Reviewed, UniProtKB/Swiss-Prot O14976 (GAK_HUMAN)

Names and origin

Protein names

Recommended name:
    Cyclin G-associated kinase
    EC=2.7.11.1

Gene names

Name:

GAK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1311 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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	Cytoplasm › perinuclear region. Golgi apparatus › trans-Golgi network. Cell junction › focal adhesion Probable. Note: Localizes to the perinuclear area and to the trans-Golgi network. Also seen on the plasma membrane, probably at focals adhesions.
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.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cell junction Cytoplasm Golgi apparatus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW heat shock protein binding Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1311	1311	Cyclin G-associated kinase		PRO_0000085958
Regions
	Domain	40 – 314	275	Protein kinase
	Domain	399 – 566	168	Phosphatase tensin-type
	Domain	572 – 710	139	C2 tensin-type
	Domain	1247 – 1311	65	J
	Compositional bias	347 – 350	4	Poly-Pro
Sites
	Active site	173	1	Proton acceptor By similarity
Amino acid modifications
	Modified residue	16	1	Phosphoserine Ref.4
	Modified residue	456	1	Phosphoserine Ref.4
	Modified residue	770	1	Phosphoserine Ref.4
	Modified residue	780	1	Phosphoserine Ref.4
	Modified residue	826	1	Phosphoserine Ref.4 Ref.5
	Modified residue	829	1	Phosphoserine Ref.4 Ref.5
	Modified residue	834	1	Phosphoserine Ref.4 Ref.5
	Modified residue	1096	1	Phosphoserine Ref.4
Natural variations
	Natural variant	144	1	S → L Ref.7		VAR_040505
	Natural variant	580	1	V → M Ref.7		VAR_040506
	Natural variant	787	1	D → Y Ref.7		VAR_040507
	Natural variant	877	1	Q → R Ref.7		VAR_040508
	Natural variant	962	1	G → D in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.7		VAR_040509
	Natural variant	1051	1	T → M Ref.7		VAR_040510
	Natural variant	1120	1	Q → H Ref.7		VAR_040511
	Natural variant	1137	1	P → L Ref.7		VAR_040512
	Natural variant	1168	1	S → N Ref.7		VAR_040513
	Natural variant	1265	1	K → R: dbSNP rs2306242. Ref.7		VAR_040514
	Natural variant	1297	1	D → N: dbSNP rs1134921. Ref.7		VAR_040515
Experimental info
	Sequence conflict	1113	1	P → A in BAA22623. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O14976-1 [UniParc]. Last modified August 29, 2001. Version 2. Checksum: 0ACE45DF57A5F981	FASTA	1,311	143,191
	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

References

	« Hide 'large scale' referencesShow '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: 9299234] [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: 15489334] [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: 10625686] [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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16; SER-456; SER-770; SER-780; SER-826; SER-829; SER-834 AND SER-1096, MASS SPECTROMETRY.
[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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-826; SER-829 AND SER-834, MASS SPECTROMETRY.
[6]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[7]	"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. , 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: 17344846] [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
EMBLGenBankDDBJ	D88435 mRNA. Translation: BAA22623.1. BC000816 mRNA. Translation: AAH00816.1. BC008668 mRNA. Translation: AAH08668.1.
IPI	IPI00298949.
RefSeq	NP_005246.2.
UniGene	Hs.369607
3D structure databases
HSSP	HSSP built from PDB template 1NZ6 based on UniProtKB Q27974.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14976. 13 interactions.
PTM databases
PhosphoSite	O14976.
Proteomic databases
PRIDE	O14976.
Genome annotation databases
Ensembl	ENSG00000178950. Homo sapiens. [Contig view]
GeneID	2580.
KEGG	hsa:2580.
Organism-specific databases
GeneCards	GC04M000832.
HGNC	HGNC:4113. GAK.
MIM	602052. gene.
PharmGKB	PA28528.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O14976.
HOVERGEN	O14976.
OMA	O14976. FTNIKDT.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	O14976.
Bgee	O14976.
CleanEx	HS_GAK.
GermOnline	ENSG00000178950. Homo sapiens.
Family and domain databases
InterPro	IPR001623. DnaJ_N. IPR018253. Heat_shock_DnaJ_CS. IPR014019. Phosphatase_tensin-typ. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR014020. Tensin_phosphatase_C2-dom. [Graphical view]
Pfam	PF00226. DnaJ. 1 hit. PF00069. Pkinase. 1 hit. PF10409. PTEN_C2. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00271. DnaJ. 1 hit. [Graphical view]
PROSITE	PS51182. C2_TENSIN. 1 hit. PS00636. DNAJ_1. False negative. PS50076. DNAJ_2. 1 hit. PS51181. PPASE_TENSIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	10201.
SOURCE	Search...

Entry information

Entry name

GAK_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)