DOK2 Gene

Name	docking protein 2, 56kDa
Description	The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DOK2 is a pivotal membrane‐associated adaptor protein that helps maintain immune homeostasis by negatively regulating several receptor‐mediated signaling pathways in hematopoietic cells. For example, in myeloid cells DOK2 becomes rapidly tyrosine phosphorylated after receptor engagement—such as by the CD200 receptor—allowing it to directly bind and recruit Ras GTPase–activating protein (RasGAP) and other effectors to dampen activating signals and thereby limit inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the hematopoietic compartment DOK2, acting in concert with its closely related family members, is essential for restraining aberrant Ras/Erk activation; mice lacking both Dok1 and Dok2 develop a myeloproliferative disease resembling chronic myelogenous leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In adaptive immunity, DOK2 attenuates early T cell receptor signaling—limiting ZAP-70 activation—to prevent overactivation that could lead to autoimmunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, DOK2 contributes to the negative regulation of toll-like receptor–mediated responses in macrophages, thereby reducing excessive production of proinflammatory mediators"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and its expression in natural killer cells helps restrain their activation and cytokine output."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, studies using DokR (an alternative designation for DOK2) have shown that its ectopic expression can impair colony formation and T cell development, reinforcing its role as an inhibitory regulator in hematopoiesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and it has also been implicated in curbing Tec kinase–mediated Ras signaling in T cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings identify DOK2 as a central inhibitory hub that modulates receptor-driven signaling to preserve immune balance and suppress tumorigenic transformation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robin Mihrshahi, A Neil Barclay, Marion H Brown "}, {"type": "b", "children": [{"type": "t", "text": "Essential roles for Dok2 and RasGAP in CD200 receptor-mediated regulation of human myeloid cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.0901531"}], "href": "https://doi.org/10.4049/jimmunol.0901531"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19786546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19786546"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Robin Mihrshahi, Marion H Brown "}, {"type": "b", "children": [{"type": "t", "text": "Downstream of tyrosine kinase 1 and 2 play opposing roles in CD200 receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1002858"}], "href": "https://doi.org/10.4049/jimmunol.1002858"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21078907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21078907"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tomoharu Yasuda, Masaki Shirakata, Atsushi Iwama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia."}]}, {"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.20041247"}], "href": "https://doi.org/10.1084/jem.20041247"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15611294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15611294"}]}, {"type": "r", "ref": 4, "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": 5, "children": [{"type": "t", "text": "Tomoharu Yasuda, Kenji Bundo, Ayako Hino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok-1 and Dok-2 are negative regulators of T cell receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/intimm/dxm015"}], "href": "https://doi.org/10.1093/intimm/dxm015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17329234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17329234"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hisaaki Shinohara, Akane Inoue, Noriko Toyama-Sorimachi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20041817"}], "href": "https://doi.org/10.1084/jem.20041817"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15699069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15699069"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Javier Celis-Gutierrez, Marilyn Boyron, Thierry Walzer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok1 and Dok2 proteins regulate natural killer cell development and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201387404"}], "href": "https://doi.org/10.15252/embj.201387404"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24963146"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24963146"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Raffi Gugasyan, Cathy Quilici, Stacey T T I, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dok-related protein negatively regulates T cell development via its RasGTPase-activating protein and Nck docking sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200112066"}], "href": "https://doi.org/10.1083/jcb.200112066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12093790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12093790"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Audrey Gérard, Cédric Favre, Fabien Garçon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1207283"}], "href": "https://doi.org/10.1038/sj.onc.1207283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14647425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14647425"}]}]}]}
Synonyms	P56DOK, P56DOK-2
Proteins	DOK2_HUMAN
NCBI Gene ID	9046
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DOK2 has 4,835 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for DOK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DOK2 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 DOK2 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 DOK2 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 DOK2 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 DOK2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DOK2 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 DOK2 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 DOK2 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 DOK2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DOK2 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 DOK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DOK2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DOK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DOK2 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 DOK2 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 DOK2 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 DOK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DOK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DOK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DOK2 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 DOK2 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 DOK2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DOK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with DOK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DOK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DOK2 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 DOK2 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 DOK2 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 DOK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DOK2 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 DOK2 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 DOK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DOK2 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 DOK2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with DOK2 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 DOK2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with DOK2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing DOK2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of DOK2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of DOK2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
	GEO Signatures of Differentially Expressed Genes for Kinase Perturbations	kinase perturbations changing expression of DOK2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.