RBCC

GAK [Confidence: low (only semi-automatic identification from reviews)]
Cyclin-G-associated kinase; 2.7.11.1

UniProt O14976
ID GAK_HUMAN Reviewed; 1311 AA.
AC O14976; Q9BVY6;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 29-AUG-2001, sequence version 2.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Cyclin-G-associated kinase;
DE EC=2.7.11.1;
GN Name=GAK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], 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] OF 981-1311.
RC TISSUE=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
RT project: 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
RT vesicles 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 MASS SPECTROMETRY.
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
RT the 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
RP SER-834, AND MASS SPECTROMETRY.
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 ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-16; SER-826; SER-829; SER-834; SER-939;
RP SER-1176 AND SER-1185, MASS SPECTROMETRY, AND CLEAVAGE OF INITIATOR
RP METHIONINE.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-826 AND SER-829, AND
RP MASS SPECTROMETRY.
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 [9]
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.,
RA Buerckstuemmer T., 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [11]
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
RP ASN-1297.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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
CC auxilin homolog that is involved in the uncoating of clathrin-
CC coated vesicles by Hsc70 in non-neuronal cells. Expression
CC oscillates slightly during the cell cycle, peaking at G1.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- INTERACTION:
CC Q9NQ11:ATP13A2; NbExp=2; IntAct=EBI-714707, EBI-6308763;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Golgi
CC apparatus, trans-Golgi network. Cell junction, focal adhesion
CC (Probable). Note=Localizes to the perinuclear area and to the
CC trans-Golgi network. Also seen on the plasma membrane, probably at
CC focal adhesions.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest in testis.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
CC protein kinase family.
CC -!- SIMILARITY: Contains 1 C2 tensin-type domain.
CC -!- SIMILARITY: Contains 1 J domain.
CC -!- SIMILARITY: Contains 1 phosphatase tensin-type domain.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
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DR EMBL; D88435; BAA22623.1; -; mRNA.
DR EMBL; BC000816; AAH00816.1; -; mRNA.
DR EMBL; BC008668; AAH08668.1; -; mRNA.
DR RefSeq; NP_005246.2; NM_005255.2.
DR UniGene; Hs.369607; -.
DR PDB; 3LL6; X-ray; 2.10 A; A/B=12-347.
DR PDB; 4C57; X-ray; 2.55 A; A/B=14-351.
DR PDB; 4C58; X-ray; 2.16 A; A=27-351.
DR PDB; 4C59; X-ray; 2.80 A; A=14-351.
DR PDBsum; 3LL6; -.
DR PDBsum; 4C57; -.
DR PDBsum; 4C58; -.
DR PDBsum; 4C59; -.
DR ProteinModelPortal; O14976; -.
DR SMR; O14976; 28-336, 400-746, 1139-1311.
DR IntAct; O14976; 5.
DR MINT; MINT-5000432; -.
DR STRING; 9606.ENSP00000314499; -.
DR BindingDB; O14976; -.
DR ChEMBL; CHEMBL4355; -.
DR GuidetoPHARMACOLOGY; 2027; -.
DR PhosphoSite; O14976; -.
DR PaxDb; O14976; -.
DR PRIDE; O14976; -.
DR DNASU; 2580; -.
DR Ensembl; ENST00000314167; ENSP00000314499; ENSG00000178950.
DR GeneID; 2580; -.
DR KEGG; hsa:2580; -.
DR UCSC; uc003gbm.4; human.
DR CTD; 2580; -.
DR GeneCards; GC04M000832; -.
DR H-InvDB; HIX0004007; -.
DR HGNC; HGNC:4113; GAK.
DR HPA; HPA027405; -.
DR HPA; HPA027459; -.
DR HPA; HPA027463; -.
DR MIM; 602052; gene.
DR neXtProt; NX_O14976; -.
DR PharmGKB; PA28528; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000034235; -.
DR HOVERGEN; HBG004322; -.
DR InParanoid; O14976; -.
DR KO; K08855; -.
DR OMA; YMCDMMA; -.
DR OrthoDB; EOG7WT40V; -.
DR PhylomeDB; O14976; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; O14976; -.
DR ChiTaRS; GAK; human.
DR GeneWiki; GAK_(protein); -.
DR GenomeRNAi; 2580; -.
DR NextBio; 10201; -.
DR PRO; PR:O14976; -.
DR ArrayExpress; O14976; -.
DR Bgee; O14976; -.
DR CleanEx; HS_GAK; -.
DR Genevestigator; O14976; -.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR Gene3D; 1.10.287.110; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR001623; DnaJ_domain.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR014019; Phosphatase_tensin-typ.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR014020; Tensin_phosphatase_C2-dom.
DR Pfam; PF00226; DnaJ; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF10409; PTEN_C2; 1.
DR SMART; SM00271; DnaJ; 1.
DR SUPFAM; SSF46565; SSF46565; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51182; C2_TENSIN; 1.
DR PROSITE; PS00636; DNAJ_1; FALSE_NEG.
DR PROSITE; PS50076; DNAJ_2; 1.
DR PROSITE; PS51181; PPASE_TENSIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; FALSE_NEG.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell junction;
KW Complete proteome; Cytoplasm; Golgi apparatus; Kinase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 1311 Cyclin-G-associated kinase.
FT /FTId=PRO_0000085958.
FT DOMAIN 40 314 Protein kinase.
FT DOMAIN 399 566 Phosphatase tensin-type.
FT DOMAIN 572 710 C2 tensin-type.
FT DOMAIN 1247 1311 J.
FT COMPBIAS 347 350 Poly-Pro.
FT ACT_SITE 173 173 Proton acceptor (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 16 16 Phosphoserine.
FT MOD_RES 456 456 Phosphoserine.
FT MOD_RES 770 770 Phosphoserine.
FT MOD_RES 826 826 Phosphoserine.
FT MOD_RES 829 829 Phosphoserine.
FT MOD_RES 834 834 Phosphoserine.
FT MOD_RES 939 939 Phosphoserine.
FT MOD_RES 1096 1096 Phosphoserine.
FT MOD_RES 1176 1176 Phosphoserine.
FT MOD_RES 1185 1185 Phosphoserine.
FT VARIANT 144 144 S -> L.
FT /FTId=VAR_040505.
FT VARIANT 580 580 V -> M (in dbSNP:rs34255232).
FT /FTId=VAR_040506.
FT VARIANT 787 787 D -> Y (in dbSNP:rs34585705).
FT /FTId=VAR_040507.
FT VARIANT 877 877 Q -> R (in dbSNP:rs149842313).
FT /FTId=VAR_040508.
FT VARIANT 962 962 G -> D (in a lung neuroendocrine
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_040509.
FT VARIANT 1051 1051 T -> M (in dbSNP:rs35227944).
FT /FTId=VAR_040510.
FT VARIANT 1120 1120 Q -> H (in dbSNP:rs55801437).
FT /FTId=VAR_040511.
FT VARIANT 1137 1137 P -> L (in dbSNP:rs56169884).
FT /FTId=VAR_040512.
FT VARIANT 1168 1168 S -> N (in dbSNP:rs56326341).
FT /FTId=VAR_040513.
FT VARIANT 1265 1265 K -> R (in dbSNP:rs2306242).
FT /FTId=VAR_040514.
FT VARIANT 1297 1297 D -> N (in dbSNP:rs1134921).
FT /FTId=VAR_040515.
FT CONFLICT 1113 1113 P -> A (in Ref. 1; BAA22623).
FT STRAND 32 35
FT STRAND 38 47
FT STRAND 50 59
FT TURN 60 62
FT STRAND 65 75
FT HELIX 76 92
FT STRAND 101 107
FT TURN 109 111
FT STRAND 115 124
FT STRAND 127 129
FT HELIX 130 138
FT HELIX 145 163
FT STRAND 165 167
FT HELIX 176 178
FT STRAND 187 189
FT HELIX 242 258
FT HELIX 286 288
FT HELIX 289 295
FT HELIX 300 302
FT HELIX 306 319
FT HELIX 329 332
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
//

