DOK1 Gene

Name	docking protein 1, 62kDa (downstream of tyrosine kinase 1)
Description	The protein encoded by this gene is part of a signal transduction pathway downstream of receptor tyrosine kinases. The encoded protein is a scaffold protein that helps form a platform for the assembly of multiprotein signaling complexes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Downstream of tyrosine kinase 1 (DOK1), also known as p62Dok, functions as an adaptor protein that modulates signals emanating from activated receptor and non‐receptor tyrosine kinases. In hematopoietic cells, DOK1 becomes tyrosine phosphorylated upon receptor engagement and facilitates the recruitment of regulators such as Ras GTPase–activating protein (RasGAP), thereby dampening Ras/MAPK pathway activity and limiting aberrant cell proliferation. This tumor‐suppressive activity is underscored by studies in BCR–ABL–driven leukemias where loss or inactivation of DOK1 (in conjunction with other family members) contributes to malignant transformation and myeloproliferative disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In solid tumors, such as epithelial ovarian and colorectal cancers, expression of DOK1 correlates with improved progression‐free survival. In ovarian cancer, for example, higher DOK1 levels are associated with enhanced sensitivity to chemotherapy and a modulation of cellular migration and proliferation, suggesting that DOK1 helps suppress pro‐metastatic gene expression. Similarly, in colorectal cancer the cytoplasmic localization of DOK1 favors activation of peroxisome proliferator–activated receptor γ (PPARγ) and repression of oncogenic promoters, whereas its nuclear presence coincides with poorer clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, oncogenic kinases such as breast tumor kinase (BRK) and Src-related kinases (for example, SRMS) have been shown to phosphorylate DOK1. This post-translational modification can promote its degradation via the ubiquitin–proteasome pathway, thereby subverting its inhibitory influence on downstream mitogenic signaling and facilitating tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in restricting mitogenic signals, DOK1 is also involved in regulating immune receptor–mediated events. Its phosphorylation in response to chemokine receptor or Fc receptor engagement contributes to the fine tuning of immune cell migration. Interaction of DOK1 with other adaptor proteins (such as Nck) can promote podosome formation, an event related to the remodeling of the extracellular matrix and regulation of cell motility, further underscoring the context-dependent functions of DOK1 in cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that DOK1 plays a multifaceted role as a negative regulator of tyrosine kinase–mediated signaling. By attenuating Ras/MAPK activation, influencing transcriptional programs via PPARγ, and modulating cell migration responses, DOK1 helps maintain cellular homeostasis and its dysregulation can contribute to oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nadia Dubé, Alan Cheng, Michel L Tremblay "}, {"type": "b", "children": [{"type": "t", "text": "The role of protein tyrosine phosphatase 1B in Ras 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.0304242101"}], "href": "https://doi.org/10.1073/pnas.0304242101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14766979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14766979"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Masaru Niki, Antonio Di Cristofano, Mingming Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Dok-1 and Dok-2 in leukemia suppression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20041306"}], "href": "https://doi.org/10.1084/jem.20041306"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15611295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15611295"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Pierre-Luc Mercier, Magdalena Bachvarova, Marie Plante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molonc.2011.07.003"}], "href": "https://doi.org/10.1016/j.molonc.2011.07.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21856257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21856257"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Teresa Friedrich, Michaela Söhn, Tobias Gutting, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2016.05.003"}], "href": "https://doi.org/10.1016/j.ebiom.2016.05.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27428427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27428427"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sayem Miah, Raghuveera Kumar Goel, Chenlu Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRK targets Dok1 for ubiquitin-mediated proteasomal degradation to promote cell proliferation and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0087684"}], "href": "https://doi.org/10.1371/journal.pone.0087684"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24523872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24523872"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tyler M Aten, Miranda M Redmond, Sheila O Weaver, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tyrosine phosphorylation of the orphan receptor ESDN/DCBLD2 serves as a scaffold for the signaling adaptor CrkL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2013.05.064"}], "href": "https://doi.org/10.1016/j.febslet.2013.05.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23770091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23770091"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sankar P Chaki, Rola Barhoumi, Gonzalo M Rivera "}, {"type": "b", "children": [{"type": "t", "text": "Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cam4.2640"}], "href": "https://doi.org/10.1002/cam4.2640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31638742"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31638742"}]}]}]}
Synonyms	P62DOK, pp62
Proteins	DOK1_HUMAN
NCBI Gene ID	1796
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DOK1 has 6,266 functional associations with biological entities spanning 8 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) extracted from 114 datasets.

Click the + buttons to view associations for DOK1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DOK1 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DOK1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of DOK1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 DOK1 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 DOK1 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 DOK1 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 DOK1 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 DOK1 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 DOK1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DOK1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of DOK1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DOK1 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 DOK1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DOK1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DOK1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DOK1 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 DOK1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DOK1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DOK1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DOK1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DOK1 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 DOK1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing DOK1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DOK1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DOK1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DOK1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DOK1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DOK1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DOK1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate DOK1 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DOK1 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 DOK1 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 DOK1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DOK1 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 DOK1 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 DOK1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DOK1 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 DOK1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with DOK1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DOK1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DOK1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.