481 499 FT TURN 501 503 FT HELIX 504 506 FT STRAND 512 513 FT STRAND 526 533 FT STRAND 538 546 FT STRAND 552 560 FT HELIX 564 567 FT TURN 568 568 FT STRAND 570 570 FT HELIX 571 588 FT TURN 589 590 FT STRAND 597 602 FT STRAND 606 607 FT TURN 611 612 FT STRAND 615 616 FT TURN 621 622 FT STRAND 626 626 FT TURN 627 627 FT TURN 629 630 FT STRAND 632 632 FT HELIX 633 644 FT STRAND 650 655 FT HELIX 657 666 FT TURN 670 671 FT STRAND 672 678 FT STRAND 682 689 FT HELIX 690 692 FT TURN 694 695 FT STRAND 702 706 FT HELIX 709 711 FT TURN 712 715 FT TURN 717 721 FT HELIX 724 731 FT TURN 732 732 FT TURN 734 737 FT HELIX 740 743 FT TURN 744 745 FT HELIX 747 763 FT TURN 764 765 FT HELIX 768 770 FT HELIX 774 777 FT TURN 779 782 FT HELIX 784 790 FT TURN 791 791 FT TURN 793 794 FT HELIX 797 806 FT TURN 807 808 FT HELIX 813 848 FT TURN 849 850 FT STRAND 854 861 FT HELIX 863 867 FT HELIX 871 882 FT TURN 884 885 FT STRAND 886 892 FT TURN 896 897 FT HELIX 898 905 FT TURN 906 906 FT HELIX 907 910 FT TURN 911 912 SQ SEQUENCE 917 AA; 102502 MW; 150A66D262687501 CRC64; MIAAQLLAYY FTELKDDQVK KIDKYLYAMR LSDETLIDIM TRFRKEMKNG LSRDFNPTAT VKMLPTFVRS IPDGSEKGDF IALDLGGSSF RILRVQVNHE KNQNVHMESE VYDTPENIVH GSGSQLFDHV AECLGDFMEK RKIKDKKLPV GFTFSFPCQQ SKIDEAILIT WTKRFKASGV EGADVVKLLN KAIKKRGDYD ANIVAVVNDT VGTMMTCGYD DQHCEVGLII GTGTNACYME ELRHIDLVEG DEGRMCINTE WGAFGDDGSL EDIRTEFDRE IDRGSLNPGK QLFEKMVSGM YLGELVRLIL VKMAKEGLLF EGRITPELLT RGKFNTSDVS AIEKNKEGLH NAKEILTRLG VEPSDDDCVS VQHVCTIVSF RSANLVAATL GAILNRLRDN KGTPRLRTTV GVDGSLYKTH PQYSRRFHKT LRRLVPDSDV RFLLSESGSG KGAAMVTAVA YRLAEQHRQI EETLAHFHLT KDMLLEVKKR MRAEMELGLR KQTHNNAVVK MLPSFVRRTP DGTENGDFLA LDLGGTNFRV LLVKIRSGKK RTVEMHNKIY AIPIEIMQGT GEELFDHIVS CISDFLDYMG IKGPRMPLGF TFSFPCQQTS LDAGILITWT KGFKATDCVG HDVVTLLRDA IKRREEFDLD VVAVVNDTVG TMMTCAYEEP TCEVGLIVGT GSNACYMEEM KNVEMVEGDQ GQMCINMEWG AFGDNGCLDD IRTHYDRLVN EYSLNAGKQR YEKMISGMYL GEIVRNILID FTKKGFLFRG QISETMKTRG IFETKFLSQI ESDRLALLQV RAILQQLGLN STCDDSILVK TVCGVVSRRA AQLCGAGMAA VVDKIRENRG LDRLNVTVGV DGTLYKLHPH FSRIMHQTVK ELSPKCNVSF LLSEDGSGKG AALITAVGVR LRTEASS // ID HXK2_HUMAN STANDARD; PRT; 917 AA. AC P52789; Q9UN82; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Hexokinase, type II (EC 2.7.1.1) (HK II) (Muscle form hexokinase). GN HK2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND VARIANT HIS-142. RC TISSUE=Blood, Muscle, and Placenta; RX MEDLINE=96238411; PubMed=8786021; RA Lehto M., Huang X., Davis E.M., Le Beau M.M., Laurila E., RA Eriksson K.F., Bell G.I., Groop L.C.; RT "Human hexokinase II gene: exon-intron organization, mutation RT screening in NIDDM, and its relationship to muscle hexokinase RT activity."; RL Diabetologia 38:1466-1474(1995). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Skeletal muscle; RX MEDLINE=94071972; PubMed=8250948; RA Deeb S.S., Malkki M., Laakso M.; RT "Human hexokinase II: sequence and homology to other hexokinases."; RL Biochem. Biophys. Res. Commun. 197:68-74(1993). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Skeletal muscle; RA Malkki M., Heikkinen S., Deeb S.S., Laakso M.; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE OF 614-739 FROM N.A. RX MEDLINE=94306348; PubMed=7518342; RA Shinohara Y., Yamamoto K., Kogure K., Ichihara J., Terada H.; RT "Steady state transcript levels of the type II hexokinase and type 1 RT glucose transporter in human tumor cell lines."; RL Cancer Lett. 82:27-32(1994). RN [5] RP VARIANTS VAL-314; CYS-353 AND GLN-775. RX MEDLINE=95189031; PubMed=7883120; RA Laakso M., Malkki M., Deeb S.S.; RT "Amino acid substitutions in hexokinase II among patients with RT NIDDM."; RL Diabetes 44:330-334(1995). RN [6] RP VARIANT HIS-142. RX MEDLINE=95189033; PubMed=7883122; RA Vidal-Puig A., Printz R.L., Stratton I.M., Granner D.K., Moller D.E.; RT "Analysis of the hexokinase II gene in subjects with insulin RT resistance and NIDDM and detection of a Gln142-->His substitution."; RL Diabetes 44:340-346(1995). RN [7] RP VARIANTS HIS-142; PHE-148; GLN-497 AND LYS-844. RX MEDLINE=95189034; PubMed=7883123; RA Echwald S.M., Bjoerbaek C., Hansen T., Clausen J.O., Vestergaard H., RA Zierath J.R., Printz R.L., Granner D.K., Pedersen O.; RT "Identification of four amino acid substitutions in hexokinase II and RT studies of relationships to NIDDM, glucose effectiveness, and insulin RT sensitivity."; RL Diabetes 44:347-353(1995). CC -!- CATALYTIC ACTIVITY: ATP + D-hexose = ADP + D-hexose 6-phosphate. CC -!- ENZYME REGULATION: Hexokinase is an allosteric enzyme inhibited by CC its product Glc-6-P. CC -!- PATHWAY: First step of several metabolic pathways. CC -!- SUBUNIT: Monomer (By similarity). CC -!- SUBCELLULAR LOCATION: Bound to the outer mitochondrial membrane. CC Its hydrophobic N-terminal sequence may be involved in membrane CC binding (By similarity). CC -!- TISSUE SPECIFICITY: Predominant hexokinase isozyme expressed in CC insulin-responsive tissues such as skeletal muscle. CC -!- DOMAIN: The N- and C-terminal halves of this hexokinase show CC extensive sequence similarity to each other. The catalytic CC activity is associated with the C-terminus while regulatory CC function is associated with the N-terminus. CC -!- POLYMORPHISM: Although found in NIDDM patients, genetic variations CC of HK2 do not contribute to the disease. CC -!- MISCELLANEOUS: In vertebrates there are four major glucose- CC phosphorylating isoenzymes, designated hexokinase I, II, III and CC IV (glucokinase). CC -!- SIMILARITY: Belongs to the hexokinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; Z46376; CAA86511.1; -. DR EMBL; Z46354; CAA86476.2; -. DR EMBL; Z46355; CAA86476.2; JOINED. DR EMBL; Z46604; CAA86476.2; JOINED. DR EMBL; Z46356; CAA86476.2; JOINED. DR EMBL; Z46357; CAA86476.2; JOINED. DR EMBL; Z46358; CAA86476.2; JOINED. DR EMBL; Z46359; CAA86476.2; JOINED. DR EMBL; Z46360; CAA86476.2; JOINED. DR EMBL; Z46361; CAA86476.2; JOINED. DR EMBL; Z46362; CAA86476.2; JOINED. DR EMBL; Z46363; CAA86476.2; JOINED. DR EMBL; Z46364; CAA86476.2; JOINED. DR EMBL; Z46365; CAA86476.2; JOINED. DR EMBL; Z46366; CAA86476.2; JOINED. DR EMBL; Z46367; CAA86476.2; JOINED. DR EMBL; Z46368; CAA86476.2; JOINED. DR EMBL; Z46369; CAA86476.2; JOINED. DR EMBL; AF148513; AAD30174.1; -. DR EMBL; D25412; BAA04999.1; -. DR EMBL; D25411; BAA04999.1; JOINED. DR PIR; S48809; JC2025. DR HSSP; P05708; 1BG3. DR Genew; HGNC:4923; HK2. DR GK; P52789; -. DR MIM; 601125; -. DR GO; GO:0004396; F:hexokinase activity; TAS. DR GO; GO:0000074; P:regulation of cell cycle; TAS. DR InterPro; IPR001312; Hexokinase. DR Pfam; PF03727; hexokinase2; 2. DR Pfam; PF00349; hexokinase; 2. DR PRINTS; PR00475; HEXOKINASE. DR ProDom; PD001109; Hexokinase; 2. DR PROSITE; PS00378; HEXOKINASES; 2. KW Transferase; Kinase; Glycolysis; Allosteric enzyme; Repeat; KW ATP-binding; Membrane; Polymorphism. FT DOMAIN 1 12 HYDROPHOBIC. FT DOMAIN 13 475 REGULATORY. FT DOMAIN 476 917 CATALYTIC. FT DOMAIN 149 175 GLUCOSE-BINDING (POTENTIAL). FT DOMAIN 597 623 GLUCOSE-BINDING (POTENTIAL). FT NP_BIND 84 89 ATP (Potential). FT NP_BIND 532 537 ATP (Potential). FT BINDING 558 558 ATP (Potential). FT VARIANT 142 142 Q -> H (does not affect activity). FT /FTId=VAR_003691. FT VARIANT 148 148 L -> F. FT /FTId=VAR_010577. FT VARIANT 314 314 A -> V. FT /FTId=VAR_010578. FT VARIANT 353 353 R -> C. FT /FTId=VAR_010579. FT VARIANT 497 497 R -> Q. FT /FTId=VAR_010580. FT VARIANT 775 775 R -> Q. FT /FTId=VAR_010581. FT VARIANT 844 844 R -> K. FT /FTId=VAR_010582. FT CONFLICT 12 12 T -> S (in Ref. 2). FT CONFLICT 406 406 L -> A (in Ref. 2). FT CONFLICT 634 634 V -> A (in Ref. 2). FT CONFLICT 803 803 T -> I (IN REF. 1; CAA86476 AND 2). FT CONFLICT 870 870 Missing (IN REF. 1; CAA86476). SQ SEQUENCE 917 AA; 102367 MW; 1C7CE801D147E3ED CRC64; MIASHLLAYF FTELNHDQVQ KVDQYLYHMR LSDETLLEIS KRFRKEMEKG LGATTHPTAA VKMLPTFVRS TPDGTEHGEF LALDLGGTNF RVLWVKVTDN GLQKVEMENQ IYAIPEDIMR GSGTQLFDHI AECLANFMDK LQIKDKKLPL GFTFSFPCHQ TKLDESFLVS WTKGFKSSGV EGRDVVALIR KAIQRRGDFD IDIVAVVNDT VGTMMTCGYD DHNCEIGLIV GTGSNACYME EMRHIDMVEG DEGRMCINME WGAFGDDGSL NDIRTEFDQE IDMGSLNPGK QLFEKMISGM YMGELVRLIL VKMAKEELLF GGKLSPELLN TGRFETKDIS DIEGEKDGIR KAREVLMRLG LDPTQEDCVA THRICQIVST RSASLCAATL AAVLQRIKEN KGEERLRSTI GVDGSVYKKH PHFAKRLHKT VRRLVPGCDV RFLRSEDGSG KGAAMVTAVA YRLADQHRAR QKTLEHLQLS HDQLLEVKRR MKVEMERGLS KETHASAPVK MLPTYVCATP DGTEKGDFLA LDLGGTNFRV LLVRVRNGKW GGVEMHNKIY AIPQEVMHGT GDELFDHIVQ CIADFLEYMG MKGVSLPLGF TFSFPCQQNS LDESILLKWT KGFKASGCEG EDVVTLLKEA IHRREEFDLD VVAVVNDTVG TMMTCGFEDP HCEVGLIVGT GSNACYMEEM RNVELVEGEE GRMCVNMEWG AFGDNGCLDD FRTEFDVAVD ELSLNPGKQR FEKMISGMYL GEIVRNILID FTKRGLLFRG RISERLKTRG IFETKFLSQI ESDCLALLQV RATLQHLGLE STCDDSIIVK EVCTVVARRA AQLCGAGMAA VVDRIRENRG LDALKVTVGV DGTLYKLHPH FAKVMHETVK DLAPKCDVSF LQSEDGSGKG AALITAVACR IREAGQR // ID HXK3_HUMAN STANDARD; PRT; 923 AA. AC P52790; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Hexokinase type III (EC 2.7.1.1) (HK III). GN HK3. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=96411670; PubMed=8812439; RA Furuta H., Nishi S., Le Beau M.M., Fernald A.A., Yano H., Bell G.I.; RT "Sequence of human hexokinase III cDNA and assignment of the human RT hexokinase III gene (HK3) to chromosome band 5q35.2 by fluorescence RT in situ hybridization."; RL Genomics 36:206-209(1996). RN [2] RP SEQUENCE OF 358-923 FROM N.A. RC TISSUE=Liver; RX MEDLINE=96351387; PubMed=8717435; RA Palma F., Agostini D., Mason P., Dacha M., Piccoli G., Biagiarelli B., RA Fiorani M., Stocchi V.; RT "Purification and characterization of the carboxyl-domain of human RT hexokinase type III expressed as fusion protein."; RL Mol. Cell. Biochem. 155:23-29(1996). CC -!- CATALYTIC ACTIVITY: ATP + D-hexose = ADP + D-hexose 6-phosphate. CC -!- ENZYME REGULATION: Hexokinase is an allosteric enzyme inhibited by CC its product Glc-6-P. CC -!- PATHWAY: First step of several metabolic pathways. CC -!- SUBUNIT: Monomer (By similarity). CC -!- DOMAIN: The N- and C-terminal halves of this hexokinase show CC extensive sequence similarity to each other. The catalytic CC activity is associated with the C-terminus while regulatory CC function is associated with the N-terminus. CC -!- MISCELLANEOUS: In vertebrates there are four major glucose- CC phosphorylating isoenzymes, designated hexokinase I, II, III and CC IV (glucokinase). CC -!- SIMILARITY: Belongs to the hexokinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U51333; AAC50732.1; -. DR EMBL; U42303; AAC50422.1; -. DR HSSP; P05708; 1BG3. DR Genew; HGNC:4925; HK3. DR GK; P52790; -. DR MIM; 142570; -. DR GO; GO:0016020; C:membrane; NAS. DR GO; GO:0005524; F:ATP binding; NAS. DR GO; GO:0004396; F:hexokinase activity; NAS. DR GO; GO:0006096; P:glycolysis; NAS. DR InterPro; IPR001312; Hexokinase. DR Pfam; PF00349; hexokinase; 2. DR Pfam; PF03727; hexokinase2; 2. DR PRINTS; PR00475; HEXOKINASE. DR ProDom; PD001109; Hexokinase; 2. DR PROSITE; PS00378; HEXOKINASES; 1. KW Transferase; Kinase; Glycolysis; Allosteric enzyme; Repeat; KW ATP-binding; Membrane. FT DOMAIN 1 488 REGULATORY. FT DOMAIN 489 923 CATALYTIC. FT DOMAIN 162 188 GLUCOSE-BINDING (POTENTIAL). FT DOMAIN 603 629 GLUCOSE-BINDING (POTENTIAL). FT NP_BIND 95 100 ATP (Potential). FT NP_BIND 542 547 ATP (Potential). FT CONFLICT 420 420 Q -> L (in Ref. 2). FT CONFLICT 431 431 E -> Q (in Ref. 2). FT CONFLICT 439 439 V -> I (in Ref. 2). FT CONFLICT 510 510 K -> R (in Ref. 2). FT CONFLICT 512 513 LR -> SE (in Ref. 2). FT CONFLICT 516 516 A -> S (in Ref. 2). FT CONFLICT 519 519 L -> S (in Ref. 2). FT CONFLICT 530 531 PD -> LT (in Ref. 2). FT CONFLICT 577 578 GQ -> AE (in Ref. 2). FT CONFLICT 604 604 L -> T (in Ref. 2). FT CONFLICT 708 708 R -> H (in Ref. 2). FT CONFLICT 718 718 F -> L (in Ref. 2). FT CONFLICT 728 728 S -> R (in Ref. 2). FT CONFLICT 750 750 M -> I (in Ref. 2). FT CONFLICT 831 831 A -> V (in Ref. 2). FT CONFLICT 836 836 A -> P (in Ref. 2). FT CONFLICT 853 853 G -> E (in Ref. 2). FT CONFLICT 918 918 A -> T (in Ref. 2). SQ SEQUENCE 923 AA; 98919 MW; D4C53841D851B5FB CRC64; MDSIGSSGLR QGEETLSCSE EGLPGPSDSS ELVQECLQQF KVTRAQLQQI QASLLGSMEQ ALRGQASPAP AVRMLPTYVG STPHGTEQGD FVVLELGATG ASLRVLWVTL TGIEGHRVEP RSQEFVIPQE VMLGAGQQLF DFAAHCLSEF LDAQPVNKQG LQLGFSFSFP CHQTGLDRST LISWTKGFRC SGVEGQDVVQ LLRDAIRRQG AYNIDVVAVV NDTVGTMMGC EPGVRPCEVG LVVDTGTNAC YMEEARHVAV LDEDRGRVCV SVEWGSLSDD GALGPVLTTF DHTLDHESLN PGAQRFEKMI GGLYLGELVR LVLAHLARCG VLFGGCTSPA LLSQGSILLE HVAEMEDPST GAARVHAILQ DLGLSPGASD VELVQHVCAA VCTRAAQLCA AALAAVLSCL QHSREQQTLQ VAVATGGRVC ERHPRFCSVL QGTVMLLAPE CDVSLIPSVD GGGRGVAMVT AVAARLAAHR RLLEETLAPF RLNHDQLAAV QAQMRKAMAK GLRGEASSLR MLPTFVRATP DGSERGDFLA LDLGGTNFRV LLVRVTTGVQ ITSEIYSIPE TVAQGSGQQL FDHIVDCIVD FQQKQGLSGQ SLPLGFTFSF PCRQLGLDQG ILLNWTKGFK ASDCEGQDVV SLLREAITRR QAVELNVVAI VNDTVGTMMS CGYEDPRCEI GLIVGTGTNA CYMEELRNVA GVPGDSGRMC INMEWGAFGD DGSLAMLSTR FDASVDQASI NPGKQRFEKM ISGMYLGEIV RHILLHLTSL GVLFRGQQIQ RLQTRDIFKT KFLSEIESDS LALRQVRAIL EDLGLPLTSD DALMVLEVCQ AVSQRAAQLC GAGVAAVVEK IRGNRGLEEL AVSVGVDGTL YKLHPRFSSL VAATVRELAP RCVVTFLQSE DGSGKGAALV TAVACRLAQL TRV // ID HXK4_HUMAN STANDARD; PRT; 465 AA. AC P35557; Q05810; DT 01-JUN-1994 (Rel. 29, Created) DT 01-JUN-1994 (Rel. 29, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Hexokinase D (EC 2.7.1.1) (Hexokinase type IV) (HK IV) (HK4) DE (Glucokinase). GN GCK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=92375100; PubMed=1354840; RA Tanizawa Y., Matsutani A., Chiu K.C., Permutt M.A.; RT "Human glucokinase gene: isolation, structural characterization, and RT identification of a microsatellite repeat polymorphism."; RL Mol. Endocrinol. 6:1070-1081(1992). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=91334452; PubMed=1871135; RA Tanizawa Y., Koranyi L.I., Welling C.M., Permutt M.A.; RT "Human liver glucokinase gene: cloning and sequence determination of RT two alternatively spliced cDNAs."; RL Proc. Natl. Acad. Sci. U.S.A. 88:7294-7297(1991). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Pancreas; RX MEDLINE=92380355; PubMed=1511800; RA Nishi S., Stoffel M., Xiang K.S., Shows T.B., Bell G.I., Takeda J.; RT "Human pancreatic beta-cell glucokinase: cDNA sequence and RT localization of the polymorphic gene to chromosome 7, band p13."; RL Diabetologia 35:743-747(1992). RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Pancreas; RX MEDLINE=92307138; PubMed=1612194; RA Koranyi L.I., Tanizawa Y., Welling C.M., Rabin D.U., Permutt M.A.; RT "Human islet glucokinase gene. Isolation and sequence analysis of RT full-length cDNA."; RL Diabetes 41:807-811(1992). RN [5] RP SEQUENCE FROM N.A., AND VARIANTS MODY2 MET-228 AND ARG-261. RC TISSUE=Placenta; RX MEDLINE=92366529; PubMed=1502186; RA Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S., RA Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M., RA Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.; RT "Human glucokinase gene: isolation, characterization, and RT identification of two missense mutations linked to early-onset RT non-insulin-dependent (type 2) diabetes mellitus."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7698-7702(1992). RN [6] RP ERRATUM. RA Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S., RA Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M., RA Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.; RL Proc. Natl. Acad. Sci. U.S.A. 89:10562-10562(1992). RN [7] RP SEQUENCE FROM N.A., VARIANT THR-107, AND VARIANT MODY2 ARG-261. RX MEDLINE=93100400; PubMed=1464666; RA Sakura H., Eto K., Kadowaki H., Simokawa K., Ueno H., Koda N., RA Fukushima Y., Akanuma Y., Yazaki Y., Kadowaki T.; RT "Structure of the human glucokinase gene and identification of a RT missense mutation in a Japanese patient with early-onset non-insulin- RT dependent diabetes mellitus."; RL J. Clin. Endocrinol. Metab. 75:1571-1573(1992). RN [8] RP SEQUENCE FROM N.A. RC TISSUE=Lung; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [9] RP 3D-STRUCTURE MODELING. RX MEDLINE=94252471; PubMed=8194664; RA St Charles R., Harrison R.W., Bell G.I., Pilkis S.J., Weber I.T.; RT "Molecular model of human beta-cell glucokinase built by analogy to RT the crystal structure of yeast hexokinase B."; RL Diabetes 43:784-791(1994). RN [10] RP VARIANT MODY2 ARG-299. RX MEDLINE=93265142; PubMed=1303265; RA Stoffel M., Patel P., Lo Y.-M.D., Hattersley A.T., Lucassen A.M., RA Page R., Bell J.I., Bell G.I., Turner R.C., Wainscoat J.S.; RT "Missense glucokinase mutation in maturity-onset diabetes of the RT young and mutation screening in late-onset diabetes."; RL Nat. Genet. 2:153-156(1992). RN [11] RP VARIANT THR-11. RX MEDLINE=93202338; PubMed=8454109; RA Chiu K.C., Tanizawa Y., Permutt M.A.; RT "Glucokinase gene variants in the common form of NIDDM."; RL Diabetes 42:579-582(1993). RN [12] RP VARIANT MODY2 PRO-131. RX MEDLINE=93266044; PubMed=8495817; RA Stoffel M., Bell K.L., Blackburn C.L., Powell K.L., Seo T.S., RA Takeda J., Vionnet N., Xiang K.-S., Gidh-Jain M., Pilkis S.J., RA Ober C., Bell G.I.; RT "Identification of glucokinase mutations in subjects with gestational RT diabetes mellitus."; RL Diabetes 42:937-940(1993). RN [13] RP VARIANT ASN-4, AND VARIANTS MODY2 LYS-70; PRO-131; THR-188; ARG-257 RP AND GLU-414. RX MEDLINE=93315503; PubMed=8325892; RA Takeda J., Gidh-Jain M., Xu L.Z., Froguel P., Velho G., Vaxillaire M., RA Cohen D., Shimada F., Makino H., Nishi S., Stoffel M., Vionnet N., RA St Charles R., Harrison R.W., Weber I.T., Bell G.I., Pilkis S.J.; RT "Structure/function studies of human beta-cell glucokinase. Enzymatic RT properties of a sequence polymorphism, mutations associated with RT diabetes, and other site-directed mutants."; RL J. Biol. Chem. 268:15200-15204(1993). RN [14] RP CHARACTERIZATION OF MODY2 VARIANTS. RX MEDLINE=93189611; PubMed=8446612; RA Gidh-Jain M., Takeda J., Xu L.Z., Lange A.J., Vionnet N., Stoffel M., RA Froguel P., Velho G., Sun D., Cohen D., Patel P., Lo Y.-M.D., RA Hattersley A.T., Luthman H., Wedell A., St Charles R., Harrison R.W., RA Weber I.T., Bell G.I., Pilkis S.J.; RT "Glucokinase mutations associated with non-insulin-dependent (type 2) RT diabetes mellitus have decreased enzymatic activity: implications for RT structure/function relationships."; RL Proc. Natl. Acad. Sci. U.S.A. 90:1932-1936(1993). RN [15] RP VARIANTS MODY2 TRP-36; MET-209 AND GLU-261. RX MEDLINE=94222222; PubMed=8168652; RA Hager J., Blanche H., Sun F., Vionnet N., Vaxillaire M., Poller W., RA Cohen D., Czernichow P., Velho G., Robert J.-J., Cohen N., Froguel P.; RT "Six mutations in the glucokinase gene identified in MODY by using a RT nonradioactive sensitive screening technique."; RL Diabetes 43:730-733(1994). RN [16] RP VARIANTS MODY2. RX MEDLINE=97201951; PubMed=9049484; RA Velho G., Blanche H., Vaxillaire M., Bellanne-Chantelot C., RA Pardini V.C., Timsit J., Passa P., Deschamps I., Robert J.-J., RA Weber I.T., Marotta D., Pilkis S.J., Lipkind G.M., Bell G.I., RA Froguel P.; RT "Identification of 14 new glucokinase mutations and description of the RT clinical profile of 42 MODY-2 families."; RL Diabetologia 40:217-224(1997). RN [17] RP VARIANTS MODY2 SER-80; LYS-221 AND CYS-227. RA Guazzini B., Gaffi D., Mainieri D., Multari G., Cordera R., RA Bertolini S., Pozza G., Meschi F., Barbetti F.; RT "Three novel missense mutations in the glucokinase gene (G80S; E221K; RT G227C) in Italian subjects with maturity-onset diabetes of the young RT (MODY)."; RL Hum. Mutat. 12:136-136(1998). RN [18] RP VARIANTS MODY2 HIS-108; SER-150; THR-259; ARG-299; TYR-382; THR-384 RP AND CYS-392. RX MEDLINE=98324778; PubMed=9662401; RA Hattersley A.T., Beards F., Ballantyne E., Appleton M., Harvey R., RA Ellard S.; RT "Mutations in the glucokinase gene of the fetus result in reduced RT birth weight."; RL Nat. Genet. 19:268-270(1998). RN [19] RP VARIANT HYPERINSULINISM MET-455. RX MEDLINE=98084322; PubMed=9435328; RA Glaser B., Kesavan P., Heyman M., Davis E., Cuesta A., Buchs A., RA Stanley C.A., Thornton P.S., Permutt M.A., Matschinsky F.M., RA Herold K.C.; RT "Familial hyperinsulinism caused by an activating glucokinase RT mutation."; RL N. Engl. J. Med. 338:226-230(1998). RN [20] RP VARIANTS MODY2 THR-110; ASP-119 AND VAL-385. RX MEDLINE=20053748; PubMed=10588527; RA Ng M.C.Y., Cockburn B.N., Lindner T.H., Yeung V.T.F., Chow C.-C., RA So W.-Y., Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S., RA Critchley J.A.J.H., Bell G.I., Chan J.C.N.; RT "Molecular genetics of diabetes mellitus in Chinese subjects: RT identification of mutations in glucokinase and hepatocyte nuclear RT factor-1alpha genes in patients with early-onset type 2 diabetes RT mellitus/MODY."; RL Diabet. Med. 16:956-963(1999). RN [21] RP VARIANT MODY2 PRO-164. RX MEDLINE=20560768; PubMed=11106831; RA Nam J.H., Lee H.C., Kim Y.H., Cha B.S., Song Y.D., Lim S.K., Kim K.R., RA Huh K.B.; RT "Identification of glucokinase mutation in subjects with post-renal RT transplantation diabetes mellitus."; RL Diabetes Res. Clin. Pract. 50:169-176(2000). RN [22] RP VARIANTS MODY2 LYS-210 AND MET-228. RX MEDLINE=21245203; PubMed=11372010; RA Njoelstad P.R., Soevik O., Cuesta-Munoz A., Bjoerkhaug L., Massa O., RA Barbetti F., Undlien D.E., Shiota C., Magnuson M.A., Molven A., RA Matschinsky F.M., Bell G.I.; RT "Neonatal diabetes mellitus due to complete glucokinase deficiency."; RL N. Engl. J. Med. 344:1588-1592(2001). CC -!- FUNCTION: Catalyzes the initial step in utilization of glucose by CC the beta-cell and liver at physiological glucose concentration. CC Glucokinase has a high km for glucose, and so it is effective only CC when glucose is abundant. The role of GCK is to provide G6P for CC the synthesis of glycogen. Pancreatic glucokinase plays an CC important role in modulating insulin secretion. Hepatic CC glucokinase helps to facilitate the uptake and conversion of CC glucose by acting as an insulin-sensitive determinant of hepatic CC glucose usage. CC -!- CATALYTIC ACTIVITY: ATP + D-hexose = ADP + D-hexose 6-phosphate. CC -!- ENZYME REGULATION: The use of alternative promoters apparently CC enables the type IV hexokinase gene to be regulated by insulin in CC the liver and glucose in the beta cell. This may constitute an CC important feedback loop for maintaining glucose homeostasis. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P35557-1; Sequence=Displayed; CC Name=2; CC IsoId=P35557-2; Sequence=VSP_002074; CC Name=3; CC IsoId=P35557-3; Sequence=VSP_002075; CC -!- TISSUE SPECIFICITY: PANCREAS (ISOFORM 1) AND LIVER (ISOFORMS 2 AND CC 3). CC -!- DISEASE: Defects in GCK are the cause of maturity-onset diabetes CC of the young, type II (MODY2) [MIM:125851]. It is a form of CC noninsulin-dependent diabetes mellitus (NIDDM) characterized by CC monogenic autosomal dominant transmission and early age of onset. CC Mutations in GCK result in mild chronic hyperglycemia due to CC reduced pancreatic beta cell responsiveness to glucose, and CC decreased net accumulation of hepatic glycogen and increased CC hepatic gluconeogenesis following meals. CC -!- DISEASE: Defects in GCK are a cause of hyperinsulinism CC [MIM:602485]; a familial autosomal dominant disease. It is the CC most common cause of persistent hypoglycemia in infancy. Unless CC early and aggressive intervention is undertaken, brain damage from CC recurrent episodes of hypoglycemia may occur. CC -!- MISCELLANEOUS: In vertebrates there are four major glucose- CC phosphorylating isoenzymes, designated hexokinase I, II, III and CC IV (glucokinase). CC -!