ID   GAK_HUMAN               Reviewed;        1311 AA.
AC   O14976; Q5U4P5; Q9BVY6;
DT   29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   29-AUG-2001, sequence version 2.
DT   27-MAR-2024, entry version 212.
DE   RecName: Full=Cyclin-G-associated kinase {ECO:0000305};
DE            EC=2.7.11.1;
GN   Name=GAK {ECO:0000312|HGNC:HGNC:4113};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
RC   TISSUE=Fibroblast;
RX   PubMed=9299234; DOI=10.1006/geno.1997.4873;
RA   Kimura S.H., Tsuruga H., Yabuta N., Endo Y., Nojima H.;
RT   "Structure, expression, and chromosomal localization of human GAK.";
RL   Genomics 44:179-187(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 981-1311 (ISOFORM 1).
RC   TISSUE=Ovary, and Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=10625686; DOI=10.1074/jbc.275.2.1365;
RA   Greener T., Zhao X., Nojima H., Eisenberg E., Greene L.E.;
RT   "Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles
RT   from non-neuronal cells.";
RL   J. Biol. Chem. 275:1365-1370(2000).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-456; SER-770;
RP   SER-826; SER-829; SER-834 AND SER-1096, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-826; SER-829 AND SER-834, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [6]
RP   FUNCTION.
RX   PubMed=18489706; DOI=10.1111/j.1600-0854.2008.00764.x;
RA   Hirst J., Sahlender D.A., Li S., Lubben N.B., Borner G.H., Robinson M.S.;
RT   "Auxilin depletion causes self-assembly of clathrin into membraneless cages
RT   in vivo.";
RL   Traffic 9:1354-1371(2008).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP   ANALYSIS] AT SER-16; SER-826; SER-829; SER-834; SER-939; SER-1176 AND
RP   SER-1185, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-826 AND SER-829, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-776; THR-794; SER-826 AND
RP   SER-829, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [14]
RP   SUBCELLULAR LOCATION.
RX   PubMed=31962345; DOI=10.1083/jcb.201908142;
RA   He K., Song E., Upadhyayula S., Dang S., Gaudin R., Skillern W., Bu K.,
RA   Capraro B.R., Rapoport I., Kusters I., Ma M., Kirchhausen T.;
RT   "Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic.";
RL   J. Cell Biol. 219:0-0(2020).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 12-347.
RG   Midwest center for structural genomics (MCSG);
RT   "Crystal structure of the human cyclin G associated kinase (GAK).";
RL   Submitted (JUL-2011) to the PDB data bank.
RN   [16]
RP   VARIANTS [LARGE SCALE ANALYSIS] LEU-144; MET-580; TYR-787; ARG-877;
RP   ASP-962; MET-1051; HIS-1120; LEU-1137; ASN-1168; ARG-1265 AND ASN-1297.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: Associates with cyclin G and CDK5. Seems to act as an auxilin
CC       homolog that is involved in the uncoating of clathrin-coated vesicles
CC       by Hsc70 in non-neuronal cells. Expression oscillates slightly during
CC       the cell cycle, peaking at G1 (PubMed:10625686). May play a role in
CC       clathrin-mediated endocytosis and intracellular trafficking, and in the
CC       dynamics of clathrin assembly/disassembly (PubMed:18489706).
CC       {ECO:0000269|PubMed:10625686, ECO:0000269|PubMed:18489706}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1;
CC   -!- INTERACTION:
CC       O14976; Q9NQ11: ATP13A2; NbExp=2; IntAct=EBI-714707, EBI-6308763;
CC       O14976; P11142: HSPA8; NbExp=7; IntAct=EBI-714707, EBI-351896;
CC       O14976; Q5S007: LRRK2; NbExp=11; IntAct=EBI-714707, EBI-5323863;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC       {ECO:0000269|PubMed:10625686}. Golgi apparatus, trans-Golgi network
CC       {ECO:0000269|PubMed:10625686}. Cell junction, focal adhesion
CC       {ECO:0000305|PubMed:10625686}. Cytoplasmic vesicle, clathrin-coated
CC       vesicle {ECO:0000269|PubMed:31962345}. Note=Localizes to the
CC       perinuclear area and to the trans-Golgi network. Also seen on the
CC       plasma membrane, probably at focal adhesions. Recruitment to clathrin-
CC       coated vesicles depends on temporal variations in phosphoinositide
CC       composition of clathrin-coated vesicles (PubMed:31962345).
