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., McKe