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

    Gene ID: 5605, updated on 17-Jun-2024

    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; 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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See MAP2K2 in Genome Data Viewer
    Location:
    19p13.3
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (4090321..4124122, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (4073480..4107423, complement)
    105.20220307 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

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    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

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • FLJ26075

    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 scaffold activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables PDZ domain binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 protein tyrosine kinase activity 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 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 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 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

    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)

    NEW Try the new Transcript table

    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_030662.4NP_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:66396
      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_2023_10

    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_006722799.3XP_006722862.1  dual specificity mitogen-activated protein kinase kinase 2 isoform X1

      Conserved Domains (2) summary
      smart00220
      Location:72276
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:70294
      PKc_like; Protein Kinases, catalytic domain
    2. XM_047439100.1XP_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_054321464.1XP_054177439.1  dual specificity mitogen-activated protein kinase kinase 2 isoform X1

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

      UniProtKB/TrEMBL
      B3KS97