CC       {ECO:0000269|PubMed:31962345}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O14976-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O14976-2; Sequence=VSP_054479;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Highest in testis.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR   EMBL; D88435; BAA22623.1; -; mRNA.
DR   EMBL; BC000816; AAH00816.1; -; mRNA.
DR   EMBL; BC008668; AAH08668.1; -; mRNA.
DR   EMBL; BC085005; AAH85005.1; -; mRNA.
DR   CCDS; CCDS3340.1; -. [O14976-1]
DR   CCDS; CCDS82902.1; -. [O14976-2]
DR   RefSeq; NP_001305063.1; NM_001318134.1. [O14976-2]
DR   RefSeq; NP_005246.2; NM_005255.3. [O14976-1]
DR   PDB; 4C57; X-ray; 2.55 A; A/B=14-351.
DR   PDB; 4C58; X-ray; 2.16 A; A=14-351.
DR   PDB; 4C59; X-ray; 2.80 A; A=14-351.
DR   PDB; 4O38; X-ray; 2.10 A; A/B=12-347.
DR   PDB; 4Y8D; X-ray; 2.10 A; A/B=14-351.
DR   PDB; 5Y7Z; X-ray; 2.80 A; A/B=25-335.
DR   PDB; 5Y80; X-ray; 2.50 A; A=25-335.
DR   PDBsum; 4C57; -.
DR   PDBsum; 4C58; -.
DR   PDBsum; 4C59; -.
DR   PDBsum; 4O38; -.
DR   PDBsum; 4Y8D; -.
DR   PDBsum; 5Y7Z; -.
DR   PDBsum; 5Y80; -.
DR   AlphaFoldDB; O14976; -.
DR   SMR; O14976; -.
DR   BioGRID; 108853; 200.
DR   IntAct; O14976; 103.
DR   MINT; O14976; -.
DR   STRING; 9606.ENSP00000314499; -.
DR   BindingDB; O14976; -.
DR   ChEMBL; CHEMBL4355; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; O14976; -.
DR   GuidetoPHARMACOLOGY; 2027; -.
DR   DEPOD; GAK; -.
DR   GlyCosmos; O14976; 1 site, 1 glycan.
DR   GlyGen; O14976; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O14976; -.
DR   PhosphoSitePlus; O14976; -.
DR   SwissPalm; O14976; -.
DR   BioMuta; GAK; -.
DR   CPTAC; CPTAC-3085; -.
DR   CPTAC; CPTAC-3086; -.
DR   EPD; O14976; -.
DR   jPOST; O14976; -.
DR   MassIVE; O14976; -.
DR   MaxQB; O14976; -.
DR   PaxDb; 9606-ENSP00000314499; -.
DR   PeptideAtlas; O14976; -.
DR   ProteomicsDB; 48350; -. [O14976-1]
DR   Pumba; O14976; -.
DR   ABCD; O14976; 2 sequenced antibodies.
DR   Antibodypedia; 22165; 363 antibodies from 34 providers.
DR   DNASU; 2580; -.
DR   Ensembl; ENST00000314167.9; ENSP00000314499.4; ENSG00000178950.18. [O14976-1]
DR   Ensembl; ENST00000511163.5; ENSP00000421361.1; ENSG00000178950.18. [O14976-2]
DR   GeneID; 2580; -.
DR   KEGG; hsa:2580; -.
