GAK
Cyclin-G-associated kinase
Also known as: DNAJC26, GAK_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O14976
- Gene
- GAK
- Ensembl
- ENSG00000178950
- Chromosome
- 4
- Canonical length
- 1311 aa
- Protein class
- Enzymes, Predicted intracellular proteins
- Subcellular location
- Golgi apparatus,Vesicles
OverviewNCBI Gene
In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and 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, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]
Canonical amino-acid sequenceUniProt
1311 residues, UniProt reviewed canonical sequence.
>O14976|GAK
1 MSLLQSALDF LAGPGSLGGA SGRDQSDFVG QTVELGELRL RVRRVLAEGG FAFVYEAQDV
61 GSGREYALKR LLSNEEEKNR AIIQEVCFMK KLSGHPNIVQ FCSAASIGKE ESDTGQAEFL
121 LLTELCKGQL VEFLKKMESR GPLSCDTVLK IFYQTCRAVQ HMHRQKPPII HRDLKVENLL
181 LSNQGTIKLC DFGSATTISH YPDYSWSAQR RALVEEEITR NTTPMYRTPE IIDLYSNFPI
241 GEKQDIWALG CILYLLCFRQ HPFEDGAKLR IVNGKYSIPP HDTQYTVFHS LIRAMLQVNP
301 EERLSIAEVV HQLQEIAAAR NVNPKSPITE LLEQNGGYGS ATLSRGPPPP VGPAGSGYSG
361 GLALAEYDQP YGGFLDILRG GTERLFTNLK DTSSKVIQSV ANYAKGDLDI SYITSRIAVM
421 SFPAEGVESA LKNNIEDVRL FLDSKHPGHY AVYNLSPRTY RPSRFHNRVS ECGWAARRAP
481 HLHTLYNICR NMHAWLRQDH KNVCVVHCMD GRAASAVAVC SFLCFCRLFS TAEAAVYMFS
541 MKRCPPGIWP SHKRYIEYMC DMVAEEPITP HSKPILVRAV VMTPVPLFSK QRSGCRPFCE
601 VYVGDERVAS TSQEYDKMRD FKIEDGKAVI PLGVTVQGDV LIVIYHARST LGGRLQAKMA
661 SMKMFQIQFH TGFVPRNATT VKFAKYDLDA CDIQEKYPDL FQVNLEVEVE PRDRPSREAP
721 PWENSSMRGL NPKILFSSRE EQQDILSKFG KPELPRQPGS TAQYDAGAGS PEAEPTDSDS
781 PPSSSADASR FLHTLDWQEE KEAETGAENA SSKESESALM EDRDESEVSD EGGSPISSEG
841 QEPRADPEPP GLAAGLVQQD LVFEVETPAV LPEPVPQEDG VDLLGLHSEV GAGPAVPPQA
901 CKAPSSNTDL LSCLLGPPEA ASQGPPEDLL SEDPLLLASP APPLSVQSTP RGGPPAAADP
961 FGPLLPSSGN NSQPCSNPDL FGEFLNSDSV TVPPSFPSAH SAPPPSCSAD FLHLGDLPGE
1021 PSKMTASSSN PDLLGGWAAW TETAASAVAP TPATEGPLFS PGGQPAPCGS QASWTKSQNP
1081 DPFADLGDLS SGLQGSPAGF PPGGFIPKTA TTPKGSSSWQ TSRPPAQGAS WPPQAKPPPK
1141 ACTQPRPNYA SNFSVIGARE ERGVRAPSFA QKPKVSENDF EDLLSNQGFS SRSDKKGPKT
1201 IAEMRKQDLA KDTDPLKLKL LDWIEGKERN IRALLSTLHT VLWDGESRWT PVGMADLVAP
1261 EQVKKHYRRA VLAVHPDKAA GQPYEQHAKM IFMELNDAWS EFENQGSRPL FLocalizationUniProt · AlphaFold · HPA
Whether an antibody against GAK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 67 nTPM
Expression across tissuesHPA
Tissue
- salivary gland: 67 nTPM
- cerebellum: 59 nTPM
- spleen: 57 nTPM
- small intestine: 54 nTPM
- colon: 53 nTPM
- stomach: 50 nTPM
Single-cell type
- neutrophils: 227 nCPM
- late spermatids: 213 nCPM
- salivary acinar cells: 189 nCPM
- endometrial glandular cells: 187 nCPM
- microglia: 163 nCPM
- foveolar cells: 159 nCPM
Immune cell
- non-classical monocyte: 24 nTPM
- eosinophil: 13 nTPM
- classical monocyte: 10 nTPM
- intermediate monocyte: 9.7 nTPM
- total PBMC: 9.4 nTPM
- gdT-cell: 8.4 nTPM
Brain region
- medulla oblongata: 72 nTPM
- cerebral cortex: 67 nTPM
- pons: 59 nTPM
- hippocampal formation: 56 nTPM
- amygdala: 56 nTPM
- thalamus: 55 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.41
- gnomAD pLI
- 0.01
- gnomAD missense Z
- 0.02
- DepMap mean gene effect
- -0.5
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- clathrin coat assembly
- clathrin coat disassembly
- clathrin-dependent endocytosis
- endoplasmic reticulum organization
- Golgi organization
- Golgi to lysosome transport
- intracellular transport
- negative regulation of neuron projection development
- protein folding
- protein localization to Golgi apparatus
- protein localization to plasma membrane
- receptor-mediated endocytosis
- regulation of clathrin coat assembly
- synaptic vesicle uncoating
Molecular functions
- ATP binding
- clathrin binding
- cyclin binding
- protein folding chaperone
- protein serine kinase activity
- protein serine/threonine kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- DnaJ domain
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Tensin phosphatase, C2 domain
- Protein-tyrosine phosphatase-like
- Tensin-type phosphatase domain
- C2 domain superfamily
- Chaperone J-domain superfamily
- Protein kinase domain
- C2 domain of PTEN tumour-suppressor protein
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of GAK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads GAK as an antibody target. Whether an autoantibody or antibody against GAK could matter depends on whether native GAK is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
GAK is annotated at the cell surface, where native GAK is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label GAK as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...