- SIMILARITY: Belongs to the hexokinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M88011; AAA51824.1; -. DR EMBL; M69051; AAB59563.1; ALT_SEQ. DR EMBL; M90298; AAA67541.1; ALT_TERM. DR EMBL; M90298; AAA67542.1; ALT_TERM. DR EMBL; M90299; AAA52562.1; -. DR EMBL; AF041022; AAB97680.1; -. DR EMBL; AF041012; AAB97680.1; JOINED. DR EMBL; AF041015; AAB97680.1; JOINED. DR EMBL; AF041016; AAB97680.1; JOINED. DR EMBL; AF041017; AAB97680.1; JOINED. DR EMBL; AF041018; AAB97680.1; JOINED. DR EMBL; AF041019; AAB97680.1; JOINED. DR EMBL; AF041020; AAB97680.1; JOINED. DR EMBL; AF041021; AAB97680.1; JOINED. DR EMBL; AF041022; AAB97681.1; -. DR EMBL; AF041013; AAB97681.1; JOINED. DR EMBL; AF041015; AAB97681.1; JOINED. DR EMBL; AF041016; AAB97681.1; JOINED. DR EMBL; AF041017; AAB97681.1; JOINED. DR EMBL; AF041018; AAB97681.1; JOINED. DR EMBL; AF041019; AAB97681.1; JOINED. DR EMBL; AF041020; AAB97681.1; JOINED. DR EMBL; AF041021; AAB97681.1; JOINED. DR EMBL; AF041022; AAB97682.1; -. DR EMBL; AF041014; AAB97682.1; JOINED. DR EMBL; AF041015; AAB97682.1; JOINED. DR EMBL; AF041016; AAB97682.1; JOINED. DR EMBL; AF041017; AAB97682.1; JOINED. DR EMBL; AF041018; AAB97682.1; JOINED. DR EMBL; AF041019; AAB97682.1; JOINED. DR EMBL; AF041020; AAB97682.1; JOINED. DR EMBL; AF041021; AAB97682.1; JOINED. DR EMBL; BC001890; AAH01890.1; -. DR PIR; A46157; A46157. DR PDB; 1GLK; 30-NOV-94. DR Genew; HGNC:4195; GCK. DR GK; P35557; -. DR MIM; 138079; -. DR MIM; 125851; -. DR MIM; 602485; -. DR GO; GO:0004340; F:glucokinase activity; TAS. DR InterPro; IPR001312; Hexokinase. DR Pfam; PF03727; hexokinase2; 1. DR Pfam; PF00349; hexokinase; 1. DR PRINTS; PR00475; HEXOKINASE. DR ProDom; PD001109; Hexokinase; 1. DR PROSITE; PS00378; HEXOKINASES; 1. KW Transferase; Kinase; Glycolysis; ATP-binding; Alternative splicing; KW Disease mutation; Polymorphism; Diabetes mellitus; 3D-structure. FT NP_BIND 78 83 ATP (Potential). FT BINDING 104 104 ATP (Potential). FT DOMAIN 145 171 GLUCOSE-BINDING (POTENTIAL). FT VARSPLIC 1 15 MLDDRARMEAAKKEK -> MAMDVTRSQAQTALTL (in FT isoform 2). FT /FTId=VSP_002074. FT VARSPLIC 1 15 MLDDRARMEAAKKEK -> MPRPRSQLPQPNSQ (in FT isoform 3). FT /FTId=VSP_002075. FT VARIANT 4 4 D -> N. FT /FTId=VAR_003692. FT VARIANT 11 11 A -> T. FT /FTId=VAR_010583. FT VARIANT 36 36 R -> W (in MODY2). FT /FTId=VAR_010584. FT VARIANT 53 53 A -> S (in MODY2). FT /FTId=VAR_010585. FT VARIANT 70 70 E -> K (in MODY2; large increase in Km FT for glucose). FT /FTId=VAR_003693. FT VARIANT 80 80 G -> A (in MODY2). FT /FTId=VAR_003694. FT VARIANT 80 80 G -> S (in MODY2). FT /FTId=VAR_003695. FT VARIANT 107 107 M -> T. FT /FTId=VAR_003696. FT VARIANT 108 108 Y -> H (in MODY2). FT /FTId=VAR_010586. FT VARIANT 110 110 I -> T (in MODY2). FT /FTId=VAR_012352. FT VARIANT 119 119 A -> D (in MODY2). FT /FTId=VAR_012353. FT VARIANT 131 131 S -> P (in MODY2; significant increase in FT the Km and in the affinity for ATP). FT /FTId=VAR_003697. FT VARIANT 137 137 H -> R (in MODY2). FT /FTId=VAR_010587. FT VARIANT 150 150 F -> S (in MODY2). FT /FTId=VAR_010588. FT VARIANT 164 164 L -> P (in MODY2). FT /FTId=VAR_012350. FT VARIANT 168 168 T -> P (in MODY2). FT /FTId=VAR_010589. FT VARIANT 175 175 G -> R (in MODY2). FT /FTId=VAR_003698. FT VARIANT 182 182 V -> M (in MODY2). FT /FTId=VAR_003699. FT VARIANT 188 188 A -> T (in MODY2; large increase in Km FT for glucose). FT /FTId=VAR_003700. FT VARIANT 203 203 V -> A (in MODY2). FT /FTId=VAR_003701. FT VARIANT 209 209 T -> M (in MODY2). FT /FTId=VAR_010590. FT VARIANT 210 210 M -> K (in MODY2). FT /FTId=VAR_012351. FT VARIANT 210 210 M -> T (in MODY2). FT /FTId=VAR_010591. FT VARIANT 213 213 C -> R (in MODY2). FT /FTId=VAR_010592. FT VARIANT 221 221 E -> K (in MODY2). FT /FTId=VAR_003702. FT VARIANT 226 226 V -> M (in MODY2). FT /FTId=VAR_003703. FT VARIANT 227 227 G -> C (in MODY2). FT /FTId=VAR_003704. FT VARIANT 228 228 T -> M (in MODY2). FT /FTId=VAR_003705. FT VARIANT 256 256 E -> K (in MODY2). FT /FTId=VAR_003706. FT VARIANT 257 257 W -> R (in MODY2; almost complete loss of FT activity). FT /FTId=VAR_003707. FT VARIANT 259 259 A -> T (in MODY2). FT /FTId=VAR_010593. FT VARIANT 261 261 G -> E (in MODY2). FT /FTId=VAR_010594. FT VARIANT 261 261 G -> R (in MODY2). FT /FTId=VAR_003708. FT VARIANT 279 279 E -> Q (in MODY2). FT /FTId=VAR_003709. FT VARIANT 299 299 G -> R (in MODY2). FT /FTId=VAR_003710. FT VARIANT 300 300 E -> Q (in MODY2). FT /FTId=VAR_003711. FT VARIANT 300 300 E -> K (in MODY2). FT /FTId=VAR_003712. FT VARIANT 309 309 L -> P (in MODY2). FT /FTId=VAR_003713. FT VARIANT 336 336 S -> L (in MODY2). FT /FTId=VAR_010595. FT VARIANT 367 367 V -> M (in MODY2). FT /FTId=VAR_010596. FT VARIANT 382 382 C -> Y (in MODY2). FT /FTId=VAR_010597. FT VARIANT 384 384 A -> T (in MODY2). FT /FTId=VAR_010598. FT VARIANT 385 385 G -> V (in MODY2). FT /FTId=VAR_012354. FT VARIANT 392 392 R -> C (in MODY2). FT /FTId=VAR_010599. FT VARIANT 414 414 K -> E (in MODY2; large increase in Km FT for glucose). FT /FTId=VAR_003714. FT VARIANT 455 455 V -> M (in hyperinsulinism). FT /FTId=VAR_003715. FT MUTAGEN 177 177 E->K: SMALL CHANGE IN ACTIVITY. FT MUTAGEN 256 256 E->A: INACTIVE ENZYME. FT MUTAGEN 414 414 K->A: SMALL CHANGE IN ACTIVITY. FT CONFLICT 107 107 M -> T (in Ref. 2). SQ SEQUENCE 465 AA; 52191 MW; 094D4A2F78096724 CRC64; MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ // ID IP3K_HUMAN STANDARD; PRT; 461 AA. AC P23677; DT 01-NOV-1991 (Rel. 20, Created) DT 01-NOV-1991 (Rel. 20, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Inositol-trisphosphate 3-kinase A (EC 2.7.1.127) (Inositol 1,4,5- DE trisphosphate 3-kinase) (IP3K) (IP3 3-kinase). GN ITPKA. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=91128380; PubMed=1847047; RA Takazawa K., Perret J., Dumont J.E., Erneux C.; RT "Molecular cloning and expression of a human brain inositol 1,4,5- RT trisphosphate 3-kinase."; RL Biochem. Biophys. Res. Commun. 174:529-535(1991). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=91088302; PubMed=2175886; RA Takazawa K., Perret J., Dumont J.E., Erneux C.; RT "Human brain inositol 1,4,5-trisphosphate 3-kinase cDNA sequence."; RL Nucleic Acids Res. 18:7141-7141(1990). CC -!- CATALYTIC ACTIVITY: ATP + 1D-myo-inositol 1,4,5-trisphosphate = CC ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate. CC -!- ENZYME REGULATION: IP3K is activated by calmodulin. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X54938; CAA38700.1; -. DR PIR; JN0129; JN0129. DR Genew; HGNC:6178; ITPKA. DR MIM; 147521; -. DR GO; GO:0008440; F:inositol-trisphosphate 3-kinase activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR005522; IPK. DR Pfam; PF03770; IPK; 1. KW Transferase; Kinase; Calmodulin-binding. FT DOMAIN 287 295 CALMODULIN-BINDING (BY SIMILARITY). SQ SEQUENCE 461 AA; 51008 MW; 18CA214A091F5B19 CRC64; MTLPGGPTGM ARPGGARPCS PGLERAPRRS VGELRLLFEA RCAAVAAAAA AGEPRARGAK RRGGQVPNGL PRAPPAPVIP QLTVTAEEPD VPPTSPGPPE RERDCLPAAG SSHLQQPRRL STSSVSSTGS SSLLEDSEDD LLSDSESRSR GNVQLEAGED VGQKNHWQKI RTMVNLPVIS PFKKRYAWVQ LAGHTGSFKA AGTSGLILKR CSEPERYCLA RLMADALRGC VPAFHGVVER DGESYLQLQD LLDGFDGPCV LDCKMGVRTY LEEELTKARE RPKLRKDMYK KMLAVDPEAP TEEEHAQRAV TKPRYMQWRE GISSSTTLGF RIEGIKKADG SCSTDFKTTR SREQVLRVFE EFVQGDEEVL RRYLNRLQQI RDTLEVSEFF RRHEVIGSSL LFVHDHCHRA GVWLIDFGKT TPLPDGQILD HRRPWEEGNR EDGYLLGLDN LIGILASLAE R // ID IP3L_HUMAN STANDARD; PRT; 946 AA. AC P27987; Q96JS1; Q9UH47; DT 01-AUG-1992 (Rel. 23, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Inositol-trisphosphate 3-kinase B (EC 2.7.1.127) (Inositol 1,4,5- DE trisphosphate 3-kinase) (IP3K) (IP3 3-kinase) (IP3K-B). GN ITPKB. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Hippocampus; RA Dewaste V.; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Colon; RA Bertsch U., Suesse S., Frerk S., Fanick W.; RT "Cloning of the complete protein coding regions for inositol 1,4,5- RT trisphosphate 3-kinase B-isoforms from rat and human."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE OF 257-946 FROM N.A. RA Donnelly S.; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE OF 442-946 FROM N.A. RC TISSUE=Brain; RX MEDLINE=91378954; PubMed=1654894; RA Takazawa K., Perret J., Dumont J.E., Erneux C.; RT "Molecular cloning and expression of a new putative inositol 1,4,5- RT trisphosphate 3-kinase isoenzyme."; RL Biochem. J. 278:883-886(1991). CC -!- CATALYTIC ACTIVITY: ATP + 1D-myo-inositol 1,4,5-trisphosphate = CC ADP + 1D-myo-inositol 1,3,4,5-tetrakisphosphate. CC -!- ENZYME REGULATION: IP3K is activated by calmodulin. Form B CC is much more sensitive to calcium/calmodulin than form A. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; Y18024; CAB65055.3; -. DR EMBL; AJ242780; CAC40650.1; -. DR EMBL; AL365444; CAD20257.1; -. DR EMBL; X57206; CAA40491.1; ALT_INIT. DR Genew; HGNC:6179; ITPKB. DR MIM; 147522; -. DR GO; GO:0008440; F:inositol-trisphosphate 3-kinase activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR005522; IPK. DR Pfam; PF03770; IPK; 1. KW Transferase; Kinase; Calmodulin-binding. FT DOMAIN 768 776 CALMODULIN-BINDING (BY SIMILARITY). FT DOMAIN 599 605 POLY-SER. FT CONFLICT 173 173 R -> H (in Ref. 2). FT CONFLICT 210 210 P -> S (in Ref. 2). FT CONFLICT 297 301 GASLT -> APSFP (in Ref. 2). FT CONFLICT 408 408 A -> S (in Ref. 2 and 3). FT CONFLICT 442 443 RV -> IP (in Ref. 4). FT CONFLICT 552 552 Q -> P (in Ref. 3). SQ SEQUENCE 946 AA; 102391 MW; 36C0C74679B1EA1D CRC64; MAVYCYALNS LVIMNSANEM KSGGGPGPSG SETPPPPRRA VLSPGSVFSP GRGASFLFPP AESLSPEEPR SPGGWRSGRR RLNSSSGSGS GSSGSSVSSP SWAGRLRGDR QQVVAAGTLS PPGPEEAKRK LRILQRELQN VQVNQKVGMF EAHIQAQSSA IQAPRSPRLG RARSPSPCPF RSSSQPPGRV LVQGARSEER RTKSWGEQCP ETSGTDSGRK GGPSLCSSQV KKGMPPLPGR AAPTGSEAQG PSAFVRMEKG IPASPRCGSP TAMEIDKRGS PTPGTRSCLA PSLGLFGASL TMATEVAARV TSTGPHRPQD LALTEPSGRA RELEDLQPPE ALVERQGQFL GSETSPAPER GGPRDGEPPG KMGKGYLPCG MPGSGEPEVG KRPEETTVSV QSAESSDALS WSRLPRALAS VGPEEARSGA PVGGGRWQLS DRVEGGSPTL GLLGGSPSAQ PGTGNVEAGI PSGRMLEPLP CWDAAKDLKE PQCPPGDRVG VQPGNSRVWQ GTMEKAGLAW TRGTGVQSEG TWESQRQDSD ALPSPELLPQ DQDKPFLRKA CSPSNIPAVI ITDMGTQEDG ALEETQGSPR GNLPLRKLSS SSASSTGFSS SYEDSEEDIS SDPERTLDPN SAFLHTLDQQ KPRVSKSWRK IKNMVHWSPF VMSFKKKYPW IQLAGHAGSF KAAANGRILK KHCESEQRCL DRLMVDVLRP FVPAYHGDVV KDGERYNQMD DLLADFDSPC VMDCKMGIRT YLEEELTKAR KKPSLRKDMY QKMIEVDPEA PTEEEKAQRA VTKPRYMQWR ETISSTATLG FRIEGIKKED GTVNRDFKKT KTREQVTEAF REFTKGNHNI LIAYRDRLKA IRTTLEVSPF FKCHEVIGSS LLFIHDKKEQ AKVWMIDFGK TTPLPEGQTL QHDVPWQEGN REDGYLSGLN NLVDILTEMS QDAPLA // ID K6PF_HUMAN STANDARD; PRT; 779 AA. AC P08237; Q16814; Q16815; DT 01-AUG-1988 (Rel. 08, Created) DT 01-AUG-1988 (Rel. 08, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE 6-phosphofructokinase, muscle type (EC 2.7.1.11) (Phosphofructokinase DE 1) (Phosphohexokinase) (Phosphofructo-1-kinase isozyme A) (PFK-A) DE (Phosphofructokinase-M). GN PFKM. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Muscle; RX MEDLINE=92009225; PubMed=1833270; RA Yamasaki T., Nakajima H., Kono N., Hotta K., Yamada K., Imai E., RA Kuwajima M., Noguchi T., Tanaka T., Tarui S.; RT "Structure of the entire human muscle phosphofructokinase-encoding RT gene: a two-promoter system."; RL Gene 104:277-282(1991). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Muscle; RX MEDLINE=89306675; PubMed=2526045; RA Sharma P.M., Reddy G.R., Vora S., Babior B.M., McLachlan A.; RT "Cloning and expression of a human muscle phosphofructokinase cDNA."; RL Gene 77:177-183(1989). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Muscle; RX MEDLINE=88030023; PubMed=2822475; RA Nakajima H., Noguchi T., Yamasaki T., Kono N., Tanaka T., Tarui S.; RT "Cloning of human muscle phosphofructokinase cDNA."; RL FEBS Lett. 223:113-116(1987). RN [4] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Brain, and Muscle; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP SEQUENCE OF 271-680 FROM N.A. (ISOFORM 2). RC TISSUE=Muscle; RX MEDLINE=90264379; PubMed=2140567; RA Sharma P.M., Reddy G.R., Babior B.M., McLachlan A.; RT "Alternative splicing of the transcript encoding the human muscle RT isoenzyme of phosphofructokinase."; RL J. Biol. Chem. 265:9006-9010(1990). RN [6] RP SEQUENCE OF 1-27 FROM N.A. RC TISSUE=Muscle; RX MEDLINE=89306652; PubMed=2526044; RA Valdez B.C., Chen Z., Sosa M.G., Younathan E.S., Chang S.H.; RT "Human 6-phosphofructo-1-kinase gene has an additional intron RT upstream of start codon."; RL Gene 76:167-169(1989). RN [7] RP REVIEW ON GSD-VII VARIANTS. RX MEDLINE=96055509; PubMed=7550225; RA Raben N., Sherman J.B.; RT "Mutations in muscle phosphofructokinase gene."; RL Hum. Mutat. 6:1-6(1995). RN [8] RP VARIANTS GSD-VII PRO-38 AND ALA-542. RX MEDLINE=94234147; PubMed=7513946; RA Tsujino S., Servidei S., Tonin P., Shanske S., Azan G., DiMauro S.; RT "Identification of three novel mutations in non-Ashkenazi Italian RT patients with muscle phosphofructokinase deficiency."; RL Am. J. Hum. Genet. 54:812-819(1994). RN [9] RP VARIANTS GSD-VII GLN-99; ASP-208 AND HIS-695. RX MEDLINE=95126102; PubMed=7825568; RA Raben N., Exelbert R., Spiegel R., Sherman J.B., Plotz P., RA Heinisch J.J.; RT "Functional expression of human mutant phosphofructokinase in yeast: RT genetic defects in French Canadian and Swiss patients with RT phosphofructokinase deficiency."; RL Am. J. Hum. Genet. 56:131-141(1995). RN [10] RP VARIANT GSD-VII CYS-685. RX MEDLINE=97044518; PubMed=8889589; RA Hamaguchi T., Nakajima H., Noguchi T., Nakagawa C., Kuwajima M., RA Kono N., Tarui S., Matsuzawa Y.; RT "Novel missense mutation (W686C) of the phosphofructokinase-M gene in RT a Japanese patient with a mild form of glycogenosis VII."; RL Hum. Mutat. 8:273-275(1996). CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 1,6-bisphosphate. CC -!- COFACTOR: Magnesium. CC -!- ENZYME REGULATION: Allosteric enzyme activated by ADP, AMP, or CC fructose bisphosphate and inhibited by ATP or citrate. CC -!- PATHWAY: Key control step of glycolysis. CC -!- SUBUNIT: Tetramer. Muscle is M4, liver is L4, and red cell is M3L, CC M2L2, or ML3. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P08237-1; Sequence=Displayed; CC Name=2; CC IsoId=P08237-2; Sequence=VSP_004667; CC -!- DISEASE: Defects in PFKM are the cause of glycogen storage disease CC VII (GSD-VII) [232800]; also known as Tarui disease. GSD-VII is CC characterized by exercise intolerance with associated nausea and CC vomiting. Short bursts of intense activity are particularly CC difficult. Severe muscle cramps and myoglobinuria develop after CC vigorous exercise. Most patients obtain a "second wind" when the CC onset of exercise is followed by a brief rest period. In time CC patients adjust their activity level and are well compensated. CC -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of CC subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) CC isoenzymes. CC -!- SIMILARITY: Belongs to the phosphofructokinase family. Two domains CC subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M59741; AAA82938.1; -. DR EMBL; M59720; AAA82938.1; JOINED. DR EMBL; M59721; AAA82938.1; JOINED. DR EMBL; M59722; AAA82938.1; JOINED. DR EMBL; M59723; AAA82938.1; JOINED. DR EMBL; M59724; AAA82938.1; JOINED. DR EMBL; M59725; AAA82938.1; JOINED. DR EMBL; M59726; AAA82938.1; JOINED. DR EMBL; M59727; AAA82938.1; JOINED. DR EMBL; M59728; AAA82938.1; JOINED. DR EMBL; M59729; AAA82938.1; JOINED. DR EMBL; M59730; AAA82938.1; JOINED. DR EMBL; M59731; AAA82938.1; JOINED. DR EMBL; M59732; AAA82938.1; JOINED. DR EMBL; M59733; AAA82938.1; JOINED. DR EMBL; M59734; AAA82938.1; JOINED. DR EMBL; M59735; AAA82938.1; JOINED. DR EMBL; M59736; AAA82938.1; JOINED. DR EMBL; M59737; AAA82938.1; JOINED. DR EMBL; M59738; AAA82938.1; JOINED. DR EMBL; M59739; AAA82938.1; JOINED. DR EMBL; M59740; AAA82938.1; JOINED. DR EMBL; M26066; AAA60068.1; -. DR EMBL; Y00698; CAA68692.1; -. DR EMBL; BC000534; AAH00534.1; -. DR EMBL; BC012799; AAH12799.1; -. DR EMBL; BC013298; AAH13298.1; -. DR EMBL; BC021203; AAH21203.1; -. DR EMBL; J05533; AAA79220.1; -. DR EMBL; M24925; AAA36436.1; -. DR PIR; A91605; KIHUFM. DR HSSP; P00512; 3PFK. DR HSC-2DPAGE; P08237; HUMAN. DR Genew; HGNC:8877; PFKM. DR GK; P08237; -. DR MIM; 232800; -. DR MIM; 171850; -. DR GO; GO:0008443; F:phosphofructokinase activity; TAS. DR GO; GO:0006110; P:regulation of glycolysis; TAS. DR InterPro; IPR000023; Ppfruckinase. DR Pfam; PF00365; PFK; 2. DR PIRSF; PIRSF000533; PFK_euk; 1. DR PRINTS; PR00476; PHFRCTKINASE. DR ProDom; PD000707; Ppfruckinase; 2. DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2. KW Kinase; Transferase; Glycolysis; Repeat; Allosteric enzyme; KW Phosphorylation; Magnesium; Multigene family; Alternative splicing; KW Disease mutation; Glycogen storage disease. FT INIT_MET 0 0 FT MOD_RES 774 774 PHOSPHORYLATION (BY SIMILARITY). FT VARSPLIC 281 311 Missing (in isoform 2). FT /FTId=VSP_004667. FT VARIANT 38 38 R -> L (in GSD-VII; Ashkenazi). FT /FTId=VAR_006063. FT VARIANT 38 38 R -> P (in GSD-VII; Italian). FT /FTId=VAR_006064. FT VARIANT 99 99 R -> Q (in GSD-VII; Swiss). FT /FTId=VAR_006065. FT VARIANT 208 208 G -> D (in GSD-VII; French Canadian). FT /FTId=VAR_006066. FT VARIANT 542 542 D -> A (in GSD-VII; Italian). FT /FTId=VAR_006067. FT VARIANT 685 685 W -> C (in GSD-VII; Japanese). FT /FTId=VAR_006068. FT VARIANT 695 695 R -> H (in GSD-VII; Swiss). FT /FTId=VAR_006069. SQ SEQUENCE 779 AA; 85051 MW; 4C9F384A7A5A5750 CRC64; THEEHHAAKT LGIGKAIAVL TSGGDAQGMN AAVRAVVRVG IFTGARVFFV HEGYQGLVDG GDHIKEATWE SVSMMLQLGG TVIGSARCKD FREREGRLRA AYNLVKRGIT NLCVIGGDGS LTGADTFRSE WSDLLSDLQK AGKITDEEAT KSSYLNIVGL VGSIDNDFCG TDMTIGTDSA LHRIMEIVDA ITTTAQSHQR TFVLEVMGRH CGYLALVTSL SCGADWVFIP ECPPDDDWEE HLCRRLSETR TRGSRLNIII VAEGAIDKNG KPITSEDIKN LVVKRLGYDT RVTVLGHVQR GGTPSAFDRI LGSRMGVEAV MALLEGTPDT PACVVSLSGN QAVRLPLMEC VQVTKDVTKA MDEKKFDEAL KLRGRSFMNN WEVYKLLAHV RPPVSKSGSH TVAVMNVGAP AAGMNAAVRS TVRIGLIQGN RVLVVHDGFE GLAKGQIEEA GWSYVGGWTG QGGSKLGTKR TLPKKSFEQI SANITKFNIQ GLVIIGGFEA YTGGLELMEG RKQFDELCIP FVVIPATVSN NVPGSDFSVG ADTALNTICT TCDRIKQSAA GTKRRVFIIE TMGGYCGYLA TMAGLAAGAD AAYIFEEPFT IRDLQANVEH LVQKMKTTVK RGLVLRNEKC NENYTTDFIF NLYSEEGKGI FDSRKNVLGH MQQGGSPTPF DRNFATKMGA KAMNWMSGKI KESYRNGRIF ANTPDSGCVL GMRKRALVFQ PVAELKDQTD FEHRIPKEQW WLKLRPILKI LAKYEIDLDT SDHAHLEHIT RKRSGEAAV // ID K6PL_HUMAN STANDARD; PRT; 780 AA. AC P17858; Q96IH4; DT 01-AUG-1990 (Rel. 15, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE 6-phosphofructokinase, liver type (EC 2.7.1.11) (Phosphofructokinase DE 1) (Phosphohexokinase) (Phosphofructo-1-kinase isozyme B) (PFK-B). GN PFKL. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=90126227; PubMed=2533063; RA Levanon D., Danciger E., Dafni N., Bernstein Y., Elson A., Moens W., RA Brandeis M., Groner Y.; RT "The primary structure of human liver type phosphofructokinase and RT its comparison with other types of PFK."; RL DNA 8:733-743(1989). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=90243256; PubMed=2139864; RA Elson A., Levanon D., Brandeis M., Dafni N., Bernstein Y., RA Danciger E., Groner Y.; RT "The structure of the human liver-type phosphofructokinase gene."; RL Genomics 7:47-56(1990). RN [3] RP SEQUENCE FROM N.A. RX MEDLINE=20289799; PubMed=10830953; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., RA Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Kidney; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 1,6-bisphosphate. CC -!- COFACTOR: Magnesium. CC -!- ENZYME REGULATION: Allosteric enzyme activated by ADP, AMP, or CC fructose bisphosphate and inhibited by ATP or citrate. CC -!- PATHWAY: Key control step of glycolysis. CC -!- SUBUNIT: Tetramer. Muscle is M4, liver is L4, and red cell is M3L, CC M2L2, or ML3. CC -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of CC subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) CC isoenzymes. CC -!- SIMILARITY: Belongs to the phosphofructokinase family. Two domains CC subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X15573; CAA33597.1; -. DR EMBL; X16911; CAB46744.1; ALT_SEQ. DR EMBL; X16912; CAB46744.1; JOINED. DR EMBL; X16913; CAB46744.1; JOINED. DR EMBL; X16914; CAB46744.1; JOINED. DR EMBL; X16915; CAB46744.1; JOINED. DR EMBL; X16916; CAB46744.1; JOINED. DR EMBL; X16917; CAB46744.1; JOINED. DR EMBL; X16918; CAB46744.1; JOINED. DR EMBL; X16919; CAB46744.1; JOINED. DR EMBL; X16920; CAB46744.1; JOINED. DR EMBL; X16921; CAB46744.1; JOINED. DR EMBL; X16922; CAB46744.1; JOINED. DR EMBL; X16923; CAB46744.1; JOINED. DR EMBL; X16924; CAB46744.1; JOINED. DR EMBL; X16925; CAB46744.1; JOINED. DR EMBL; X16926; CAB46744.1; JOINED. DR EMBL; X16927; CAB46744.1; JOINED. DR EMBL; X16928; CAB46744.1; JOINED. DR EMBL; X16929; CAB46744.1; JOINED. DR EMBL; X16930; CAB46744.1; JOINED. DR EMBL; AP001754; BAA95561.1; -. DR EMBL; BC007536; AAH07536.1; -. DR HSSP; P00512; 3PFK. DR Genew; HGNC:8876; PFKL. DR GK; P17858; -. DR MIM; 171860; -. DR MIM; 171850; -. DR GO; GO:0006000; P:fructose metabolism; TAS. DR InterPro; IPR000023; Ppfruckinase. DR Pfam; PF00365; PFK; 2. DR PIRSF; PIRSF000533; PFK_euk; 1. DR PRINTS; PR00476; PHFRCTKINASE. DR ProDom; PD000707; Ppfruckinase; 2. DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2. KW Kinase; Transferase; Glycolysis; Repeat; Allosteric enzyme; KW Phosphorylation; Magnesium; Multigene family; Polymorphism. FT VARIANT 81 81 G -> A. FT /FTId=VAR_006070. FT VARIANT 151 151 W -> R. FT /FTId=VAR_006071. FT CONFLICT 27 27 A -> R (in Ref. 1 and 2). FT CONFLICT 89 89 C -> S (in Ref. 1 and 2). FT CONFLICT 389 389 A -> T (in Ref. 1 and 2). SQ SEQUENCE 780 AA; 85048 MW; DB8D6CE1E20CC854 CRC64; MAAVDLEKLR ASGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE GGENIKQANW LSVSNIIQLG GTIIGSARCK AFTTREGRRA AAYNLVQHGI TNLCVIGGDG SLTGANIFRS EWGSLLEELV AEGKISETTA WTYSHLNIAG LVGSIDNDFC GTDMTIGTDS ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE NFMCERLGET RSRGSRLNII IIAEGAIDRN GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVTLSG NQSVRLPLME CVQMTKEVQK AMDDKRFDEA TQLRGGSFEN NWNIYKLLAH QKPPKEKSNF SLAILNVGAP AAGMNAAVRS AVRTGISHGH TVYVVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKGQLESI VENIRIYGIH ALLVVGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN IHDLKVNVEH MTEKMKTDIQ RGLVLRNEKC HDYYTTEFLY NLYSSEGKGV FDCRTNVLGH LQQGGAPTPF DRNYGTKLGV KAMLWLSEKL REVYRKGRVF ANAPDSACVI GLKKKAVAFS PVTELKKDTD FEHRMPREQW WLSLRLMLKM LAQYRISMAA YVSGELEHVT RRTLSMDKGF // ID K6PP_HUMAN STANDARD; PRT; 784 AA. AC Q01813; DT 01-JUL-1993 (Rel. 26, Created) DT 01-FEB-1996 (Rel. 33, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE 6-phosphofructokinase, type C (EC 2.7.1.11) (Phosphofructokinase DE 1) (Phosphohexokinase) (Phosphofructo-1-kinase isozyme C) (PFK-C) DE (6-phosphofructokinase, platelet type). GN PFKP OR PFKF. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Pancreatic islets; RX MEDLINE=94161770; PubMed=8117307; RA Eto K., Sakura H., Yasuda K., Hayakawa T., Kawasaki E., RA Moriuchi R., Nagataki S., Yazaki Y., Kadowaki T.; RT "Cloning of a complete protein-coding sequence of human platelet-type RT phosphofructokinase isozyme from pancreatic islet."; RL Biochem. Biophys. Res. Commun. 198:990-998(1994). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Brain, and Placenta; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP SEQUENCE OF 484-784 FROM N.A. RX MEDLINE=92028938; PubMed=1834056; RA Simpson C.J., Fothergill-Gilmore L.A.; RT "Isolation and sequence of a cDNA encoding human platelet RT phosphofructokinase."; RL Biochem. Biophys. Res. Commun. 180:197-203(1991). CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 1,6-bisphosphate. CC -!- COFACTOR: Magnesium. CC -!- ENZYME REGULATION: Allosteric enzyme activated by ADP, AMP, or CC fructose bisphosphate and inhibited by ATP or citrate. CC -!- PATHWAY: Key control step of glycolysis. CC -!- SUBUNIT: Tetramer. Muscle is M4, liver is L4, and red cell is M3L, CC M2L2, or ML3. A subunit composition with a higher proportion of CC platelet type subunits is found in platelets, brain and CC fibroblasts. CC -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of CC subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) CC isoenzymes. CC -!