DR   MANE-Select; ENST00000314167.9; ENSP00000314499.4; NM_005255.4; NP_005246.2.
DR   UCSC; uc003gbm.6; human. [O14976-1]
DR   AGR; HGNC:4113; -.
DR   CTD; 2580; -.
DR   DisGeNET; 2580; -.
DR   GeneCards; GAK; -.
DR   HGNC; HGNC:4113; GAK.
DR   HPA; ENSG00000178950; Low tissue specificity.
DR   MIM; 602052; gene.
DR   neXtProt; NX_O14976; -.
DR   OpenTargets; ENSG00000178950; -.
DR   PharmGKB; PA28528; -.
DR   VEuPathDB; HostDB:ENSG00000178950; -.
DR   eggNOG; KOG0431; Eukaryota.
DR   eggNOG; KOG1989; Eukaryota.
DR   eggNOG; KOG2283; Eukaryota.
DR   GeneTree; ENSGT00940000159527; -.
DR   HOGENOM; CLU_007537_0_0_1; -.
DR   InParanoid; O14976; -.
DR   OMA; HYKNTNL; -.
DR   OrthoDB; 103262at2759; -.
DR   PhylomeDB; O14976; -.
DR   TreeFam; TF105165; -.
DR   PathwayCommons; O14976; -.
DR   Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR   Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR   SignaLink; O14976; -.
DR   SIGNOR; O14976; -.
DR   BioGRID-ORCS; 2580; 454 hits in 1196 CRISPR screens.
DR   ChiTaRS; GAK; human.
DR   GeneWiki; GAK_(protein); -.
DR   GenomeRNAi; 2580; -.
DR   Pharos; O14976; Tchem.
DR   PRO; PR:O14976; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; O14976; Protein.
DR   Bgee; ENSG00000178950; Expressed in pancreatic ductal cell and 206 other cell types or tissues.
DR   ExpressionAtlas; O14976; baseline and differential.
DR   GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0098793; C:presynapse; IEA:GOC.
DR   GO; GO:0031982; C:vesicle; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR   GO; GO:0030332; F:cyclin binding; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc.
DR   GO; GO:0051087; F:protein-folding chaperone binding; TAS:BHF-UCL.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; TAS:BHF-UCL.
DR   GO; GO:0048268; P:clathrin coat assembly; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0072318; P:clathrin coat disassembly; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0072583; P:clathrin-dependent endocytosis; IMP:UniProtKB.
DR   GO; GO:0007029; P:endoplasmic reticulum organization; ISS:ParkinsonsUK-UCL.
DR   GO; GO:0007030; P:Golgi organization; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0090160; P:Golgi to lysosome transport; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0046907; P:intracellular transport; IMP:UniProtKB.
DR   GO; GO:0010977; P:negative regulation of neuron projection development; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0034067; P:protein localization to Golgi apparatus; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0072659; P:protein localization to plasma membrane; IMP:ParkinsonsUK-UCL.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IMP:ParkinsonsUK-UCL.
DR   GO; GO:1905443; P:regulation of clathrin coat assembly; IMP:UniProtKB.
DR   GO; GO:0016191; P:synaptic vesicle uncoating; ISS:BHF-UCL.
DR   CDD; cd06257; DnaJ; 1.
DR   CDD; cd14564; PTP_GAK; 1.
DR   CDD; cd14036; STKc_GAK; 1.
DR   Gene3D; 2.60.40.1110; -; 1.
DR   Gene3D; 1.10.287.110; DnaJ domain; 1.
DR   Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR001623; DnaJ_domain.
DR   InterPro; IPR036869; J_dom_sf.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   InterPro; IPR014020; Tensin_C2-dom.
DR   InterPro; IPR029023; Tensin_phosphatase.
DR   PANTHER; PTHR23172; AUXILIN/CYCLIN G-ASSOCIATED KINASE-RELATED; 1.
