MAP3K2 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase kinase 2
Description	The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase preferentially activates other kinases involved in the MAP kinase signaling pathway. This kinase has been shown to directly phosphorylate and activate Ikappa B kinases, and thus plays a role in NF-kappa B signaling pathway. This kinase has also been found to bind and activate protein kinase C-related kinase 2, which suggests its involvement in a regulated signaling process. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAP3K2 (also known as MEKK2) is emerging as a pivotal regulator of multiple mitogen‐activated protein kinase (MAPK) cascades that affect both normal physiology and disease. For instance, lysine methylation of MAP3K2 by the methyltransferase SMYD3 potentiates Ras‐driven signaling, thereby enhancing the activation of the downstream MAPK module and contributing to oncogenic transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In bone biology, the E3 ubiquitin ligase Smurf1 regulates osteoblast function by targeting MAP3K2 for ubiquitination and proteasomal degradation, which in turn modulates the activity of the JNK cascade and influences bone formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Functional analysis of the MAP3K2 protein has further revealed that its PB1 domain mediates critical interactions with downstream effectors such as MEK5, thereby enabling the selective activation of the ERK5 pathway in response to various stimuli."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of cancer, elevated MAP3K2 expression has been associated with markers of poor prognosis; for example, studies in squamous cell carcinomas demonstrate that increased MAP3K2 levels correlate with the presence of activated cancer‐associated fibroblasts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, targeting MAP3K2 by specific microRNAs, such as miR‑520b, has been shown to inhibit tumor cell proliferation in hepatocellular carcinoma, underscoring its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In addition, regulatory axes involving noncoding RNAs—for example, a miR‑325/MAP3K2 interplay in cutaneous melanoma—illustrate how dysregulation of MAP3K2 contributes to enhanced migration and proliferation of tumor cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Finally, loss‐of‐function studies in breast cancer models have demonstrated that MAP3K2 is required for tumor growth and metastasis through its control of ERK5 activation, emphasizing its broader role in oncogenic signaling circuits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pawel K Mazur, Nicolas Reynoird, Purvesh Khatri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13320"}], "href": "https://doi.org/10.1038/nature13320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24847881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24847881"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Motozo Yamashita, Sai-Xia Ying, Gen-Mu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.01.035"}], "href": "https://doi.org/10.1016/j.cell.2005.01.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15820682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15820682"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kazuhiro Nakamura, Gary L Johnson "}, {"type": "b", "children": [{"type": "t", "text": "PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C300313200"}], "href": "https://doi.org/10.1074/jbc.C300313200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12912994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12912994"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jaroslav Valach, Zdeněk Fík, Hynek Strnad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Smooth muscle actin-expressing stromal fibroblasts in head and neck squamous cell carcinoma: increased expression of galectin-1 and induction of poor prognosis factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.27550"}], "href": "https://doi.org/10.1002/ijc.27550"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22447203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22447203"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Scot J Matkovich, Yuanxin Hu, William H Eschenbacher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct and indirect involvement of microRNA-499 in clinical and experimental cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.112.265736"}], "href": "https://doi.org/10.1161/CIRCRESAHA.112.265736"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22752967"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22752967"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xige Chen, Juan Gao, Yanhua Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA FOXD3-AS1 promotes proliferation, invasion and migration of cutaneous malignant melanoma via regulating miR-325/MAP3K2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Pharmacother (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biopha.2019.109438"}], "href": "https://doi.org/10.1016/j.biopha.2019.109438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31541886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31541886"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "M R Cronan, K Nakamura, N L Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defining MAP3 kinases required for MDA-MB-231 cell tumor growth and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.544"}], "href": "https://doi.org/10.1038/onc.2011.544"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22139075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22139075"}]}]}]}
Synonyms	MEKK2, MEKK2B
Proteins	M3K2_HUMAN
NCBI Gene ID	10746
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP3K2 has 8,469 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 133 datasets.

Click the + buttons to view associations for MAP3K2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP3K2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP3K2 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 MAP3K2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP3K2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAP3K2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP3K2 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 MAP3K2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAP3K2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAP3K2 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 MAP3K2 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 MAP3K2 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 MAP3K2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP3K2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAP3K2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAP3K2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MAP3K2 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 MAP3K2 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 MAP3K2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with MAP3K2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MAP3K2 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 MAP3K2 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 MAP3K2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAP3K2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for MAP3K2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MAP3K2 gene from the ENCODE Histone Modification Site Profiles dataset.