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O14976 (GAK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-G-associated kinase

EC=2.7.11.1
Gene names
Name:GAK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1311 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1. Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subcellular location

Cytoplasmperinuclear region. Golgi apparatustrans-Golgi network. Cell junctionfocal adhesion Probable. Note: Localizes to the perinuclear area and to the trans-Golgi network. Also seen on the plasma membrane, probably at focal adhesions. Ref.3

Tissue specificity

Ubiquitous. Highest in testis.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Contains 1 C2 tensin-type domain.

Contains 1 J domain.

Contains 1 phosphatase tensin-type domain.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATP13A2Q9NQ112EBI-714707,EBI-6308763

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 13111310Cyclin-G-associated kinase
PRO_0000085958

Regions

Domain40 – 314275Protein kinase
Domain399 – 566168Phosphatase tensin-type
Domain572 – 710139C2 tensin-type
Domain1247 – 131165J
Compositional bias347 – 3504Poly-Pro

Sites

Active site1731Proton acceptor By similarity

Amino acid modifications

Modified residue21N-acetylserine Ref.6 Ref.7
Modified residue161Phosphoserine Ref.4 Ref.7
Modified residue4561Phosphoserine Ref.4
Modified residue7701Phosphoserine Ref.4
Modified residue8261Phosphoserine Ref.4 Ref.5 Ref.7 Ref.8
Modified residue8291Phosphoserine Ref.4 Ref.5 Ref.7 Ref.8 Ref.10
Modified residue8341Phosphoserine Ref.4 Ref.5 Ref.7
Modified residue9391Phosphoserine Ref.7
Modified residue10961Phosphoserine Ref.4
Modified residue11761Phosphoserine Ref.7
Modified residue11851Phosphoserine Ref.7

Natural variations

Natural variant1441S → L. Ref.12
VAR_040505
Natural variant5801V → M. Ref.12
Corresponds to variant rs34255232 [ dbSNP | Ensembl ].
VAR_040506
Natural variant7871D → Y. Ref.12
Corresponds to variant rs34585705 [ dbSNP | Ensembl ].
VAR_040507
Natural variant8771Q → R. Ref.12
Corresponds to variant rs149842313 [ dbSNP | Ensembl ].
VAR_040508
Natural variant9621G → D in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.12
VAR_040509
Natural variant10511T → M. Ref.12
Corresponds to variant rs35227944 [ dbSNP | Ensembl ].
VAR_040510
Natural variant11201Q → H. Ref.12
Corresponds to variant rs55801437 [ dbSNP | Ensembl ].
VAR_040511
Natural variant11371P → L. Ref.12
Corresponds to variant rs56169884 [ dbSNP | Ensembl ].
VAR_040512
Natural variant11681S → N. Ref.12
Corresponds to variant rs56326341 [ dbSNP | Ensembl ].
VAR_040513
Natural variant12651K → R. Ref.12
Corresponds to variant rs2306242 [ dbSNP | Ensembl ].
VAR_040514
Natural variant12971D → N. Ref.12
Corresponds to variant rs1134921 [ dbSNP | Ensembl ].
VAR_040515

Experimental info

Sequence conflict11131P → A in BAA22623. Ref.1

Secondary structure

.................................................... 1311
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O14976 [UniParc].

Last modified August 29, 2001. Version 2.
Checksum: 0ACE45DF57A5F981

FASTA1,311143,191
        10         20         30         40         50         60 
MSLLQSALDF LAGPGSLGGA SGRDQSDFVG QTVELGELRL RVRRVLAEGG FAFVYEAQDV 

        70         80         90        100        110        120 
GSGREYALKR LLSNEEEKNR AIIQEVCFMK KLSGHPNIVQ FCSAASIGKE ESDTGQAEFL 

       130        140        150        160        170        180 
LLTELCKGQL VEFLKKMESR GPLSCDTVLK IFYQTCRAVQ HMHRQKPPII HRDLKVENLL 

       190        200        210        220        230        240 
LSNQGTIKLC DFGSATTISH YPDYSWSAQR RALVEEEITR NTTPMYRTPE IIDLYSNFPI 

       250        260        270        280        290        300 
GEKQDIWALG CILYLLCFRQ HPFEDGAKLR IVNGKYSIPP HDTQYTVFHS LIRAMLQVNP 

       310        320        330        340        350        360 
EERLSIAEVV HQLQEIAAAR NVNPKSPITE LLEQNGGYGS ATLSRGPPPP VGPAGSGYSG 

       370        380        390        400        410        420 
GLALAEYDQP YGGFLDILRG GTERLFTNLK DTSSKVIQSV ANYAKGDLDI SYITSRIAVM 

       430        440        450        460        470        480 
SFPAEGVESA LKNNIEDVRL FLDSKHPGHY AVYNLSPRTY RPSRFHNRVS ECGWAARRAP 

       490        500        510        520        530        540 
HLHTLYNICR NMHAWLRQDH KNVCVVHCMD GRAASAVAVC SFLCFCRLFS TAEAAVYMFS 

       550        560        570        580        590        600 
MKRCPPGIWP SHKRYIEYMC DMVAEEPITP HSKPILVRAV VMTPVPLFSK QRSGCRPFCE 

       610        620        630        640        650        660 
VYVGDERVAS TSQEYDKMRD FKIEDGKAVI PLGVTVQGDV LIVIYHARST LGGRLQAKMA 

       670        680        690        700        710        720 
SMKMFQIQFH TGFVPRNATT VKFAKYDLDA CDIQEKYPDL FQVNLEVEVE PRDRPSREAP 

