O14976 (GAK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cyclin-G-associated kinase
EC=2.7.11.1

Gene names

Name:

GAK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1311 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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 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.

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	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA 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 protein serine/threonine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATP13A2	Q9NQ11	2	EBI-714707,EBI-6308763

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 1311

1310

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

2

1

N-acetylserine Ref.6

Modified residue

16

1

Phosphoserine Ref.4 Ref.6

Modified residue

456

1

Phosphoserine Ref.4

Modified residue

770

1

Phosphoserine Ref.4

Modified residue

826

1

Phosphoserine Ref.4 Ref.5 Ref.6 Ref.7

Modified residue

829

1

Phosphoserine Ref.4 Ref.5 Ref.6 Ref.7 Ref.9

Modified residue

834

1

Phosphoserine Ref.4 Ref.5 Ref.6

Modified residue

939

1

Phosphoserine Ref.6

Modified residue

1096

1

Phosphoserine Ref.4

Modified residue

1176

1

Phosphoserine Ref.6

Modified residue

1185

1

Phosphoserine Ref.6

Natural variations

Natural variant

144

1

S → L. Ref.10

VAR_040505

Natural variant

580

1

V → M. Ref.10
Corresponds to variant rs34255232 [ dbSNP | Ensembl ].

VAR_040506

Natural variant

787

1

D → Y. Ref.10
Corresponds to variant rs34585705 [ dbSNP | Ensembl ].

VAR_040507

Natural variant

877

1

Q → R. Ref.10

VAR_040508

Natural variant

962

1

G → D in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.10

VAR_040509

Natural variant

1051

1

T → M. Ref.10
Corresponds to variant rs35227944 [ dbSNP | Ensembl ].

VAR_040510

Natural variant

1120

1

Q → H. Ref.10
Corresponds to variant rs55801437 [ dbSNP | Ensembl ].

VAR_040511

Natural variant

1137

1

P → L. Ref.10
Corresponds to variant rs56169884 [ dbSNP | Ensembl ].

VAR_040512

Natural variant

1168

1

S → N. Ref.10
Corresponds to variant rs56326341 [ dbSNP | Ensembl ].

VAR_040513

Natural variant

1265

1

K → R. Ref.10
Corresponds to variant rs2306242 [ dbSNP | Ensembl ].

VAR_040514

Natural variant

1297

1

D → N. Ref.10
Corresponds to variant rs1134921 [ dbSNP | Ensembl ].

VAR_040515

Experimental info

Sequence conflict

1113

1

P → A in BAA22623. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1311

Helix Strand Turn

Details...

Beta strand

32 – 35

4

Beta strand

38 – 47

10

Beta strand

50 – 59

10

Turn

60 – 62

3

Beta strand

65 – 75

11

Helix

76 – 92

17

Beta strand

101 – 107

7

Turn

109 – 111

3

Beta strand

115 – 124

10

Beta strand

127 – 129

3

Helix

130 – 138

9

Helix

145 – 163

19

Beta strand

165 – 167

3

Helix

176 – 178

3

Beta strand

187 – 189

3

Helix

242 – 258

17

Helix

286 – 288

3

Helix

289 – 295

7

Helix

300 – 302

3

Helix

306 – 319

14

Helix

329 – 332

4

Sequences

	Sequence		Length	Mass (Da)
	O14976 [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] [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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"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, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE.
[7]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[8]	"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].
[9]	"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, MASS SPECTROMETRY.
[10]	"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] [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.

IPI

IPI00298949.

RefSeq

NP_005246.2. NM_005255.2.

UniGene

Hs.369607.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LL6	X-ray	2.10	A/B	12-347	[»]

ProteinModelPortal

O14976.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14976. 5 interactions.

MINT

MINT-5000432.

STRING

9606.ENSP00000314499.

PTM databases

PhosphoSite

O14976.

Proteomic databases

PaxDb

O14976.

PRIDE

O14976.

Protocols and materials databases

DNASU

2580.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000314167; ENSP00000314499; ENSG00000178950.

GeneID

2580.

KEGG

hsa:2580.

UCSC

uc003gbm.4. human.

Organism-specific databases

CTD

2580.

GeneCards

GC04M000832.

H-InvDB

HIX0004007.

HGNC

HGNC:4113. GAK.

HPA

HPA027405.
HPA027459.
HPA027463.

MIM

602052. gene.

neXtProt

NX_O14976.

PharmGKB

PA28528.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000034235.

HOVERGEN

HBG004322.

InParanoid

O14976.

KO

K08855.

OMA

ERLFTNI.

PhylomeDB

O14976.

Enzyme and pathway databases

Reactome

REACT_11123. Membrane Trafficking.

SignaLink

O14976.

Gene expression databases

ArrayExpress

O14976.

Bgee

O14976.

CleanEx

HS_GAK.

Genevestigator

O14976.

GermOnline

ENSG00000178950. Homo sapiens.

Family and domain databases

Gene3D

1.10.287.110. 1 hit.

InterPro

IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR001623. DnaJ_domain.
IPR011009. Kinase-like_dom.
IPR014019. Phosphatase_tensin-typ.
IPR000719. Prot_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR014020. Tensin_phosphatase_C2-dom.
[Graphical view]

Pfam

PF00226. DnaJ. 1 hit.
PF00069. Pkinase. 1 hit.
PF10409. PTEN_C2. 1 hit.
[Graphical view]

SMART

SM00271. DnaJ. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF46565. DnaJ_N. 1 hit.
SSF56112. Kinase_like. 1 hit.

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

BindingDB

O14976.

ChEMBL

CHEMBL4355.

ChiTaRS

GAK. human.

GenomeRNAi

2580.

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:	May 29, 2013
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.