MAP2K7 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase 7
Description	The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically activates MAPK8/JNK1 and MAPK9/JNK2, and this kinase itself is phosphorylated and activated by MAP kinase kinase kinases including MAP3K1/MEKK1, MAP3K2/MEKK2,MAP3K3/MEKK5, and MAP4K2/GCK. This kinase is involved in the signal transduction mediating the cell responses to proinflammatory cytokines, and environmental stresses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAP2K7 (also known as MKK7) is emerging as a critical signal transducer that specifically activates the c‐Jun N‐terminal kinase (JNK) pathway in response to diverse cellular stimuli. For example, in neurons, MAP2K7 is activated downstream of dual leucine‐zipper kinase (DLK) upon apolipoprotein E receptor engagement, thereby enhancing amyloid‐β precursor protein transcription and amyloid‐β synthesis, events linked to Alzheimer’s disease pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In ovarian carcinoma cells, activation of the JNK pathway via MAP2K7 contributes to cisplatin‐induced apoptosis, as demonstrated by sensitization to cell death upon adenovirus‐mediated delivery of recombinant MAP2K7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In immune and stress‐related signaling, MAP2K7 functions as a nodal point whose activity is tightly regulated by binding partners; for instance, Gadd45β directly interacts with MAP2K7 to block its catalytic activity and suppress excessive JNK activation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while the tumor suppressor CYLD likewise negatively regulates MAP2K7 activation in response to immune receptor engagement."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic inactivation studies have underscored the essential role of MAP2K7 in cell proliferation and development; inactivation leads to embryonic lethality, G2/M cell cycle arrest, and premature senescence in mouse models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In other contexts, MAP2K7 integrates upstream signals from kinases such as MLK3—where factors like AKT modulate its capacity to evoke JNK activation—and influences key cellular outcomes ranging from the regulation of glucocorticoid receptor function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "to stress responses that govern tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, constitutive activation studies using a modified MAP2K7 (MKK7D) have revealed that sustained JNK activation in cardiomyocytes can lead to contractile dysfunction and arrhythmogenic remodeling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while in other systems, the forced stimulation of MAP2K7 triggers signaling cascades that impair glucocorticoid receptor transcriptional activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "or promote oncogene‐induced autophagic cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Furthermore, the context‐dependent activation of JNK via MAP2K7 is highlighted by evidence showing that selective MAPK inhibitors can inadvertently trigger a compensatory activation of the MLK3–MKK4/MAP2K7–JNK axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and by reports that inflammatory cues such as those mediated by EMMPRIN rely on a Rac1/PI3K/Akt/IKK cascade that converges on MAP2K7 to induce key cytokines."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies delineate a versatile role for MAP2K7 as an essential mediator that transduces upstream stress, mitogenic, and inflammatory signals to the JNK cascade, thereby influencing a broad spectrum of biological processes including neurodegeneration, chemotherapy response, developmental cell cycle progression, and cardiac remodeling.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yu-Wen Alvin Huang, Bo Zhou, Marius Wernig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2016.12.044"}], "href": "https://doi.org/10.1016/j.cell.2016.12.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28111074"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28111074"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Abdellah Mansouri, Lon D Ridgway, Anita L Korapati, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells."}]}, {"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.M208134200"}], "href": "https://doi.org/10.1074/jbc.M208134200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12637505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12637505"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Salvatore Papa, Francesca Zazzeroni, Concetta Bubici, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1093"}], "href": "https://doi.org/10.1038/ncb1093"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14743220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14743220"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "William Reiley, Minying Zhang, Shao-Cong Sun "}, {"type": "b", "children": [{"type": "t", "text": "Negative regulation of JNK signaling by the tumor suppressor CYLD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M411049200"}], "href": "https://doi.org/10.1074/jbc.M411049200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15496400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15496400"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Teiji Wada, Nicholas Joza, Hai-ying M Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MKK7 couples stress signalling to G2/M cell-cycle progression and cellular senescence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1098"}], "href": "https://doi.org/10.1038/ncb1098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15039780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15039780"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Manoj K Barthwal, Pradeep Sathyanarayana, Chanakya N Kundu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival."}]}, {"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.M211598200"}], "href": "https://doi.org/10.1074/jbc.M211598200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12458207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12458207"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ron Chen, Purvesh Khatri, Pawel K Mazur, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-13-2775"}], "href": "https://doi.org/10.1158/0008-5472.CAN-13-2775"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24654231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24654231"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Brian G Petrich, Benjamin C Eloff, Deborah L Lerner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted activation of c-Jun N-terminal kinase in vivo induces restrictive cardiomyopathy and conduction defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M314142200"}], "href": "https://doi.org/10.1074/jbc.M314142200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14742426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14742426"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zoltán Szatmáry, Michael J Garabedian, Jan Vilcek "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of glucocorticoid receptor-mediated transcriptional activation by p38 mitogen-activated protein (MAP) kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M406568200"}], "href": "https://doi.org/10.1074/jbc.M406568200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15292225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15292225"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Joo-Yun Byun, Chang-Hwan Yoon, Sungkwan An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Rac1/MKK7/JNK pathway signals upregulation of Atg5 and subsequent autophagic cell death in response to oncogenic Ras."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgp235"}], "href": "https://doi.org/10.1093/carcin/bgp235"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19783847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19783847"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Harish Muniyappa, Kumuda C Das "}, {"type": "b", "children": [{"type": "t", "text": "Activation of c-Jun N-terminal kinase (JNK) by widely used specific p38 MAPK inhibitors SB202190 and SB203580: a MLK-3-MKK7-dependent mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2007.12.003"}], "href": "https://doi.org/10.1016/j.cellsig.2007.12.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18222647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18222647"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Balachandar Venkatesan, Anthony J Valente, Sumanth D Prabhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EMMPRIN activates multiple transcription factors in cardiomyocytes, and induces interleukin-18 expression via Rac1-dependent PI3K/Akt/IKK/NF-kappaB andMKK7/JNK/AP-1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2010.05.007"}], "href": "https://doi.org/10.1016/j.yjmcc.2010.05.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20538003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20538003"}]}]}]}
Synonyms	MKK7, MAPKK7, JNKK2, MEK 7, PRKMK7, MEK, SAPKK-4, SAPKK4
Proteins	MP2K7_HUMAN
NCBI Gene ID	5609
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP2K7 has 7,700 functional associations with biological entities spanning 8 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) extracted from 125 datasets.

Click the + buttons to view associations for MAP2K7 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP2K7 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 MAP2K7 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 MAP2K7 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 MAP2K7 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 MAP2K7 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 MAP2K7 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 MAP2K7 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP2K7 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP2K7 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 MAP2K7 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 MAP2K7 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 MAP2K7 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP2K7 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 MAP2K7 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP2K7 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAP2K7 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP2K7 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 MAP2K7 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP2K7 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 MAP2K7 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MAP2K7 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAP2K7 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MAP2K7 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 MAP2K7 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing MAP2K7 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP2K7 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAP2K7 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAP2K7 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MAP2K7 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MAP2K7 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 MAP2K7 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 MAP2K7 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MAP2K7 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 MAP2K7 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 MAP2K7 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MAP2K7 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 MAP2K7 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP2K7 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with MAP2K7 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 MAP2K7 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of MAP2K7 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.