MIM 602052
*RECORD*
*FIELD* NO
602052
*FIELD* TI
*602052 CYCLIN G-ASSOCIATED KINASE; GAK
*FIELD* TX

CLONING

In all eukaryotes, the cell cycle is governed by cyclin-dependent
read moreprotein kinases (CDKs), whose activities are regulated by cyclins and
CDK inhibitors in a diverse array of mechanisms that involve the control
of phosphorylation-dephosphorylation of ser/thr or tyr residues. Cyclins
are molecules that possess a consensus domain called the 'cyclin box.'
In mammalian cells, 9 cyclin species have been identified to this time,
and they are referred to as cyclins A (123835) through I. Cyclin G
(601578) is a direct transcriptional target of the p53 tumor suppressor
gene product (191170) and thus functions downstream of p53. Kimura et
al. (1997) reported the cloning of a cDNA encoding the human homolog of
GAK, an association partner of cyclin G and CDK5 (123831), which had
previously been cloned in the rat. They showed that the cDNA encodes a
protein of 1,311 amino acids containing all the unique motifs
characteristic of rat GAK. The expression profiles of GAK and cyclin G
during the synchronized HeLa cell cycle showed that GAK expression
oscillates slightly, peaking at the G1 phase, although histone H1 kinase
activity remained constant throughout the cell cycle. Northern blot
analysis showed that GAK is expressed ubiquitously, with the highest
level of expression being observed in the testis.

MAPPING

By fluorescence in situ hybridization, Kimura et al. (1997) assigned the
GAK gene to chromosome 4p16.

MOLECULAR GENETICS

For a discussion of a possible association between variation in the GAK
gene and susceptibility to the development of Parkinson disease, see
168600.

*FIELD* RF
1. Kimura, S. H.; Tsuruga, H.; Yabuta, N.; Endo, Y.; Nojima, H.:
Structure, expression, and chromosomal localization of human GAK. Genomics 44:
179-187, 1997.

*FIELD* CD
Victor A. McKusick: 10/14/1997

*FIELD* ED
wwang: 09/23/2010
ckniffin: 9/17/2010
alopez: 3/15/2010
mark: 10/14/1997

RBCC Red Blood Cell Collection

Full text data of GAK