DR   PANTHER; PTHR23172:SF34; CYCLIN-G-ASSOCIATED KINASE; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   Pfam; PF10409; PTEN_C2; 1.
DR   SMART; SM00271; DnaJ; 1.
DR   SMART; SM01326; PTEN_C2; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF46565; Chaperone J-domain; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51182; C2_TENSIN; 1.
DR   PROSITE; PS50076; DNAJ_2; 1.
DR   PROSITE; PS51181; PPASE_TENSIN; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   Genevisible; O14976; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW   Cell junction; Cytoplasm; Cytoplasmic vesicle; Golgi apparatus; Kinase;
KW   Methylation; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:19369195,
FT                   ECO:0007744|PubMed:19413330"
FT   CHAIN           2..1311
FT                   /note="Cyclin-G-associated kinase"
FT                   /id="PRO_0000085958"
FT   DOMAIN          40..314
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          399..566
FT                   /note="Phosphatase tensin-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT   DOMAIN          572..710
FT                   /note="C2 tensin-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00589"
FT   DOMAIN          1247..1311
FT                   /note="J"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00286"
FT   REGION          709..729
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          749..788
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          801..860
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          913..1035
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1047..1150
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        801..822
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        965..996
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1066..1080
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1110..1128
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1130..1144
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        173
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:19369195,
FT                   ECO:0007744|PubMed:19413330"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P97874"
FT   MOD_RES         16
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:19369195"
FT   MOD_RES         456
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976"
FT   MOD_RES         770
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976"
FT   MOD_RES         776
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         783
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         794
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         811
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P97874"
FT   MOD_RES         826
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT   MOD_RES         829
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         834
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT   MOD_RES         939
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195"
FT   MOD_RES         1096
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976"
FT   MOD_RES         1123
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q99KY4"
FT   MOD_RES         1176
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195"
FT   MOD_RES         1185
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19369195"
FT   VAR_SEQ         49..127
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_054479"
FT   VARIANT         144
FT                   /note="S -> L (in dbSNP:rs768962219)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040505"
FT   VARIANT         580
FT                   /note="V -> M (in dbSNP:rs34255232)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040506"
FT   VARIANT         787
FT                   /note="D -> Y (in dbSNP:rs34585705)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040507"
FT   VARIANT         877
FT                   /note="Q -> R (in dbSNP:rs149842313)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040508"
FT   VARIANT         962
FT                   /note="G -> D (in a lung neuroendocrine carcinoma sample;
FT                   somatic mutation; dbSNP:rs773153935)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040509"
FT   VARIANT         1051
FT                   /note="T -> M (in dbSNP:rs35227944)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040510"
FT   VARIANT         1120
FT                   /note="Q -> H (in dbSNP:rs55801437)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040511"