- SIMILARITY: Belongs to the phosphofructokinase family. Two domains CC subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; D25328; BAA04998.1; -. DR EMBL; BC002536; AAH02536.1; -. DR EMBL; BC029138; AAH29138.1; -. DR EMBL; M64784; AAA36435.1; -. DR PIR; JC2055; JC2055. DR HSSP; P00512; 3PFK. DR Genew; HGNC:8878; PFKP. DR GK; Q01813; -. DR MIM; 171840; -. DR GO; GO:0005945; C:6-phosphofructokinase complex; NAS. DR GO; GO:0003872; F:6-phosphofructokinase activity; TAS. DR GO; GO:0006096; P:glycolysis; NAS. DR InterPro; IPR000023; Ppfruckinase. DR Pfam; PF00365; PFK; 2. DR PIRSF; PIRSF000533; PFK_euk; 1. DR PRINTS; PR00476; PHFRCTKINASE. DR ProDom; PD000707; Ppfruckinase; 2. DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2. KW Kinase; Transferase; Glycolysis; Repeat; Allosteric enzyme; KW Phosphorylation; Magnesium; Multigene family. FT CONFLICT 484 485 PG -> IP (in Ref. 3). FT CONFLICT 498 498 Missing (in Ref. 3). FT CONFLICT 699 699 A -> E (in Ref. 3). SQ SEQUENCE 784 AA; 85596 MW; 22522E77E9AF80F6 CRC64; MDADDSRAPK GSLRKFLEHL SGAGKAIGVL TSGGDAQGMN AAVRAVVRMG IYVGAKVYFI YEGYQGMVDG GSNIAEADWE SVSSILQVGG TIIGSARCQA FRTREGRLKA ACNLLQRGIT NLCVIGGDGS LTGANLFRKE WSGLLEELAR NGQIDKEAVQ KYAYLNVVGM VGSIDNDFCG TDMTIGTDSA LHRIIEVVDA IMTTAQSHQR TFVLEVMGRH CGYLALVSAL ACGADWVFLP ESPPEEGWEE QMCVKLSENR ARKKRLNIII VAEGAIDTQN KPITSEKIKE LVVTQLGYDT RVTILGHVQR GGTPSAFDRI LASRMGVEAV IALLEATPDT PACVVSLNGN HAVRLPLMEC VQMTQDVQKA MDERRFQDAV RLRGRSFAGN LNTYKRLAIK LPDDQIPKTN CNVAVINVGA PAAGMNAAVR SAVRVGIADG HRMLAIYDGF DGFAKGQIKE IGWTDVGGWT GQGGSILGTK RVLPGKYLEE IATQMRTHSI NALLIIGGFE AYLGLLELSA AREKHEEFCV PMVMVPATVS NNVPGSDFSI GADTALNTIT DTCDRIKQSA SGTKRRVFII ETMGGYCGYL ANMGGLAAGA DAAYIFEEPF DIRDLQSNVE HLTEKMKTTI QRGLVLRNES CSENYTTDFI YQLYSEEGKG VFDCRKNVLG HMQQGGAPSP FDRNFGTKIS ARAMEWITAK LKEARGRGKK FTTDDSICVL GISKRNVIFQ PVAELKKQTD FEHRIPKEQW WLKLRPLMKI LAKYKASYDV SDSGQLEHVQ PWSV // ID KAD1_HUMAN STANDARD; PRT; 194 AA. AC P00568; Q9BVK9; Q9UQC7; DT 21-JUL-1986 (Rel. 01, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Adenylate kinase isoenzyme 1 (EC 2.7.4.3) (ATP-AMP transphosphorylase) DE (AK1) (Myokinase). GN AK1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE. RC TISSUE=Skeletal muscle; RX MEDLINE=77003085; PubMed=183954; RA von Zabern I., Wittmann-Liebold B., Untucht-Grau R., Schirmer R.H., RA Pai E.F.; RT "Primary and tertiary structure of the principal human adenylate RT kinase."; RL Eur. J. Biochem. 68:281-290(1976). RN [2] RP SEQUENCE FROM N.A., AND VARIANT TRP-128. RX MEDLINE=89255503; PubMed=2542324; RA Matsuura S., Igarashi M., Tanizawa Y., Yamada M., Kishi F., RA Kajii T., Fujii H., Miwa S., Sakurai M., Nakazawa A.; RT "Human adenylate kinase deficiency associated with hemolytic anemia. RT A single base substitution affecting solubility and catalytic RT activity of the cytosolic adenylate kinase."; RL J. Biol. Chem. 264:10148-10155(1989). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Retina; RA Noma T.; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Colon; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: This small ubiquitous enzyme is essential for CC maintenance and cell growth. CC -!- CATALYTIC ACTIVITY: ATP + AMP = ADP + ADP. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- POLYMORPHISM: This enzyme represents the most common of at least CC five alleles. CC -!- DISEASE: Deficiency in AK1 is the cause of a form of hemolytic CC anemia. CC -!- SIMILARITY: Belongs to the adenylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; J04809; AAA51686.1; -. DR EMBL; AB021871; BAA78534.1; -. DR EMBL; BC001116; AAH01116.1; -. DR PIR; A33508; KIHUA. DR HSSP; P00571; 3ADK. DR Genew; HGNC:361; AK1. DR GK; P00568; -. DR MIM; 103000; -. DR GO; GO:0004017; F:adenylate kinase activity; TAS. DR InterPro; IPR000850; Adenylate_kin. DR InterPro; IPR006267; Adenylate_kin1. DR Pfam; PF00406; ADK; 1. DR PRINTS; PR00094; ADENYLTKNASE. DR ProDom; PD000657; Adenylate_kin; 1. DR TIGRFAMs; TIGR01360; aden_kin_iso1; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; 1. KW Transferase; Kinase; ATP-binding; Acetylation; Disease mutation. FT MOD_RES 1 1 ACETYLATION. FT NP_BIND 15 23 ATP (By similarity). FT ACT_SITE 36 36 FT ACT_SITE 93 93 FT VARIANT 128 128 R -> W (in hemolytic anemia). FT /FTId=VAR_004021. FT CONFLICT 9 9 K -> N (in Ref. 4). FT CONFLICT 127 127 Q -> R (in Ref. 1). FT CONFLICT 181 181 S -> E (in Ref. 1). SQ SEQUENCE 194 AA; 21635 MW; 95EC5AAA92D1F00F CRC64; MEEKLKKTKI IFVVGGPGSG KGTQCEKIVQ KYGYTHLSTG DLLRSEVSSG SARGKKLSEI MEKGQLVPLE TVLDMLRDAM VAKVNTSKGF LIDGYPREVQ QGEEFERRIG QPTLLLYVDA GPETMTQRLL KRGETSGRVD DNEETIKKRL ETYYKATEPV IAFYEKRGIV RKVNAEGSVD SVFSQVCTHL DALK // ID KAD2_HUMAN STANDARD; PRT; 238 AA. AC P54819; Q16856; Q8TCY2; Q8TCY3; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Adenylate kinase isoenzyme 2, mitochondrial (EC 2.7.4.3) (ATP-AMP DE transphosphorylase). GN AK2 OR ADK2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Liver; RX MEDLINE=97000211; PubMed=8843353; RA Lee Y., Kim J.W., Lee I.A., Kang H.B., Choe Y.K., Lee H.G., RA Lim J.S., Kim H.J., Park C., Choe I.S.; RT "Cloning and characterization of cDNA for human adenylate kinase 2A."; RL Biochem. Mol. Biol. Int. 39:833-842(1996). RN [2] RP SEQUENCE FROM N.A. (ISOFORM 2). RC TISSUE=Fetal liver; RX MEDLINE=98162934; PubMed=9504408; RA Lee Y., Kim J.W., Lee S.M., Kim H.J., Lee K.S., Park C., Choe I.S.; RT "Cloning and expression of human adenylate kinase 2 isozymes: RT differential expression of adenylate kinase 1 and 2 in human muscle RT tissues."; RL J. Biochem. 123:47-54(1998). RN [3] RP SEQUENCE FROM N.A. (ISOFORMS 1 AND 2). RX MEDLINE=98094237; PubMed=9434148; RA Noma T., Song S., Yoon Y.-S., Tanaka S., Nakazawa A.; RT "cDNA cloning and tissue-specific expression of the gene encoding RT human adenylate kinase isozyme 2."; RL Biochim. Biophys. Acta 1395:34-39(1998). RN [4] RP SEQUENCE FROM N.A. (ISOFORMS 3 AND 4). RA Guo J.; RT "Novel isoforms of human adenylate kinase 2."; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP SEQUENCE FROM N.A. (ISOFORM 1). RC TISSUE=Uterus; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: This small ubiquitous enzyme is essential for CC maintenance and cell growth. CC -!- CATALYTIC ACTIVITY: ATP + AMP = ADP + ADP. CC -!- SUBUNIT: Monomer (By similarity). CC -!- SUBCELLULAR LOCATION: Mitochondrial intermembrane space. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=AK2A; CC IsoId=P54819-1; Sequence=Displayed; CC Name=2; Synonyms=AK2B; CC IsoId=P54819-2; Sequence=VSP_002790; CC Name=3; Synonyms=AK2C; CC IsoId=P54819-3; Sequence=VSP_002791; CC Name=4; Synonyms=AK2D; CC IsoId=P54819-4; Sequence=VSP_002792, VSP_002793, VSP_002794; CC -!- TISSUE SPECIFICITY: ABUNDANT IN HEART. CC -!- SIMILARITY: Belongs to the adenylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U39945; AAC52061.1; -. DR EMBL; U84371; AAB41790.1; -. DR EMBL; U54645; AAC13881.1; -. DR EMBL; AB005621; BAC16747.1; -. DR EMBL; AB005622; BAC16748.1; -. DR EMBL; AY080899; AAL87027.1; -. DR EMBL; AY080900; AAL87028.1; -. DR EMBL; BC009405; AAH09405.1; -. DR PIR; G02248; G02248. DR PIR; JC5893; JC5893. DR HSSP; P08166; 1AK2. DR Genew; HGNC:362; AK2. DR MIM; 103020; -. DR GO; GO:0004017; F:adenylate kinase activity; TAS. DR InterPro; IPR006259; Adenyl_kin_sub. DR InterPro; IPR000850; Adenylate_kin. DR InterPro; IPR007862; ADK_lid. DR Pfam; PF00406; ADK; 1. DR Pfam; PF05191; ADK_lid; 1. DR PRINTS; PR00094; ADENYLTKNASE. DR ProDom; PD000657; Adenylate_kin; 1. DR TIGRFAMs; TIGR01351; adk; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; 1. KW Transferase; Kinase; ATP-binding; Mitochondrion; Alternative splicing. FT INIT_MET 0 0 By similarity. FT NP_BIND 21 29 ATP (By similarity). FT VARSPLIC 231 238 CKDLVMFI -> S (in isoform 2). FT /FTId=VSP_002790. FT VARSPLIC 177 238 DNEKALKIRLQAYHTQTTPLIEYYRKRGIHSAIDASQTPDV FT VFASILAAFSKATCKDLVMFI -> IGQAKRSFLRLAKISF FT DVLIKKALA (in isoform 3). FT /FTId=VSP_002791. FT VARSPLIC 1 47 Missing (in isoform 4). FT /FTId=VSP_002792. FT VARSPLIC 176 177 DD -> GL (in isoform 4). FT /FTId=VSP_002793. FT VARSPLIC 178 238 Missing (in isoform 4). FT /FTId=VSP_002794. SQ SEQUENCE 238 AA; 26346 MW; 34B3844F355EC3D1 CRC64; APSVPAAEPE YPKGIRAVLL GPPGAGKGTQ APRLAENFCV CHLATGDMLR AMVASGSELG KKLKATMDAG KLVSDEMVVE LIEKNLETPL CKNGFLLDGF PRTVRQAEML DDLMEKRKEK LDSVIEFSIP DSLLIRRITG RLIHPKSGRS YHEEFNPPKE PMKDDITGEP LIRRSDDNEK ALKIRLQAYH TQTTPLIEYY RKRGIHSAID ASQTPDVVFA SILAAFSKAT CKDLVMFI // ID KAD3_HUMAN STANDARD; PRT; 226 AA. AC Q9UIJ7; Q9H576; Q9NPB4; DT 16-OCT-2001 (Rel. 40, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE GTP:AMP phosphotransferase mitochondrial (EC 2.7.4.10) (AK3) DE (Adenylate kinase 3 alpha like 1). GN AK3L1 OR AKL3L. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RA Noma T.; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Placenta; RA Isogai T., Ota T., Hayashi K., Sugiyama T., Otsuki T., Suzuki Y., RA Nishikawa T., Nagai K., Sugano S., Shiratori A., Sudo H., RA Wagatsuma M., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Chiba Y., Ishida S., Murakawa K., Ono Y., Takiguchi S., RA Watanabe S., Kimura K., Murakami K., Ishii S., Kawai Y., Saito K., RA Yamamoto J., Wakamatsu A., Nakamura Y., Nagahari K., Masuho Y., RA Ninomiya K., Iwayanagi T., Aotsuka S., Yoshikawa Y., Matsunawa H., RA Sasaki N., Ishibashi T., Fujimori K., Tanai H., Kimata M., RA Watanabe M., Hiraoka S., Kanehori K.; RT "NEDO human cDNA sequencing project."; RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Lymph; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE OF 91-226 FROM N.A. RA Lloyd D.; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. CC -!- CATALYTIC ACTIVITY: GTP + AMP = GDP + ADP. CC -!- SUBUNIT: Monomer (By similarity). CC -!- SUBCELLULAR LOCATION: Mitochondrial matrix (By similarity). CC -!- SIMILARITY: Belongs to the adenylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AB021870; BAA87913.1; -. DR EMBL; AK001553; BAA91753.1; -. DR EMBL; AK001951; BAA91996.1; -. DR EMBL; AK027534; BAB55183.1; -. DR EMBL; BC013771; AAH13771.1; -. DR EMBL; AL136231; CAC12706.1; -. DR HSSP; P08760; 2AK3. DR Genew; HGNC:17376; AK3L1. DR InterPro; IPR000850; Adenylate_kin. DR InterPro; IPR006259; Adenyl_kin_sub. DR InterPro; IPR007862; ADK_lid. DR Pfam; PF00406; ADK; 1. DR Pfam; PF05191; ADK_lid; 1. DR PRINTS; PR00094; ADENYLTKNASE. DR ProDom; PD000657; Adenylate_kin; 1. DR TIGRFAMs; TIGR01351; adk; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; 1. KW Transferase; Kinase; GTP-binding; Mitochondrion. FT INIT_MET 0 0 By similarity. FT NP_BIND 13 21 GTP (By similarity). FT CONFLICT 4 4 A -> G (in Ref. 1). FT CONFLICT 37 37 S -> R (in Ref. 1). FT CONFLICT 56 56 K -> Q (in Ref. 1). FT CONFLICT 68 70 DVM -> YVT (in Ref. 1). SQ SEQUENCE 226 AA; 25434 MW; 9FFD81FEC2C0ACBC CRC64; GASARLLRAV IMGAPGSGKG TVSSRITTHF ELKHLSSGDL LRDNMLRGTE IGVLAKAFID QGKLIPDDVM TRLALHELKN LTQYSWLLDG FPRTLPQAEA LDRAYQIDTV INLNVPFEVI KQRLTARWIH PASGRVYNIE FNPPKTVGID DLTGEPLIQR EDDKPETVIK RLKAYEDQTK PVLEYYQKKG VLETFSGTET NKIWPYVYAF LQTKVPQRSQ KASVTP // ID KAD4_HUMAN STANDARD; PRT; 223 AA. AC P27144; DT 01-AUG-1992 (Rel. 23, Created) DT 01-AUG-1992 (Rel. 23, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Adenylate kinase isoenzyme 4, mitochondrial (EC 2.7.4.3) (ATP-AMP DE transphosphorylase). GN AK3 OR AK4. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=92347846; PubMed=1639383; RA Xu G., O'Connell P., Stevens J., White R.; RT "Characterization of human adenylate kinase 3 (AK3) cDNA and mapping RT of the AK3 pseudogene to an intron of the NF1 gene."; RL Genomics 13:537-542(1992). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Lung; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- CATALYTIC ACTIVITY: GTP + AMP = GDP + ADP. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Mitochondrial matrix. CC -!- SIMILARITY: Belongs to the adenylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X60673; CAA43088.1; -. DR EMBL; BC016180; AAH16180.1; -. DR PIR; A42820; KIHUA3. DR HSSP; P08760; 2AK3. DR Genew; HGNC:363; AK3. DR MIM; 103030; -. DR InterPro; IPR006259; Adenyl_kin_sub. DR InterPro; IPR000850; Adenylate_kin. DR InterPro; IPR007862; ADK_lid. DR Pfam; PF00406; ADK; 1. DR Pfam; PF05191; ADK_lid; 1. DR PRINTS; PR00094; ADENYLTKNASE. DR ProDom; PD000657; Adenylate_kin; 1. DR TIGRFAMs; TIGR01351; adk; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; 1. KW Transferase; Kinase; GTP-binding; Mitochondrion. FT NP_BIND 12 20 GTP (By similarity). SQ SEQUENCE 223 AA; 25268 MW; 653341A8EB3BC723 CRC64; MASKLLRAVI LGPPGSGKGT VCQRIAQNFG LQHLSSGHFL RENIKASTEV GEMAKQYIEK SLLVPDHVIT RLMMSELENR RGQHWLLDGF PRTLGQAEAL DKICEVDLVI SLNIPFETLK DRLSRRWIHP PSGRVYNLDF NPPHVHGIDD VTGEPLVQQE DDKPEAVAAR LRQYKDVAKP VIELYKSRGV LHQFSGTETN KIWPYVYTLF SNKITPIQSK EAY // ID KAD5_HUMAN STANDARD; PRT; 198 AA. AC Q9Y6K8; Q96EC9; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Adenylate kinase isoenzyme 5 (EC 2.7.4.3) (ATP-AMP DE transphosphorylase). GN AK5. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=99234026; PubMed=10215863; RA Van Rompay A.R., Johansson M., Karlsson A.; RT "Identification of a novel human adenylate kinase. cDNA cloning, RT expression analysis, chromosome localization and characterization of RT the recombinant protein."; RL Eur. J. Biochem. 261:509-517(1999). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Active on AMP and dAMP with ATP as a donor. When GTP is CC used as phosphate donor, the enzyme phosphorylates AMP, CMP, and CC to a small extent dCMP. CC -!- CATALYTIC ACTIVITY: ATP + AMP = ADP + ADP. CC -!- SUBUNIT: Monomer (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- TISSUE SPECIFICITY: Brain specific. CC -!- SIMILARITY: Belongs to the adenylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF062595; AAD27956.1; -. DR EMBL; BC012467; AAH12467.1; -. DR HSSP; P00571; 3ADK. DR Genew; HGNC:365; AK5. DR MIM; 608009; -. DR GO; GO:0005829; C:cytosol; TAS. DR GO; GO:0004017; F:adenylate kinase activity; TAS. DR GO; GO:0006172; P:ADP biosynthesis; TAS. DR GO; GO:0006173; P:dADP biosynthesis; TAS. DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthesis; TAS. DR InterPro; IPR000850; Adenylate_kin. DR InterPro; IPR006267; Adenylate_kin1. DR Pfam; PF00406; ADK; 1. DR PRINTS; PR00094; ADENYLTKNASE. DR ProDom; PD000657; Adenylate_kin; 1. DR TIGRFAMs; TIGR01360; aden_kin_iso1; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; 1. KW Transferase; Kinase; ATP-binding. FT NP_BIND 18 26 ATP (By similarity). FT NP_BIND 41 70 AMP (By similarity). FT ACT_SITE 39 39 By similarity. FT ACT_SITE 96 96 By similarity. FT CONFLICT 197 197 Missing (in Ref. 2). SQ SEQUENCE 198 AA; 22087 MW; 8E8FA514CB7C3B58 CRC64; MGGFMEDLRK CKIIFIIGGP GSGKGTQCEK LVEKYGFTHL STGELLREEL ASESERSKLI RDIMERGDLV PSGIVLELLK EAMVASLGDT RGFLIDGYPR EVKQGEEFGR RIGDPQLVIC MDCSADTMTN RLLQRSRSSL PVDDTTKTIA KRLEAYYRAS IPVIAYYETK TQLHKINAEG TPEDVFLQLC TAIDSIIF // ID KAD7_HUMAN STANDARD; PRT; 723 AA. AC Q96M32; Q8IYP6; DT 10-OCT-2003 (Rel. 42, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Putative adenylate kinase 7 (EC 2.7.4.3). GN AK7. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND VARIANT GLN-102. RC TISSUE=Testis; RA Suzuki O., Sasaki N., Aotsuka S., Shoji T., Ichihara T., Shiohata N., RA Matsumoto K., Hirano M., Sano S., Nomura R., Yoshikawa Y., RA Matsumura Y., Moriya S., Chiba E., Momiyama H., Onogawa S., RA Kaeriyama S., Satoh N., Matsunawa H., Takahashi E., Kataoka R., RA Kuga N., Kuroda A., Satoh I., Kamata K., Takami S., Terashima Y., RA Watanabe M., Sugiyama T., Irie R., Otsuki T., Sato H., Wakamatsu A., RA Ishii S., Yamamoto J., Isono Y., Kawai-Hio Y., Saito K., Nishikawa T., RA Kimura K., Yamashita H., Matsuo K., Nakamura Y., Sekine M., RA Kikuchi H., Kanda K., Wagatsuma M., Murakawa K., Kanehori K., RA Takahashi-Fujii A., Oshima A., Sugiyama A., Kawakami B., Suzuki Y., RA Sugano S., Nagahari K., Masuho Y., Nagai K., Isogai T.; RT "NEDO human cDNA sequencing project."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RX PubMed=12508121; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- CATALYTIC ACTIVITY: ATP + AMP = ADP + ADP. CC -!- SIMILARITY: In the central section; belongs to the adenylate CC kinase family. CC -!- SIMILARITY: In the C-terminal section; belongs to the dpy-30 CC family. CC -!- CAUTION: Ref.3 sequence differs from that shown due to a stop CC codon in position 657. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AK057426; BAB71480.1; -. DR EMBL; AL163051; -; NOT_ANNOTATED_CDS. DR EMBL; AL359240; -; NOT_ANNOTATED_CDS. DR EMBL; BC035256; AAH35256.1; ALT_TERM. DR Genew; HGNC:20091; AK7. DR InterPro; IPR007858; Dpy-30. DR Pfam; PF05186; Dpy-30; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; FALSE_NEG. KW Transferase; Kinase; ATP-binding; Coiled coil; Polymorphism. FT DOMAIN 46 458 COILED COIL (POTENTIAL). FT DOMAIN 366 502 ADENYLATE KINASE. FT DOMAIN 609 677 COILED COIL (POTENTIAL). FT DOMAIN 679 723 DPY-30. FT NP_BIND 374 381 ATP (Potential). FT DOMAIN 616 674 GLU-RICH. FT DOMAIN 3 6 POLY-GLU. FT DOMAIN 51 58 POLY-GLU. FT DOMAIN 420 432 POLY-GLU. FT DOMAIN 497 502 POLY-GLU. FT VARIANT 102 102 R -> Q (in dbSNP:2369679). FT /FTId=VAR_017059. FT CONFLICT 272 272 P -> L (in Ref. 1). FT CONFLICT 410 410 E -> G (in Ref. 1). FT CONFLICT 605 605 I -> T (in Ref. 3). FT CONFLICT 657 657 Missing (in Ref. 3). SQ SEQUENCE 723 AA; 82672 MW; 8E5FE865A9DA0AFB CRC64; MAEEEETAAL TEKVIRTQRV FINLLDSYSS GNIGKFLSNC VVGASLEEIT EEEEEEDENK SAMLEASSTK VKEGTFQIVG TLSKPDSPRP DFAVETYSAI SREDLLMRLL ECDVIIYNIT ESSQQMEEAI WAVSALSEEV SHFEKRKLFI LLSTVMTWAR SKALDPEDSE VPFTEEDYRR RKSHPNFLDH INAEKMVLKF GKKARKFAAY VVAAGLQYGA EGGMLHTFFK MAWLGEIPAL PVFGDGTNVI PTIHVLDLAG VIQNVIDHVP KPHYLVAVDE SVHTLEDIVK CISKNTGPGK IQKIPRENAY LTKDLTQDCL DHLLVNLRME ALFVKENFNI RWAAQTGFVE NINTILKEYK QSRGLMPIKI CILGPPAVGK SSIAKELAKY YKLHHIQLKD VISEAIAKLE AIVAPNDVGE GEEEVEEEEE EENVEDAQEL LDGIKESMEQ NAGQLDDQYI IRFMKEKLKS MPCRNQGYIL DGFPKTYDQA KDLFNQEDEE EEDDVRGRMF PFDKLIIPEF VCALDASDEF LKERVINLPE SIVAGTHYSQ DRFLRALSNY RDINIDDETV FNYFDELEIH PIHIDVGKLE DAQNRLAIKQ LIKEIGEPRN YGLTDEEKAE EERKAAEERL AREAAEEAER EHQEAVEMAE KIARWEEWNK RLEEVKREER ELLEAQSIPL RNYLMTYVMP TLIQGLNECC NVRPEDPVDF LAEYLFKNNP EAQ // ID KCRB_HUMAN STANDARD; PRT; 381 AA. AC P12277; DT 01-OCT-1989 (Rel. 12, Created) DT 01-OCT-1989 (Rel. 12, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Creatine kinase, B chain (EC 2.7.3.2) (B-CK). GN CKB OR CKBB. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=88085186; PubMed=3692484; RA Mariman E.C.M., Broers C.A.M., Claesen C.A.A., Tesser G.I., RA Wieringa B.; RT "Structure and expression of the human creatine kinase B gene."; RL Genomics 1:126-137(1987). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=87195439; PubMed=2883200; RA Kaye F.J., McBride O.W., Battey J.F., Gazder A.F., Sausville E.A.; RT "Human creatine kinase-B complementary DNA. Nucleotide sequence, gene RT expression in lung cancer, and chromosomal assignment to two distinct RT loci."; RL J. Clin. Invest. 79:1412-1420(1987). RN [3] RP SEQUENCE FROM N.A. RX MEDLINE=87213302; PubMed=3034271; RA Villarreal-Levy G., Ma T.S., Kerner S.A., Roberts R., Perryman M.B.; RT "Human creatine kinase: isolation and sequence analysis of cDNA RT clones for the B subunit, development of subunit specific probes and RT determination of gene copy number."; RL Biochem. Biophys. Res. Commun. 144:1116-1127(1987). RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=89366665; PubMed=2771648; RA Mariman E.C.M., Schepens J.T.G., Wieringa B.; RT "Complete nucleotide sequence of the human creatine kinase B gene."; RL Nucleic Acids Res. 17:6385-6385(1989). RN [5] RP SEQUENCE FROM N.A. RC TISSUE=Brain, Eye, and Lung; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [6] RP SEQUENCE OF 1-97 FROM N.A. RX MEDLINE=88115393; PubMed=2828370; RA Daouk G.H., Kaddurah-Daouk R., Putney S., Kingston R., Schimmel P.; RT "Isolation of a functional human gene for brain creatine kinase."; RL J. Biol. Chem. 263:2442-2446(1988). RN [7] RP MUTAGENESIS OF CYS-283; ASP-340 AND ARG-292. RX MEDLINE=94242786; PubMed=8186255; RA Lin L., Perryman M.B., Friedman D., Roberts R., Ma T.S.; RT "Determination of the catalytic site of creatine kinase by site- RT directed mutagenesis."; RL Biochim. Biophys. Acta 1206:97-104(1994). CC -!- FUNCTION: Reversibly catalyzes the transfer of phosphate between CC ATP and various phosphogens (e.g. creatine phosphate). Creatine CC kinase isoenzymes play a central role in energy transduction in CC tissues with large, fluctuating energy demands, such as skeletal CC muscle, heart, brain and spermatozoa. CC -!- CATALYTIC ACTIVITY: ATP + creatine = ADP + phosphocreatine. CC -!- SUBUNIT: Dimer of identical or nonidentical chains. With MM being CC the major form in skeletal muscle and myocardium, MB existing in CC myocardium, and BB existing in many tissues, especially brain. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- SIMILARITY: Belongs to the ATP:guanido phosphotransferase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; L47647; AAA76852.1; -. DR EMBL; X15334; CAA33389.1; -. DR EMBL; M21243; AAC31758.1; ALT_SEQ. DR EMBL; M21237; AAC31758.1; JOINED. DR EMBL; M21238; AAC31758.1; JOINED. DR EMBL; M21239; AAC31758.1; JOINED. DR EMBL; M21240; AAC31758.1; JOINED. DR EMBL; M21241; AAC31758.1; JOINED. DR EMBL; M21242; AAC31758.1; JOINED. DR EMBL; M16364; AAA76850.1; -. DR EMBL; M16451; AAA76851.1; -. DR EMBL; BC001190; AAH01190.1; -. DR EMBL; BC004914; AAH04914.1; -. DR EMBL; BC008323; AAH08323.1; -. DR EMBL; BC010002; AAH10002.1; -. DR EMBL; BC019259; AAH19259.1; -. DR EMBL; BC019281; AAH19281.1; -. DR EMBL; M22356; AAA52024.1; -. DR EMBL; M22355; AAA52024.1; JOINED. DR PIR; S15935; KIHUCB. DR HSSP; P05122; 1QH4. DR PHCI-2DPAGE; P12277; -. DR HSC-2DPAGE; P12277; HUMAN. DR Genew; HGNC:1991; CKB. DR MIM; 123280; -. DR GO; GO:0004111; F:creatine kinase activity; TAS. DR InterPro; IPR000749; ATP-gua_Ptrans. DR Pfam; PF00217; ATP-gua_Ptrans; 1. DR Pfam; PF02807; ATP-gua_PtransN; 1. DR PROSITE; PS00112; GUANIDO_KINASE; 1. KW Transferase; Kinase; Multigene family. FT ACT_SITE 283 283 FT MUTAGEN 283 283 C->S,Y: COMPLETE LOSS OF ACTIVITY. FT MUTAGEN 292 292 R->H,L,Q: COMPLETE LOSS OF ACTIVITY. FT MUTAGEN 292 292 R->K: 42% OF WILD-TYPE ACTIVITY. FT MUTAGEN 340 340 D->E: NO CHANGE IN ACTIVITY. FT CONFLICT 41 42 EL -> DV (in Ref. 3). FT CONFLICT 78 78 D -> G (in Ref. 2 and 6). FT CONFLICT 98 99 GG -> RR (in Ref. 3). FT CONFLICT 105 106 EH -> DD (in Ref. 3). FT CONFLICT 130 130 R -> G (in Ref. 2). FT CONFLICT 132 132 R -> A (in Ref. 3). FT CONFLICT 215 216 RG -> AR (in Ref. 3). FT CONFLICT 296 296 H -> D (in Ref. 3). SQ SEQUENCE 381 AA; 42644 MW; 637AA67A86AE3059 CRC64; MPFSNSHNAL KLRFPAEDEF PDLSAHNNHM AKVLTPELYA ELRAKSTPSG FTLDDVIQTG VDNPGHPYIM TVGCVAGDEE SYEVFKDLFD PIIEDRHGGY KPSDEHKTDL NPDNLQGGDD LDPNYVLSSR VRTGRSIRGF CLPPHCSRGE RRAIEKLAVE ALSSLDGDLA GRYYALKSMT EAEQQQLIDD HFLFDKPVSP LLLASGMARD WPDARGIWHN DNKTFLVWVN EEDHLRVISM QKGGNMKEVF TRFCTGLTQI ETLFKSKDYE FMWNPHLGYI LTCPSNLGTG LRAGVHIKLP NLGKHEKFSE VLKRLRLQKR GTGGVDTAAV GGVFDVSNAD RLGFSEVELV QMVVDGVKLL IEMEQRLEQG QAIDDLMPAQ K // ID KCRM_HUMAN STANDARD; PRT; 381 AA. AC P06732; Q96QL9; DT 01-JAN-1988 (Rel. 06, Created) DT 01-NOV-1990 (Rel. 16, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Creatine kinase, M chain (EC 2.7.3.2) (M-CK). GN CKM OR CKMM. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=89034220; PubMed=2903158; RA Trask R.V., Strauss A.W., Billadello J.J.; RT "Developmental regulation and tissue-specific expression of the human RT muscle creatine kinase gene."; RL J. Biol. Chem. 263:17142-17149(1988). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=87048887; PubMed=3778496; RA Perryman M.B., Kerner S.A., Bohlmeyer T.J., Roberts R.; RT "Isolation and sequence analysis of a full-length cDNA for human M RT creatine kinase."; RL Biochem. Biophys. Res. Commun. 