DYRK2 Gene

Name	dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2
Description	DYRK2 belongs to a family of protein kinases whose members are presumed to be involved in cellular growth and/or development. The family is defined by structural similarity of their kinase domains and their capability to autophosphorylate on tyrosine residues. DYRK2 has demonstrated tyrosine autophosphorylation and catalyzed phosphorylation of histones H3 and H2B in vitro. Two isoforms of DYRK2 have been isolated. The predominant isoform, isoform 1, lacks a 5' terminal insert. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Dual‐specificity tyrosine‐phosphorylation‐regulated kinase 2 (DYRK2) plays a multifaceted role in regulating cellular homeostasis and tumorigenesis. In response to genotoxic stress, DYRK2 translocates into the nucleus where it directly phosphorylates p53 at serine 46 to trigger apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and its stability is itself regulated by ATM‐mediated phosphorylation that prevents MDM2‐dependent degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, DYRK2 acts as a molecular scaffold for an E3 ubiquitin ligase complex (EDD–DDB1–VprBP), a function independent of its catalytic activity that is essential for substrate phosphorylation and subsequent degradation (for example of katanin p60)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to controlling apoptotic signaling, DYRK2 enhances proteostasis by phosphorylating the 19S proteasome subunit Rpt3 at threonine 25 to promote proteasome activity and proper cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " It also functions as a priming kinase for oncoproteins such as c‐Jun and c‐Myc, thereby facilitating their phosphorylation‐dependent recognition by downstream ubiquitin ligases and modulating the G1/S transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Likewise, DYRK2 phosphorylates the EMT mediator Snail to enhance its degradation, thus impeding epithelial–mesenchymal transition and cancer cell invasiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these roles, DYRK2 phosphorylates TERT, the catalytic subunit of telomerase, which targets TERT for ubiquitin‐mediated degradation and suppresses telomerase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " It also modulates the stability of the human pregnane X receptor (hPXR) through phosphorylation that facilitates its ubiquitination by UBR5"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and phosphorylates SIAH2 at multiple residues to enhance its E3 ligase activity in hypoxic responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer, reduced DYRK2 expression or activity leads to attenuated degradation of oncogenic transcription factors and EMT regulators, contributing to enhanced cell proliferation, invasiveness, and stem cell self‐renewal. For instance, in leukemia stem/progenitor cells, loss of DYRK2 results in c‐Myc stabilization and impaired p53 activation, thus promoting tumor maintenance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "; similarly, genetic studies have linked DYRK2 variants to increased breast cancer risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In neuronal cells, its substrate specificity is underscored by selective phosphorylation of CRMP4 among related isoforms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, emerging evidence has highlighted a context‐dependent duality in DYRK2 function—wherein in some settings its activity contributes to proteostasis and cancer cell survival, while in others it acts as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Naoe Taira, Keishi Nihira, Tomoko Yamaguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2007.02.007"}], "href": "https://doi.org/10.1016/j.molcel.2007.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17349958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17349958"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Naoe Taira, Hiroyuki Yamamoto, Tomoko Yamaguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the apoptotic response to DNA damage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.042341"}], "href": "https://doi.org/10.1074/jbc.M109.042341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19965871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19965871"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Subbareddy Maddika, Junjie Chen "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase DYRK2 is a scaffold that facilitates assembly of an E3 ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1848"}], "href": "https://doi.org/10.1038/ncb1848"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19287380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19287380"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xing Guo, Xiaorong Wang, Zhiping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3289"}], "href": "https://doi.org/10.1038/ncb3289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26655835"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26655835"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Naoe Taira, Rei Mimoto, Morito Kurata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI60818"}], "href": "https://doi.org/10.1172/JCI60818"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22307329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22307329"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rei Mimoto, Naoe Taira, Hiroyuki Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DYRK2 controls the epithelial-mesenchymal transition in breast cancer by degrading Snail."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2013.06.005"}], "href": "https://doi.org/10.1016/j.canlet.2013.06.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23791882"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23791882"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Hae-Yun Jung, Xin Wang, Sohee Jun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.416792"}], "href": "https://doi.org/10.1074/jbc.M112.416792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23362280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23362280"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Su Sien Ong, Asli N Goktug, Ayesha Elias, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stability of the human pregnane X receptor is regulated by E3 ligase UBR5 and serine/threonine kinase DYRK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20130558"}], "href": "https://doi.org/10.1042/BJ20130558"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24438055"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24438055"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Moisés Pérez, Carmen García-Limones, Inés Zapico, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutual regulation between SIAH2 and DYRK2 controls hypoxic and genotoxic signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jmcb/mjs047"}], "href": "https://doi.org/10.1093/jmcb/mjs047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22878263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22878263"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chun Shik Park, Andrew H Lewis, Taylor J Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A KLF4-DYRK2-mediated pathway regulating self-renewal in CML stem cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood.2018875922"}], "href": "https://doi.org/10.1182/blood.2018875922"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31515251"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31515251"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Núria Bonifaci, Bohdan Górski, Bartlomiej Masojć, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exploring the link between germline and somatic genetic alterations in breast carcinogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0014078"}], "href": "https://doi.org/10.1371/journal.pone.0014078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21124932"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21124932"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Adam R Cole, Frédéric Causeret, Gokhan Yadirgi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct priming kinases contribute to differential regulation of collapsin response mediator proteins by glycogen synthase kinase-3 in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M513344200"}], "href": "https://doi.org/10.1074/jbc.M513344200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16611631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16611631"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Vasudha Tandon, Laureano de la Vega, Sourav Banerjee "}, {"type": "b", "children": [{"type": "t", "text": "Emerging roles of DYRK2 in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.REV120.015217"}], "href": "https://doi.org/10.1074/jbc.REV120.015217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33376136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33376136"}]}]}]}
Proteins	DYRK2_HUMAN
NCBI Gene ID	8445
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DYRK2 has 6,718 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 128 datasets.

Click the + buttons to view associations for DYRK2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DYRK2 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 DYRK2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with DYRK2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DYRK2 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 DYRK2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DYRK2 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 DYRK2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of DYRK2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DYRK2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DYRK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DYRK2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DYRK2 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 DYRK2 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 DYRK2 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 DYRK2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DYRK2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DYRK2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DYRK2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DYRK2 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 DYRK2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for DYRK2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DYRK2 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 DYRK2 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 DYRK2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DYRK2 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 DYRK2 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 DYRK2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DYRK2 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 DYRK2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with DYRK2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.