FT   VARIANT         1137
FT                   /note="P -> L (in dbSNP:rs56169884)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040512"
FT   VARIANT         1168
FT                   /note="S -> N (in dbSNP:rs56326341)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040513"
FT   VARIANT         1265
FT                   /note="K -> R (in dbSNP:rs2306242)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040514"
FT   VARIANT         1297
FT                   /note="D -> N (in dbSNP:rs1134921)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040515"
FT   CONFLICT        607
FT                   /note="R -> C (in Ref. 2; AAH85005)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1113
FT                   /note="P -> A (in Ref. 1; BAA22623)"
FT                   /evidence="ECO:0000305"
FT   TURN            27..30
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          32..35
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          38..47
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          50..59
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   TURN            60..62
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          65..75
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           76..92
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          101..107
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   TURN            109..111
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          115..124
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          127..129
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           130..138
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           145..163
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          165..167
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           176..178
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   STRAND          179..181
FT                   /evidence="ECO:0007829|PDB:4Y8D"
FT   STRAND          187..189
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           208..219
FT                   /evidence="ECO:0007829|PDB:5Y80"
FT   HELIX           224..226
FT                   /evidence="ECO:0007829|PDB:5Y80"
FT   HELIX           229..232
FT                   /evidence="ECO:0007829|PDB:5Y80"
FT   HELIX           242..258
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   TURN            262..265
FT                   /evidence="ECO:0007829|PDB:5Y80"
FT   HELIX           268..272
FT                   /evidence="ECO:0007829|PDB:5Y80"
FT   HELIX           286..288
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           289..295
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           300..302
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           306..319
FT                   /evidence="ECO:0007829|PDB:4O38"
FT   HELIX           329..332
FT                   /evidence="ECO:0007829|PDB:4O38"
SQ   SEQUENCE   1311 AA;  143191 MW;  0ACE45DF57A5F981 CRC64;
     MSLLQSALDF LAGPGSLGGA SGRDQSDFVG QTVELGELRL RVRRVLAEGG FAFVYEAQDV
     GSGREYALKR LLSNEEEKNR AIIQEVCFMK KLSGHPNIVQ FCSAASIGKE ESDTGQAEFL
     LLTELCKGQL VEFLKKMESR GPLSCDTVLK IFYQTCRAVQ HMHRQKPPII HRDLKVENLL
     LSNQGTIKLC DFGSATTISH YPDYSWSAQR RALVEEEITR NTTPMYRTPE IIDLYSNFPI
     GEKQDIWALG CILYLLCFRQ HPFEDGAKLR IVNGKYSIPP HDTQYTVFHS LIRAMLQVNP
     EERLSIAEVV HQLQEIAAAR NVNPKSPITE LLEQNGGYGS ATLSRGPPPP VGPAGSGYSG
     GLALAEYDQP YGGFLDILRG GTERLFTNLK DTSSKVIQSV ANYAKGDLDI SYITSRIAVM
     SFPAEGVESA LKNNIEDVRL FLDSKHPGHY AVYNLSPRTY RPSRFHNRVS ECGWAARRAP
     HLHTLYNICR NMHAWLRQDH KNVCVVHCMD GRAASAVAVC SFLCFCRLFS TAEAAVYMFS
     MKRCPPGIWP SHKRYIEYMC DMVAEEPITP HSKPILVRAV VMTPVPLFSK QRSGCRPFCE
     VYVGDERVAS TSQEYDKMRD FKIEDGKAVI PLGVTVQGDV LIVIYHARST LGGRLQAKMA
     SMKMFQIQFH TGFVPRNATT VKFAKYDLDA CDIQEKYPDL FQVNLEVEVE PRDRPSREAP
     PWENSSMRGL NPKILFSSRE EQQDILSKFG KPELPRQPGS TAQYDAGAGS PEAEPTDSDS
     PPSSSADASR FLHTLDWQEE KEAETGAENA SSKESESALM EDRDESEVSD EGGSPISSEG
     QEPRADPEPP GLAAGLVQQD LVFEVETPAV LPEPVPQEDG VDLLGLHSEV GAGPAVPPQA
     CKAPSSNTDL LSCLLGPPEA ASQGPPEDLL SEDPLLLASP APPLSVQSTP RGGPPAAADP
     FGPLLPSSGN NSQPCSNPDL FGEFLNSDSV TVPPSFPSAH SAPPPSCSAD FLHLGDLPGE
     PSKMTASSSN PDLLGGWAAW TETAASAVAP TPATEGPLFS PGGQPAPCGS QASWTKSQNP
     DPFADLGDLS SGLQGSPAGF PPGGFIPKTA TTPKGSSSWQ TSRPPAQGAS WPPQAKPPPK
     ACTQPRPNYA SNFSVIGARE ERGVRAPSFA QKPKVSENDF EDLLSNQGFS SRSDKKGPKT
     IAEMRKQDLA KDTDPLKLKL LDWIEGKERN IRALLSTLHT VLWDGESRWT PVGMADLVAP
     EQVKKHYRRA VLAVHPDKAA GQPYEQHAKM IFMELNDAWS EFENQGSRPL F
//