       730        740        750        760        770        780 
PWENSSMRGL NPKILFSSRE EQQDILSKFG KPELPRQPGS TAQYDAGAGS PEAEPTDSDS 

       790        800        810        820        830        840 
PPSSSADASR FLHTLDWQEE KEAETGAENA SSKESESALM EDRDESEVSD EGGSPISSEG 

       850        860        870        880        890        900 
QEPRADPEPP GLAAGLVQQD LVFEVETPAV LPEPVPQEDG VDLLGLHSEV GAGPAVPPQA 

       910        920        930        940        950        960 
CKAPSSNTDL LSCLLGPPEA ASQGPPEDLL SEDPLLLASP APPLSVQSTP RGGPPAAADP 

       970        980        990       1000       1010       1020 
FGPLLPSSGN NSQPCSNPDL FGEFLNSDSV TVPPSFPSAH SAPPPSCSAD FLHLGDLPGE 

      1030       1040       1050       1060       1070       1080 
PSKMTASSSN PDLLGGWAAW TETAASAVAP TPATEGPLFS PGGQPAPCGS QASWTKSQNP 

      1090       1100       1110       1120       1130       1140 
DPFADLGDLS SGLQGSPAGF PPGGFIPKTA TTPKGSSSWQ TSRPPAQGAS WPPQAKPPPK 

      1150       1160       1170       1180       1190       1200 
ACTQPRPNYA SNFSVIGARE ERGVRAPSFA QKPKVSENDF EDLLSNQGFS SRSDKKGPKT 

      1210       1220       1230       1240       1250       1260 
IAEMRKQDLA KDTDPLKLKL LDWIEGKERN IRALLSTLHT VLWDGESRWT PVGMADLVAP 

      1270       1280       1290       1300       1310 
EQVKKHYRRA VLAVHPDKAA GQPYEQHAKM IFMELNDAWS EFENQGSRPL F 

« Hide

References

« Hide 'large scale' references
[1]"Structure, expression, and chromosomal localization of human GAK."
Kimura S.H., Tsuruga H., Yabuta N., Endo Y., Nojima H.
Genomics 44:179-187(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Tissue: Fibroblast.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 981-1311.
Tissue: Placenta.
[3]"Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells."
Greener T., Zhao X., Nojima H., Eisenberg E., Greene L.E.
J. Biol. Chem. 275:1365-1370(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[4]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-456; SER-770; SER-826; SER-829; SER-834 AND SER-1096, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-826; SER-829 AND SER-834, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-826; SER-829; SER-834; SER-939; SER-1176 AND SER-1185, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[8]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-826 AND SER-829, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Crystal structure of the human cyclin G associated kinase (GAK)."
Midwest center for structural genomics (MCSG)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 12-347.
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-144; MET-580; TYR-787; ARG-877; ASP-962; MET-1051; HIS-1120; LEU-1137; ASN-1168; ARG-1265 AND ASN-1297.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D88435 mRNA. Translation: BAA22623.1.
BC000816 mRNA. Translation: AAH00816.1.
BC008668 mRNA. Translation: AAH08668.1.
RefSeqNP_005246.2. NM_005255.2.
UniGeneHs.369607.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4C57X-ray2.55A/B14-351[»]
4C58X-ray2.16A27-351[»]
4C59X-ray2.80A14-351[»]
4O38X-ray2.10A/B12-347[»]
ProteinModelPortalO14976.
SMRO14976. Positions 25-334, 400-746, 1139-1311.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108853. 10 interactions.
IntActO14976. 5 interactions.
MINTMINT-5000432.
STRING9606.ENSP00000314499.

Chemistry

BindingDBO14976.
ChEMBLCHEMBL4355.
GuidetoPHARMACOLOGY2027.

PTM databases

PhosphoSiteO14976.

Proteomic databases

PaxDbO14976.
PRIDEO14976.

Protocols and materials databases

DNASU2580.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314167; ENSP00000314499; ENSG00000178950.
GeneID2580.
KEGGhsa:2580.
UCSCuc003gbm.4. human.

Organism-specific databases

CTD2580.
GeneCardsGC04M000832.
H-InvDBHIX0004007.
HGNCHGNC:4113. GAK.
HPAHPA027405.
HPA027459.
HPA027463.
MIM602052. gene.
neXtProtNX_O14976.
PharmGKBPA28528.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000034235.
HOVERGENHBG004322.
InParanoidO14976.
KOK08855.
OMAYMCDMMA.
OrthoDBEOG7WT40V.
PhylomeDBO14976.
TreeFamTF105165.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.
SignaLinkO14976.

Gene expression databases

ArrayExpressO14976.
BgeeO14976.
CleanExHS_GAK.
GenevestigatorO14976.

Family and domain databases

Gene3D1.10.287.110. 1 hit.
InterProIPR000008. C2_dom.
IPR001623. DnaJ_domain.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR014020. Tensin_C2-dom.
[Graphical view]
PfamPF00226. DnaJ. 1 hit.
PF00069. Pkinase. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]
SMARTSM00271. DnaJ. 1 hit.
[Graphical view]
SUPFAMSSF46565. SSF46565. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51182. C2_TENSIN. 1 hit.
PS50076. DNAJ_2. 1 hit.
PS51181. PPASE_TENSIN. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGAK. human.
GeneWikiGAK_(protein).
GenomeRNAi2580.
NextBio10201.
PROO14976.
SOURCESearch...

Entry information

Entry nameGAK_HUMAN
AccessionPrimary (citable) accession number: O14976
Secondary accession number(s): Q9BVY6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: August 29, 2001
Last modified: April 16, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM