GAK Gene

HGNC Family	Heat shock proteins, C2 domain containing
Name	cyclin G associated kinase
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin G–associated kinase (GAK) is a multifunctional serine/threonine kinase whose principal role is to regulate clathrin‐mediated trafficking. Early studies revealed that GAK acts as an essential cofactor for Hsc70‐dependent uncoating of clathrin‐coated vesicles—a process fundamental to receptor recycling and intracellular trafficking (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, GAK is critical for proper mitotic progression; its depletion leads to defects in centrosome maturation, abnormal spindle formation, and activation of the spindle‐assembly checkpoint (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genome‐wide association studies have consistently identified risk variants in the GAK/DGKQ region that are associated with Parkinson’s disease, implicating this kinase in neurodegenerative processes (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": " Furthermore, GAK forms part of a protein complex with Parkinson’s disease–linked proteins such as LRRK2 and Rab7L1, which promotes the clearance of Golgi‐derived vesicles through the autophagy–lysosome system, thereby linking vesicle dynamics to neuroprotective pathways (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside of neural tissues, GAK also modulates diverse signaling pathways. For instance, it influences receptor turnover and downstream signaling in pathways mediated by the epidermal growth factor receptor and the androgen receptor. In prostate cancer, GAK interacts with the androgen receptor to enhance transcriptional activity even at low ligand concentrations, a mechanism that may contribute to progression toward androgen independence (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, structural studies of the GAK catalytic domain have revealed significant conformational plasticity. Such insights not only enhance our understanding of its role in vesicle trafficking and cell-cycle regulation but also provide a foundation for the rational design of inhibitors aimed at mitigating its off-target effects during kinase inhibitor therapy (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dong-Won Lee, Xufeng Wu, Evan Eisenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.03092"}], "href": "https://doi.org/10.1242/jcs.03092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16895969"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16895969"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jennifer Hirst, Daniela A Sahlender, Sam Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Auxilin depletion causes self-assembly of clathrin into membraneless cages in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2008.00764.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2008.00764.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18489706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18489706"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lei Zhang, Ole Gjoerup, Thomas M Roberts "}, {"type": "b", "children": [{"type": "t", "text": "The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0403175101"}], "href": "https://doi.org/10.1073/pnas.0403175101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15240878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15240878"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hiroyuki Shimizu, Ippei Nagamori, Norikazu Yabuta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.052795"}], "href": "https://doi.org/10.1242/jcs.052795"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19654208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19654208"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Taye H Hamza, Cyrus P Zabetian, Albert Tenesa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.642"}], "href": "https://doi.org/10.1038/ng.642"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20711177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20711177"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nathan Pankratz, Jemma B Wilk, Jeanne C Latourelle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomewide association study for susceptibility genes contributing to familial Parkinson disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-008-0582-9"}], "href": "https://doi.org/10.1007/s00439-008-0582-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18985386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18985386"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nathan Pankratz, Gary W Beecham, Anita L DeStefano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meta-analysis of Parkinson's disease: identification of a novel locus, RIT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.22687"}], "href": "https://doi.org/10.1002/ana.22687"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22451204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22451204"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shannon L Rhodes, Janet S Sinsheimer, Yvette Bordelon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Replication of GWAS associations for GAK and MAPT in Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Hum Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1469-1809.2010.00616.x"}], "href": "https://doi.org/10.1111/j.1469-1809.2010.00616.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21058943"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21058943"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alexandra Dumitriu, Chris D Pacheco, Jemma B Wilk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin-G-associated kinase modifies α-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddr026"}], "href": "https://doi.org/10.1093/hmg/ddr026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21258085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21258085"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Alexandria Beilina, Iakov N Rudenko, Alice Kaganovich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1318306111"}], "href": "https://doi.org/10.1073/pnas.1318306111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24510904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24510904"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Mira R Ray, Latif A Wafa, Helen Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin G-associated kinase: a novel androgen receptor-interacting transcriptional coactivator that is overexpressed in hormone refractory prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.21469"}], "href": "https://doi.org/10.1002/ijc.21469"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16161052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16161052"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Apirat Chaikuad, Tracy Keates, Cécile Vincke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20131399"}], "href": "https://doi.org/10.1042/BJ20131399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24438162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24438162"}]}]}]}
Synonyms	DNAJ26, DNAJC26
Proteins	GAK_HUMAN
NCBI Gene ID	2580
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GAK has 6,674 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 128 datasets.

Click the + buttons to view associations for GAK from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GAK Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by GAK gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GAK gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of GAK gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of GAK gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of GAK gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of GAK gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of GAK gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GAK gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of GAK gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GAK gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of GAK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with GAK gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GAK protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GAK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GAK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of GAK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing GAK protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of GAK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GAK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GAK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing GAK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing GAK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GAK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with GAK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of GAK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GAK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GAK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GAK gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GAK gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of GAK protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with GAK gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with GAK gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with GAK gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with GAK gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with GAK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GAK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at GAK gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of GAK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GAK gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing GAK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.