140:981-989(1986). RN [3] RP SEQUENCE FROM N.A. RA Lamerdin J.E., McCready P.M., Skowronski E., Viswanathan V., RA Burkhart-Schultz K., Gordon L., Dias J., Ramirez M., Stilwagen S., RA Phan H., Velasco N., Do L., Regala W., Terry A., Garnes J., RA Danganan L., Erler A., Christensen M., Georgescu A., Avila J., Liu S., RA Attix C., Andreise T., Trankheim M., Amico-Keller G., Coefield J., RA Duarte S., Lucas S., Bruce R., Thomas P., Quan G., Kronmiller B., RA Arellano A., Saunders C., Ow D., Nolan M., Trong S., Kobayashi A., RA Olsen A.S., Carrano A.V.; RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP SEQUENCE OF 257-327 FROM N.A. RX MEDLINE=87181666; PubMed=3031982; RA Nigro J.M., Schweinfest C.W., Rajkovic A., Pavlovic J., Jamal S., RA Dottin R.P., Hart J.T., Kamarck M.E., Rae P.M.M., Carty M.D., RA Martin-Deleon P.; RT "cDNA cloning and mapping of the human creatine kinase M gene to RT 19q13."; RL Am. J. Hum. Genet. 40:115-125(1987). RN [6] RP SEQUENCE OF 1-30 FROM N.A. RX MEDLINE=90202921; PubMed=1690725; RA Hamburg R.J., Friedman D.L., Olson E.N., Ma T.S., Cortez M.D., RA Goodman C., Puleo P.R., Perryman M.B.; RT "Muscle creatine kinase isoenzyme expression in adult human brain."; RL J. Biol. Chem. 265:6403-6409(1990). CC -!- FUNCTION: Reversibly catalyzes the transfer of phosphate between CC ATP and various phosphogens (e.g. creatine phosphate). Creatine CC kinase isoenzymes play a central role in energy transduction in CC tissues with large, fluctuating energy demands, such as skeletal CC muscle, heart, brain and spermatozoa. CC -!- CATALYTIC ACTIVITY: ATP + creatine = ADP + phosphocreatine. CC -!- SUBUNIT: Dimer of identical or nonidentical chains. With MM being CC the major form in skeletal muscle and myocardium, MB existing in CC myocardium, and BB existing in many tissues, especially brain. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- SIMILARITY: Belongs to the ATP:guanido phosphotransferase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M21494; AAA96609.1; -. DR EMBL; M21488; AAA96609.1; JOINED. DR EMBL; M21489; AAA96609.1; JOINED. DR EMBL; M21490; AAA96609.1; JOINED. DR EMBL; M21491; AAA96609.1; JOINED. DR EMBL; M21492; AAA96609.1; JOINED. DR EMBL; M21493; AAA96609.1; JOINED. DR EMBL; M14780; AAA52025.1; -. DR EMBL; AC005781; AAC62841.1; -. DR EMBL; BC007462; AAH07462.1; -. DR EMBL; M16440; AAA52026.1; ALT_SEQ. DR PIR; A31793; KIHUCM. DR PDB; 1I0E; 01-APR-03. DR HSC-2DPAGE; P06732; HUMAN. DR Genew; HGNC:1994; CKM. DR MIM; 123310; -. DR GO; GO:0004111; F:creatine kinase activity; TAS. DR InterPro; IPR000749; ATP-gua_Ptrans. DR Pfam; PF00217; ATP-gua_Ptrans; 1. DR Pfam; PF02807; ATP-gua_PtransN; 1. DR PROSITE; PS00112; GUANIDO_KINASE; 1. KW Transferase; Kinase; Multigene family; 3D-structure. FT ACT_SITE 283 283 By similarity. FT CONFLICT 47 47 T -> I (in Ref. 2). FT CONFLICT 130 130 R -> P (in Ref. 2). FT CONFLICT 193 193 L -> Q (in Ref. 2). FT CONFLICT 210 210 D -> H (in Ref. 2). FT CONFLICT 215 215 R -> P (in Ref. 2). FT CONFLICT 225 225 F -> L (in Ref. 4). FT CONFLICT 324 324 G -> A (in Ref. 2). SQ SEQUENCE 381 AA; 43101 MW; 418FEAD0C2E138C8 CRC64; MPFGNTHNKF KLNYKPEEEY PDLSKHNNHM AKVLTLELYK KLRDKETPSG FTVDDVIQTG VDNPGHPFIM TVGCVAGDEE SYEVFKELFD PIISDRHGGY KPTDKHKTDL NHENLKGGDD LDPNYVLSSR VRTGRSIKGY TLPPHCSRGE RRAVEKLSVE ALNSLTGEFK GKYYPLKSMT EKEQQQLIDD HFLFDKPVSP LLLASGMARD WPDARGIWHN DNKSFLVWVN EEDHLRVISM EKGGNMKEVF RRFCVGLQKI EEIFKKAGHP FMWNQHLGYV LTCPSNLGTG LRGGVHVKLA HLSKHPKFEE ILTRLRLQKR GTGGVDTAAV GSVFDVSNAD RLGSSEVEQV QLVVDGVKLM VEMEKKLEKG QSIDDMIPAQ K // ID KCRS_HUMAN STANDARD; PRT; 419 AA. AC P17540; Q8N1E1; DT 01-AUG-1990 (Rel. 15, Created) DT 01-AUG-1990 (Rel. 15, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Creatine kinase, sarcomeric mitochondrial precursor (EC 2.7.3.2) (S- DE MtCK) (Mib-CK) (Basic-type mitochondrial creatine kinase). GN CKMT2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Heart; RX MEDLINE=90216724; PubMed=2324105; RA Haas R.C., Strauss A.W.; RT "Separate nuclear genes encode sarcomere-specific and ubiquitous RT human mitochondrial creatine kinase isoenzymes."; RL J. Biol. Chem. 265:6921-6927(1990). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP SEQUENCE OF 40-65. RX MEDLINE=89123390; PubMed=2914937; RA Haas R.C., Korenfeld C., Zhang Z., Perryman B., Roman D., RA Strauss A.W.; RT "Isolation and characterization of the gene and cDNA encoding human RT mitochondrial creatine kinase."; RL J. Biol. Chem. 264:2890-2897(1989). CC -!- FUNCTION: Reversibly catalyzes the transfer of phosphate between CC ATP and various phosphogens (e.g. creatine phosphate). Creatine CC kinase isoenzymes play a central role in energy transduction in CC tissues with large, fluctuating energy demands, such as skeletal CC muscle, heart, brain and spermatozoa. CC -!- CATALYTIC ACTIVITY: ATP + creatine = ADP + phosphocreatine. CC -!- SUBUNIT: Exists as an octamer composed of four MTCK homodimers. CC -!- SUBCELLULAR LOCATION: Mitochondrial inner membrane; outer side. CC -!- TISSUE SPECIFICITY: Sarcomere-specific. Found only in heart and CC skeletal muscles. CC -!- MISCELLANEOUS: Mitochondrial creatine kinase binds cardiolipin. CC -!- SIMILARITY: Belongs to the ATP:guanido phosphotransferase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; J05401; AAA60561.1; -. DR EMBL; BC029140; AAH29140.1; -. DR PIR; A35756; A35756. DR HSSP; P11009; 1CRK. DR HSC-2DPAGE; P17540; HUMAN. DR Genew; HGNC:1996; CKMT2. DR MIM; 123295; -. DR GO; GO:0005739; C:mitochondrion; TAS. DR GO; GO:0004111; F:creatine kinase activity; TAS. DR GO; GO:0006936; P:muscle contraction; TAS. DR InterPro; IPR000749; ATP-gua_Ptrans. DR Pfam; PF00217; ATP-gua_Ptrans; 1. DR Pfam; PF02807; ATP-gua_PtransN; 1. DR PROSITE; PS00112; GUANIDO_KINASE; 1. KW Transferase; Kinase; Multigene family; Mitochondrion; Transit peptide. FT TRANSIT 1 39 Mitochondrion. FT CHAIN 40 419 CREATINE KINASE, SARCOMERIC FT MITOCHONDRIAL. FT DOMAIN 40 64 CARDIOLIPIN-BINDING (BY SIMILARITY). FT ACT_SITE 317 317 By similarity. FT CONFLICT 74 74 S -> A (in Ref. 2). SQ SEQUENCE 419 AA; 47520 MW; F20E8721F93A2996 CRC64; MASIFSKLLT GRNASLLFAT MGTSVLTTGY LLNRQKVCAE VREQPRLFPP SADYPDLRKH NNCMAECLTP AIYSKLRNKV TPNGYTLDQC IQTGVDNPGH PFIKTVGMVA GDEESYEVFA DLFDPVIKLR HNGYDPRVMK HTTDLDASKI TQGQFDEHYV LSSRVRTGRS IRGLSLPPAC TRAERREVEN VAITALEGLK GDLAGRYYKL SEMTEQDQQR LIDDHFLFDK PVSPLLTCAG MARDWPDARG IWHNYDKTFL IWINEEDHTR VISMEKGGNM KRVFERFCRG LKEVERLIQE RGWEFMWNER LGYILTCPSN LGTGLRAGVH VRIPKLSKDP RFSKILENLR LQKRGTGGVD TAAVADVYDI SNIDRIGRSE VELVQIVIDG VNYLVDCEKK LERGQDIKVP PPLPQFGKK // ID KCRU_HUMAN STANDARD; PRT; 417 AA. AC P12532; DT 01-OCT-1989 (Rel. 12, Created) DT 01-OCT-1989 (Rel. 12, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Creatine kinase, ubiquitous mitochondrial precursor (EC 2.7.3.2) (U- DE MtCK) (Mia-CK) (Acidic-type mitochondrial creatine kinase). GN CKMT1 OR CKMT. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=89123390; PubMed=2914937; RA Haas R.C., Korenfeld C., Zhang Z., Perryman B., Roman D., RA Strauss A.W.; RT "Isolation and characterization of the gene and cDNA encoding human RT mitochondrial creatine kinase."; RL J. Biol. Chem. 264:2890-2897(1989). RN [2] RP SEQUENCE FROM N.A. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Lung; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Reversibly catalyzes the transfer of phosphate between CC ATP and various phosphogens (e.g. creatine phosphate). Creatine CC kinase isoenzymes play a central role in energy transduction in CC tissues with large, fluctuating energy demands, such as skeletal CC muscle, heart, brain and spermatozoa. CC -!- CATALYTIC ACTIVITY: ATP + creatine = ADP + phosphocreatine. CC -!- SUBUNIT: Exists as an octamer composed of four MTCK homodimers. CC -!- SUBCELLULAR LOCATION: Mitochondrial inner membrane; outer side. CC -!- MISCELLANEOUS: Mitochondrial creatine kinase binds cardiolipin. CC -!- SIMILARITY: Belongs to the ATP:guanido phosphotransferase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; J04469; AAA98744.1; -. DR EMBL; BT006628; AAP35274.1; -. DR EMBL; BC001926; AAH01926.1; -. DR EMBL; BC006467; AAH06467.1; -. DR PIR; A31431; A30789. DR PDB; 1QK1; 24-JUL-03. DR Genew; HGNC:1995; CKMT1. DR MIM; 123290; -. DR GO; GO:0005739; C:mitochondrion; TAS. DR GO; GO:0004111; F:creatine kinase activity; TAS. DR InterPro; IPR000749; ATP-gua_Ptrans. DR Pfam; PF00217; ATP-gua_Ptrans; 1. DR Pfam; PF02807; ATP-gua_PtransN; 1. DR PROSITE; PS00112; GUANIDO_KINASE; 1. KW Transferase; Kinase; Multigene family; Mitochondrion; Transit peptide; KW 3D-structure. FT TRANSIT 1 39 Mitochondrion. FT CHAIN 40 417 CREATINE KINASE, UBIQUITOUS FT MITOCHONDRIAL. FT DOMAIN 40 64 CARDIOLIPIN-BINDING (BY SIMILARITY). FT ACT_SITE 316 316 By similarity. FT TURN 42 43 FT STRAND 46 46 FT HELIX 49 52 FT TURN 57 58 FT STRAND 61 61 FT HELIX 62 66 FT HELIX 69 75 FT TURN 76 77 FT TURN 81 82 FT HELIX 86 95 FT STRAND 104 104 FT TURN 112 113 FT HELIX 114 117 FT TURN 118 118 FT HELIX 119 129 FT TURN 130 132 FT TURN 135 137 FT HELIX 146 148 FT TURN 156 158 FT STRAND 159 168 FT STRAND 170 170 FT TURN 171 172 FT TURN 176 178 FT HELIX 181 195 FT TURN 196 197 FT HELIX 200 202 FT STRAND 204 208 FT HELIX 209 211 FT HELIX 214 223 FT TURN 224 224 FT HELIX 233 236 FT TURN 237 247 FT STRAND 249 253 FT TURN 254 255 FT STRAND 258 262 FT STRAND 268 275 FT HELIX 279 298 FT TURN 299 301 FT STRAND 304 304 FT STRAND 306 307 FT TURN 308 310 FT STRAND 311 312 FT HELIX 317 319 FT STRAND 321 321 FT TURN 322 322 FT STRAND 325 331 FT HELIX 333 337 FT TURN 339 340 FT HELIX 341 348 FT TURN 349 349 FT STRAND 350 353 FT TURN 359 361 FT STRAND 366 371 FT HELIX 379 400 FT TURN 401 403 SQ SEQUENCE 417 AA; 47036 MW; 274DAC2E9A8AD882 CRC64; MAGPFSRLLS ARPGLRLLAL AGAGSLAAGF LLRPEPVRAA SERRRLYPPS AEYPDLRKHN NCMASHLTPA VYARLCDKTT PTGWTLDQCI QTGVDNPGHP FIKTVGMVAG DEETYEVFAD LFDPVIQERH NGYDPRTMKH TTDLDASKIR SGYFDERYVL SSRVRTGRSI RGLSLPPACT RAERREVERV VVDALSGLKG DLAGRYYRLS EMTEAEQQQL IDDHFLFDKP VSPLLTAAGM ARDWPDARGI WHNNEKSFLI WVNEEDHTRV ISMEKGGNMK RVFERFCRGL KEVERLIQER GWEFMWNERL GYILTCPSNL GTGLRAGVHI KLPLLSKDSR FPKILENLRL QKRGTGGVDT AATGGVFDIS NLDRLGKSEV ELVQLVIDGV NYLIDCERRL ERGQDIRIPT PVIHTKH // ID KCY_HUMAN STANDARD; PRT; 196 AA. AC P30085; Q96C07; Q9UBQ8; Q9UIA2; DT 01-APR-1993 (Rel. 25, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE UMP-CMP kinase (EC 2.7.4.14) (Cytidylate kinase) (Deoxycytidylate DE kinase) (Cytidine monophosphate kinase). GN UCK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RA Van Rompay A.R., Johansson M., Karlsson A.; RT "Cloning of human UMP-CMP kinase cDNA."; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Hypothalamus; RX MEDLINE=20402571; PubMed=10931946; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal RT axis and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Pituitary; RA Song H., Peng Y., Dai M., Huang Q., Mao Y., Zhang Q., Mao M., Fu G., RA Luo M., Chen J., Hu R.; RT "Human UMP-CMP kinase gene."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. RA Pearman T., Castro H., Stafforini D.M., Zimmerman G.A., McIntyre T.M., RA Prescott S.M.; RT "Sequence and characterization of a novel human cytidine monophosphate RT (CMP) kinase."; RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP SEQUENCE FROM N.A. RC TISSUE=Muscle; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [6] RP SEQUENCE OF 1-29. RC TISSUE=Liver; RX MEDLINE=94147969; PubMed=8313870; RA Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C., RA Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F.; RT "Human liver protein map: update 1993."; RL Electrophoresis 14:1216-1222(1993). RN [7] RP SEQUENCE OF 1-10. RC TISSUE=Liver; RX MEDLINE=93162045; PubMed=1286669; RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F., RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R., RA Appel R.D., Hughes G.J.; RT "Human liver protein map: a reference database established by RT microsequencing and gel comparison."; RL Electrophoresis 13:992-1001(1992). CC -!- FUNCTION: Catalyzes specific phosphoryl transfer from ATP to UMP CC and CMP. CC -!- CATALYTIC ACTIVITY: ATP + (d)CMP = ADP + (d)CDP. CC -!- SIMILARITY: Belongs to the adenylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF070416; AAF17709.1; ALT_INIT. DR EMBL; AF112216; AAF17204.1; -. DR EMBL; AF110643; AAD48583.1; -. DR EMBL; AF259961; AAG22609.1; -. DR EMBL; BC014961; AAH14961.1; ALT_INIT. DR HSSP; P20425; 1QF9. DR SWISS-2DPAGE; P30085; HUMAN. DR Siena-2DPAGE; P30085; -. DR GK; P30085; -. DR GO; GO:0005737; C:cytoplasm; TAS. DR GO; GO:0005634; C:nucleus; TAS. DR GO; GO:0004849; F:uridine kinase activity; TAS. DR GO; GO:0009220; P:pyrimidine ribonucleotide biosynthesis; TAS. DR InterPro; IPR000850; Adenylate_kin. DR InterPro; IPR006266; UMP_CMP_kinase. DR Pfam; PF00406; ADK; 1. DR PRINTS; PR00094; ADENYLTKNASE. DR ProDom; PD000657; Adenylate_kin; 1. DR TIGRFAMs; TIGR01359; UMP_CMP_kin_fam; 1. DR PROSITE; PS00113; ADENYLATE_KINASE; 1. KW Transferase; Kinase; Pyrimidine biosynthesis; ATP-binding. FT NP_BIND 10 18 ATP (By similarity). FT CONFLICT 27 27 Y -> I (in Ref. 6). SQ SEQUENCE 196 AA; 22222 MW; 6837B1E6D7543768 CRC64; MKPLVVFVLG GPGAGKGTQC ARIVEKYGYT HLSAGELLRD ERKNPDSQYG ELIEKYIKEG KIVPVEITIS LLKREMDQTM AANAQKNKFL IDGFPRNQDN LQGWNKTMDG KADVSFVLFF DCNNEICIER CLERGKSSGR SDDNRESLEK RIQTYLQSTK PIIDLYEEMG KVKKIDASKS VDEVFDEVVQ IFDKEG // ID KDGA_HUMAN STANDARD; PRT; 735 AA. AC P23743; O75481; O75482; O75483; DT 01-NOV-1991 (Rel. 20, Created) DT 01-NOV-1995 (Rel. 32, Last sequence update) DT 16-OCT-2001 (Rel. 40, Last annotation update) DE Diacylglycerol kinase, alpha (EC 2.7.1.107) (Diglyceride kinase) (DGK- DE alpha) (DAG kinase alpha) (80 kDa diacylglycerol kinase). GN DGKA OR DAGK1 OR DAGK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Lymphocytes; RX MEDLINE=91085550; PubMed=2175712; RA Schaap D., de Widt J., van der Wal J., Vandekerckhove J., RA van Damme J., Gussow D., Ploegh H.L., van Blitterswijk W.J., RA van der Bendl R.L.; RT "Purification, cDNA-cloning and expression of human diacylglycerol RT kinase."; RL FEBS Lett. 275:151-158(1990). RN [2] RP SEQUENCE FROM N.A., AND ALTERNATIVE SPLICING. RA Champagne C.M.E., Maeda H., Takashiba S., van Dyke T.E.; RT "Alternative splicing of diacylglycerol kinase alpha expressed in RT human neutrophils."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP MAPPING. RX MEDLINE=94235961; PubMed=8180475; RA Hart T.C., Champagne C., Zhou J., van Dyke T.E.; RT "Assignment of the gene for diacylglycerol kinase (DAGK) to human RT chromosome 12."; RL Mamm. Genome 5:123-124(1994). RN [4] RP MAPPING. RX MEDLINE=95048385; PubMed=7959783; RA Hart T.C., Zhou J., Champagne C., van Dyke T.E., Rao P.N., RA Pettenati M.J.; RT "Assignment of the human diacylglycerol kinase gene (DAGK) to 12q13.3 RT using fluorescence in situ hybridization analysis."; RL Genomics 22:246-247(1994). CC -!- FUNCTION: Upon cell stimulation converts the second messenger CC diacylglycerol into phosphatidate, initiating the resynthesis of CC phosphatidylinositols and attenuating protein kinase C activity. CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- ENZYME REGULATION: Stimulated by calcium and phosphatidylserine. CC Phosphorylated by protein kinase C. CC -!- SUBUNIT: Monomer. CC -!- TISSUE SPECIFICITY: Lymphocytes and oligodendroglial cells. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 2 zinc-dependent phorbol-ester and DAG CC binding domains. CC -!- SIMILARITY: Contains 2 EF-hand calcium-binding domains. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X62535; CAA44396.1; -. DR EMBL; AF064769; AAC34804.1; -. DR EMBL; AF064767; AAC34802.1; -. DR EMBL; AF064768; AAC34803.1; -. DR PIR; S12969; S12969. DR Genew; HGNC:2849; DGKA. DR MIM; 125855; -. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR GO; GO:0007242; P:intracellular signaling cascade; TAS. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR InterPro; IPR002048; EF-hand. DR Pfam; PF00130; DAG_PE-bind; 2. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR Pfam; PF00036; efhand; 2. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR ProDom; PD000012; EF-hand; 1. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR SMART; SM00054; EFh; 2. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; 2. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; 2. DR PROSITE; PS00018; EF_HAND; 2. KW Transferase; Kinase; Calcium-binding; Phorbol-ester binding; KW Repeat; Multigene family. FT CA_BIND 123 134 EF-HAND 1 (PROBABLE). FT CA_BIND 168 179 EF-HAND 2 (PROBABLE). FT DOMAIN 206 253 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 270 319 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 374 500 CATALYTIC-A (POTENTIAL). FT DOMAIN 520 701 CATALYTIC-B (POTENTIAL). FT CONFLICT 339 339 L -> P (in Ref. 2). FT CONFLICT 379 379 V -> L (in Ref. 2). FT CONFLICT 385 385 S -> W (in Ref. 2). FT CONFLICT 684 684 E -> G (in Ref. 2). FT CONFLICT 699 699 V -> G (in Ref. 2). FT CONFLICT 715 715 N -> K (in Ref. 2). SQ SEQUENCE 735 AA; 82672 MW; ACAA0AD19DF4D510 CRC64; MAKERGLISP SDFAQLQKYM EYSTKKVSDV LKLFEDGEMA KYVQGDAIGY EGFQQFLKIY LEVDNVPRHL SLALFQSFET GHCLNETNVT KDVVCLNDVS CYFSLLEGGR PEDKLEFTFK LYDTDRNGIL DSSEVDKIIL QMMRVAEYLD WDVSELRPIL QEMMKEIDYD GSGSVSQAEW VRAGATTVPL LVLLGLEMTL KDDGQHMWRP KRFPRPVYCN LCESSIGLGK QGLSCNLCKY TVHDQCAMKA LPCEVSTYAK SRKDIGVQSH VWVRGGCESG RCDRCQKKIR IYHSLTGLHC VWCHLEIHDD CLQAVGHECD CGLLRDHILP PSSIYPSVLA SGPDRKNSKT SQKTMDDLNL STSEALRIDP VPNTHPLLVF VNPKSGGKQG QRVLWKFQYI LNPRQVFNLL KDGPEIGLRL FKDVPDSRIL VCGGDGTVGW ILETIDKANL PVLPPVAVLP LGTGNDLARC LRWGGGYEGQ NLAKILKDLE MSKVVHMDRW SVEVIPQQTE EKSDPVPFQI INNYFSIGVD ASIAHRFHIM REKYPEKFNS RMKNKLWYFE FATSESIFST CKKLEESLTV EICGKPLDLS NLSLEGIAVL NIPSMHGGSN LWGDTRRPHG DIYGINQALG ATAKVITDPD ILKTCVPDLS DKRLEVVGLE GAIEMGQIYT KLKNAGRRLA KCSEITFHTT KTLPMQIDVE PWMQTPCTIK ITHKNQMPML MGPPPRSTNF FGFLS // ID KDGB_HUMAN STANDARD; PRT; 804 AA. AC Q9Y6T7; Q9UQ29; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Diacylglycerol kinase, beta (EC 2.7.1.107) (Diglyceride kinase) (DGK- DE beta) (DAG kinase beta) (90 kDa diacylglycerol kinase). GN DGKB OR DAGK2 OR KIAA0718. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE OF 1-49 FROM N.A. RA Sun H., Bauer C., Sandberg B.; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE OF 63-804 FROM N.A. RC TISSUE=Brain; RX MEDLINE=99087487; PubMed=9872452; RA Nagase T., Ishikawa K.-I., Suyama M., Kikuno R., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [3] RP SEQUENCE FROM N.A. RA Caricasole A., Caldara F., Sala C.F.; RT "Novel proteins."; RL Patent number WO0047723, 17-AUG-2000. CC -!- FUNCTION: Exhibit high phosphorylation activity for long-chain CC diacylglycerols (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- ENZYME REGULATION: Stimulated by phosphatidylserine (By CC similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasmic (By similarity). CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AC006150; AAD28352.1; -. DR EMBL; AB018261; BAA34438.1; -. DR EMBL; AX032742; CAC09945.1; -. DR HSSP; P02593; 1CTR. DR Genew; HGNC:2850; DGKB. DR MIM; 604070; -. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR002048; EF-hand. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR Pfam; PF00130; DAG_PE-bind; 2. DR Pfam; PF00036; efhand; 2. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR ProDom; PD000012; EF-hand; 1. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR SMART; SM00054; EFh; 2. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; 2. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; 2. DR PROSITE; PS00018; EF_HAND; 2. KW Transferase; Kinase; Calcium-binding; Phorbol-ester binding; KW Repeat; Multigene family. FT CA_BIND 162 173 EF-HAND 1 (POTENTIAL). FT CA_BIND 207 218 EF-HAND 2 (POTENTIAL). FT DOMAIN 245 294 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 309 358 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 436 562 CATALYTIC-A (POTENTIAL). FT DOMAIN 582 762 CATALYTIC-B (POTENTIAL). SQ SEQUENCE 804 AA; 90595 MW; CBCABD2339BFE176 CRC64; MTNQEKWAHL SPSEFSQLQK YAEYSTKKLK DVLEEFHGNG VLAKYNPEGK QDILNQTIDF EGFKLFMKTF LEAELPDDFT AHLFMSFSNK FPHSSPMVKS KPALLSGGLR MNKGAITPPR TTSPANTCSP EVIHLKDIVC YLSLLERGRP EDKLEFMFRL YDTDGNGFLD SSELENIISQ MMHVAEYLEW DVTELNPILH EMMEEIDYDH DGTVSLEEWI QGGMTTIPLL VLLGLENNVK DDGQHVWRLK HFNKPAYCNL CLNMLIGVGK QGLCCSFCKY TVHERCVARA PPSCIKTYVK SKRNTDVMHH YWVEGNCPTK CDKCHKTVKC YQGLTGLHCV WCQITLHNKC ASHLKPECDC GPLKDHILPP TTICPVVLQT LPTSGVSVPE ERQSTVKKEK SGSQQPNKVI DKNKMQRANS VTVDGQGLQV TPVPGTHPLL VFVNPKSGGK QGERIYRKFQ YLLNPRQVYS LSGNGPMPGL NFFRDVPDFR VLACGGDGTV GWVLDCIEKA NVGKHPPVAI LPLGTGNDLA RCLRWGGGYE GENLMKILKD IENSTEIMLD RWKFEVIPND KDEKGDPVPY SIINNYFSIG VDASIAHRFH IMREKHPEKF NSRMKNKFWY FEFGTSETFS ATCKKLHESV EIECDGVQID LINISLEGIA ILNIPSMHGG SNLWGESKKR RSHRRIEKKG SDKRTTVTDA KELKFASQDL SDQLLEVVGL EGAMEMGQIY TGLKSAGRRL AQCSCVVIRT SKSLPMQIDG EPWMQTPCTI KITHKNQAPM LMGPPPKTGL FCSLVKRTRN RSKE // ID KDGD_HUMAN STANDARD; PRT; 1195 AA. AC Q16760; Q14158; DT 01-NOV-1997 (Rel. 35, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Diacylglycerol kinase, delta (EC 2.7.1.107) (Diglyceride kinase) DE (DGK-delta) (DAG kinase delta) (130 kDa diacylglycerol kinase) DE (Fragment). GN DGKD OR KIAA0145. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE OF 26-1195 FROM N.A. RC TISSUE=Hepatoma, and Testis; RX MEDLINE=96215245; PubMed=8626538; RA Sakane F., Imai S., Kai M., Wada I., Kanoh H.; RT "Molecular cloning of a novel diacylglycerol kinase isozyme with a RT pleckstrin homology domain and a C-terminal tail similar to those of RT the EPH family of protein-tyrosine kinases."; RL J. Biol. Chem. 271:8394-8401(1996). RN [2] RP SEQUENCE FROM N.A. RA Nomura N.; RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE OF 516-1195 FROM N.A. RC TISSUE=Bone marrow; RX MEDLINE=96127530; PubMed=8590280; RA Nagase T., Seki N., Tanaka A., Ishikawa K.-I., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. IV. RT The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by RT analysis of cDNA clones from human cell line KG-1."; RL DNA Res. 2:167-174(1995). CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- ENZYME REGULATION: Partially inhibited by phosphatidylserine. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. Can be loosely bound to the CC membranes. CC -!- TISSUE SPECIFICITY: Most abundant in skeletal muscle. Detected to CC a lesser extent in testis, colon, peripheral blood leukocytes, and CC hepatoma cells. Undetectable in the brain, retina, or thymus. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 2 zinc-dependent phorbol-ester and DAG CC binding domains. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 sterile alpha motif (SAM) domain. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; D73409; BAA11134.1; -. DR EMBL; D63479; BAA09766.2; -. DR Genew; HGNC:2851; DGKD. DR MIM; 601826; -. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR InterPro; IPR001849; PH. DR InterPro; IPR001660; SAM. DR Pfam; PF00130; DAG_PE-bind; 2. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00536; SAM; 1. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00454; SAM; 1. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; 2. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; 2. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50105; SAM_DOMAIN; 1. KW Transferase; Kinase; Phorbol-ester binding; Repeat; Multigene family. FT NON_TER 1 1 FT DOMAIN 34 127 PH. FT DOMAIN 145 194 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 217 267 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 300 427 CATALYTIC-A (POTENTIAL). FT DOMAIN 744 901 CATALYTIC-B (POTENTIAL). FT DOMAIN 1126 1189 SAM. FT CONFLICT 26 33 TSGQIRQK -> MNMFLYFQ (in Ref. 1). FT CONFLICT 492 492 V -> P (in Ref. 1). FT CONFLICT 809 815 RPIPLPS -> DPSHSPV (in Ref. 1). FT CONFLICT 941 941 L -> V (in Ref. 1). FT CONFLICT 1037 1037 Missing (in Ref. 1). SQ SEQUENCE 1195 AA; 132825 MW; 78C57125EDB41462 CRC64; PPEESSDSEP EAEPGSPQKL IRKVSTSGQI RQKTIIKEGM LTKQNNSFQR SKRRYFKLRG RTLYYAKTAK SIIFDEVDLT DASVAESSTK NVNNSFTVIT PCRKLILCAD NRKEMEDWIA ALKTVQNREH FEPTQYSMDH FSGMHNWYAC SHARPTYCNV CREALSGVTS HGLSCEVCKF KAHKRCAVRA TNNCKWTTLA SIGKDIIEDA DGIAMPHQWL EGNLPVSAKC TVCDKTCGSV LRLQDWRCLW CKAMVHTSCK ESLLTKCPLG LCKVSVIPPT ALNSIDSDGF WKASCPPSCT SPLLVFVNSK SGDNQGVKFL RRFKQLLNPA QVFDLMNGGP HLGLRLFQKF DTFRILVCGG DGSVGWVLSE IDSLNLHKQC QLGVLPLGTG NDLARVLGWG SACDDDTQLP QILEKLERAS TKMLDRWSVM AYEAKLPRQA SSSTVTEDFS EDSEVQQILF YEDSVAAHLS KILTSDQHSV VISSAKVLCE TVKDFVARVG KAYEKTTESS EESEVMAKKC SVLKEKLDSL LKTLDDESQA SSSLPNPPPT IAEEAEDGDG SGSICGSTGD RLVASACPAR PQIFRPREQL MLRANSLKKA IRQIIEHTEK AVDEQNAQTQ EQEGFVLGLS ESEEKMDHRV CPPLSHSESF GVPKGRSQRK VSKSPCEKLI SKGSLSLGSS ASLPPQPGSR DGLPALNTKI LYPNVRAGMS GSLPGGSVIS RLLINADPFN SEPETLEYYT EKCVMNNYFG IGLDAKISLD FNNKRDEHPE KCRSRTKNMM WYGVLGTKEL LHRTYKNLEQ KVLLECDGRP IPLPSLQGIA VLNIPSYAGG TNFWGGTKED DTFAAPSFDD KILEVVAVFG SMQMAVSRVI RLQHHRIAQC RTVKISILGD EGVPVQVDGE AWVQPPGYIR IVHKNRAQTL TRDRAFESTL KSWEDKQKCE LPRPPSCSLH PEMLSEEEAT QMDQFGQAAG VLIHSIREIA QSHRDMEQEL AHAVNASSKS MDRVYGKPRT TEGLNCSFVL EMVNNFRALR SETELLLSGK MALQLDPPQK EQLGSALAEM DRQLRRLADT PWLCQSAEPG DEESVMLDLA KRSRSGKFRL VTKFKKEKNN KNKEAHSSLG APVHLWGTEE VAAWLEHLSL CEYKDIFTRH DIRGSELLHL ERRDLKDLGV TKVGHMKRIL CGIKELSRSA PAVEA // ID KDGE_HUMAN STANDARD; PRT; 567 AA. AC P52429; Q9UKQ3; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Diacylglycerol kinase, epsilon (EC 2.7.1.107) (Diglyceride kinase) DE (DGK-epsilon) (DAG kinase epsilon). GN DGKE OR DAGK5. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Umbilical vein endothelial cells; RX MEDLINE=96215320; PubMed=8626589; RA Tang W., Bunting M., Zimmerman G.A., McIntyre T.M., Prescott S.M.; RT "Molecular cloning of a novel human diacylglycerol kinase highly RT selective for arachidonate-containing substrates."; RL J. Biol. Chem. 271:10237-10241(1996). RN [2] RP SEQUENCE OF 1-154 FROM N.A. RX MEDLINE=20035825; PubMed=10571048; RA Tang W., Bardien S., Bhattacharya S.S., Prescott S.M.; RT "Characterization of the human diacylglycerol kinase epsilon gene and RT its assessment as a candidate for inherited retinitis pigmentosa."; RL Gene 239:185-192(1999). CC -!- FUNCTION: Highly selective for arachidonate-containing species of CC diacylglycerol (DAG). May terminate signals transmitted through CC arachidonoyl-DAG or may contribute to the synthesis of CC phospholipids with defined fatty acid composition. CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- TISSUE SPECIFICITY: Expressed predominantly in testis. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 2 zinc-dependent phorbol-ester and DAG CC binding domains. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U49379; AAC50497.1; -. DR EMBL; AF136745; AAD45666.1; -. DR Genew; HGNC:2852; DGKE. DR MIM; 601440; -. DR GO; GO:0005524; F:ATP binding; TAS. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR GO; GO:0008654; P:phospholipid biosynthesis; TAS. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR InterPro; IPR002219; DAG_PE-bind. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR Pfam; PF00130; DAG_PE-bind; 2. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; 2. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; 2. KW Transferase; Kinase; Phorbol-ester binding; Multigene family; KW Transmembrane; Repeat. FT TRANSMEM 22 42 Potential. FT TRANSMEM 436 456 Potential. FT DOMAIN 60 108 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 125 177 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 217 350 CATALYTIC-A (POTENTIAL). FT DOMAIN 369 524 CATALYTIC-B (POTENTIAL). SQ SEQUENCE 567 AA; 63927 MW; BC334AD15FB4D0B4 CRC64; MEAERRPAPG SPSEGLFADG HLILWTLCSV LLPVFITFWC SLQRSRRQLH RRDIFRKSKH GWRDTDLFSQ PTYCCVCAQH ILQGAFCDCC GLRVDEGCLR KADKRFQCKE IMLKNDTKVL DAMPHHWIRG NVPLCSYCMV CKQQCGCQPK LCDYRCIWCQ KTVHDECMKN SLKNEKCDFG EFKNLIIPPS YLTSINQMRK DKKTDYEVLA SKLGKQWTPL IILANSRSGT NMGEGLLGEF RILLNPVQVF DVTKTPPIKA LQLCTLLPYY SARVLVCGGD GTVGWVLDAV DDMKIKGQEK YIPQVAVLPL GTGNDLSNTL GWGTGYAGEI PVAQVLRNVM EADGIKLDRW KVQVTNKGYY NLRKPKEFTM NNYFSVGPDA LMALNFHAHR EKAPSLFSSR ILNKAVYLFY GTKDCLVQEC KDLNKKVELE LDGERVALPS LEGIIVLNIG YWGGGCRLWE GMGDETYPLA RHDDGLLEVV GVYGSFHCAQ IQVKLANPFR IGQAHTVRLI LKCSMMPMQV DGEPWAQGPC TVTITHKTHA MMLYFSGEQT DDDISSTSDQ EDIKATE // ID KDGG_HUMAN STANDARD; PRT; 791 AA. AC P49619; DT 01-FEB-1996 (Rel. 33, Created) DT 01-FEB-1996 (Rel. 33, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Diacylglycerol kinase, gamma (EC 2.7.1.107) (Diglyceride kinase) (DGK- DE gamma) (DAG kinase gamma). GN DGKG OR DAGK3. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Liver; RX MEDLINE=94308084; PubMed=8034597; RA Kai M., Sakane F., Imai S.-I., Wada I., Kanoh H.; RT "Molecular cloning of a diacylglycerol kinase isozyme predominantly RT expressed in human retina with a truncated and inactive enzyme RT expression in most other human cells."; RL J. Biol. Chem. 269:18492-18498(1994). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=99168758; PubMed=10071200; RA Stoehr H., Klein J., Gehrig A., Koehler M.R., Jurklies B., Kellner U., RA Leo-Kottler B., Schmid M., Weber B.H.F.; RT "Mapping and genomic characterization of the gene encoding RT diacylglycerol kinase gamma (DAGK3): assessment of its role in RT dominant optic atrophy (OPA1)."; RL Hum. Genet. 104:99-105(1999). CC -!- FUNCTION: Reverses the normal flow of glycerolipid biosynthesis by CC phosphorylating diacylglycerol back to phosphatidic acid. CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- ENZYME REGULATION: Requires phosphatidylserine for maximal CC activity. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. Can be loosely bound to the CC membranes. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P49619-1; Sequence=Displayed; CC Name=Short; CC IsoId=P49619-2; Sequence=VSP_001267; CC Note=May be inactive; CC -!- TISSUE SPECIFICITY: Predominantly expressed in retina and in a CC much lesser extent in the brain. Other tissues contain extremely CC low levels of DGK-gamma. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 2 zinc-dependent phorbol-ester and DAG CC binding domains. CC -!- SIMILARITY: Contains 2 EF-hand calcium-binding domains. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; D26135; BAA05132.1; -. DR EMBL; AF020945; AAC04686.1; -. DR EMBL; AF020922; AAC04686.1; JOINED. DR EMBL; AF020923; AAC04686.1; JOINED. DR EMBL; AF020924; AAC04686.1; JOINED. DR EMBL; AF020925; AAC04686.1; JOINED. DR EMBL; AF020926; AAC04686.1; JOINED. DR EMBL; AF020927; AAC04686.1; JOINED. DR EMBL; AF020928; AAC04686.1; JOINED. DR EMBL; AF020929; AAC04686.1; JOINED. DR EMBL; AF020930; AAC04686.1; JOINED. DR EMBL; AF020931; AAC04686.1; JOINED. DR EMBL; AF020932; AAC04686.1; JOINED. DR EMBL; AF020933; AAC04686.1; JOINED. DR EMBL; AF020934; AAC04686.1; JOINED. DR EMBL; AF020935; AAC04686.1; JOINED. DR EMBL; AF020936; AAC04686.1; JOINED. DR EMBL; AF020937; AAC04686.1; JOINED. DR EMBL; AF020938; AAC04686.1; JOINED. DR EMBL; AF020939; AAC04686.1; JOINED. DR EMBL; AF020940; AAC04686.1; JOINED. DR EMBL; AF020941; AAC04686.1; JOINED. DR EMBL; AF020942; AAC04686.1; JOINED. DR EMBL; AF020943; AAC04686.1; JOINED. DR EMBL; AF020944; AAC04686.1; JOINED. DR PIR; A53691; A53691. DR Genew; HGNC:2853; DGKG. DR MIM; 601854; -. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR002048; EF-hand. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR Pfam; PF00130; DAG_PE-bind; 1. DR Pfam; PF00036; efhand; 2. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR ProDom; PD000012; EF-hand; 1. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR SMART; SM00054; EFh; 2. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; 2. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; 2. DR PROSITE; PS00018; EF_HAND; 2. KW Transferase; Kinase; Calcium-binding; Phorbol-ester binding; KW Repeat; Multigene family; Alternative splicing. FT DOMAIN 151 156 POLY-SER. FT CA_BIND 188 199 EF-HAND 1 (POTENTIAL). FT CA_BIND 233 244 EF-HAND 2 (POTENTIAL). FT DOMAIN 272 321 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 337 383 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 432 558 CATALYTIC-A (POTENTIAL). FT DOMAIN 578 752 CATALYTIC-B (POTENTIAL). FT VARSPLIC 451 475 Missing (in isoform Short). FT /FTId=VSP_001267. SQ SEQUENCE 791 AA; 88996 MW; C7DD07F5B285FF62 CRC64; MGEERWVSLT PEEFDQLQKY SEYSSKKIKD ALTEFNEGGS LKQYDPHEPI SYDVFKLFMR AYLEVDLPQP LSTHLFLAFS QKPRHETSDH PTEGASNSEA NSADTNIQNA DNATKADEAC APDTESNMAE KQAPAEDQVA ATPLEPPVPR SSSSESPVVY LKDVVCYLSL LETGRPQDKL EFMFRLYDSD ENGLLDQAEM DCIVNQMLHI AQYLEWDPTE LRPILKEMLQ GMDYDRDGFV SLQEWVHGGM TTIPLLVLLG MDDSGSKGDG GHAWTMKHFK KPTYCNFCHI MLMGVRKQGL CCTYCKYTVH ERCVSKNIPG CVKTYSKAKR SGEVMQHAWV EGNSSVKCDR CHKSIKCYQS VTARHCVWCR MTFHRKCELS TLCDGGELRD HILLPTSICP ITRDRPGEKS DGCVSAKGEL VMQYKIIPTP GTHPLLVLVN PKSGGRQGER ILRKFHYLLN PKQVFNLDNG GPTPGLNFFR DTPDFRVLAC GGDGTVGWIL DCIDKANFAK HPPVAVLPLG TGNDLARCLR WGGGYEGGSL TKILKDIEQS PLVMLDRWHL EVIPREEVEN GDQVPYSIMN NYFSIGVDAS IAHRFHVMRE KHPEKFNSRM KNKLWYFEFG TSETFAATCK KLHDHIELEC DGVGVDLSNI FLEGIAILNI PSMYGGTNLW GENKKNRAVI RESRKGVTDP KELKFCVQDL SDQLLEVVGL EGAMEMGQIY TGLKSAGRRL AQCASVTIRT NKLLPMQVDG EPWMQPCCTI KITHKNQAPM MMGPPQKSSF FSLRRKSRSK D // ID KDGI_HUMAN STANDARD; PRT; 1065 AA. AC O75912; Q9NZ49; DT 16-OCT-2001 (Rel. 40, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Diacylglycerol kinase, iota (EC 2.7.1.107) (Diglyceride kinase) (DGK- DE iota) (DAG kinase iota). GN DGKI. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Retina; RX MEDLINE=99047655; PubMed=9830018; RA Ding L., Traer E., McIntyre T.M., Zimmerman G.A., Prescott S.M.; RT "The cloning and characterization of a novel human diacylglycerol RT kinase, DGK-iota."; RL J. Biol. Chem. 273:32746-32752(1998). RN [2] RP SEQUENCE OF 135-1065 FROM N.A., AND VARIANT PHE-153. RX MEDLINE=20173854; PubMed=10706894; RA Bowne S.J., Sullivan L.S., Ding L., Traer E., Prescott S.M., RA Birch D.G., Kennan A., Humphries P., Daiger S.P.; RT "Evaluation of human diacylglycerol kinase iota, DGKI, a homolog of RT Drosophila rdgA, in inherited retinopathy mapping to 7q."; RL Mol. Vision 6:6-9(2000). CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- SUBCELLULAR LOCATION: Nuclear and cytoplasmic. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 2 zinc-dependent phorbol-ester and DAG CC binding domains. CC -!- SIMILARITY: Contains 2 ANK repeats. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AF061936; AAC62010.1; -. DR EMBL; AF219939; AAF43006.1; -. DR EMBL; AF219907; AAF43006.1; JOINED. DR EMBL; AF219908; AAF43006.1; JOINED. DR EMBL; AF219909; AAF43006.1; JOINED. DR EMBL; AF219910; AAF43006.1; JOINED. DR EMBL; AF219911; AAF43006.1; JOINED. DR EMBL; AF219912; AAF43006.1; JOINED. DR EMBL; AF219913; AAF43006.1; JOINED. DR EMBL; AF219914; AAF43006.1; JOINED. DR EMBL; AF219915; AAF43006.1; JOINED. DR EMBL; AF219916; AAF43006.1; JOINED. DR EMBL; AF219917; AAF43006.1; JOINED. DR EMBL; AF219918; AAF43006.1; JOINED. DR EMBL; AF219919; AAF43006.1; JOINED. DR EMBL; AF219920; AAF43006.1; JOINED. DR EMBL; AF219921; AAF43006.1; JOINED. DR EMBL; AF219922; AAF43006.1; JOINED. DR EMBL; AF219923; AAF43006.1; JOINED. DR EMBL; AF219924; AAF43006.1; JOINED. DR EMBL; AF219925; AAF43006.1; JOINED. DR EMBL; AF219926; AAF43006.1; JOINED. DR EMBL; AF219927; AAF43006.1; JOINED. DR EMBL; AF219928; AAF43006.1; JOINED. DR EMBL; AF219929; AAF43006.1; JOINED. DR EMBL; AF219930; AAF43006.1; JOINED. DR EMBL; AF219931; AAF43006.1; JOINED. DR EMBL; AF219932; AAF43006.1; JOINED. DR EMBL; AF219933; AAF43006.1; JOINED. DR EMBL; AF219934; AAF43006.1; JOINED. DR EMBL; AF219935; AAF43006.1; JOINED. DR EMBL; AF219936; AAF43006.1; JOINED. DR EMBL; AF219937; AAF43006.1; JOINED. DR EMBL; AF219938; AAF43006.1; JOINED. DR Genew; HGNC:2855; DGKI. DR MIM; 604072; -. DR GO; GO:0005737; C:cytoplasm; TAS. DR GO; GO:0005634; C:nucleus; TAS. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR InterPro; IPR002110; ANK. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR Pfam; PF00023; ank; 2. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR SMART; SM00248; ANK; 2. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR PROSITE; PS50088; ANK_REPEAT; 2. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; FALSE_NEG. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; FALSE_NEG. KW Transferase; Kinase; ANK repeat; Repeat; Nuclear protein; KW Multigene family; Polymorphism. FT DOMAIN 178 232 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 251 309 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 374 500 CATALYTIC-A (POTENTIAL). FT DOMAIN 526 683 CATALYTIC-B (POTENTIAL). FT REPEAT 958 990 ANK 1. FT REPEAT 997 1026 ANK 2. FT DOMAIN 20 31 POLY-ALA. FT DOMAIN 69 74 POLY-SER. FT DOMAIN 95 102 POLY-ALA. FT VARIANT 153 153 L -> F. FT /FTId=VAR_010190. FT CONFLICT 160 160 A -> P (in Ref. 2). SQ SEQUENCE 1065 AA; 116996 MW; B84971AA7630A799 CRC64; MDAAGRGCHL LPLPAARGPA RAPAAAAAAA ASPPGPCSGA ACAPSAAAGA GAMNPSSSAG EEKGATGGSS SSGSGAGSCC LGAEGGADPR GAGSAAAAGA AALDEPAAAG QKEKDEALEE KLRNLTFRKQ VSYRKAISRA GLQHLAPAHP LSLPVANGPA KEPRATLDWS ENAVNGEHLW LETNVSGDLC YLGEENCQVR FAKSALRRKC AVCKIVVHTA CIEQLEKINF RCKPTFREGG SRSPRENFVR HHWVHRRRQE GKCKQCGKGF QQKFSFHSKE IVAISCSWCK QAFHNKVTCF MLHHIEEPCS LGAHAAVIVP PTWIIKVKKP QNSLKASNRK KKRTSFKRKA SKRGMEQENK GRPFVIKPIS SPLMKPLLVF VNPKSGGNQG TKVLQMFMWY LNPRQVFDLS QEGPKDALEL YRKVPNLRIL ACGGDGTVGW ILSILDELQL SPQPPVGVLP LGTGNDLART LNWGGGYTDE PVSKILCQVE DGTVVQLDRW NLHVERNPDL PPEELEDGVC KLPLNVFNNY FSLGFDAHVT LEFHESREAN PEKFNSRFRN KMFYAGAAFS DFLQRSSRDL SKHVKVVCDG TDLTPKIQEL KFQCIVFLNI PRYCAGTMPW GNPGDHHDFE PQRHDDGYIE VIGFTMASLA ALQVGGHGER LHQCREVMLL TYKSIPMQVD GEPCRLAPAM IRISLRNQAN MVQKSKRRTS MPLLNDPQSV PDRLRIRVNK ISLQDYEGFH YDKEKLREAS ISDWLRTIAG ELVQSFGAIP LGILVVRGDC DLETCRMYID RLQEDLQSVS SGSQRVHYQD HETSFPRALS AQRLSPRWCF LDDRSQEHLH FVMEISQDEI FILDPDMVVS QPAGTPPGMP DLVVEQASGI SDWWNPALRK RMLSDSGLGM IAPYYEDSDL KDLSHSRVLQ SPVSSEDHAI LQAVIAGDLM KLIESYKNGG SLLIQGPDHC SLLHYAAKTG NGEIVKYILD HGPSELLDMA DSETGETALH KAACQRNRAV CQLLVDAGAS LRKTDSKGKT PQERAQQAGD PDLAAYLESR QNYKVIGHED LETAV // ID KDGT_HUMAN STANDARD; PRT; 942 AA. AC P52824; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Diacylglycerol kinase, theta (EC 2.7.1.107) (Diglyceride kinase) (DGK- DE theta) (DAG kinase theta). GN DGKQ OR DAGK4. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=95331799; PubMed=7607687; RA Pilz A., Schaap D., Hunt D., Fitzgibbon J.; RT "Chromosomal localization of three mouse diacylglycerol kinase (DAGK) RT genes: genes sharing sequence homology to the Drosophila retinal RT degeneration A (rdgA) gene."; RL Genomics 26:599-601(1995). CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 3 zinc-dependent phorbol-ester and DAG CC binding domains. CC -!- SIMILARITY: Contains 1 Ras-associating domain. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; L38707; AAA98749.1; -. DR HSSP; P04049; 1FAR. DR Genew; HGNC:2856; DGKQ. DR MIM; 601207; -. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR000159; RA_domain. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR Pfam; PF00130; DAG_PE-bind; 3. DR Pfam; PF00788; RA; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR SMART; SM00109; C1; 3. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR SMART; SM00314; RA; 1. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; 3. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; 3. DR PROSITE; PS50200; RA; 1. KW Transferase; Kinase; Phorbol-ester binding; Repeat; Multigene family. FT DOMAIN 61 108 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 122 168 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 184 234 PHORBOL-ESTER AND DAG BINDING 3. FT DOMAIN 395 494 RAS-ASSOCIATING. FT DOMAIN 586 715 CATALYTIC-A (POTENTIAL). FT DOMAIN 741 893 CATALYTIC-B (POTENTIAL). SQ SEQUENCE 942 AA; 101403 MW; 26F8D135B248477E CRC64; MAAAAEPGAR AWLGGGSPRP GSPACSPVLG SGGRARPGPG PGPGRDRAGG VRARARAAPG HSFRKVTLTK PTFCHLCSDF IWGLAGFLCD VCNFMSHEKC LKHVRIPCTS VAPSLVRVPV AHCFGPRGLH KRKFCAVCRK VLEAPALHCE VCELHLHPDC VPFACSDCRQ CHQDGHQDHD THHHHWREGN LPSGARCEVC RKTCGSSDVL AGVRCEWCGV QAHSLCSAAL APECGFGRLR SLVLPPACVR LLPGGFSKTQ SFRIVEAAEP GEGGDGADGS AAVGPGRETQ ATPESGKQTL KIFDGDDAVR RSQFRLVTVS RLAGAEEVLE AALRAHHIPE DPGHLELCRL PPSSQACDAW AGGKAGSAVI SEEGRSPGSG EATPEAWVIR ALPRAQEVLK IYPGWLKVGV AYVSVRVTPK STARSVVLEV LPLLGRQAES PESFQLVEVA MGCRHVQRTM LMDEQPLLDR LQDIRQMSVR QVSQTRFYVA ESRDVAPHVS LFVGGLPPGL SPEEYSSLLH EAGATKATVV SVSHIYSSQG AVVLDVACFA EAERLYMLLK DMAVRGRLLT ALVLPDLLHA KLPPDSCPLL VFVNPKSGGL KGRDLLCSFR KLLNPHQVFD LTNGGPLPGL HLFSQVPCFR VLVCGGDGTV GWVLGALEET RYRLACPEPS VAILPLGTGN DLGRVLRWGA GYSGEDPFSV LLSVDEADAV LMDRWTILLD AHEAGSAEND TADAEPPKIV QMSNYCGIGI DAELSLDFHQ AREEEPGKFT SRLHNKGVYV RVGLQKISHS RSLHKQIRLQ VERQEVELPS IEGLIFINIP SWGSGADLWG SDSDTRFEKP RMDDGLLEVV GVTGVVHMGQ VQGGLRSGIR IAQGSYFRVT LLKATPVQVD GEPWVQAPGH MIISAAGPKV HMLRKAKQKP RRAGTTRDAR ADRAPAPESD PR // ID KDGZ_HUMAN STANDARD; PRT; 1117 AA. AC Q13574; O00542; DT 01-NOV-1997 (Rel. 35, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Diacylglycerol kinase, zeta (EC 2.7.1.107) (Diglyceride kinase) (DGK- DE zeta) (DAG kinase zeta). GN DGKZ OR DAGK6. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM SHORT). RC TISSUE=Endothelial cells; RX MEDLINE=96215319; PubMed=8626588; RA Bunting M., Tang W., Zimmerman G.A., McIntyre T.M., Prescott S.M.; RT "Molecular cloning and characterization of a novel human RT diacylglycerol kinase zeta."; RL J. Biol. Chem. 271:10230-10236(1996). RN [2] RP SEQUENCE FROM N.A. (ISOFORM LONG). RC TISSUE=Skeletal muscle; RX MEDLINE=97303161; PubMed=9159104; RA Ding L., Bunting M., Topham M.K., McIntyre T.M., Zimmerman G.A., RA Prescott S.M.; RT "Alternative splicing of the human diacylglycerol kinase zeta gene in RT muscle."; RL Proc. Natl. Acad. Sci. U.S.A. 94:5519-5524(1997). RN [3] RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX MEDLINE=98379993; PubMed=9716136; RA Topham M.K., Bunting M., Zimmerman G.A., McIntyre T.M., RA Blackshear P.J., Prescott S.M.; RT "Protein kinase C regulates the nuclear localization of diacylglycerol RT kinase-zeta."; RL Nature 394:697-700(1998). RN [4] RP INTERACTION WITH SNTG1, AND MUTAGENESIS OF 1115-THR-ALA-1116. RX MEDLINE=21336641; PubMed=11352924; RA Hogan A., Shepherd L., Chabot J., Quenneville S., Prescott S.M., RA Topham M.K., Gee S.H.; RT "Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. RT Regulation of nuclear localization by PDZ interactions."; RL J. Biol. Chem. 276:26526-26533(2001). CC -!- FUNCTION: Displays a strong preference for 1,2-diacylglycerols CC over 1,3-diacylglycerols, but lacks substrate specificity among CC molecular species of long chain diacylglycerols. CC -!- CATALYTIC ACTIVITY: ATP + 1,2-diacylglycerol = ADP + 1,2- CC diacylglycerol 3-phosphate. CC -!- SUBUNIT: Interacts with the PDZ domain of the syntrophin SNTG1. CC -!- SUBCELLULAR LOCATION: Nuclear and cytoplasmic. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q13574-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q13574-2; Sequence=VSP_001268; CC -!- TISSUE SPECIFICITY: Highest levels in brain, and substantial CC levels in skeletal muscle, heart, and pancreas. CC -!- PTM: Phosphorylation of the MARCKS homology domain by PKC reduces CC nuclear accumulation of DGK-zeta. CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase CC family. CC -!- SIMILARITY: Contains 2 zinc-dependent phorbol-ester and DAG CC binding domains. CC -!- SIMILARITY: Contains 2 ANK repeats. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U51477; AAC50478.1; -. DR EMBL; U94905; AAB60859.1; -. DR Genew; HGNC:2857; DGKZ. DR MIM; 601441; -. DR GO; GO:0005634; C:nucleus; TAS. DR GO; GO:0005524; F:ATP binding; TAS. DR GO; GO:0004143; F:diacylglycerol kinase activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR002110; ANK. DR InterPro; IPR002219; DAG_PE-bind. DR InterPro; IPR000756; DAGKa. DR InterPro; IPR001206; DAGKc. DR Pfam; PF00023; ank; 2. DR Pfam; PF00609; DAGKa; 1. DR Pfam; PF00781; DAGKc; 1. DR ProDom; PD002939; DAGKa; 1. DR ProDom; PD005043; DAGKc; 1. DR SMART; SM00248; ANK; 2. DR SMART; SM00109; C1; 2. DR SMART; SM00045; DAGKa; 1. DR SMART; SM00046; DAGKc; 1. DR PROSITE; PS50088; ANK_REPEAT; 2. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS00479; DAG_PE_BIND_DOM_1; FALSE_NEG. DR PROSITE; PS50081; DAG_PE_BIND_DOM_2; FALSE_NEG. KW Transferase; Kinase; Phorbol-ester binding; Repeat; ANK repeat; KW Nuclear protein; Multigene family; Phosphorylation; KW Alternative splicing. FT DOMAIN 287 341 PHORBOL-ESTER AND DAG BINDING 1. FT DOMAIN 361 419 PHORBOL-ESTER AND DAG BINDING 2. FT DOMAIN 448 462 MARCKS HOMOLOGY. FT DOMAIN 482 608 CATALYTIC-A (POTENTIAL). FT DOMAIN 635 792 CATALYTIC-B (POTENTIAL). FT REPEAT 1011 1041 ANK 1. FT REPEAT 1046 1075 ANK 2. FT DOMAIN 256 261 POLY-PRO. FT DOMAIN 448 451 POLY-LYS. FT DOMAIN 560 563 POLY-PRO. FT VARSPLIC 1 243 METFFRRHFRGKVPGPGEGQRRPSSVGLPTGKARRRSPAGQ FT ASSSLAQRRRSSAQLQGCLLSCGVRAQGSSRRRSSTVPPSC FT NPRFIVDKVLTPQPTTVGAQLLGAPLLLTGLVGMNEEEGVQ FT EDVVAEASSAIQPGTKTPGPPPPRGAQPLLPLPRYVRRASS FT HCCPADAVYDHALWGLHGYYRRLSQRRPSGQHPGPGGRRAS FT GTTAGTMLPTRVRPLSRRRQVALRRKAAGPQAWSALLA -> FT MEPRDGSPEARSSDSESASASSSGSERDAGPEPDKAPRRLN FT KRRFPGLRLFGHR (in isoform Short). FT /FTId=VSP_001268. FT MUTAGEN 1115 1116 TA->NS: LOSS OF INTERACTION WITH SNTG1. SQ SEQUENCE 1117 AA; 124122 MW; 213BC8ADDB4E1402 CRC64; METFFRRHFR GKVPGPGEGQ RRPSSVGLPT GKARRRSPAG QASSSLAQRR RSSAQLQGCL LSCGVRAQGS SRRRSSTVPP SCNPRFIVDK VLTPQPTTVG AQLLGAPLLL TGLVGMNEEE GVQEDVVAEA SSAIQPGTKT PGPPPPRGAQ PLLPLPRYVR RASSHCCPAD AVYDHALWGL HGYYRRLSQR RPSGQHPGPG GRRASGTTAG TMLPTRVRPL SRRRQVALRR KAAGPQAWSA LLAKAITKSG LQHLAPPPPT PGAPCSESER QIRSTVDWSE SATYGEHIWF ETNVSGDFCY VGEQYCVARM LKSVSRRKCA ACKIVVHTPC IEQLEKINFR CKPSFRESGS RNVREPTFVR HHWVHRRRQD GKCRHCGKGF QQKFTFHSKE IVAISCSWCK QAYHSKVSCF MLQQIEEPCS LGVHAAVVIP PTWILRARRP QNTLKASKKK KRASFKRKSS KKGPEEGRWR PFIIRPTPSP LMKPLLVFVN PKSGGNQGAK IIQSFLWYLN PRQVFDLSQG GPKEALEMYR KVHNLRILAC GGDGTVGWIL STLDQLRLKP PPPVAILPLG TGNDLARTLN WGGGYTDEPV SKILSHVEEG NVVQLDRWDL HAEPNPEAGP EDRDEGATDR LPLDVFNNYF SLGFDAHVTL EFHESREANP EKFNSRFRNK MFYAGTAFSD FLMGSSKDLA KHIRVVCDGM DLTPKIQDLK PQCVVFLNIP RYCAGTMPWG HPGEHHDFEP QRHDDGYLEV IGFTMTSLAA LQVGGHGERL TQCREVVLTT SKAIPVQVDG EPCKLAASRI RIALRNQATM VQKAKRRSAA PLHSDQQPVP EQLRIQVSRV SMHDYEALHY DKEQLKEASV PLGTVVVPGD SDLELCRAHI ERLQQEPDGA GAKSPTCQKL SPKWCFLDAT TASRFYRIDR AQEHLNYVTE IAQDEIYILD PELLGASARP DLPTPTSPLP TSPCSPTPRS LQGDAAPPQG EELIEAAKRN DFCKLQELHR AGGDLMHRDE QSRTLLHHAV STGSKDVVRY LLDHAPPEIL DAVEENGETC LHQAAALGQR TICHYIVEAG ASLMKTDQQG DTPRQRAEKA QDTELAAYLE NRQHYQMIQR EDQETAV // ID KGUA_HUMAN STANDARD; PRT; 196 AA. AC Q16774; DT 01-NOV-1997 (Rel. 35, Created) DT 01-NOV-1997 (Rel. 35, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Guanylate kinase (EC 2.7.4.8) (GMP kinase). GN GUK1 OR GMK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Retina; RX MEDLINE=96213684; PubMed=8647247; RA Fitzgibbon J., Katsanis N., Wells D., Delhanty J., Vallins W., RA Hunt D.M.; RT "Human guanylate kinase (GUK1): cDNA sequence, expression and RT chromosomal localisation."; RL FEBS Lett. 385:185-188(1996). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=96279248; PubMed=8663313; RA Brady W.A., Kokoris M.S., Fitzgibbon M., Black M.E.; RT "Cloning, characterization, and modeling of mouse and human guanylate RT kinases."; RL J. Biol. Chem. 271:16734-16740(1996). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Lung; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Essential for recycling GMP and indirectly, cGMP. CC -!- CATALYTIC ACTIVITY: ATP + GMP = ADP + GDP. CC -!- SUBUNIT: Monomer (By similarity). CC -!