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Protein

Cyclin-G-associated kinase

Gene

GAK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 G1.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei173Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chaperone binding Source: BHF-UCL
  • cyclin binding Source: ParkinsonsUK-UCL
  • protein serine/threonine kinase activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-432722 Golgi Associated Vesicle Biogenesis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiO14976

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-G-associated kinase (EC:2.7.11.1)
Gene namesi
Name:GAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000178950.16
HGNCiHGNC:4113 GAK
MIMi602052 gene
neXtProtiNX_O14976

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Golgi apparatus

Pathology & Biotechi

Organism-specific databases

DisGeNETi2580
OpenTargetsiENSG00000178950
PharmGKBiPA28528

Chemistry databases

ChEMBLiCHEMBL4355
GuidetoPHARMACOLOGYi2027

Polymorphism and mutation databases

BioMutaiGAK

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000859582 – 1311Cyclin-G-associated kinaseAdd BLAST1310

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei2PhosphoserineBy similarity1
Modified residuei16PhosphoserineCombined sources1
Modified residuei456PhosphoserineCombined sources1
Modified residuei770PhosphoserineCombined sources1
Modified residuei776PhosphothreonineCombined sources1
Modified residuei783PhosphoserineCombined sources1
Modified residuei794PhosphothreonineCombined sources1
Modified residuei811PhosphoserineBy similarity1
Modified residuei826PhosphoserineCombined sources1
Modified residuei829PhosphoserineCombined sources1
Modified residuei834PhosphoserineCombined sources1
Modified residuei939PhosphoserineCombined sources1
Modified residuei1096PhosphoserineCombined sources1
Modified residuei1123Omega-N-methylarginineBy similarity1
Modified residuei1176PhosphoserineCombined sources1
Modified residuei1185PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiO14976
MaxQBiO14976
PaxDbiO14976
PeptideAtlasiO14976
PRIDEiO14976
ProteomicsDBi48350

PTM databases

iPTMnetiO14976
PhosphoSitePlusiO14976

Expressioni

Tissue specificityi

Ubiquitous. Highest in testis.

Gene expression databases

BgeeiENSG00000178950 Expressed in 230 organ(s), highest expression level in endothelial cell
CleanExiHS_GAK
ExpressionAtlasiO14976 baseline and differential
GenevisibleiO14976 HS

Organism-specific databases

HPAiHPA027405
HPA027459
HPA027463

Interactioni

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108853, 97 interactors
IntActiO14976, 87 interactors
MINTiO14976
STRINGi9606.ENSP00000314499

Chemistry databases

BindingDBiO14976

Structurei

Secondary structure

11311
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14976
SMRiO14976
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 314Protein kinasePROSITE-ProRule annotationAdd BLAST275
Domaini399 – 566Phosphatase tensin-typePROSITE-ProRule annotationAdd BLAST168
Domaini572 – 710C2 tensin-typePROSITE-ProRule annotationAdd BLAST139
Domaini1247 – 1311JPROSITE-ProRule annotationAdd BLAST65

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi347 – 350Poly-Pro4

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0431 Eukaryota
KOG1989 Eukaryota
KOG2283 Eukaryota
ENOG410Y515 LUCA
GeneTreeiENSGT00760000119113
HOGENOMiHOG000034235
HOVERGENiHBG004322
InParanoidiO14976
KOiK08855
OMAiRPSRFHN
OrthoDBiEOG091G06HJ
PhylomeDBiO14976
TreeFamiTF105165

Family and domain databases

CDDicd06257 DnaJ, 1 hit
Gene3Di1.10.287.110, 1 hit
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR001623 DnaJ_domain
IPR036869 J_dom_sf
IPR011009 Kinase-like_dom_sf
IPR029021 Prot-tyrosine_phosphatase-like
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR014020 Tensin_C2-dom
IPR029023 Tensin_phosphatase
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF10409 PTEN_C2, 1 hit
SMARTiView protein in SMART
SM00271 DnaJ, 1 hit
SM01326 PTEN_C2, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF46565 SSF46565, 1 hit
SSF52799 SSF52799, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51182 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

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O14976-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSLLQSALDF LAGPGSLGGA SGRDQSDFVG QTVELGELRL RVRRVLAEGG
60 70 80 90 100
FAFVYEAQDV GSGREYALKR LLSNEEEKNR AIIQEVCFMK KLSGHPNIVQ
110 120 130 140 150
FCSAASIGKE ESDTGQAEFL LLTELCKGQL VEFLKKMESR GPLSCDTVLK
160 170 180 190 200
IFYQTCRAVQ HMHRQKPPII HRDLKVENLL LSNQGTIKLC DFGSATTISH
210 220 230 240 250
YPDYSWSAQR RALVEEEITR NTTPMYRTPE IIDLYSNFPI GEKQDIWALG
260 270 280 290 300
CILYLLCFRQ HPFEDGAKLR IVNGKYSIPP HDTQYTVFHS LIRAMLQVNP
310 320 330 340 350
EERLSIAEVV HQLQEIAAAR NVNPKSPITE LLEQNGGYGS ATLSRGPPPP
360 370 380 390 400
VGPAGSGYSG GLALAEYDQP YGGFLDILRG GTERLFTNLK DTSSKVIQSV
410 420 430 440 450
ANYAKGDLDI SYITSRIAVM SFPAEGVESA LKNNIEDVRL FLDSKHPGHY
460 470 480 490 500
AVYNLSPRTY RPSRFHNRVS ECGWAARRAP HLHTLYNICR NMHAWLRQDH
510 520 530 540 550
KNVCVVHCMD GRAASAVAVC SFLCFCRLFS TAEAAVYMFS MKRCPPGIWP
560 570 580 590 600
SHKRYIEYMC DMVAEEPITP HSKPILVRAV VMTPVPLFSK QRSGCRPFCE
610 620 630 640 650
VYVGDERVAS TSQEYDKMRD FKIEDGKAVI PLGVTVQGDV LIVIYHARST
660 670 680 690 700
LGGRLQAKMA SMKMFQIQFH TGFVPRNATT VKFAKYDLDA CDIQEKYPDL
710 720 730 740 750
FQVNLEVEVE PRDRPSREAP PWENSSMRGL NPKILFSSRE EQQDILSKFG
760 770 780 790 800
KPELPRQPGS TAQYDAGAGS PEAEPTDSDS PPSSSADASR FLHTLDWQEE
810 820 830 840 850
KEAETGAENA SSKESESALM EDRDESEVSD EGGSPISSEG QEPRADPEPP
860 870 880 890 900
GLAAGLVQQD LVFEVETPAV LPEPVPQEDG VDLLGLHSEV GAGPAVPPQA
910 920 930 940 950
CKAPSSNTDL LSCLLGPPEA ASQGPPEDLL SEDPLLLASP APPLSVQSTP
960 970 980 990 1000
RGGPPAAADP FGPLLPSSGN NSQPCSNPDL FGEFLNSDSV TVPPSFPSAH
1010 1020 1030 1040 1050
SAPPPSCSAD FLHLGDLPGE PSKMTASSSN PDLLGGWAAW TETAASAVAP
1060 1070 1080 1090 1100
TPATEGPLFS PGGQPAPCGS QASWTKSQNP DPFADLGDLS SGLQGSPAGF
1110 1120 1130 1140 1150
PPGGFIPKTA TTPKGSSSWQ TSRPPAQGAS WPPQAKPPPK ACTQPRPNYA
1160 1170 1180 1190 1200
SNFSVIGARE ERGVRAPSFA QKPKVSENDF EDLLSNQGFS SRSDKKGPKT
1210 1220 1230 1240 1250
IAEMRKQDLA KDTDPLKLKL LDWIEGKERN IRALLSTLHT VLWDGESRWT
1260 1270 1280 1290 1300
PVGMADLVAP EQVKKHYRRA VLAVHPDKAA GQPYEQHAKM IFMELNDAWS
1310
EFENQGSRPL F
Length:1,311
Mass (Da):143,191
Last modified:August 29, 2001 - v2
Checksum:i0ACE45DF57A5F981
GO
Isoform 2 (identifier: O14976-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     49-127: Missing.

Note: No experimental confirmation available.
Show »
Length:1,232
Mass (Da):134,464
Checksum:i483EE5F6B8416FDB
GO

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RAW3D6RAW3_HUMAN
Cyclin-G-associated kinase
GAK
138Annotation score:
D6RC24D6RC24_HUMAN
Cyclin-G-associated kinase
GAK
70Annotation score:
D6RE78D6RE78_HUMAN
Cyclin G associated kinase, isoform...
GAK hCG_1982003
118Annotation score:
H0Y8H5H0Y8H5_HUMAN
Cyclin-G-associated kinase
GAK
467Annotation score:
A0A087X1U9A0A087X1U9_HUMAN
Cyclin-G-associated kinase
GAK
416Annotation score:
D6RAQ7D6RAQ7_HUMAN
Cyclin-G-associated kinase
GAK
75Annotation score:
H0Y9M4H0Y9M4_HUMAN
Cyclin-G-associated kinase
GAK
69Annotation score:
H0YA39H0YA39_HUMAN
Cyclin-G-associated kinase
GAK
255Annotation score:
D6RF16D6RF16_HUMAN
Cyclin-G-associated kinase
GAK
49Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti607R → C in AAH85005 (PubMed:15489334).Curated1
Sequence conflicti1113P → A in BAA22623 (PubMed:9299234).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040505144S → L1 PublicationCorresponds to variant dbSNP:rs768962219Ensembl.1
Natural variantiVAR_040506580V → M1 PublicationCorresponds to variant dbSNP:rs34255232Ensembl.1
Natural variantiVAR_040507787D → Y1 PublicationCorresponds to variant dbSNP:rs34585705Ensembl.1
Natural variantiVAR_040508877Q → R1 PublicationCorresponds to variant dbSNP:rs149842313Ensembl.1
Natural variantiVAR_040509962G → D in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0405101051T → M1 PublicationCorresponds to variant dbSNP:rs35227944Ensembl.1
Natural variantiVAR_0405111120Q → H1 PublicationCorresponds to variant dbSNP:rs55801437Ensembl.1
Natural variantiVAR_0405121137P → L1 PublicationCorresponds to variant dbSNP:rs56169884Ensembl.1
Natural variantiVAR_0405131168S → N1 PublicationCorresponds to variant dbSNP:rs56326341Ensembl.1
Natural variantiVAR_0405141265K → R1 PublicationCorresponds to variant dbSNP:rs2306242Ensembl.1
Natural variantiVAR_0405151297D → N1 PublicationCorresponds to variant dbSNP:rs1134921Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05447949 – 127Missing in isoform 2. 1 PublicationAdd BLAST79

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D88435 mRNA Translation: BAA22623.1
BC000816 mRNA Translation: AAH00816.1
BC008668 mRNA Translation: AAH08668.1
BC085005 mRNA Translation: AAH85005.1
CCDSiCCDS3340.1 [O14976-1]
CCDS82902.1 [O14976-2]
RefSeqiNP_001305063.1, NM_001318134.1 [O14976-2]
NP_005246.2, NM_005255.3 [O14976-1]
UniGeneiHs.369607

Genome annotation databases

EnsembliENST00000314167; ENSP00000314499; ENSG00000178950 [O14976-1]
ENST00000511163; ENSP00000421361; ENSG00000178950 [O14976-2]
GeneIDi2580
KEGGihsa:2580
UCSCiuc003gbm.6 human [O14976-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D88435 mRNA Translation: BAA22623.1
BC000816 mRNA Translation: AAH00816.1
BC008668 mRNA Translation: AAH08668.1
BC085005 mRNA Translation: AAH85005.1
CCDSiCCDS3340.1 [O14976-1]
CCDS82902.1 [O14976-2]
RefSeqiNP_001305063.1, NM_001318134.1 [O14976-2]
NP_005246.2, NM_005255.3 [O14976-1]
UniGeneiHs.369607

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4C57X-ray2.55A/B14-351[»]
4C58X-ray2.16A27-351[»]
4C59X-ray2.80A14-351[»]
4O38X-ray2.10A/B12-347[»]
4Y8DX-ray2.10A/B14-351[»]
5Y7ZX-ray2.80A/B25-335[»]
5Y80X-ray2.50A25-335[»]
ProteinModelPortaliO14976
SMRiO14976
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108853, 97 interactors
IntActiO14976, 87 interactors
MINTiO14976
STRINGi9606.ENSP00000314499

Chemistry databases

BindingDBiO14976
ChEMBLiCHEMBL4355
GuidetoPHARMACOLOGYi2027

PTM databases

iPTMnetiO14976
PhosphoSitePlusiO14976

Polymorphism and mutation databases

BioMutaiGAK

Proteomic databases

EPDiO14976
MaxQBiO14976
PaxDbiO14976
PeptideAtlasiO14976
PRIDEiO14976
ProteomicsDBi48350

Protocols and materials databases

DNASUi2580
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000314167; ENSP00000314499; ENSG00000178950 [O14976-1]
ENST00000511163; ENSP00000421361; ENSG00000178950 [O14976-2]
GeneIDi2580
KEGGihsa:2580
UCSCiuc003gbm.6 human [O14976-1]

Organism-specific databases

CTDi2580
DisGeNETi2580
EuPathDBiHostDB:ENSG00000178950.16
GeneCardsiGAK
H-InvDBiHIX0004007
HGNCiHGNC:4113 GAK
HPAiHPA027405
HPA027459
HPA027463
MIMi602052 gene
neXtProtiNX_O14976
OpenTargetsiENSG00000178950
PharmGKBiPA28528
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0431 Eukaryota
KOG1989 Eukaryota
KOG2283 Eukaryota
ENOG410Y515 LUCA
GeneTreeiENSGT00760000119113
HOGENOMiHOG000034235
HOVERGENiHBG004322
InParanoidiO14976
KOiK08855
OMAiRPSRFHN
OrthoDBiEOG091G06HJ
PhylomeDBiO14976
TreeFamiTF105165

Enzyme and pathway databases

ReactomeiR-HSA-432722 Golgi Associated Vesicle Biogenesis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiO14976

Miscellaneous databases

ChiTaRSiGAK human
GeneWikiiGAK_(protein)
GenomeRNAii2580
PROiPR:O14976
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178950 Expressed in 230 organ(s), highest expression level in endothelial cell
CleanExiHS_GAK
ExpressionAtlasiO14976 baseline and differential
GenevisibleiO14976 HS

Family and domain databases

CDDicd06257 DnaJ, 1 hit
Gene3Di1.10.287.110, 1 hit
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR001623 DnaJ_domain
IPR036869 J_dom_sf
IPR011009 Kinase-like_dom_sf
IPR029021 Prot-tyrosine_phosphatase-like
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR014020 Tensin_C2-dom
IPR029023 Tensin_phosphatase
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PF10409 PTEN_C2, 1 hit
SMARTiView protein in SMART
SM00271 DnaJ, 1 hit
SM01326 PTEN_C2, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF46565 SSF46565, 1 hit
SSF52799 SSF52799, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51182 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
ProtoNetiSearch...

Entry informationi

Entry nameiGAK_HUMAN
AccessioniPrimary (citable) accession number: O14976
Secondary accession number(s): Q5U4P5, Q9BVY6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2001
Last sequence update: August 29, 2001
Last modified: October 10, 2018
This is version 181 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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