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

Summary

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
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: mouse all
NEW: Try the new Data Table view

Genomic context

Location:: 19p13.3

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109.20201120	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (4090321..4124184, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (4090319..4124126, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Results indicate that some MEK1/2 mutations exert their function not only by their elevated intrinsic activity, but also by modulation of regulatory elements such as protein stability or dephosphorylation.
Title: Intrinsically active MEK variants are differentially regulated by proteinases and phosphatases.
MAP2K2 mutation is associated with cardio-facio-cutaneous syndrome.
Title: MAP2K2 mutation as a cause of cardio-facio-cutaneous syndrome in an infant with a severe and fatal course of the disease.
Here the authors identified a direct interaction of both MEK1 and MEK2 with AKT. The interaction between MEK and AKT affects cell migration and adhesion, but not proliferation. The specific mechanism of action of the MEK-AKT complex involves phosphorylation of the migration-related transcription factor FoxO1.
Title: Direct binding of MEK1 and MEK2 to AKT induces Foxo1 phosphorylation, cellular migration and metastasis.
Data show that SAM and SH3 domain containing 1 protein (SASH1) binds with mitogen-activated protein kinase kinase 2 (MAP2K2), and SASH1 mutations promote binding between SASH1 and MAP2K2.
Title: p53 regulates ERK1/2/CREB cascade via a novel SASH1/MAP2K2 crosstalk to induce hyperpigmentation.
findings demonstrate the interaction of tRNA with MEK2 in pancreatic cancer cells and suggest that tRNA may impact MEK2 activity in cancer cells
Title: Interaction of tRNA with MEK2 in pancreatic cancer cells.
Report a synthetic lethal interaction of cetuximab in combination with MEK1/2 inhibition for the NRAS mutant subgroup of metastatic colorectal cancer.
Title: Synthetic lethal interaction of cetuximab with MEK1/2 inhibition in NRAS-mutant metastatic colorectal cancer.
There are no other biomarkers correlated with treatment responses following MEK1/2 inhibition.
Title: Allosteric MEK1/2 inhibitors including cobimetanib and trametinib in the treatment of cutaneous melanomas.
MEK2 was essential for the phosphorylation of MKK3/MKK6 and p38 MAPK that directly impacted on cyclin D1 expression.
Title: MEK2 controls the activation of MKK3/MKK6-p38 axis involved in the MDA-MB-231 breast cancer cell survival: Correlation with cyclin D1 expression.

Submit: New GeneRIF Correction See all GeneRIFs (100)

Phenotypes

Go to the top of the page Help

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 4 MedGen: C3809007 OMIM: 615280 GeneReviews: Cardiofaciocutaneous Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated (2015-05-27) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated (2015-05-27) ClinGen Genome Curation Page

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

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

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

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

Homology

Homologs of the MAP2K2 gene: The MAP2K2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, S.cerevisiae, K.lactis, E.gossypii, A.thaliana, and rice.
Orthologs from Annotation Pipeline: 324 organisms have orthologs with human gene MAP2K2
Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
ERK1 and ERK2 cascade	TAS Traceable Author Statement more info
MAPK cascade	TAS Traceable Author Statement more info
activation of MAPK activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activation of MAPK activity	TAS Traceable Author Statement more info	PubMed
negative regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
peptidyl-serine autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of production of miRNAs involved in gene silencing by miRNA	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of Golgi inheritance	TAS Traceable Author Statement more info	PubMed
regulation of early endosome to late endosome transport	TAS Traceable Author Statement more info	PubMed
regulation of stress-activated MAPK cascade	TAS Traceable Author Statement more info	PubMed

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

General protein information

Go to the top of the page Help

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_109587.1

EC 2.7.12.2

XP_006722862.1

EC 2.7.12.2

XP_016882478.1

EC 2.7.12.2

XP_016882479.1

EC 2.7.12.2

XP_016882480.1

EC 2.7.12.2

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Data Table view

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_030662.4 → NP_109587.1 dual specificity mitogen-activated protein kinase kinase 2

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

Related

ENSP00000262948.3, ENST00000262948.9

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

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p13 Primary Assembly

Range

4090321..4124184 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006722799.2 → XP_006722862.1 dual specificity mitogen-activated protein kinase kinase 2 isoform X3

Conserved Domains (2) summary

smart00220
Location:72 → 276

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:70 → 294

PKc_like; Protein Kinases, catalytic domain
XM_017026990.1 → XP_016882479.1 dual specificity mitogen-activated protein kinase kinase 2 isoform X2
XM_017026989.1 → XP_016882478.1 dual specificity mitogen-activated protein kinase kinase 2 isoform X1
XM_017026991.1 → XP_016882480.1 dual specificity mitogen-activated protein kinase kinase 2 isoform X4