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

Gene ID: 5605, updated on 10-Dec-2024

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
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (4090321..4124122, complement)
RS_2024_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_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancers GRCh37_chr19:4006760-4007651 and GRCh37_chr19:4007652-4008542 Neighboring gene protein inhibitor of activated STAT 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:4043682-4044414 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13750 Neighboring gene zinc finger and BTB domain containing 7A Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9868 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9869 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13751 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9870 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9871 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:4062546-4063053 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13752 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9872 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9873 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9874 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9875 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9876 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9877 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9878 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9879 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9880 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:4068686-4068844 Neighboring gene MPRA-validated peak3265 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13753 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13754 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13755 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:4089732-4090508 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13757 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13758 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:4116105-4116291 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9881 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9882 Neighboring gene Sharpr-MPRA regulatory region 2607 Neighboring gene Sharpr-MPRA regulatory region 6873 Neighboring gene MPRA-validated peak3267 silencer Neighboring gene cAMP responsive element binding protein 3 like 3 Neighboring gene Sharpr-MPRA regulatory region 11650 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13759 Neighboring gene sirtuin 6

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. A full-length 3D structure for MAPK/ERK kinase 2 (MEK2). Liang H, et al. Sci China Life Sci, 2011 Apr. PMID 21509657
  2. MAP2K2 Delays Recovery in Murine Models of Acute Lung Injury and Associates with Acute Respiratory Distress Syndrome Outcome. Gong KQ, et al. Am J Respir Cell Mol Biol, 2022 May. PMID 35157553, Free PMC Article
  3. O-GlcNAcylation of MEK2 promotes the proliferation and migration of breast cancer cells. Xu Y, et al. Glycobiology, 2021 Jun 3. PMID 33226073
  4. MAP2K2 mutation as a cause of cardio-facio-cutaneous syndrome in an infant with a severe and fatal course of the disease. Gos M, et al. Am J Med Genet A, 2018 Jul. PMID 29799162
  5. Concurrent occurrence of an inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving MAP2K2 in a patient with developmental delay, distinctive facial features, and lambdoid synostosis. Shimojima K, et al. Eur J Med Genet, 2016 Nov. PMID 27751966

See all (260) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. MEK1/2 activity modulates TREM2 cell surface recruitment.
    Title: MEK1/2 activity modulates TREM2 cell surface recruitment.
  9. 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.
  10. 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 4
MedGen: C3809007 OMIM: 615280 GeneReviews: Cardiofaciocutaneous Syndrome
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ26075

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables JUN kinase kinase activity 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 scaffold activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables PDZ domain binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables histone H2AXY142 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3Y41 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
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 activity TAS
Traceable Author Statement
more info
  
enables protein serine/threonine/tyrosine kinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables scaffold protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in ERBB2-ERBB3 signaling pathway IEA
Inferred from Electronic Annotation
more info
  
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 JNK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in Schwann cell development IEA
Inferred from Electronic Annotation
more info
  
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in epithelial cell proliferation involved in lung morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in face development IEA
Inferred from Electronic Annotation
more info
  
involved_in heart development IEA
Inferred from Electronic Annotation
more info
  
involved_in insulin-like growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in myelination IEA
Inferred from Electronic Annotation
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 axonogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cell motility IEA
Inferred from Electronic Annotation
more info
  
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 TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of axon regeneration 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 TAS
Traceable Author Statement
more info
 PubMed 
involved_in thymus development IEA
Inferred from Electronic Annotation
more info
  
involved_in thyroid gland development IEA
Inferred from Electronic Annotation
more info
  
involved_in trachea formation IEA
Inferred from Electronic Annotation
more info
  
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 cytoplasmic side of plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
 PubMed 
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 TAS
Traceable Author Statement
more info
 PubMed 
located_in late endosome TAS
Traceable Author Statement
more info
 PubMed 
located_in microtubule IDA
Inferred from Direct Assay
more info
 PubMed 
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 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_109587.1
XP_006722862.1
XP_047295056.1
XP_054177439.1
XP_054177440.1

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

  1. NG_007996.1 RefSeqGene

    Range
    5001..38808
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_750

mRNA and Protein(s)

  1. 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
    ENSP00000262948.4, 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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    4090321..4124122 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006722799.3 → XP_006722862.1  dual specificity mitogen-activated protein kinase kinase 2 isoform X1

    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

  2. XM_047439100.1 → XP_047295056.1  dual specificity mitogen-activated protein kinase kinase 2 isoform X2

    UniProtKB/TrEMBL
    B3KS97
    Related
    ENST00000689792.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    4073480..4107423 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321464.1 → XP_054177439.1  dual specificity mitogen-activated protein kinase kinase 2 isoform X1

  2. XM_054321465.1 → XP_054177440.1  dual specificity mitogen-activated protein kinase kinase 2 isoform X2

    UniProtKB/TrEMBL
    B3KS97
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P36507.1 GenPept UniProtKB/Swiss-Prot:P36507

Gene LinkOut

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