- SIMILARITY: Belongs to the guanylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; L76200; AAC37598.1; -. DR EMBL; U66895; AAC50659.1; -. DR EMBL; BC006249; AAH06249.1; -. DR EMBL; BC009914; AAH09914.1; -. DR PIR; S68864; S68864. DR HSSP; P15454; 1GKY. DR Genew; HGNC:4693; GUK1. DR GK; Q16774; -. DR MIM; 139270; -. DR GO; GO:0004385; F:guanylate kinase activity; TAS. DR GO; GO:0006183; P:GTP biosynthesis; TAS. DR InterPro; IPR008144; Guanylate_kin. DR InterPro; IPR008145; Guanylt/Ca. DR Pfam; PF00625; Guanylate_kin; 1. DR SMART; SM00072; GuKc; 1. DR PROSITE; PS00856; GUANYLATE_KINASE_1; 1. DR PROSITE; PS50052; GUANYLATE_KINASE_2; 1. KW Transferase; Kinase; ATP-binding; Acetylation. FT INIT_MET 0 0 By similarity. FT NP_BIND 10 17 ATP (By similarity). FT MOD_RES 1 1 ACETYLATION (BY SIMILARITY). SQ SEQUENCE 196 AA; 21594 MW; C4727A7E2AA261B3 CRC64; SGPRPVVLSG PSGAGKSTLL KRLLQEHSGI FGFSVSHTTR NPRPGEENGK DYYFVTREVM QRDIAAGDFI EHAEFSGNLY GTSKVAVQAV QAMNRICVLD VDLQGVRNIK ATDLRPIYIS VQPPSLHVLE QRLRQRNTET EESLVKRLAA AQADMESSKE PGLFDVVIIN DSLDQAYAEL KEALSEEIKK AQRTGA // ID KHK_HUMAN STANDARD; PRT; 298 AA. AC P50053; Q99532; Q9BRJ3; Q9UMN1; DT 01-OCT-1996 (Rel. 34, Created) DT 01-OCT-1996 (Rel. 34, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Ketohexokinase (EC 2.7.1.3) (Hepatic fructokinase). GN KHK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., VARIANTS FRUCTOSURIA ARG-40 AND THR-43, AND RP VARIANT ILE-49. RX MEDLINE=95135420; PubMed=7833921; RA Bonthron D.T., Brady N., Donaldson I.A., Steinmann B.; RT "Molecular basis of essential fructosuria: molecular cloning and RT mutational analysis of human ketohexokinase (fructokinase)."; RL Hum. Mol. Genet. 3:1627-1631(1994). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Lung; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP SEQUENCE OF 1-26 AND 71-298 FROM N.A., AND ALTERNATIVE SPLICING. RX MEDLINE=99013450; PubMed=9799106; RA Hayward B.E., Bonthron D.T.; RT "Structure and alternative splicing of the ketohexokinase gene."; RL Eur. J. Biochem. 257:85-91(1998). CC -!- CATALYTIC ACTIVITY: ATP + D-fructose = ADP + D-fructose 1- CC phosphate. CC -!- ENZYME REGULATION: Requires potassium. Inhibition by ADP. CC -!- PATHWAY: Primary metabolism of dietary fructose in mammals. CC -!- SUBUNIT: DIMER OF A-A, A-C OR C-C (PROBABLE). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; CC IsoId=P50053-1; Sequence=Displayed; CC Name=C; CC IsoId=P50053-2; Sequence=VSP_004669; CC -!- TISSUE SPECIFICITY: Most abundant in liver, kidney, gut, spleen CC and pancreas. Low levels also found in adrenal, muscle, brain and CC eye. CC -!- DISEASE: Defects in KHK are the cause of fructosuria [MIM:229800]. CC Fructosuria is a benign defect of intermediary metabolism. CC -!- SIMILARITY: Belongs to the carbohydrate kinase pfkB family. CC -!- CAUTION: Form C has not yet been fully sequenced in its N-terminal CC (from 1-69). CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X78678; CAA55347.1; -. DR EMBL; X78677; CAA55346.1; -. DR EMBL; BC006233; AAH06233.1; -. DR EMBL; Y09336; CAA70516.1; -. DR EMBL; Y09341; CAA70522.1; -. DR EMBL; Y09341; CAA70523.1; -. DR EMBL; Y09340; CAA70521.1; -. DR EMBL; AJ005168; CAA06409.1; -. DR Genew; HGNC:6315; KHK. DR GK; P50053; -. DR MIM; 229800; -. DR GO; GO:0004454; F:ketohexokinase activity; TAS. DR InterPro; IPR002173; PfkB. DR Pfam; PF00294; pfkB; 1. DR PROSITE; PS00583; PFKB_KINASES_1; FALSE_NEG. DR PROSITE; PS00584; PFKB_KINASES_2; FALSE_NEG. KW Transferase; Kinase; Alternative splicing; Disease mutation; KW Polymorphism. FT VARSPLIC 72 115 VLDDLRRYSVDLRYTVFQTTGSVPIATVIINEASGSRTILY FT YDR -> LVADFRRRGVDVSQVAWQSKGDTPSSCCIINNSN FT GNRTIVLHDT (in isoform C). FT /FTId=VSP_004669. FT VARIANT 40 40 G -> R (in fructosuria). FT /FTId=VAR_006072. FT VARIANT 43 43 A -> T (in fructosuria). FT /FTId=VAR_006073. FT VARIANT 49 49 V -> I. FT /FTId=VAR_006074. FT VARIANT 159 159 R -> G (either a polymorphism or a FT cloning artifact). FT /FTId=VAR_006075. SQ SEQUENCE 298 AA; 32730 MW; 1BA47BDC60C1B89F CRC64; MEEKQILCVG LVVLDVISLV DKYPKEDSEI RCLSQRWQRG GNASNSCTVL SLLGAPCAFM GSMAPGHVAD FVLDDLRRYS VDLRYTVFQT TGSVPIATVI INEASGSRTI LYYDRSLPDV SATDFEKVDL TQFKWIHIEG RNASEQVKML QRIDAHNTRQ PPEQKIRVSV EVEKPREELF QLFGYGDVVF VSKDVAKHLG FQSAEEALRG LYGRVRKGAV LVCAWAEEGA DALGPDGKLL HSDAFPPPRV VDTLGAGDTF NASVIFSLSQ GRSVQEALRF GCQVAGKKCG LQGFDGIV // ID KICE_HUMAN STANDARD; PRT; 395 AA. AC Q9Y259; Q13388; DT 30-MAY-2000 (Rel. 39, Created) DT 30-MAY-2000 (Rel. 39, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Choline/ethanolamine kinase [Includes: Choline kinase (EC 2.7.1.32) DE (CK); Ethanolamine kinase (EC 2.7.1.82) (EK)]. GN CHKL OR CHETK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RA Yamazaki N.; RT "Human gene for choline/ethanolamine kinase."; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [2] RP SEQUENCE FROM N.A. RA Smink L.J., Huckle E.J.; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE FROM N.A. RA Adams M.D.; RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases. CC -!- CATALYTIC ACTIVITY: ATP + choline = ADP + O-phosphocholine. CC -!- CATALYTIC ACTIVITY: ATP + ethanolamine = ADP + O- CC phosphoethanolamine. CC -!- SIMILARITY: Belongs to the choline/ethanolamine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AB029885; BAA82511.1; -. DR EMBL; AB029886; BAA82512.1; -. DR EMBL; AL096780; CAB46629.1; -. DR EMBL; AL096781; CAB46630.1; -. DR EMBL; U62317; AAB03342.2; -. DR Genew; HGNC:1938; CHKL. DR InterPro; IPR002573; Choline_kinase. DR Pfam; PF01633; Choline_kinase; 1. KW Transferase; Kinase. FT ACT_SITE 240 240 By similarity. SQ SEQUENCE 395 AA; 45271 MW; 18367468B22FB9CE CRC64; MAAEATAVAG SGAVGGCLAK DGLQQSKCPD TTPKRRRASS LSRDAERRAY QWCREYLGGA WRRVQPEELR VYPVSGGLSN LLFRCSLPDH LPSVGEEPRE VLLRLYGAIL QGVDSLVLES VMFAILAERS LGPQLYGVFP EGRLEQYIPS RPLKTQELRE PVLSAAIATK MAQFHGMEMP FTKEPHWLFG TMERYLKQIQ DLPPTGLPEM NLLEMYSLKD EMGNLRKLLE STPSPVVFCH NDIQEGNILL LSEPENADSL MLVDFEYSSY NYRGFDIGNH FCEWVYDYTH EEWPFYKARP TDYPTQEQQL HFIRHYLAEA KKGETLSQEE QRKLEEDLLV EVSRYALASH FFWGLWSILQ ASMSTIEFGY LDYAQSRFQF YFQQKGQLTS VHSSS // ID KICH_HUMAN STANDARD; PRT; 456 AA. AC P35790; DT 01-JUN-1994 (Rel. 29, Created) DT 01-JUN-1994 (Rel. 29, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Choline kinase (EC 2.7.1.32) (CK) (CHETK-alpha). GN CHK OR CKI. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=92316236; PubMed=1618328; RA Hosaka K., Tanaka S., Nikawa J.-I., Yamashita S.; RT "Cloning of a human choline kinase cDNA by complementation of the RT yeast cki mutation."; RL FEBS Lett. 304:229-232(1992). CC -!- FUNCTION: May have a regulatory role in phosphatidylcholine CC synthesis. CC -!- CATALYTIC ACTIVITY: ATP + choline = ADP + O-phosphocholine. CC -!- PATHWAY: CDP-choline and CDP-ethanolamine pathways; initial step. CC -!- SUBUNIT: Homotetramer (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- SIMILARITY: Belongs to the choline/ethanolamine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; D10704; BAA01547.1; -. DR PIR; S23104; S23104. DR Genew; HGNC:1937; CHK. DR MIM; 118491; -. DR GO; GO:0004103; F:choline kinase activity; TAS. DR GO; GO:0004871; F:signal transducer activity; TAS. DR GO; GO:0006629; P:lipid metabolism; TAS. DR GO; GO:0006869; P:lipid transport; TAS. DR InterPro; IPR002573; Choline_kinase. DR Pfam; PF01633; Choline_kinase; 1. KW Transferase; Kinase. FT DOMAIN 50 84 PRO-RICH. FT ACT_SITE 303 303 By similarity. SQ SEQUENCE 456 AA; 52065 MW; BD8D13D102178E97 CRC64; MKTKFCTGGE AEPSPLGLLL SCGSGSAAPA PGVGQQRDAA SDLESKQLAP TAALALPPPP PLPLPLPLPQ PPPPQPPADE QPEPRARRRA YLWCKEFLPG AWRGLREDEF HISVIRGGLS NMLFQCSLPD TTATLGDEPR KVLLRLYGAI LQMRSCNKEG SEQAQKENEF QGAEAMVLES VMFAILAERS LGPKLYGIFP QGRLEQFIPS RRLDTEELSL PDISAEIAEK MATFHGMKMP FNKEPKWLFG TMEKYLKEVL RIKFTEESRI KKLHKLLSYN LPLELENLRS LLESTPSPVV FCHNDCQEGN ILLLEGRENS EKQKLMLIDF EYSSYNYRGF DIGNHFCEWM YDYSYEKYPF FRANIRKYPT KKQQLHFISS YLPAFQNDFE NLSTEEKSII KEEMLLEVNR FALASHFLWG LWSIVQAKIS SIEFGYMDYA QARFDAYFHQ KRKLGV // ID KIME_HUMAN STANDARD; PRT; 396 AA. AC Q03426; DT 01-OCT-1993 (Rel. 27, Created) DT 01-OCT-1993 (Rel. 27, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Mevalonate kinase (EC 2.7.1.36) (MK). GN MVK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND VARIANT THR-301. RX MEDLINE=92317034; PubMed=1377680; RA Schafer B.L., Bishop R.W., Kratunis V.J., Kalinowski S.S., RA Mosley S.T., Gibson K.M., Tanaka R.D.; RT "Molecular cloning of human mevalonate kinase and identification of a RT missense mutation in the genetic disease mevalonic aciduria."; RL J. Biol. Chem. 267:13229-13238(1992). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Hepatoma; RX MEDLINE=94134441; PubMed=8302606; RA Graef E., Caselmann W.H., Wells J., Koshy R.; RT "Insertional activation of mevalonate kinase by hepatitis B virus DNA RT in a human hepatoma cell line."; RL Oncogene 9:81-87(1994). RN [3] RP SEQUENCE FROM N.A., VARIANTS HIDS PRO-20; PRO-39; LEU-135; THR-148; RP THR-268 AND ILE-377, AND VARIANTS MEVALONICACIDURIA PRO-20; PHE-264; RP THR-268; THR-334 AND MET-310. RX MEDLINE=21214737; PubMed=11313768; RA Houten S.M., Koster J., Romeijn G.-J., Frenkel J., Di Rocco M., RA Caruso U., Landrieu P., Kelley R.I., Kuis W., Poll-The B.T., RA Gibson K.M., Wanders R.J.A., Waterham H.R.; RT "Organization of the mevalonate kinase (MVK) gene and identification RT of novel mutations causing mevalonic aciduria and RT hyperimmunoglobulinaemia D and periodic fever syndrome."; RL Eur. J. Hum. Genet. 9:253-259(2001). RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Skin; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP VARIANTS MEVALONICACIDURIA ILE-243; PHE-264; PRO-265 AND THR-268. RX MEDLINE=99347937; PubMed=10417275; RA Hinson D.D., Ross R.M., Krisans S., Shaw J.L., Kozich V., RA Rolland M.-O., Divry P., Mancini J., Hoffmann G.F., Gibson K.M.; RT "Identification of a mutation cluster in mevalonate kinase deficiency, RT including a new mutation in a patient of Mennonite ancestry."; RL Am. J. Hum. Genet. 65:327-335(1999). RN [6] RP VARIANTS MEVALONICACIDURIA MET-310 AND THR-334. RX MEDLINE=99330561; PubMed=10401001; RA Houten S.M., Romeijn G.J., Koster J., Gray R.G.F., Darbyshire P., RA Smit G.P.A., de Klerk J.B.C., Duran R., Gibson K.M., Wanders R.J.A., RA Waterham H.R.; RT "Identification and characterization of three novel missense mutations RT in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of RT isoprene biosynthesis."; RL Hum. Mol. Genet. 8:1523-1528(1999). RN [7] RP VARIANTS HIDS PRO-20; THR-268 AND ILE-377. RX MEDLINE=99295935; PubMed=10369261; RA Houten S.M., Kuis W., Duran M., de Koning T.J., van Royen-Kerkhof A., RA Romeijn G.J., Frenkel J., Dorland L., de Barse M.M.J., RA Huijbers W.A.R., Rijkers G.T., Waterham H.R., Wanders R.J.A., RA Poll-The B.T.; RT "Mutations in MVK, encoding mevalonate kinase, cause RT hyperimmunoglobulinaemia D and periodic fever syndrome."; RL Nat. Genet. 22:175-177(1999). RN [8] RP VARIANTS HIDS LEU-167; THR-268 AND ILE-377. RX MEDLINE=99295936; PubMed=10369262; RA Drenth J.P.H., Cuisset L., Grateau G., Vasseur C., RA van der Velde-Visser S.D., de Jong J.G.N., Beckmann J.S., RA van der Meer J.W.M., Delpech M.; RT "Mutations in the gene encoding mevalonate kinase cause hyper-IgD and RT periodic fever syndrome."; RL Nat. Genet. 22:178-181(1999). RN [9] RP VARIANTS HIDS ASN-20; PRO-20; PRO-39; LEU-150; LEU-167; ARG-202; RP GLN-215; THR-268; SER-309; ARG-326 AND ILE-377, VARIANT RP MEVALONICACIDURIA THR-334, AND VARIANT ASN-52. RX MEDLINE=21214738; PubMed=11313769; RA Cuisset L., Drenth J.P.H., Simon A., Vincent M.F., RA van der Velde-Visser S.D., van der Meer J.W.M., Grateau G., RA Delpech M.; RT "Molecular analysis of MVK mutations and enzymatic activity in RT hyper-IgD and periodic fever syndrome."; RL Eur. J. Hum. Genet. 9:260-266(2001). CC -!- FUNCTION: May be a regulatory site in cholesterol biosynthetic CC pathway. CC -!- CATALYTIC ACTIVITY: ATP + (R)-mevalonate = ADP + (R)-5- CC phosphomevalonate. CC -!- ENZYME REGULATION: Farnesyl- and geranyl-pyrophosphates are CC competitive inhibitors. CC -!- PATHWAY: Cholesterol biosynthesis, mevalonate catabolism. CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Cytoplasmic and peroxisomal. CC -!- DISEASE: Defects in MVK are the cause of mevalonicaciduria CC [MIM:251170]. It is an accumulation of mevalonic acid which cause CC a variety of symptoms such as psychomotor retardation, dysmorphic CC features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, CC hypotonia, myopathy, and ataxia. CC -!- DISEASE: Defects in MVK are the cause of hyperimmunoglobulinemia D CC and periodic fever syndrome (HIDS) [MIM:260920]. HIDS is an CC autosomal recessive disease characterized by recurrent epidoses of CC unexplained high fever associated with skin rash, diarrhea, CC adenopathy (swollen, tender lymph nodes), athralgias and/or CC arthritis. Concentration of IgD, and often IgA, are above normal. CC -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase CC subfamily. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M88468; AAB59362.1; -. DR EMBL; X75311; CAA53060.1; -. DR EMBL; X75311; CAA53059.1; ALT_INIT. DR EMBL; AF217535; AAF82407.1; -. DR EMBL; AF217528; AAF82407.1; JOINED. DR EMBL; AF217529; AAF82407.1; JOINED. DR EMBL; AF217530; AAF82407.1; JOINED. DR EMBL; AF217531; AAF82407.1; JOINED. DR EMBL; AF217532; AAF82407.1; JOINED. DR EMBL; AF217533; AAF82407.1; JOINED. DR EMBL; AF217534; AAF82407.1; JOINED. DR EMBL; BC016140; AAH16140.1; -. DR PIR; A42919; A42919. DR Genew; HGNC:7530; MVK. DR MIM; 251170; -. DR MIM; 260920; -. DR GO; GO:0004496; F:mevalonate kinase activity; TAS. DR GO; GO:0008299; P:isoprenoid biosynthesis; TAS. DR InterPro; IPR001174; Galkinase. DR InterPro; IPR006204; GHMP_kinase. DR InterPro; IPR006203; GHMPknse_ATP. DR InterPro; IPR006205; Mev_gal_kin. DR InterPro; IPR006206; Mev_galkinase. DR Pfam; PF00288; GHMP_kinases; 1. DR PRINTS; PR00960; LMBPPROTEIN. DR PRINTS; PR00959; MEVGALKINASE. DR TIGRFAMs; TIGR00549; mevalon_kin; 1. DR PROSITE; PS00627; GHMP_KINASES_ATP; 1. KW Transferase; Kinase; Cholesterol biosynthesis; ATP-binding; KW Peroxisome; Disease mutation; Polymorphism. FT NP_BIND 138 148 ATP (By similarity). FT VARIANT 20 20 H -> N (in HIDS). FT /FTId=VAR_010956. FT VARIANT 20 20 H -> P (in HIDS and mevalonicaciduria). FT /FTId=VAR_004022. FT VARIANT 39 39 L -> P (in HIDS). FT /FTId=VAR_010957. FT VARIANT 52 52 S -> N. FT /FTId=VAR_010958. FT VARIANT 135 135 S -> L (in HIDS). FT /FTId=VAR_010959. FT VARIANT 148 148 A -> T (in HIDS). FT /FTId=VAR_010960. FT VARIANT 150 150 S -> L (in HIDS). FT /FTId=VAR_010961. FT VARIANT 167 167 P -> L (in HIDS). FT /FTId=VAR_004023. FT VARIANT 202 202 G -> R (in HIDS). FT /FTId=VAR_010962. FT VARIANT 215 215 R -> Q (in HIDS). FT /FTId=VAR_010963. FT VARIANT 243 243 T -> I (in mevalonicaciduria). FT /FTId=VAR_010964. FT VARIANT 264 264 L -> F (in mevalonicaciduria). FT /FTId=VAR_010965. FT VARIANT 265 265 L -> P (in mevalonicaciduria). FT /FTId=VAR_010966. FT VARIANT 268 268 I -> T (in HIDS and mevalonicaciduria). FT /FTId=VAR_004024. FT VARIANT 301 301 N -> T (in mevalonicaciduria; diminished FT activity). FT /FTId=VAR_004025. FT VARIANT 309 309 G -> S (in HIDS). FT /FTId=VAR_010967. FT VARIANT 310 310 V -> M (in mevalonicaciduria). FT /FTId=VAR_009068. FT VARIANT 326 326 G -> R (in HIDS). FT /FTId=VAR_010968. FT VARIANT 334 334 A -> T (in mevalonicaciduria). FT /FTId=VAR_004026. FT VARIANT 377 377 V -> I (in HIDS; most frequent mutation). FT /FTId=VAR_004027. SQ SEQUENCE 396 AA; 42451 MW; C8F6B629B58CD229 CRC64; MLSEVLLVSA PGKVILHGEH AVVHGKVALA VSLNLRTFLR LQPHSNGKVD LSLPNIGIKR AWDVARLQSL DTSFLEQGDV TTPTSEQVEK LKEVAGLPDD CAVTERLAVL AFLYLYLSIC RKQRALPSLD IVVWSELPPG AGLGSSAAYS VCLAAALLTV CEEIPNPLKD GDCVNRWTKE DLELINKWAF QGERMIHGNP SGVDNAVSTW GGALRYHQGK ISSLKRSPAL QILLTNTKVP RNTRALVAGV RNRLLKFPEI VAPLLTSIDA ISLECERVLG EMGEAPAPEQ YLVLEELIDM NQHHLNALGV GHASLDQLCQ VTRARGLHSK LTGAGGGGCG ITLLKPGLEQ PEVEATKQAL TSCGFDCLET SIGAPGVSIH SATSLDSRVQ QALDGL // ID KITH_EBV STANDARD; PRT; 607 AA. AC P03177; DT 21-JUL-1986 (Rel. 01, Created) DT 01-NOV-1995 (Rel. 32, Last sequence update) DT 30-MAY-2000 (Rel. 39, Last annotation update) DE Thymidine kinase (EC 2.7.1.21). GN TK OR BXLF1. OS Epstein-barr virus (strain B95-8) (Human herpesvirus 4). OC Viruses; dsDNA viruses, no RNA stage; Herpesviridae; OC Gammaherpesvirinae; Lymphocryptovirus. OX NCBI_TaxID=10377; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=85035713; PubMed=6092825; RA Bankier A.T., Deininger P.L., Farrell P.J., Barrell B.G.; RT "Sequence analysis of the 17,166 base-pair EcoRI fragment C of B95-8 RT Epstein-Barr virus."; RL Mol. Biol. Med. 1:21-45(1983). RN [2] RP IDENTIFICATION OF PROTEIN. RX MEDLINE=87004565; PubMed=3019675; RA Littler E., Zeuthen J., McBride A.A., Soerensen E.T., Powell K.L., RA Walsh-Arrand J.E., Arrand J.R.; RT "Identification of an Epstein-Barr virus-coded thymidine kinase."; RL EMBO J. 5:1959-1966(1986). CC -!- CATALYTIC ACTIVITY: ATP + thymidine = ADP + thymidine 5'- CC phosphate. CC -!- SIMILARITY: Belongs to the herpesviruses thymidine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; V01555; CAA24799.1; -. DR PIR; A00615; KIBETE. DR InterPro; IPR001889; TK_herpes. DR Pfam; PF00693; TK_herpes; 1. DR ProDom; PD001519; TK_herpes; 1. KW Transferase; Kinase; DNA synthesis; Early protein; ATP-binding. FT NP_BIND 291 298 ATP (Probable). SQ SEQUENCE 607 AA; 67193 MW; 97A4CCDB598A09F1 CRC64; MAGFPGKEAG PPGGWRKCQE DESPENERHE NFYAEIDDFA PSVLTPTGSD SGAGEEDDDG LYQVPTHWPP LMAPTGLSGE RVPCRTQAAV TSNTGNSPGS RHTSCPFTLP RGAQPPAPAH QKPTAPTPKP RSRECGPSKT PDPFSWFRKT SCTEGGADST SRSFMYQKGF EEGLAGLGLD DKSDCESEDE SNFRRPSSHS ALKQKNGGKG KPSGLFEHLA AHGREFSKLS KHAAQLKRLS GSVMNVLNLD DAQDTRQAKA QRKESMRVPI VTHLTNHVPV IKPACSLFLE GAPGVGKTTM LNHLKAVFGD LTIVVPEPMR YWTHVYENAI KAMHKNVTRA RHGREDTSAE VLACQMKFTT PFRVLASRKR SLLVTESGAR SVAPLDCWIL HDRHLLSASV VFPLMLLRSQ LLSYSDFIQV LATFTADPGD TIVWMKLNVE ENMRRLKKRG RKHESGLDAG YLKSVNDAYH AVYCAWLLTQ YFAPEDIVKV CAGLTTITTV CHQSHTPIIR SGVAEKLYKN SIFSVLKEVI QPFRADAVLL EVCLAFTRTL AYLQFVLVDL SEFQDDLPGC WTEIYMQALK NPAIRSQFFD WAGLSKVISD FERGNRD // ID KITH_HUMAN STANDARD; PRT; 234 AA. AC P04183; Q969V0; DT 20-MAR-1987 (Rel. 04, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Thymidine kinase, cytosolic (EC 2.7.1.21). GN TK1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=85085935; PubMed=6549046; RA Bradshaw H.D. Jr., Deininger P.L.; RT "Human thymidine kinase gene: molecular cloning and nucleotide RT sequence of a cDNA expressible in mammalian cells."; RL Mol. Cell. Biol. 4:2316-2320(1984). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=87277399; PubMed=3301530; RA Flemington E., Bradshaw H.D. Jr., Traina-Dorge V., Slagel V., RA Deininger P.L.; RT "Sequence, structure and promoter characterization of the human RT thymidine kinase gene."; RL Gene 52:267-277(1987). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Lymph, and Uterus; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP PHOSPHORYLATION OF SER-13. RX MEDLINE=98241568; PubMed=9575153; RA Chang Z.F., Huang D.Y., Chi L.M.; RT "Serine 13 is the site of mitotic phosphorylation of human thymidine RT kinase."; RL J. Biol. Chem. 273:12095-12100(1998). CC -!- CATALYTIC ACTIVITY: ATP + thymidine = ADP + thymidine 5'- CC phosphate. CC -!- SUBCELLULAR LOCATION: Cytoplasmic. CC -!- PTM: Phosphorylated on Ser-13 in mitosis. CC -!- MISCELLANEOUS: Two forms have been identified in animal cells, one CC in cytosol and one in mitochondria. Activity of the cytosolic CC enzyme is high in proliferating cells and peaks during the S-phase CC of the cell cycle; it is very low in resting cells. CC -!- SIMILARITY: Belongs to the thymidine kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; K02581; AAA61187.1; -. DR EMBL; M15205; AAA61191.1; -. DR EMBL; BC007872; AAH07872.1; -. DR EMBL; BC007986; AAH07986.1; -. DR PIR; A27318; KIHUT. DR Genew; HGNC:11830; TK1. DR GK; P04183; -. DR MIM; 188300; -. DR GO; GO:0004797; F:thymidine kinase activity; TAS. DR GO; GO:0006139; P:nucleobase, nucleoside, nucleotide and nucl...; TAS. DR InterPro; IPR001267; TK_cell. DR Pfam; PF00265; TK; 1. DR PROSITE; PS00603; TK_CELLULAR_TYPE; 1. KW Transferase; Kinase; DNA synthesis; ATP-binding; Phosphorylation. FT NP_BIND 26 33 ATP (Probable). FT MOD_RES 13 13 PHOSPHORYLATION. FT CONFLICT 106 106 V -> M (in Ref. 1 and 2). SQ SEQUENCE 234 AA; 25468 MW; 76901415C631EF21 CRC64; MSCINLPTVL PGSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQYKC LVIKYAKDTR YSSSFCTHDR NTMEALPACL LRDVAQEALG VAVIGIDEGQ FFPDIVEFCE AMANAGKTVI VAALDGTFQR KPFGAILNLV PLAESVVKLT AVCMECFREA AYTKRLGTEK EVEVIGGADK YHSVCRLCYF KKASGQPAGP DNKENCPVPG KPGEAVAARK LFAPQQILQC SPAN // ID KITM_HUMAN STANDARD; PRT; 266 AA. AC O00142; O15238; DT 01-NOV-1997 (Rel. 35, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Thymidine kinase 2, mitochondrial precursor (EC 2.7.1.21) (Mt-TK). GN TK2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. (ISOFORM SHORT). RC TISSUE=Liver; RX MEDLINE=97236800; PubMed=9079672; RA Johansson M., Karlsson A.; RT "Cloning of the cDNA and chromosome localization of the gene for RT human thymidine kinase 2."; RL J. Biol. Chem. 272:8454-8458(1997). RN [2] RP SEQUENCE FROM N.A. (ISOFORM LONG), AND REVISIONS TO 37 AND 240-241. RA Wang L.; RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP SEQUENCE OF 34-266 FROM N.A. (ISOFORM LONG), SEQUENCE OF 34-61 RP (ISOFORM LONG), AND CHARACTERIZATION. RC TISSUE=Brain; RX MEDLINE=99142705; PubMed=9989599; RA Wang L., Munch-Petersen B., Herrstroem Sjoeberg A., Hellman U., RA Bergman T., Joernvall H., Eriksson S.; RT "Human thymidine kinase 2: molecular cloning and characterisation of RT the enzyme activity with antiviral and cytostatic nucleoside RT substrates."; RL FEBS Lett. 443:170-174(1999). CC -!- FUNCTION: Deoxyribonucleoside kinase that phosphorylates CC thymidine, deoxycytidine, and deoxyuridine. Also phosphorylates CC anti-viral and anti-cancer nucleoside analogs. CC -!- CATALYTIC ACTIVITY: ATP + thymidine = ADP + thymidine 5'- CC phosphate. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Mitochondrial. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=O00142-1; Sequence=Displayed; CC Name=Short; CC IsoId=O00142-2; Sequence=VSP_003028; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver, pancreas, CC muscle, and brain. CC -!- SIMILARITY: Belongs to the DCK/DGK family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U77088; AAC51167.1; -. DR EMBL; Y10498; CAA71523.3; -. DR Genew; HGNC:11831; TK2. DR MIM; 188250; -. DR GO; GO:0004797; F:thymidine kinase activity; TAS. DR GO; GO:0006139; P:nucleobase, nucleoside, nucleotide and nucl...; TAS. DR InterPro; IPR002624; dNK. DR Pfam; PF01712; dNK; 1. KW Transferase; Kinase; DNA synthesis; ATP-binding; Mitochondrion; KW Transit peptide; Alternative splicing. FT TRANSIT 1 33 Mitochondrion. FT CHAIN 34 266 THYMIDINE KINASE 2. FT NP_BIND 57 64 ATP (Potential). FT VARSPLIC 1 41 MLLWPLRGWAARALRCFGPGSRGSPASGPGPRRVQRRAWPP FT -> MGAFCQRPSS (in isoform Short). FT /FTId=VSP_003028. FT CONFLICT 61 61 S -> G (in Ref. 1). FT CONFLICT 241 241 Missing (in Ref. 1). SQ SEQUENCE 266 AA; 31142 MW; 5387470F210F8695 CRC64; MLLWPLRGWA ARALRCFGPG SRGSPASGPG PRRVQRRAWP PDKEQEKEKK SVICVEGNIA SGKTTCLEFF SNATDVEVLT EPVSKWRNVR GHNPLGLMYH DASRWGLTLQ TYVQLTMLDR HTRPQVSSVR LMERSIHSAR YIFVENLYRS GKMPEVDYVV LSEWFDWILR NMDVSVDLIV YLRTNPETCY QRLKKRCREE EKVIPLEYLE AIHHLHEEWL IKGSLFPMAA PVLVIEADHH HMERMLELFE QNRDRILTPE NRKHCP // ID KPR1_HUMAN STANDARD; PRT; 317 AA. AC P09329; DT 01-MAR-1989 (Rel. 10, Created) DT 01-OCT-1989 (Rel. 12, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Ribose-phosphate pyrophosphokinase I (EC 2.7.6.1) (Phosphoribosyl DE pyrophosphate synthetase I) (PPRibP) (PRS-I). GN PRPS1. OS Homo sapiens (Human), and OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606, 10116; RN [1] RP SEQUENCE FROM N.A. RC SPECIES=Human; TISSUE=Lymphoblast; RX MEDLINE=90174926; PubMed=2155397; RA Roessler B.J., Bell G., Heidler S., Seino S., Becker M., Palella T.D.; RT "Cloning of two distinct copies of human phosphoribosylpyrophosphate RT synthetase cDNA."; RL Nucleic Acids Res. 18:193-193(1990). RN [2] RP SEQUENCE FROM N.A. RC SPECIES=Human; RX MEDLINE=91324322; PubMed=1650777; RA Sonoda T., Taira M., Ishijima S., Ishizuka T., Iizaka T., Tatibana M.; RT "Complete nucleotide sequence of human phosphoribosyl pyrophosphate RT synthetase subunit I (PRS I) cDNA and a comparison with human and rat RT PRPS gene families."; RL J. Biochem. 