MAP2K2 mitogen-activated protein kinase kinase 2 [ Homo sapiens (human) ]

Gene ID: 5605, updated on 16-Jun-2026

Summary

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Official Symbol: MAP2K2provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase 2provided by HGNC
Primary source: HGNC:HGNC:6842
See related: Ensembl:ENSG00000126934 MIM:601263; AllianceGenome:HGNC:6842
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CFC4; MEK2; MKK2; MAPKK2; PRKMK2
Summary: The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in duodenum (RPKM 32.3), testis (RPKM 26.3) and 25 other tissues See more
Orthologs: all
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Genomic context

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See MAP2K2 in Genome Data Viewer

Location:: 19p13.3

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (4090321..4124122, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (4073480..4107423, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (4090319..4124119, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Lung Fibroblasts Take up Breast Cancer Cell-derived Extracellular Vesicles Partially Through MEK2-dependent Macropinocytosis.
Title: Lung Fibroblasts Take up Breast Cancer Cell-derived Extracellular Vesicles Partially Through MEK2-dependent Macropinocytosis.
MAP2K2 Delays Recovery in Murine Models of Acute Lung Injury and Associates with Acute Respiratory Distress Syndrome Outcome.
Title: MAP2K2 Delays Recovery in Murine Models of Acute Lung Injury and Associates with Acute Respiratory Distress Syndrome Outcome.
YTHDF2 promotes multiple myeloma cell proliferation via STAT5A/MAP2K2/p-ERK axis.
Title: YTHDF2 promotes multiple myeloma cell proliferation via STAT5A/MAP2K2/p-ERK axis.
O-GlcNAcylation of MEK2 promotes the proliferation and migration of breast cancer cells.
Title: O-GlcNAcylation of MEK2 promotes the proliferation and migration of breast cancer cells.
The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma.
Title: The Predictive Value of MAP2K1/2 Mutations on Efficiency of Immunotherapy in Melanoma.
The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation.
Title: The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation.
Dual Inhibition of DKC1 and MEK1/2 Synergistically Restrains the Growth of Colorectal Cancer Cells.
Title: Dual Inhibition of DKC1 and MEK1/2 Synergistically Restrains the Growth of Colorectal Cancer Cells.
MEK1/2 activity modulates TREM2 cell surface recruitment.
Title: MEK1/2 activity modulates TREM2 cell surface recruitment.
MEK2 is a critical modulating mechanism to down-regulate GCIP stability and function in cancer cells.
Title: MEK2 is a critical modulating mechanism to down-regulate GCIP stability and function in cancer cells.
USP21-mediated deubiquitination and stabilization of MEK2 plays a critical role in hepatocellular carcinoma development.
Title: The deubiquitinase USP21 stabilizes MEK2 to promote tumor growth.

Submit: New GeneRIF Correction See all GeneRIFs (108)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cardiofaciocutaneous syndrome 1 MedGen: CN029449 OMIM: 115150 GeneReviews: Cardiofaciocutaneous Syndrome	Compare labs
Cardiofaciocutaneous syndrome 4 MedGen: C3809007 OMIM: 615280 GeneReviews: Cardiofaciocutaneous Syndrome	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The transcription factors and kinases c-Jun, JNK, MEK, p38 MAPK, STAT-3, JAK-1, TFII D, TFII F, eIF-4E, and RNA polymerase II are induced by HIV-1 gp120	PubMed
Nef	nef	HIV-1 Nef expression in primary T cells upregulates MEK1/2 activities, which induces the increased phosphorylation of ERK1/2	PubMed
Tat	tat	HIV-1 Tat activates PRKCQ (PKC-theta) kinase activity, which leads to RELA (NFkB), NRAS, RAF1, MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK3 (ERK1), and MAPK1 (ERK2) activation, in Jurkat T cells that stably express Tat	PubMed
	tat	HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways	PubMed
	tat	Tat and IFN-gamma synergistically induce the expression of CXCL10, which is inhibited by MEK1/2 inhibitor and the p38 mitogen-activated protein kinase (MAPK) inhibitor	PubMed
	tat	MAP2K2 is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells	PubMed
	tat	HIV-1 Tat activates mitogen-activated protein kinases ERK1 and ERK2 through the activation of MEK1 and MEK2, leading to induction of IL-8, IL-10, IP-10, iNOS, superoxide and TNF-alpha, as well as the activation of CREB and increased albumin permeability	PubMed
Vpr	vpr	Inhibition of MEK1,2 impairs HIV-1 Vpr-induced BID cleavage	PubMed
	vpr	Overexpression of HIV-1 Vpr decreases phosphorylation of MEK2	PubMed
	vpr	HIV-1 Vpr downregulates expression of genes involved in the MEK2-ERK pathway, including MAP2K2 (MEK2) and MKNK2	PubMed
nucleocapsid	gag	Mitogen-activated protein kinase kinase 2 (MAP2K2) is downregulated in HIV-1 Tat and NC cotransfection of HEK 293T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

