MAP2K1 Gene

HGNC Family	Mitogen-activated protein kinase cascade
Name	mitogen-activated protein kinase kinase 1
Description	The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n MAP2K1, also known as MEK1, is a dual‐specificity kinase that occupies a central node within the RAS–RAF–MEK–ERK (MAPK) signaling cascade. It is responsible for relaying proliferative, differentiative, and survival signals from activated RAF kinases to ERK1/2, thereby controlling essential cellular processes such as cell growth, metabolism, and apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the oncogenic context, MAP2K1 activity is frequently co-opted to drive resistance to targeted therapies. For instance, in BRAF‐mutant melanomas, reactivation of the MAPK pathway—whether via mutant NRAS, upregulation of receptor tyrosine kinases, or activation by alternative agonists like COT/Tpl2—often confers resistance to RAF inhibitors while simultaneously predicting sensitivity to MEK inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in non–small‐cell lung cancer, combined targeting of BRAF and MAP2K1 (with agents such as trametinib) has demonstrated significant anticancer activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in tumor biology, MAP2K1 is instrumental in mediating inflammatory and developmental responses. In monocytes, for example, activation of a Toll‐like receptor–dependent pathway engages MAP2K1 to trigger proinflammatory cytokine production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, transient MAP2K1 activation is pivotal during early adipogenesis and in ovarian granulosa cells where it facilitates transcriptional programs necessary for differentiation and ovulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, emerging evidence indicates that noncanonical mechanisms that modulate MAP2K1 activity can contribute to adaptive resistance and alterations in tumor metabolism. For instance, copper‐dependent enhancement of MEK1 phosphorylation has been shown to impact MAPK pathway activation and influence sensitivity to BRAF inhibitors, while cross-talk with other signaling modules (such as TGF‐β–mediated noncanonical pathways) further underscores the complexity of its regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies establish MAP2K1 as a pivotal mediator that integrates a broad spectrum of extracellular cues into appropriate intracellular responses. Its central role in both normal physiology and pathological conditions—including cancer, inflammation, and metabolic dysfunction—renders it a promising target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ramin Nazarian, Hubing Shi, Qi Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09626"}], "href": "https://doi.org/10.1038/nature09626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21107323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21107323"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michelle C Mendoza, E Emrah Er, John Blenis "}, {"type": "b", "children": [{"type": "t", "text": "The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Biochem Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tibs.2011.03.006"}], "href": "https://doi.org/10.1016/j.tibs.2011.03.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21531565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21531565"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cory M Johannessen, Jesse S Boehm, So Young Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COT drives resistance to RAF inhibition through MAP kinase pathway reactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09627"}], "href": "https://doi.org/10.1038/nature09627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21107320"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21107320"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "David Planchard, Benjamin Besse, Harry J M Groen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lancet Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1470-2045(16)30146-2"}], "href": "https://doi.org/10.1016/S1470-2045(16"}, {"type": "t", "text": "30146-2) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27283860"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27283860"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alex A Adjei, Roger B Cohen, Wilbur Franklin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Oncol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1200/JCO.2007.14.4956"}], "href": "https://doi.org/10.1200/JCO.2007.14.4956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18390968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18390968"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jérôme Cros, Nicolas Cagnard, Kevin Woollard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2010.08.012"}], "href": "https://doi.org/10.1016/j.immuni.2010.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20832340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20832340"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Deepanwita Prusty, Bae-Hang Park, Kathryn E Davis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207776200"}], "href": "https://doi.org/10.1074/jbc.M207776200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12270934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12270934"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Heng-Yu Fan, Zhilin Liu, Masayuki Shimada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1171396"}], "href": "https://doi.org/10.1126/science.1171396"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19443782"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19443782"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Donita C Brady, Matthew S Crowe, Michelle L Turski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Copper is required for oncogenic BRAF signalling and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13180"}], "href": "https://doi.org/10.1038/nature13180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24717435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24717435"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kadoaki Ohashi, Lecia V Sequist, Maria E Arcila, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1203530109"}], "href": "https://doi.org/10.1073/pnas.1203530109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22773810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22773810"}]}]}]}
Synonyms	MKK1, PRKMK1, CFC3, MAPKK1, MEK1
Proteins	MP2K1_HUMAN
NCBI Gene ID	5604
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MAP2K1 has 16,512 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 154 datasets.

Click the + buttons to view associations for MAP2K1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MAP2K1 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 MAP2K1 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 MAP2K1 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 MAP2K1 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 MAP2K1 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 MAP2K1 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 MAP2K1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving MAP2K1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MAP2K1 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 MAP2K1 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 MAP2K1 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 MAP2K1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP2K1 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 MAP2K1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with MAP2K1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MAP2K1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MAP2K1 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 MAP2K1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MAP2K1 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 MAP2K1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with MAP2K1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MAP2K1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of MAP2K1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MAP2K1 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 MAP2K1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MAP2K1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MAP2K1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing MAP2K1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing MAP2K1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MAP2K1 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 MAP2K1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing MAP2K1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MAP2K1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MAP2K1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MAP2K1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MAP2K1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MAP2K1 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 MAP2K1 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 MAP2K1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate MAP2K1 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for MAP2K1 protein from the DGIdb Drug Targets 2026 dataset.