109:361-364(1991). RN [3] RP SEQUENCE FROM N.A. RC SPECIES=Human; TISSUE=Lymph; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE FROM N.A. RC SPECIES=Rat; TISSUE=Liver; RX MEDLINE=88033052; PubMed=2822704; RA Taira M., Ishijima S., Kita K., Yamada K., Iizasa T., Tatibana M.; RT "Nucleotide and deduced amino acid sequences of two distinct cDNAs RT for rat phosphoribosylpyrophosphate synthetase."; RL J. Biol. Chem. 262:14867-14870(1987). RN [5] RP SEQUENCE FROM N.A. RC SPECIES=Rat; RX MEDLINE=90067855; PubMed=2555779; RA Ishijima S., Taira M., Tatibana M.; RT "Complete cDNA sequence of rat phosphoribosylpyrophosphate synthetase RT subunit I (PRS I)."; RL Nucleic Acids Res. 17:8860-8860(1989). RN [6] RP SEQUENCE FROM N.A. RC SPECIES=Rat; RX MEDLINE=90154083; PubMed=2154494; RA Shimada H., Taira M., Yamada K., Iizasa T., Tatibana M.; RT "Structure of the rat PRPS1 gene encoding phosphoribosylpyrophosphate RT synthetase subunit I."; RL J. Biol. Chem. 265:3956-3960(1990). RN [7] RP VARIANTS PRPS-RELATED SER-113 AND HIS-182. RC SPECIES=Human; RA Roessler B.J., Palella T.D., Heidler S., Becker M.A.; RT "Identification of distinct PRPS1 mutations in two patients with RT X-linked phosphoribosylpyrophosphate synthetase superactivity."; RL Clin. Res. 39:267A-267A(1991). RN [8] RP VARIANTS PRPS-RELATED HIS-51; SER-113; ILE-128; HIS-182; VAL-189 AND RP GLN-192. RC SPECIES=Human; RX MEDLINE=96066677; PubMed=7593598; RA Becker M.A., Smith P.R., Taylor W., Mustafi R., Switzer R.L.; RT "The genetic and functional basis of purine nucleotide RT feedback-resistant phosphoribosylpyrophosphate synthetase RT superactivity."; RL J. Clin. Invest. 96:2133-2141(1995). CC -!- CATALYTIC ACTIVITY: ATP + D-ribose 5-phosphate = AMP + 5-phospho- CC alpha-D-ribose 1-diphosphate. CC -!- COFACTOR: Both inorganic phosphate and magnesium ion are required CC for enzyme stability and activity. CC -!- PATHWAY: Utilized by both the de novo and the salvage pathways by CC which endogenously formed or exogenously added pyrimidine, purine, CC or pyridine bases are converted to the corresponding CC ribonucleoside monophosphates. CC -!- DISEASE: Defects in PRPS1 are the cause of PRPS-related gout CC [MIM:311850]; also known as gout due to PRPS1 superactivity. It is CC a familial disorder characterized by excessive purine production, CC gout and uric acid urolithiasis. CC -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase CC family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M29392; AAA41960.1; -. DR EMBL; M31084; AAA41959.1; -. DR EMBL; M31078; AAA41959.1; JOINED. DR EMBL; M31079; AAA41959.1; JOINED. DR EMBL; M31080; AAA41959.1; JOINED. DR EMBL; M31082; AAA41959.1; JOINED. DR EMBL; M31083; AAA41959.1; JOINED. DR EMBL; X15331; CAA33386.1; -. DR EMBL; BC001605; AAH01605.1; -. DR EMBL; D00860; BAA00733.1; -. DR EMBL; M17258; AAA41963.1; -. DR EMBL; X16554; CAA34555.1; -. DR PIR; A35465; KIRTR1. DR PIR; JX0159; KIHUR1. DR HSSP; P14193; 1DKU. DR Genew; HGNC:9462; PRPS1. DR GK; P09329; -. DR MIM; 311850; -. DR GO; GO:0004749; F:ribose-phosphate diphosphokinase activity; TAS. DR GO; GO:0007399; P:neurogenesis; TAS. DR GO; GO:0006144; P:purine base metabolism; TAS. DR InterPro; IPR000842; PRPP_synthetase. DR InterPro; IPR000836; PRTransferase. DR InterPro; IPR005946; RibP_Ppkin. DR Pfam; PF00156; Pribosyltran; 1. DR TIGRFAMs; TIGR01251; ribP_PPkin; 1. DR PROSITE; PS00114; PRPP_SYNTHETASE; 1. KW Nucleotide biosynthesis; Transferase; Kinase; Magnesium; KW Multigene family; Gout; Disease mutation. FT INIT_MET 0 0 FT METAL 127 127 MAGNESIUM (POTENTIAL). FT METAL 129 129 MAGNESIUM (POTENTIAL). FT METAL 138 138 MAGNESIUM (POTENTIAL). FT METAL 142 142 MAGNESIUM (POTENTIAL). FT DOMAIN 211 226 BINDING OF PHOSPHORIBOSYLPYROPHOSPHATE FT (POTENTIAL). FT VARIANT 51 51 D -> H (in PRPS-related gout). FT /FTId=VAR_016044. FT VARIANT 113 113 N -> S (in PRPS-related gout). FT /FTId=VAR_004163. FT VARIANT 128 128 L -> I (in PRPS-related gout). FT /FTId=VAR_016045. FT VARIANT 182 182 D -> H (in PRPS-related gout). FT /FTId=VAR_004164. FT VARIANT 189 189 A -> V (in PRPS-related gout). FT /FTId=VAR_016046. FT VARIANT 192 192 H -> Q (in PRPS-related gout). FT /FTId=VAR_016047. SQ SEQUENCE 317 AA; 34703 MW; 5EB0961050726999 CRC64; PNIKIFSGSS HQDLSQKIAD RLGLELGKVV TKKFSNQETC VEIGESVRGE DVYIVQSGCG EINDNLMELL IMINACKIAS ASRVTAVIPC FPYARQDKKD KSRAPISAKL VANMLSVAGA DHIITMDLHA SQIQGFFDIP VDNLYAEPAV LKWIRENISE WRNCTIVSPD AGGAKRVTSI ADRLNVDFAL IHKERKKANE VDRMVLVGDV KDRVAILVDD MADTCGTICH AADKLLSAGA TRVYAILTHG IFSGPAISRI NNACFEAVVV TNTIPQEDKM KHCSKIQVID ISMILAEAIR RTHNGESVSY LFSHVPL // ID KPR2_HUMAN STANDARD; PRT; 317 AA. AC P11908; DT 01-OCT-1989 (Rel. 12, Created) DT 01-OCT-1989 (Rel. 12, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Ribose-phosphate pyrophosphokinase II (EC 2.7.6.1) (Phosphoribosyl DE pyrophosphate synthetase II) (PPRibP) (PRS-II). GN PRPS2. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=89171273; PubMed=2538352; RA Iizasa T., Taira M., Shimada H., Ishijima S., Tatibana M.; RT "Molecular cloning and sequencing of human cDNA for phosphoribosyl RT pyrophosphate synthetase subunit II."; RL FEBS Lett. 244:47-50(1989). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=90164248; PubMed=2560337; RA Iizasa T., Taira M., Shimada H., Tatibana M.; RT "Deduced amino acid sequence from human phosphoribosylpyrophosphate RT synthetase subunit II cDNA."; RL Adv. Exp. Med. Biol. 253A:519-523(1989). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Testis; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- CATALYTIC ACTIVITY: ATP + D-ribose 5-phosphate = AMP + 5-phospho- CC alpha-D-ribose 1-diphosphate. CC -!- COFACTOR: Both inorganic phosphate and magnesium ion are required CC for enzyme stability and activity. CC -!- ENZYME REGULATION: Activated by Mg(2+) and inorganic phosphate and CC competitive or non-competitive inhibited by ADP, CC 2,3-bisphosphoglyceride or GDP. CC -!- PATHWAY: Utilized by both the de novo and the salvage pathways by CC which endogenously formed or exogenously added pyrimidine, purine, CC or pyridine bases are converted to the corresponding CC ribonucleoside monophosphates. CC -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase CC family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; Y00971; CAA68785.1; -. DR EMBL; BC030019; AAH30019.1; -. DR EMBL; BC040483; AAH40483.1; -. DR PIR; S02778; KIHUR2. DR HSSP; P14193; 1DKU. DR Genew; HGNC:9465; PRPS2. DR MIM; 311860; -. DR GO; GO:0004749; F:ribose-phosphate diphosphokinase activity; TAS. DR GO; GO:0006139; P:nucleobase, nucleoside, nucleotide and nucl...; TAS. DR InterPro; IPR000842; PRPP_synthetase. DR InterPro; IPR000836; PRTransferase. DR InterPro; IPR005946; RibP_Ppkin. DR Pfam; PF00156; Pribosyltran; 1. DR TIGRFAMs; TIGR01251; ribP_PPkin; 1. DR PROSITE; PS00114; PRPP_SYNTHETASE; 1. KW Nucleotide biosynthesis; Transferase; Kinase; Magnesium; KW Multigene family. FT INIT_MET 0 0 FT METAL 127 127 MAGNESIUM (POTENTIAL). FT METAL 129 129 MAGNESIUM (POTENTIAL). FT METAL 138 138 MAGNESIUM (POTENTIAL). FT METAL 142 142 MAGNESIUM (POTENTIAL). FT DOMAIN 211 226 BINDING OF PHOSPHORIBOSYLPYROPHOSPHATE FT (POTENTIAL). SQ SEQUENCE 317 AA; 34638 MW; 6AC206CD31C7EE08 CRC64; PNIVLFSGSS HQDLSQRVAD RLGLELGKVV TKKFSNQETS VEIGESVRGE DVYIIQSGCG EINDNLMELL IMINACKIAS SSRVTAVIPC FPYARQDKKD KSRAPISAKL VANMLSVAGA DHIITMDLHA SQIQGFFDIP VDNLYAEPAV LQWIRENIAE WKNCIIVSPD AGGAKRVTSI ADRLNVEFAL IHKERKKANE VDRMVLVGDV KDRVAILVDD MADTCGTICH AADKLLSAGA TKVYAILTHG IFSGPAISRI NNAAFEAVVV TNTIPQEDKM KHCTKIQVID ISMILAEAIR RTHNGESVSY LFSHVPL // ID KPR3_HUMAN STANDARD; PRT; 317 AA. AC P21108; DT 01-FEB-1991 (Rel. 17, Created) DT 01-FEB-1991 (Rel. 17, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Ribose-phosphate pyrophosphokinase III (EC 2.7.6.1) (Phosphoribosyl DE pyrophosphate synthetase III) (PRS-III). GN PRPS3. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND SEQUENCE OF 1-10. RC TISSUE=Testis; RX MEDLINE=90375519; PubMed=2168892; RA Taira M., Iizasa T., Shimada H., Kudoh J., Shimizu N., Tatibana M.; RT "A human testis-specific mRNA for phosphoribosylpyrophosphate RT synthetase that initiates from a non-AUG codon."; RL J. Biol. Chem. 265:16491-16497(1990). CC -!- CATALYTIC ACTIVITY: ATP + D-ribose 5-phosphate = AMP + 5-phospho- CC alpha-D-ribose 1-diphosphate. CC -!- COFACTOR: Both inorganic phosphate and magnesium ion are required CC for enzyme stability and activity. CC -!- PATHWAY: Utilized by both the de novo and the salvage pathways by CC which endogenously formed or exogenously added pyrimidine, purine, CC or pyridine bases are converted to the corresponding CC ribonucleoside monophosphates. CC -!- TISSUE SPECIFICITY: Testis. CC -!- SIMILARITY: Belongs to the ribose-phosphate pyrophosphokinase CC family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M57423; AAB59463.1; -. DR PIR; A37893; KIHUR3. DR HSSP; P14193; 1DKR. DR SWISS-2DPAGE; P21108; HUMAN. DR GO; GO:0004749; F:ribose-phosphate diphosphokinase activity; NAS. DR GO; GO:0009156; P:ribonucleoside monophosphate biosynthesis; NAS. DR InterPro; IPR000842; PRPP_synthetase. DR InterPro; IPR000836; PRTransferase. DR InterPro; IPR005946; RibP_Ppkin. DR Pfam; PF00156; Pribosyltran; 1. DR TIGRFAMs; TIGR01251; ribP_PPkin; 1. DR PROSITE; PS00114; PRPP_SYNTHETASE; 1. KW Nucleotide biosynthesis; Transferase; Kinase; Magnesium. FT INIT_MET 0 0 FT METAL 127 127 MAGNESIUM (POTENTIAL). FT METAL 129 129 MAGNESIUM (POTENTIAL). FT METAL 138 138 MAGNESIUM (POTENTIAL). FT METAL 142 142 MAGNESIUM (POTENTIAL). FT DOMAIN 211 226 BINDING OF PHOSPHORIBOSYLPYROPHOSPHATE FT (POTENTIAL). SQ SEQUENCE 317 AA; 34708 MW; 722E5D80B65150AF CRC64; PNIKIFSGSS HQDLSQKIAD RLGLELGKVV TKKFSNQETC VEIDESVRGE DVYIVQSGCG EINDSLMELL IMINACKIAS ASRVTAVIPC FPYARQDKKD KSRSPISAKL VANMLSIAGA DHIITMDLHA SQIQGFFDIP VDNLYAEPTV LKWIRENIPE WKNCIIVSPD AGGAKRVTSI ADQLNVDFAL IHKERKKANE VDCIVLVGDV NDRVAILVDD MADTCVTICL AADKLLSAGA TRVYAILTHG IFSGPAISRI NTACFEAVVV TNTIPQDEKM KHCSKIRVID ISMILAEAIR RTHNGESVSY LFSHVPL // ID KPY1_HUMAN STANDARD; PRT; 530 AA. AC P14618; Q96E76; Q9BWB5; DT 01-APR-1990 (Rel. 14, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Pyruvate kinase, M1 isozyme (EC 2.7.1.40) (Pyruvate kinase muscle DE isozyme) (Cytosolic thyroid hormone-binding protein) (CTHBP) (THBP1). GN PKM2 OR PKM. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=90046696; PubMed=2813362; RA Kato H., Fukuda T., Parkison C., McPhie P., Cheng S.-Y.; RT "Cytosolic thyroid hormone-binding protein is a monomer of pyruvate RT kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7861-7865(1989). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=91249787; PubMed=2040271; RA Takenaka M., Noguchi T., Sadahiro S., Hirai H., Yamada K., Matsuda T., RA Imai E., Tanaka T.; RT "Isolation and characterization of the human pyruvate kinase M gene."; RL Eur. J. Biochem. 198:101-106(1991). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Eye, Kidney, Lung, Muscle, and Ovary; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP SEQUENCE OF 1-31. RC TISSUE=Platelet; RX MEDLINE=22608298; PubMed=12665801; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., RA Thomas G.R., Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass RT spectrometric identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). CC -!- CATALYTIC ACTIVITY: ATP + pyruvate = ADP + phosphoenolpyruvate. CC -!- COFACTOR: Requires magnesium and potassium. CC -!- PATHWAY: Glycolysis; final step. CC -!- SUBUNIT: Homotetramer. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=M1; CC IsoId=P14618-1; Sequence=Displayed; CC Name=M2; CC IsoId=P14786-1; Sequence=External; CC -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals: CC L, R, M1 and M2. L type is major isozyme in the liver, R is found CC in red cells, M1 is the main form in muscle, heart and brain, and CC M2 is found in early fetal tissues. CC -!- SIMILARITY: Belongs to the pyruvate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X56494; CAA39849.1; -. DR EMBL; M26252; AAA36672.1; -. DR EMBL; BC000481; AAH00481.1; -. DR EMBL; BC007640; AAH07640.1; -. DR EMBL; BC007952; AAH07952.1; -. DR EMBL; BC012811; AAH12811.1; -. DR EMBL; BC035198; AAH35198.1; -. DR PIR; S30038; S30038. DR HSSP; P11974; 1PKN. DR Genew; HGNC:9021; PKM2. DR MIM; 179050; -. DR GO; GO:0005829; C:cytosol; NAS. DR GO; GO:0004743; F:pyruvate kinase activity; TAS. DR GO; GO:0006096; P:glycolysis; NAS. DR InterPro; IPR001697; Pyruvate_kinase. DR Pfam; PF00224; PK; 1. DR Pfam; PF02887; PK_C; 1. DR PRINTS; PR01050; PYRUVTKNASE. DR ProDom; PD001009; Pyruvate_kinase; 1. DR TIGRFAMs; TIGR01064; pyruv_kin; 1. DR PROSITE; PS00110; PYRUVATE_KINASE; 1. KW Transferase; Kinase; Glycolysis; Multigene family; Magnesium; KW Alternative splicing. FT INIT_MET 0 0 FT ACT_SITE 269 269 By similarity. FT METAL 271 271 MAGNESIUM (POTENTIAL). FT METAL 292 292 MAGNESIUM (POTENTIAL). FT METAL 293 293 MAGNESIUM (POTENTIAL). FT CONFLICT 6 6 E -> Q (IN REF. 3; AAH12811). FT CONFLICT 102 102 I -> Y (in Ref. 1). FT CONFLICT 131 131 V -> L (in Ref. 1). FT CONFLICT 203 203 G -> V (IN REF. 3; AAH35198). FT CONFLICT 338 338 R -> P (in Ref. 2). FT CONFLICT 506 506 D -> H (IN REF. 3; AAH12811). SQ SEQUENCE 530 AA; 57805 MW; AA94C376A9DD8BAD CRC64; SKPHSEAGTA FIQTQQLHAA MADTFLEHMC RLDIDSPPIT ARNTGIICTI GPASRSVETL KEMIKSGMNV ARLNFSHGTH EYHAETIKNV RTATESFASD PILYRPVAVA LDTKGPEIRT GLIKGSGTAE VELKKGATLK ITLDNAYMEK CDENILWLDY KNICKVVEVG SKIYVDDGLI SLQVKQKGAD FLVTEVENGG SLGSKKGVNL PGAAVDLPAV SEKDIQDLKF GVEQDVDMVF ASFIRKASDV HEVRKVLGEK GKNIKIISKI ENHEGVRRFD EILEASDGIM VARGDLGIEI PAEKVFLAQK MMIGRCNRAG KPVICATQML ESMIKKPRPT RAEGSDVANA VLDGADCIML SGETAKGDYP LEAVRMQHLI AREAEAAIYH LQLFEELRRL APITSDPTEA TAVGAVEASF KCCSGAIIVL TKSGRSAHQV ARYRPRAPII AVTRNPQTAR QAHLYRGIFP VLCKDPVQEA WAEDVDLRVN FAMNVGKARG FFKKGDVVIV LTGWRPGSGF TNTMRVVPVP // ID KPY2_HUMAN STANDARD; PRT; 530 AA. AC P14786; Q9UPF2; DT 01-APR-1990 (Rel. 14, Created) DT 01-APR-1990 (Rel. 14, Last sequence update) DT 28-FEB-2003 (Rel. 41, Last annotation update) DE Pyruvate kinase, M2 isozyme (EC 2.7.1.40). GN PKM2 OR PKM. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=89211988; PubMed=2854097; RA Tani K., Yoshida M.C., Satoh H., Mitamura K., Noguchi T., Tanaka T., RA Fujii H., Miwa S.; RT "Human M2-type pyruvate kinase: cDNA cloning, chromosomal assignment RT and expression in hepatoma."; RL Gene 73:509-516(1988). RN [2] RP SEQUENCE OF 367-530 FROM N.A. RX MEDLINE=98125741; PubMed=9466265; RA Williams J.M., Chen G.C., Zhu L., Rest R.F.; RT "Using the yeast two-hybrid system to identify human epithelial cell RT proteins that bind gonococcal Opa proteins: intracellular gonococci RT bind pyruvate kinase via their Opa proteins and require host pyruvate RT for growth."; RL Mol. Microbiol. 27:171-186(1998). CC -!- CATALYTIC ACTIVITY: ATP + pyruvate = ADP + phosphoenolpyruvate. CC -!- COFACTOR: Requires magnesium and potassium. CC -!- PATHWAY: Glycolysis; final step. CC -!- SUBUNIT: Homotetramer. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=M2; CC IsoId=P14786-1; Sequence=Displayed; CC Name=M1; CC IsoId=P14618-1; Sequence=External; CC -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals: CC L, R, M1 and M2. L type is major isozyme in the liver, R is found CC in red cells, M1 is the main form in muscle, heart and brain, and CC M2 is found in early fetal tissues. CC -!- SIMILARITY: Belongs to the pyruvate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; M23725; AAA36449.1; -. DR EMBL; AF025439; AAC39559.1; -. DR PIR; S30038; S30038. DR HSSP; P11974; 1PKN. DR Aarhus/Ghent-2DPAGE; 3509; NEPHGE. DR Genew; HGNC:9021; PKM2. DR GK; P14786; -. DR MIM; 179050; -. DR GO; GO:0004743; F:pyruvate kinase activity; TAS. DR GO; GO:0006096; P:glycolysis; NAS. DR InterPro; IPR001697; Pyruvate_kinase. DR Pfam; PF00224; PK; 1. DR Pfam; PF02887; PK_C; 1. DR PRINTS; PR01050; PYRUVTKNASE. DR ProDom; PD001009; Pyruvate_kinase; 1. DR TIGRFAMs; TIGR01064; pyruv_kin; 1. DR PROSITE; PS00110; PYRUVATE_KINASE; 1. KW Transferase; Kinase; Glycolysis; Multigene family; Magnesium; KW Alternative splicing. FT INIT_MET 0 0 FT ACT_SITE 269 269 By similarity. FT METAL 271 271 MAGNESIUM (POTENTIAL). FT METAL 292 292 MAGNESIUM (POTENTIAL). FT METAL 293 293 MAGNESIUM (POTENTIAL). FT DOMAIN 388 432 INTERSUBUNIT CONTACT. FT CONFLICT 378 378 N -> H (in Ref. 2). SQ SEQUENCE 530 AA; 57782 MW; F6AEFCB6CFDD8DCD CRC64; SKPHSEAGTA FIQTQQLHAA MADTFLEHMC RLDIDSPPIT ARNTGIICTI GPASRSVETL KEMIKSGMNV ARLNFSHGTH EYHAETIKNV RTATESFASD PILYRPVAVA LDTKGPEIRT GLIKGSGTAE VELKKGATLK ITLDNAYMEK CDENILWLDY KNICKVVEVG SKIYVDDGLI SLQVKQKGAD FLVTEVENGG SLGSKKGVNL PGAAVDLPAV SEKDIQDLKF GVEQDVDMVF ASFIRKASDV HEVRKVLGEK GKNIKIISKI ENHEGVRRFD EILEASDGIM VARGDLGIEI PAEKVFLAQK MMIGRCNRAG KPVICATQML ESMIKKPRPT RAEGSDVANA VLDGADCIML SGETAKGDYP LEAVRMQNLI AREAEAAIYH LQLFEELRRL APITSDPTEA TAVGAVEASF KCCSGAIIVL TKSGRSAHQV ARYRPRAPII AVTRNPQTAR QAHLYRGIFP VLCKDPVQEA WAEDVDLRVN FAMNVGKARG FFKKGDVVIV LTGWRPGSGF TNTMRVVPVP // ID KPYR_HUMAN STANDARD; PRT; 574 AA. AC P30613; P11973; DT 01-APR-1993 (Rel. 25, Created) DT 30-MAY-2000 (Rel. 39, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Pyruvate kinase, isozymes R/L (EC 2.7.1.40) (R-type/L-type pyruvate DE kinase) (Red cell/liver pyruvate kinase). GN PKLR OR PKL OR PK1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND VARIANT CNSHA TOKYO/BEIRUT MET-384. RX MEDLINE=91376115; PubMed=1896471; RA Kanno H., Fujii H., Hirono A., Miwa S.; RT "cDNA cloning of human R-type pyruvate kinase and identification of a RT single amino acid substitution (Thr384-->Met) affecting enzymatic RT stability in a pyruvate kinase variant (PK Tokyo) associated with RT hereditary hemolytic anemia."; RL Proc. Natl. Acad. Sci. U.S.A. 88:8218-8221(1991). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=88158079; PubMed=3126495; RA Tani K., Fujii H., Nagata S., Miwa S.; RT "Human liver type pyruvate kinase: complete amino acid sequence and RT the expression in mammalian cells."; RL Proc. Natl. Acad. Sci. U.S.A. 85:1792-1795(1988). RN [3] RP REVISIONS TO 130 AND 232. RA Kanno H.; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP SEQUENCE FROM N.A. (ISOFORM R-TYPE). RC TISSUE=Pancreas; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP SEQUENCE OF 470-574 FROM N.A. RX MEDLINE=87184521; PubMed=3566732; RA Tani K., Fujii H., Tsutsumi H., Sukegawa J., Toyoshima K., RA Yoshida M.C., Noguchi T., Tanaka T., Miwa S.; RT "Human liver type pyruvate kinase: cDNA cloning and chromosomal RT assignment."; RL Biochem. Biophys. Res. Commun. 143:431-438(1987). RN [6] RP SEQUENCE OF 365-431 FROM N.A., AND VARIANT CNSHA OSAKA PHE-368. RX MEDLINE=93236593; PubMed=8476433; RA Kanno H., Fujii H., Tsujino G., Miwa S.; RT "Molecular basis of impaired pyruvate kinase isozyme conversion in RT erythroid cells: a single amino acid substitution near the active RT site and decreased mRNA content of the R-type PK."; RL Biochem. Biophys. Res. Commun. 192:46-52(1993). RN [7] RP REVIEW ON VARIANTS. RX MEDLINE=96263732; PubMed=8664896; RA Beutler E., Baronciani L.; RT "Mutations in pyruvate kinase."; RL Hum. Mutat. 7:1-6(1996). RN [8] RP REVIEW ON VARIANTS. RX MEDLINE=96400713; PubMed=8807089; RA Baronciani L., Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase."; RL Blood Cells Mol. Dis. 22:85-89(1996). RN [9] RP REVIEW ON VARIANTS. RX MEDLINE=97230013; PubMed=9075576; RA Baronciani L., Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase (1st RT update)."; RL Blood Cells Mol. Dis. 22:259-264(1996). RN [10] RP REVIEW ON VARIANTS. RX MEDLINE=99187977; PubMed=10087985; RA Baronciani L., Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase (2nd RT update)."; RL Blood Cells Mol. Dis. 24:273-279(1998). RN [11] RP REVIEW ON VARIANTS. RX MEDLINE=20238076; PubMed=10772876; RA Bianchi P., Zanella A.; RT "Hematologically important mutations: red cell pyruvate kinase (third RT update)."; RL Blood Cells Mol. Dis. 26:47-53(2000). RN [12] RP VARIANTS CNSHA LINZ CYS-163 AND TOKYO/BEIRUT MET-384. RX MEDLINE=91208396; PubMed=2018831; RA Neubauer B., Lakomek M., Winkler H., Parke M., Hofferbert S., RA Schroter W.; RT "Point mutations in the L-type pyruvate kinase gene of two children RT with hemolytic anemia caused by pyruvate kinase deficiency."; RL Blood 77:1871-1875(1991). RN [13] RP VARIANT CNSHA FUKUSHIMA/MAEBASHI LYS-421. RX MEDLINE=92163106; PubMed=1536957; RA Kanno H., Fujii H., Hirono A., Omine M., Miwa S.; RT "Identical point mutations of the R-type pyruvate kinase (PK) cDNA RT found in unrelated PK variants associated with hereditary hemolytic RT anemia."; RL Blood 79:1347-1350(1992). RN [14] RP VARIANT CNSHA SAPPORO GLN-426. RX MEDLINE=93244440; PubMed=8481523; RA Kanno H., Fujii H., Miwa S.; RT "Low substrate affinity of pyruvate kinase variant (PK Sapporo) RT caused by a single amino acid substitution (426 Arg-->Gln) associated RT with hereditary hemolytic anemia."; RL Blood 81:2439-2441(1993). RN [15] RP VARIANTS CNSHA ASP-134; PRO-155; HIS-359; TRP-486; VAL-495 AND RP GLN-510. RX MEDLINE=93248282; PubMed=8483951; RA Baronciani L., Beutler E.; RT "Analysis of pyruvate kinase-deficiency mutations that produce RT nonspherocytic hemolytic anemia."; RL Proc. Natl. Acad. Sci. U.S.A. 90:4324-4327(1993). RN [16] RP VARIANT CNSHA AMISH HIS-479. RX MEDLINE=94214145; PubMed=8161798; RA Kanno H., Ballas S.K., Miwa S., Fujii H., Bowman H.S.; RT "Molecular abnormality of erythrocyte pyruvate kinase deficiency in RT the Amish."; RL Blood 83:2311-2316(1994). RN [17] RP VARIANTS CNSHA SER-332; SER-336; LYS-354 DEL; ASP-361; THR-392; RP HIS-498; GLN-510 AND TRP-532. RX MEDLINE=94235845; PubMed=8180378; RA Lenzner C., Nuernberg P., Thiele B.-J., Reis A., Brabec V., RA Sakalova A., Jacobasch G.; RT "Mutations in the pyruvate kinase L gene in patients with hereditary RT hemolytic anemia."; RL Blood 83:2817-2822(1994). RN [18] RP VARIANTS CNSHA GLU-331; ALA-341; LYS-393; SER-393; ASP-458; MET-460 RP AND HIS-498. RX MEDLINE=95221622; PubMed=7706479; RA Baronciani L., Beutler E.; RT "Molecular study of pyruvate kinase deficient patients with RT hereditary nonspherocytic hemolytic anemia."; RL J. Clin. Invest. 95:1702-1709(1995). RN [19] RP VARIANTS CNSHA. RA Baronciani L., Westwood B., Beutler E.; RT "Study of the molecular defects in pyruvate kinase (PK) deficient RT patients affected by hereditary nonspherocytic hemolytic anemia RT (HNHA)."; RL J. Invest. Med. 43:341A-341A(1995). RN [20] RP VARIANT PYRUVATE KINASE HYPERACTIVITY GLU-37. RX MEDLINE=97245895; PubMed=9090535; RA Beutler E., Westwood B., van Zwieten R., Roos D.; RT "G-to-T transition at cDNA nt 110 (K37Q) in the PKLR (pyruvate RT kinase) gene is the molecular basis of a case of hereditary increase RT of red blood cell ATP."; RL Hum. Mutat. 9:282-285(1997). RN [21] RP VARIANTS CNSHA GLN-172; GLN-337; HIS-339; THR-357; ILE-408; THR-431; RP TRP-486 AND GLN-532. RX MEDLINE=99043610; PubMed=9827908; RA Zarza R., Alvarez R., Pujades A., Nomdedeu B., Carrera A., Estella J., RA Remacha A., Sanchez J.M., Morey M., Cortes T., Perez Lungmus G., RA Bureo E., Vives Corrons J.L.; RT "Molecular characterization of the PK-LR gene in pyruvate kinase RT deficient Spanish patients."; RL Br. J. Haematol. 