RH17501 (e-PCR)
- UniSTS:24846

L17705 (e-PCR)
- UniSTS:66091

D8S2278 (e-PCR)
- UniSTS:473906

RH12333 (e-PCR)
- UniSTS:24957

D12S84 (e-PCR), detects polymorphism
- UniSTS:50589

RH104182 (e-PCR)
- UniSTS:98507

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MAP kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables MAP kinase kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables MAP kinase kinase activity	IEA Inferred from Electronic Annotation more info
enables MAP kinase scaffold activity	IEA Inferred from Electronic Annotation more info
enables MAP kinase scaffold activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables PDZ domain binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine kinase activity	EXP Inferred from Experiment more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activator activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein serine/threonine/tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein tyrosine kinase activity	EXP Inferred from Experiment more info	PubMed
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables scaffold protein binding	IEA Inferred from Electronic Annotation more info
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ERK1 and ERK2 cascade	TAS Traceable Author Statement more info
involved_in MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-serine autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of Golgi inheritance	IEA Inferred from Electronic Annotation more info
involved_in regulation of Golgi inheritance	TAS Traceable Author Statement more info	PubMed
involved_in regulation of early endosome to late endosome transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of early endosome to late endosome transport	TAS Traceable Author Statement more info	PubMed
involved_in regulation of stress-activated MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in regulation of stress-activated MAPK cascade	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	TAS Traceable Author Statement more info	PubMed
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	EXP Inferred from Experiment more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info	PubMed
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in early endosome	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in focal adhesion	IEA Inferred from Electronic Annotation more info
located_in focal adhesion	TAS Traceable Author Statement more info	PubMed
located_in late endosome	IEA Inferred from Electronic Annotation more info
located_in late endosome	TAS Traceable Author Statement more info	PubMed
located_in membrane	EXP Inferred from Experiment more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in microtubule	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed
located_in nucleus	TAS Traceable Author Statement more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in peroxisomal membrane	HDA more info	PubMed

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 2

Names: ERK activator kinase 2; MAP kinase kinase 2; MAPK/ERK kinase 2; mitogen-activated protein kinase kinase 2, p45

NP_001427617.1

EC 2.7.12.2

NP_001427618.1

EC 2.7.12.2

NP_109587.1

EC 2.7.12.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007996.1 RefSeqGene

Range

5001..38808

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_750

mRNA and Protein(s)

NM_001440688.1 → NP_001427617.1 dual specificity mitogen-activated protein kinase kinase 2 isoform 2

Status: REVIEWED

Source sequence(s)

AC016586

UniProtKB/TrEMBL

A0ACI8UCI8

Related

ENSP00000615919.1, ENST00000945860.1
NM_001440689.1 → NP_001427618.1 dual specificity mitogen-activated protein kinase kinase 2 isoform 3

Status: REVIEWED

Source sequence(s)

AC016586

UniProtKB/TrEMBL

B3KS97

Related

ENST00000689792.1
NM_030662.4 → NP_109587.1 dual specificity mitogen-activated protein kinase kinase 2 isoform 1

See identical proteins and their annotated locations for NP_109587.1

Status: REVIEWED

Source sequence(s)

AA312322, BC000471

Consensus CDS

CCDS12120.1

UniProtKB/Swiss-Prot

P36507

UniProtKB/TrEMBL

A0ACI8T030

Related

ENSP00000262948.4, ENST00000262948.10

Conserved Domains (1) summary

cd06649
Location:66 → 396

PKc_MEK2; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2