103:377-382(1998). RN [22] RP VARIANT CNSHA CONAKRY TYR-130. RX MEDLINE=99101396; PubMed=9886305; RA Cohen-Solal M., Prehu C., Wajcman H., Poyart C., RA Bardakdjian-Michau J., Kister J., Prome D., Valentin C., Bachir D., RA Galacteros F.; RT "A new sickle cell disease phenotype associating Hb S trait, severe RT pyruvate kinase deficiency (PK Conakry), and an alpha-2 globin gene RT variant (Hb Conakry)."; RL Br. J. Haematol. 103:950-956(1998). RN [23] RP VARIANTS CNSHA SER-332; PRO-337; TRP-486; CYS-498 AND GLN-510. RX MEDLINE=98141680; PubMed=9482576; RA Pastore L., della Morte R., Frisso G., Alfinito F., Vitale D., RA Calise R.M., Ferraro F., Zagari A., Rotoli B., Salvatore F.; RT "Novel mutations and structural implications in R-type pyruvate RT kinase-deficient patients from Southern Italy."; RL Hum. Mutat. 11:127-134(1998). RN [24] RP VARIANTS CNSHA MET-335; LYS-338 DEL; GLY-387; ASP-394 AND VAL-394. RX MEDLINE=21226334; PubMed=11328279; RA Zanella A., Bianchi P., Fermo E., Iurlo A., Zappa M., Vercellati C., RA Boschetti C., Baronciani L., Cotton F.; RT "Molecular characterization of the PK-LR gene in sixteen pyruvate RT kinase-deficient patients."; RL Br. J. Haematol. 113:43-48(2001). CC -!- CATALYTIC ACTIVITY: ATP + pyruvate = ADP + phosphoenolpyruvate. CC -!- COFACTOR: Requires magnesium and potassium. CC -!- PATHWAY: Glycolysis; final step. CC -!- SUBUNIT: Homotetramer. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=R-type; CC IsoId=P30613-1; Sequence=Displayed; CC Name=L-type; CC IsoId=P30613-2; Sequence=VSP_002883; CC -!- DISEASE: Defects in PKLR are the cause of pyruvate kinase CC hyperactivity [MIM:102900]; also known as high red cell ATP CC syndrome. This autosomal dominant phenotype is characterized by CC increase of red blood cell ATP. CC -!- DISEASE: Defects in PKLR are a cause of chronic nonspherocytic CC hemolytic anemia (CNSHA) [MIM:266200]; also called hereditary CC nonspherocytic hemolytic anemia (HNSHA). CC -!- MISCELLANEOUS: There are 4 isozymes of pyruvate kinase in mammals: CC L, R, M1 and M2. L type is major isozyme in the liver, R is found CC in red cells, M1 is the main form in muscle, heart and brain, and CC M2 is found in early fetal tissues. CC -!- SIMILARITY: Belongs to the pyruvate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AB015983; BAA31706.1; -. DR EMBL; M15465; AAA60104.1; -. DR EMBL; BC025737; AAH25737.1; -. DR EMBL; S60712; AAB26262.1; -. DR PIR; I52269; KIHUPL. DR PIR; I52269; KIHUPR. DR PDB; 1LIU; 11-SEP-02. DR PDB; 1LIW; 11-SEP-02. DR SWISS-2DPAGE; P30613; HUMAN. DR Genew; HGNC:9020; PKLR. DR GK; P30613; -. DR MIM; 266200; -. DR MIM; 102900; -. DR GO; GO:0004743; F:pyruvate kinase activity; TAS. DR InterPro; IPR001697; Pyruvate_kinase. DR Pfam; PF00224; PK; 1. DR Pfam; PF02887; PK_C; 1. DR PRINTS; PR01050; PYRUVTKNASE. DR ProDom; PD001009; Pyruvate_kinase; 1. DR TIGRFAMs; TIGR01064; pyruv_kin; 1. DR PROSITE; PS00110; PYRUVATE_KINASE; 1. KW Transferase; Kinase; Glycolysis; Multigene family; Phosphorylation; KW Magnesium; Alternative splicing; Disease mutation; 3D-structure. FT MOD_RES 43 43 PHOSPHORYLATION (BY PKA). FT ACT_SITE 313 313 By similarity. FT METAL 315 315 MAGNESIUM (POTENTIAL). FT METAL 336 336 MAGNESIUM (POTENTIAL). FT METAL 337 337 MAGNESIUM (POTENTIAL). FT VARSPLIC 1 33 MSIQENISSLQLRSWVSKSQRDLAKSILIGAPG -> ME FT (in isoform L-type). FT /FTId=VSP_002883. FT VARIANT 37 37 G -> E (in pyruvate kinase FT hyperactivity). FT /FTId=VAR_011435. FT VARIANT 80 80 S -> P (in CNSHA). FT /FTId=VAR_011436. FT VARIANT 86 86 R -> P (in CNSHA). FT /FTId=VAR_011437. FT VARIANT 90 90 I -> N (in CNSHA). FT /FTId=VAR_011438. FT VARIANT 95 95 G -> R (in CNSHA). FT /FTId=VAR_011439. FT VARIANT 107 107 M -> T (in CNSHA). FT /FTId=VAR_004028. FT VARIANT 111 111 G -> R (in CNSHA). FT /FTId=VAR_011440. FT VARIANT 115 115 A -> P (in CNSHA; Val de Marne). FT /FTId=VAR_011441. FT VARIANT 120 120 S -> F (in CNSHA; Beaujon). FT /FTId=VAR_011442. FT VARIANT 130 130 S -> Y (in CNSHA; Conakry). FT /FTId=VAR_011443. FT VARIANT 131 131 Missing (in CNSHA). FT /FTId=VAR_004029. FT VARIANT 134 134 V -> D (in CNSHA). FT /FTId=VAR_004030. FT VARIANT 153 153 I -> T (in CNSHA). FT /FTId=VAR_011474. FT VARIANT 155 155 L -> P (in CNSHA). FT /FTId=VAR_004031. FT VARIANT 159 159 G -> V (in CNSHA). FT /FTId=VAR_011444. FT VARIANT 163 163 R -> C (in CNSHA; Linz). FT /FTId=VAR_004033. FT VARIANT 172 172 E -> Q (in CNSHA; Sassari). FT /FTId=VAR_004032. FT VARIANT 219 219 I -> T (in CNSHA). FT /FTId=VAR_011475. FT VARIANT 221 221 D -> DD (in CNSHA). FT /FTId=VAR_004034. FT VARIANT 222 222 G -> A (in CNSHA; Katsushika). FT /FTId=VAR_011445. FT VARIANT 263 263 G -> R (in CNSHA). FT /FTId=VAR_011447. FT VARIANT 263 263 G -> W (in CNSHA). FT /FTId=VAR_011448. FT VARIANT 275 275 G -> R (in CNSHA). FT /FTId=VAR_004035. FT VARIANT 281 281 D -> N (in CNSHA). FT /FTId=VAR_004036. FT VARIANT 287 287 F -> V (in CNSHA). FT /FTId=VAR_004037. FT VARIANT 288 288 V -> L (in CNSHA; Moriguchi). FT /FTId=VAR_011449. FT VARIANT 293 293 D -> N (in CNSHA). FT /FTId=VAR_011446. FT VARIANT 295 295 A -> V (in CNSHA). FT /FTId=VAR_011450. FT VARIANT 310 310 I -> N (in CNSHA; Dordrecht). FT /FTId=VAR_011451. FT VARIANT 314 314 I -> T (in CNSHA; Hong Kong). FT /FTId=VAR_004038. FT VARIANT 315 315 E -> K (in CNSHA). FT /FTId=VAR_011452. FT VARIANT 331 331 D -> E (in CNSHA; Parma). FT /FTId=VAR_004039. FT VARIANT 331 331 D -> N (in CNSHA). FT /FTId=VAR_011453. FT VARIANT 332 332 G -> S (in CNSHA). FT /FTId=VAR_004040. FT VARIANT 335 335 V -> M (in CNSHA). FT /FTId=VAR_011476. FT VARIANT 336 336 A -> S (in CNSHA). FT /FTId=VAR_004041. FT VARIANT 337 337 R -> P (in CNSHA). FT /FTId=VAR_004042. FT VARIANT 337 337 R -> Q (in CNSHA). FT /FTId=VAR_004043. FT VARIANT 339 339 D -> H (in CNSHA). FT /FTId=VAR_004044. FT VARIANT 341 341 G -> A (in CNSHA). FT /FTId=VAR_004045. FT VARIANT 341 341 G -> D (in CNSHA). FT /FTId=VAR_011454. FT VARIANT 342 342 I -> F (in CNSHA). FT /FTId=VAR_011455. FT VARIANT 348 348 K -> N (in CNSHA; Kamata). FT /FTId=VAR_011456. FT VARIANT 348 348 Missing (in CNSHA; Brescia). FT /FTId=VAR_011457. FT VARIANT 352 352 A -> D (in CNSHA). FT /FTId=VAR_011477. FT VARIANT 354 354 Missing (in CNSHA). FT /FTId=VAR_004046. FT VARIANT 357 357 I -> T (in CNSHA). FT /FTId=VAR_004047. FT VARIANT 359 359 R -> C (in CNSHA; Aomori). FT /FTId=VAR_004048. FT VARIANT 359 359 R -> H (in CNSHA). FT /FTId=VAR_004049. FT VARIANT 361 361 N -> D (in CNSHA). FT /FTId=VAR_004050. FT VARIANT 364 364 G -> D (in CNSHA; Tjaereborg). FT /FTId=VAR_011458. FT VARIANT 368 368 V -> F (in CNSHA; Osaka). FT /FTId=VAR_004051. FT VARIANT 376 376 S -> I (in CNSHA). FT /FTId=VAR_011459. FT VARIANT 384 384 T -> M (in CNSHA; Tokyo/Beirut; most FT common mutation in Japanese population). FT /FTId=VAR_004052. FT VARIANT 385 385 R -> W (in CNSHA). FT /FTId=VAR_011478. FT VARIANT 387 387 E -> G (in CNSHA). FT /FTId=VAR_011460. FT VARIANT 390 390 D -> N (in CNSHA; Mantova). FT /FTId=VAR_011461. FT VARIANT 392 392 A -> T (in CNSHA). FT /FTId=VAR_004053. FT VARIANT 393 393 N -> K (in CNSHA). FT /FTId=VAR_004054. FT VARIANT 393 393 N -> S (in CNSHA; Paris). FT /FTId=VAR_004055. FT VARIANT 394 394 A -> D (in CNSHA). FT /FTId=VAR_011462. FT VARIANT 394 394 A -> V (in CNSHA). FT /FTId=VAR_011463. FT VARIANT 401 401 C -> CS (in CNSHA). FT /FTId=VAR_004056. FT VARIANT 408 408 T -> A (in CNSHA; Hirosaki). FT /FTId=VAR_011464. FT VARIANT 408 408 T -> I (in CNSHA). FT /FTId=VAR_004057. FT VARIANT 421 421 Q -> K (in CNSHA; FT Fukushima/Maebashi/Sendai). FT /FTId=VAR_004058. FT VARIANT 426 426 R -> Q (in CNSHA; Sapporo). FT /FTId=VAR_004059. FT VARIANT 426 426 R -> W (in CNSHA; Naniwa). FT /FTId=VAR_004060. FT VARIANT 427 427 E -> A (in CNSHA). FT /FTId=VAR_011465. FT VARIANT 427 427 E -> D (in CNSHA). FT /FTId=VAR_011466. FT VARIANT 431 431 A -> T (in CNSHA). FT /FTId=VAR_004061. FT VARIANT 458 458 G -> D (in CNSHA). FT /FTId=VAR_004062. FT VARIANT 459 459 A -> V (in CNSHA). FT /FTId=VAR_004063. FT VARIANT 460 460 V -> M (in CNSHA). FT /FTId=VAR_004064. FT VARIANT 468 468 A -> G (in CNSHA). FT /FTId=VAR_011479. FT VARIANT 468 468 A -> V (in CNSHA; Hadano). FT /FTId=VAR_004065. FT VARIANT 477 477 T -> A (in CNSHA). FT /FTId=VAR_011467. FT VARIANT 479 479 R -> H (in CNSHA; Amish). FT /FTId=VAR_011480. FT VARIANT 485 485 S -> F (in CNSHA). FT /FTId=VAR_011468. FT VARIANT 486 486 R -> W (in CNSHA; frequent mutation). FT /FTId=VAR_004066. FT VARIANT 488 488 R -> Q (in CNSHA). FT /FTId=VAR_011469. FT VARIANT 490 490 R -> W (in CNSHA). FT /FTId=VAR_004067. FT VARIANT 495 495 A -> T (in CNSHA). FT /FTId=VAR_011470. FT VARIANT 495 495 A -> V (in CNSHA). FT /FTId=VAR_004068. FT VARIANT 498 498 R -> C (in CNSHA). FT /FTId=VAR_004069. FT VARIANT 498 498 R -> H (in CNSHA). FT /FTId=VAR_004070. FT VARIANT 504 504 R -> L (in CNSHA). FT /FTId=VAR_011471. FT VARIANT 510 510 R -> Q (in CNSHA; the most common FT mutation in European population). FT /FTId=VAR_004071. FT VARIANT 511 511 G -> R (in CNSHA). FT /FTId=VAR_011472. FT VARIANT 531 531 R -> C (in CNSHA). FT /FTId=VAR_011473. FT VARIANT 532 532 R -> Q (in CNSHA). FT /FTId=VAR_004072. FT VARIANT 532 532 R -> W (in CNSHA). FT /FTId=VAR_004073. FT VARIANT 552 552 V -> M (in CNSHA). FT /FTId=VAR_004074. FT VARIANT 557 557 G -> A (in CNSHA). FT /FTId=VAR_011481. FT VARIANT 559 559 R -> G (in CNSHA). FT /FTId=VAR_004075. FT VARIANT 566 566 N -> K (in CNSHA). FT /FTId=VAR_004076. FT VARIANT 569 569 R -> Q (in CNSHA). FT /FTId=VAR_011482. FT CONFLICT 423 423 A -> R (in Ref. 2). FT TURN 59 60 FT HELIX 61 64 FT TURN 65 65 FT HELIX 69 73 FT TURN 74 75 FT TURN 78 79 FT STRAND 89 93 FT HELIX 96 98 FT HELIX 101 110 FT TURN 111 111 FT STRAND 112 118 FT TURN 119 120 FT HELIX 124 139 FT TURN 140 143 FT TURN 145 147 FT STRAND 152 156 FT STRAND 163 164 FT STRAND 176 177 FT TURN 179 180 FT STRAND 182 185 FT STRAND 199 200 FT STRAND 202 202 FT TURN 205 206 FT HELIX 207 210 FT TURN 213 214 FT STRAND 216 219 FT TURN 220 223 FT STRAND 224 227 FT STRAND 238 242 FT STRAND 244 245 FT STRAND 251 253 FT TURN 255 256 FT HELIX 266 277 FT TURN 278 279 FT STRAND 282 285 FT TURN 286 287 FT HELIX 291 301 FT HELIX 303 305 FT STRAND 309 314 FT HELIX 317 321 FT TURN 322 322 FT HELIX 323 329 FT STRAND 332 336 FT HELIX 337 343 FT HELIX 346 348 FT HELIX 349 363 FT TURN 364 364 FT STRAND 367 370 FT TURN 373 374 FT HELIX 375 378 FT TURN 379 379 FT HELIX 385 397 FT TURN 398 398 FT STRAND 401 404 FT HELIX 406 409 FT TURN 410 410 FT HELIX 414 431 FT HELIX 434 444 FT HELIX 451 466 FT TURN 467 467 FT STRAND 470 474 FT HELIX 479 486 FT TURN 487 487 FT STRAND 492 497 FT HELIX 500 505 FT HELIX 506 508 FT TURN 510 511 FT STRAND 512 516 FT HELIX 525 543 FT TURN 544 544 FT TURN 548 549 FT STRAND 551 557 FT STRAND 565 572 SQ SEQUENCE 574 AA; 61830 MW; 3B430896832032F5 CRC64; MSIQENISSL QLRSWVSKSQ RDLAKSILIG APGGPAGYLR RASVAQLTQE LGTAFFQQQQ LPAAMADTFL EHLCLLDIDS EPVAARSTSI IATIGPASRS VERLKEMIKA GMNIARLNFS HGSHEYHAES IANVREAVES FAGSPLSYRP VAIALDTKGP EIRTGILQGG PESEVELVKG SQVLVTVDPA FRTRGNANTV WVDYPNIVRV VPVGGRIYID DGLISLVVQK IGPEGLVTQV ENGGVLGSRK GVNLPGAQVD LPGLSEQDVR DLRFGVEHGV DIVFASFVRK ASDVAAVRAA LGPEGHGIKI ISKIENHEGV KRFDEILEVS DGIMVARGDL GIEIPAEKVF LAQKMMIGRC NLAGKPVVCA TQMLESMITK PRPTRAETSD VANAVLDGAD CIMLSGETAK GNFPVEAVKM QHAIAREAEA AVYHRQLFEE LRRAAPLSRD PTEVTAIGAV EAAFKCCAAA IIVLTTTGRS AQLLSRYRPR AAVIAVTRSA QAARQVHLCR GVFPLLYREP PEAIWADDVD RRVQFGIESG KLRGFLRVGD LVIVVTGWRP GSGYTNIMRV LSIS // ID KTHY_HUMAN STANDARD; PRT; 212 AA. AC P23919; Q9BUX4; DT 01-MAR-1992 (Rel. 21, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Thymidylate kinase (EC 2.7.4.9) (dTMP kinase). GN DTYMK OR TYMK OR TMPK OR CDC8. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=91204436; PubMed=2017365; RA Su J.Y., Sclafani R.A.; RT "Molecular cloning and expression of the human deoxythymidylate kinase RT gene in yeast."; RL Nucleic Acids Res. 19:823-827(1991). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=94296549; PubMed=8024690; RA Huang S.H., Tang A., Drisco B., Zhang S.Q., Seeger R., Li C., RA Jong A.; RT "Human dTMP kinase: gene expression and enzymatic activity coinciding RT with cell cycle progression and cell growth."; RL DNA Cell Biol. 13:461-471(1994). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Muscle; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Catalyzes the conversion of dTMP to dTDP. CC -!- CATALYTIC ACTIVITY: ATP + thymidine 5'-phosphate = ADP + thymidine CC 5'-diphosphate. CC -!- PATHWAY: Biosynthesis of dTTP from dTMP. CC -!- SIMILARITY: Belongs to the thymidylate kinase family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; X54729; CAA38528.1; -. DR EMBL; L16991; AAA21719.1; -. DR EMBL; BC001827; AAH01827.1; -. DR PIR; S26845; S26845. DR PDB; 1E2D; 21-FEB-02. DR PDB; 1E2E; 21-FEB-02. DR PDB; 1E2F; 24-JUN-03. DR PDB; 1E2G; 21-FEB-02. DR PDB; 1E2Q; 24-JUN-03. DR PDB; 1E98; 18-JUL-03. DR PDB; 1E99; 18-JUL-03. DR PDB; 1E9A; 18-JUL-03. DR PDB; 1E9B; 01-AUG-03. DR PDB; 1E9C; 18-JUL-03. DR PDB; 1E9D; 18-JUL-03. DR PDB; 1E9E; 18-JUL-03. DR PDB; 1E9F; 18-JUL-03. DR PDB; 1NMX; 18-MAR-03. DR PDB; 1NMY; 18-MAR-03. DR PDB; 1NMZ; 18-MAR-03. DR PDB; 1NN0; 18-MAR-03. DR PDB; 1NN5; 18-MAR-03. DR Genew; HGNC:3061; DTYMK. DR GK; P23919; -. DR MIM; 188345; -. DR GO; GO:0004798; F:thymidylate kinase activity; TAS. DR GO; GO:0007049; P:cell cycle; TAS. DR InterPro; IPR000062; Thymidylate_kin. DR Pfam; PF02223; Thymidylate_kin; 1. DR TIGRFAMs; TIGR00041; DTMP_kinase; 1. DR PROSITE; PS01331; THYMIDYLATE_KINASE; 1. KW Transferase; Kinase; Nucleotide biosynthesis; ATP-binding; KW 3D-structure. FT NP_BIND 13 20 ATP (Probable). FT CONFLICT 31 37 CAAGHRA -> SRGPPP (in Ref. 1). FT CONFLICT 58 58 Q -> K (in Ref. 2). FT CONFLICT 183 184 SI -> RL (in Ref. 1). FT CONFLICT 190 191 EL -> DI (in Ref. 3). FT STRAND 8 12 FT TURN 15 16 FT HELIX 19 32 FT TURN 33 34 FT STRAND 37 41 FT TURN 45 46 FT HELIX 48 57 FT TURN 58 59 FT HELIX 65 77 FT TURN 78 79 FT HELIX 80 88 FT TURN 89 90 FT STRAND 92 96 FT HELIX 99 106 FT TURN 107 108 FT TURN 110 111 FT HELIX 114 118 FT HELIX 119 121 FT TURN 122 123 FT STRAND 125 125 FT STRAND 129 134 FT HELIX 137 140 FT TURN 141 142 FT TURN 150 151 FT HELIX 154 167 FT TURN 168 169 FT TURN 171 172 FT STRAND 175 179 FT TURN 180 181 FT HELIX 184 202 FT TURN 203 204 FT STRAND 209 209 FT TURN 210 212 SQ SEQUENCE 212 AA; 23833 MW; E42876625B3096DA CRC64; MAARRGALIV LEGVDRAGKS TQSRKLVEAL CAAGHRAELL RFPERSTEIG KLLSSYLQKK SDVEDHSVHL LFSANRWEQV PLIKEKLSQG VTLVVDRYAF SGVAFTGAKE NFSLDWCKQP DVGLPKPDLV LFLQLQLADA AKRGAFGHER YENGAFQERA LRCFHQLMKD TTLNWKMVDA SKSIEAVHEE LRVLSEDAIR TATEKPLGEL WK // ID M4K1_HUMAN STANDARD; PRT; 833 AA. AC Q92918; DT 10-OCT-2003 (Rel. 42, Created) DT 10-OCT-2003 (Rel. 42, Last sequence update) DT 10-OCT-2003 (Rel. 42, Last annotation update) DE Mitogen-activated protein kinase kinase kinase kinase 1 (EC 2.7.1.37) DE (MAPK/ERK kinase kinase kinase 1) (MEK kinase kinase 1) (MEKKK 1) DE (Hematopoietic progenitor kinase). GN MAP4K1 OR HPK1. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH RP MAP3K1. RC TISSUE=Fetal liver; RX MEDLINE=96421968; PubMed=8824585; RA Hu M.C.-T., Qiu W.R., Wang X., Meyer C.F., Tan T.-H.; RT "Human HPK1, a novel human hematopoietic progenitor kinase that RT activates the JNK/SAPK kinase cascade."; RL Genes Dev. 10:2251-2264(1996). CC -!- FUNCTION: May play a role in the response to environmental stress. CC Appears to act upstream of the c-jun N-terminal pathway. CC -!- FUNCTION: May play a role in hematopoietic lineage decisions and CC growth regulation (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Magnesium. CC -!- SUBUNIT: Interacts with MAP3K1. CC -!- TISSUE SPECIFICITY: Expressed primarily in hematopoietic organs, CC including bone marrow, spleen and thymus. Also expressed at very CC low levels in lung, kidney, mammary glands and small CC intestine. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. STE20 CC subfamily. CC -!- SIMILARITY: Contains 1 CNH domain. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U66464; AAB97983.1; -. DR HSSP; Q63450; 1A06. DR Genew; HGNC:6863; MAP4K1. DR MIM; 601983; -. DR GO; GO:0005524; F:ATP binding; IDA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA. DR GO; GO:0007257; P:activation of JUNK; TAS. DR GO; GO:0006468; P:protein amino acid phosphorylation; IDA. DR GO; GO:0007243; P:protein kinase cascade; IDA. DR GO; GO:0045610; P:regulation of hemocyte differentiation; ISS. DR GO; GO:0006950; P:response to stress; IDA. DR InterPro; IPR001180; Citron. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR002290; Ser_thr_pkinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR001245; Tyr_pkinase. DR Pfam; PF00780; CNH; 1. DR Pfam; PF00069; pkinase; 1. DR PRINTS; PR00109; TYRKINASE. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00036; CNH; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; FALSE_NEG. KW ATP-binding; Transferase; Kinase; Serine/threonine-protein kinase. FT DOMAIN 17 274 PROTEIN KINASE. FT DOMAIN 501 807 CNH. FT NP_BIND 23 31 ATP (By similarity). FT BINDING 46 46 ATP (By similarity). FT ACT_SITE 137 137 By similarity. SQ SEQUENCE 833 AA; 91296 MW; 3C98CF01BE42E151 CRC64; MDVVDPDIFN RDPRDHYDLL QRLGGGTYGE VFKARDKVSG DLVALKMVKM EPDDDVSTLQ KEILILKTCR HANIVAYHGS YLWLQKLWIC MEFCGAGSLQ DIYQVTGSLS ELQISYVCRE VLQGLAYLHS QKKIHRDIKG ANILINDAGE VRLADFGISA QIGATLARRL SFIGTPYWMA PEVAAVALKG GYNELCDIWS LGITAIELAE LQPPLFDVHP LRVLFLMTKS GYQPPRLKEK GKWSAAFHNF IKVTLTKSPK KRPSATKMLS HQLVSQPGLN RGLILDLLDK LKNPGKGPSI GDIEDEEPEL PPAIPRRIRS THRSSSLGIP DADCCRRHME FRKLRGMETR PPANTARLQP PRDLRSSSPR KQLSESSDDD YDDVDIPTPA EDTPPPLPPK PKFRSPSDEG PGSMGDDGQL SPGVLVRCAS GPPPNSPRPG PPPSTSSPHL TAHSEPSLWN PPSRELDKPP LLPPKKEKMK RKGCALLVKL FNGCPLRIHS TAAWTHPSTK DQHLLLGAEE GIFILNRNDQ EATLEMLFPS RTTWVYSINN VLMSLSGKTP HLYSHSILGL LERKETRAGN PIAHISPHRL LARKNMVSTK IQDTKGCRAC CVAEGASSGG PFLCGALETS VVLLQWYQPM NKFLLVRQVL FPLPTPLSVF ALLTGPGSEL PAVCIGVSPG RPGKSVLFHT VRFGALSCWL GEMSTEHRGP VQVTQVEEDM VMVLMDGSVK LVTPEGSPVR GLRTPEIPMT EAVEAVAMVG GQLQAFWKHG VQVWALGSDQ LLQELRDPTL TFRLLGSPRL ECSGTISPHC NLLLPGSSNS PASASRVAGI TGL // ID NAGK_HUMAN STANDARD; PRT; 344 AA. AC Q9UJ70; Q9BS29; Q9BVP0; DT 28-FEB-2003 (Rel. 41, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE N-acetylglucosamine kinase (EC 2.7.1.59) (GlcNAc kinase). GN NAGK. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND TISSUE SPECIFICITY. RX MEDLINE=20285356; PubMed=10824116; RA Hinderlich S., Berger M., Schwarzkopf M., Effertz K., Reutter W.; RT "Molecular cloning and characterization of murine and human N- RT acetylglucosamine kinase."; RL Eur. J. Biochem. 267:3301-3308(2000). RN [2] RP SEQUENCE FROM N.A. RC TISSUE=Kidney, and Skin; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP PHOSPHORYLATION OF TYR-205. RX MEDLINE=22107313; PubMed=12112843; RA Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G., RA Fitzgerald D.J.; RT "Identification of the phosphotyrosine proteome from thrombin RT activated platelets."; RL Proteomics 2:642-648(2002). CC -!- FUNCTION: Converts endogenous N-acetylglucosamine (GlcNAc), a CC major component of complex carbohydrates, from lysosomal CC degradation or nutritional sources into GlcNAc 6-phosphate. Also CC has ManNAc kinase activity (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + N-acetyl-D-glucosamine = ADP + N-acetyl- CC D-glucosamine 6-phosphate. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; AJ242910; CAB61848.1; -. DR EMBL; BC001029; AAH01029.1; -. DR EMBL; BC005371; AAH05371.1; -. DR Genew; HGNC:17174; NAGK. DR MIM; 606828; -. DR GO; GO:0006044; P:N-acetylglucosamine metabolism; TAS. DR GO; GO:0006051; P:N-acetylmannosamine metabolism; TAS. DR InterPro; IPR002731; ATPase_BadF. DR Pfam; PF01869; BcrAD_BadFG; 1. KW Kinase; Transferase; ATP-binding; Phosphorylation. FT MOD_RES 205 205 PHOSPHORYLATION. FT CONFLICT 38 38 W -> R (IN REF. 2; AAH05371). FT CONFLICT 60 60 A -> V (IN REF. 2; AAH05371). FT CONFLICT 70 70 S -> I (in Ref. 1). FT CONFLICT 121 121 V -> I (in Ref. 1). SQ SEQUENCE 344 AA; 37375 MW; FCBB6B328EF4D515 CRC64; MAAIYGGVEG GGTRSEVLLV SEDGKILAEA DGLSTNHWLI GTDKCVERIN EMVNRAKRKA GVDPLVPLRS LGLSLSGGDQ EDAGRILIEE LRDRFPYLSE SYLITTDAAG SIATATPDGG VVLISGTGSN CRLINPDGSE SGCGGWGHMM GDEGSAYWIA HQAVKIVFDS IDNLEAAPHD IGYVKQAMFH YFQVPDRLGI LTHLYRDFDK CRFAGFCRKI AEGAQQGDPL SRYIFRKAGE MLGRHIVAVL PEIDPVLFQG KIGLPILCVG SVWKSWELLK EGFLLALTQG REIQAQNFFS SFTLMKLRHS SALGGASLGA RHIGHLLPMD YSANAIAFYS YTFS // ID NDK3_HUMAN STANDARD; PRT; 169 AA. AC Q13232; Q9BWH4; DT 15-DEC-1998 (Rel. 37, Created) DT 28-FEB-2003 (Rel. 41, Last sequence update) DT 15-MAR-2004 (Rel. 43, Last annotation update) DE Nucleoside diphosphate kinase 3 (EC 2.7.4.6) (NDK 3) (NDP kinase 3) DE (nm23-H3) (DR-nm23). GN NME3. OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A. RX MEDLINE=95365382; PubMed=7638209; RA Venturelli D., Martinez R., Melotti P., Casella I., Peschle C., RA Cucco C., Spampinato G., Darzynkiewicz Z., Calabretta B.; RT "Overexpression of DR-nm23, a protein encoded by a member of the nm23 RT gene family, inhibits granulocyte differentiation and induces RT apoptosis in 32Dc13 myeloid cells."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7435-7439(1995). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=21096910; PubMed=11157797; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., RA Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., RA Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 RT Mb of the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Eye; RX MEDLINE=22388257; PubMed=12477932; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length RT human and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates CC other than ATP (By similarity). Has probably a role for in normal CC hematopoiesis inhibits granulocyte differentiation and induces CC apoptosis. CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP + CC nucleoside triphosphate. CC -!- DEVELOPMENTAL STAGE: Preferentially expressed at early stages of CC myeloid differentiation of highly purified CD34+ cells. CC -!- SIMILARITY: Belongs to the NDK family. CC -------------------------------------------------------------------------- CC This SWISS-PROT entry is copyright. It is produced through a collaboration CC between the Swiss Institute of Bioinformatics and the EMBL outstation - CC the European Bioinformatics Institute. There are no restrictions on its CC use by non-profit institutions as long as its content is in no way CC modified and this statement is not removed. Usage by and for commercial CC entities requires a license agreement (See http://www.isb-sib.ch/announce/ CC or send an email to license@isb-sib.ch). CC -------------------------------------------------------------------------- DR EMBL; U29656; AAA85097.1; -. DR EMBL; AE006639; AAK61291.1; -. DR EMBL; BC000250; AAH00250.1; -. DR PIR; I39074; I39074. DR HSSP; P08879; 1NSQ. DR Genew; HGNC:7851; NME3. DR MIM; 601817; -. DR GO; GO:0006917; P:induction of apoptosis; TAS. DR InterPro; IPR001564; NDK. DR Pfam; PF00334; NDK; 1. DR PRINTS; PR01243; NUCDPKINASE. DR ProDom; PD001018; NDK; 1. DR SMART; SM00562; NDK; 1. DR PROSITE; PS00469; NDP_KINASES; 1. KW Transferase; Kinase; ATP-binding. FT ACT_SITE 135 135 By similarity. FT CONFLICT 60 60 A -> S (in Ref. 1). FT CONFLICT 131 131 Missing (in Ref. 1). SQ SEQUENCE 169 AA; 19015 MW; CCA41A122A37202D CRC64; MICLVLTIFA NLFPAACTGA HERTFLAVKP DGVQRRLVGE IVRRFERKGF KLVALKLVQA SEELLREHYA ELRERPFYGR LVKYMASGPV VAMVWQGLDV VRTSRALIGA TNPADAPPGT IRGDFCIEVG KNLIHGSDSV ESARREIALW FRADELLCWE DSAGHWLYE // ID NDK6_HUMAN STANDARD; PRT; 186 AA. AC O75414; Q96E73; Q9BQ63;