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    MAPK12 mitogen-activated protein kinase 12 [ Homo sapiens (human) ]

    Gene ID: 6300, updated on 2-Nov-2024

    Summary

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    Official Symbol
    MAPK12provided by HGNC
    Official Full Name
    mitogen-activated protein kinase 12provided by HGNC
    Primary source
    HGNC:HGNC:6874
    See related
    Ensembl:ENSG00000188130 MIM:602399; AllianceGenome:HGNC:6874
    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
    ERK3; ERK6; ERK-6; SAPK3; PRKM12; SAPK-3; MAPK 12; P38GAMMA
    Summary
    Activation of members of the mitogen-activated protein kinase family is a major mechanism for transduction of extracellular signals. Stress-activated protein kinases are one subclass of MAP kinases. The protein encoded by this gene functions as a signal transducer during differentiation of myoblasts to myotubes. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in brain (RPKM 6.0), prostate (RPKM 5.7) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAPK12 in Genome Data Viewer
    Location:
    22q13.33
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (50252901..50261683, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (50759904..50768686, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (50691330..50700112, complement)

    Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50658024-50658666 Neighboring gene tubulin gamma complex component 6 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50676935-50677436 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50677437-50677936 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19307 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50682041-50682971 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19309 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13958 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50685959-50686881 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50688039-50688885 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13959 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19311 Neighboring gene histone deacetylase 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50697131-50697703 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50698428-50698928 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13960 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13961 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13962 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13963 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50700498-50701229 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13964 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13965 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13966 Neighboring gene mitogen-activated protein kinase 11 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50710106-50710645 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50710646-50711186 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13968 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr22:50720546-50721745 Neighboring gene plexin B2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13969 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19312 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:50738869-50739425 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:50739426-50739982 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13970 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr22:50743729-50744928 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:50745236-50745386 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13971 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13972

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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

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    Related articles in PubMed

    1. NMR Characterization of Information Flow and Allosteric Communities in the MAP Kinase p38γ. Aoto PC, et al. Sci Rep, 2016 Jun 29. PMID 27353957, Free PMC Article
    2. The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness. Chen M, et al. J Cell Physiol, 2019 Aug. PMID 30569573, Free PMC Article
    3. A novel role for atypical MAPK kinase ERK3 in regulating breast cancer cell morphology and migration. Al-Mahdi R, et al. Cell Adh Migr, 2015. PMID 26588708, Free PMC Article
    4. Targeting p38γ to inhibit human colorectal cancer cell progression. Su C, et al. Biochem Biophys Res Commun, 2019 Sep 10. PMID 31349971
    5. Analysis of ERK3 intracellular localization: dynamic distribution during mitosis and apoptosis. Aredia F, et al. Eur J Histochem, 2015 Dec 1. PMID 26708186, Free PMC Article

    See all (125) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. LOC730101 transmitted by exosomes facilitates laryngeal squamous cell carcinoma tumorigenesis via regulation of p38 MAPK gamma.
      Title: LOC730101 transmitted by exosomes facilitates laryngeal squamous cell carcinoma tumorigenesis via regulation of p38 MAPK gamma.
    2. G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.
      Title: G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.
    3. The pro-tumorigenic activity of p38gamma overexpression in nasopharyngeal carcinoma.
      Title: The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.
    4. Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice.
      Title: Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice.
    5. P38GAMMA silencing inhibits colorectal cancer (CRC) cell growth and migration. P38GAMMA silencing induces apoptosis activation in CRC cells. Ectopic P38GAMMA overexpression promotes CRC cell progression in vitro.
      Title: Targeting p38γ to inhibit human colorectal cancer cell progression.
    6. these results indicate that ERK3 acts as a potent suppressor of melanoma cell growth and invasiveness
      Title: The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness.
    7. p38 MAPK gamma (p38gamma) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle; p38gamma shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members; biopsies of human hepatocellular carcinoma show high expression of p38gamma, suggesting that p38gamma could be a therapeutic target in the treatment of this disease
      Title: p38γ is essential for cell cycle progression and liver tumorigenesis.
    8. IFN-gamma receptor stimulation requires ULK1-mediated activation of MLK3 and ERK5
      Title: IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5.
    9. p38gamma was up-regulated in breast cancer, which exerts a great influence on the cell growth, cell mobility, invasiveness, and apoptosis of MDA-MB-231 cells and also affected the metabolism
      Title: Impact of p38γ mitogen-activated protein kinase (MAPK) on MDA-MB-231 breast cancer cells using metabolomic approach.
    10. Our findings suggest that L290P/V mutations of ERK3 may confer increased invasiveness to cancers.
      Title: L290P/V mutations increase ERK3's cytoplasmic localization and migration/invasion-promoting capability in cancer cells.
    Submit: New GeneRIF Correction See all GeneRIFs (46)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 binding to CD4 results in activation of the mitogen-activated protein kinase (MAPK) in CD4(+) lymphocytes prestimulated through their T-cell receptor (TCR) PubMed
    reverse transcriptase gag-pol MEK1 in HIV-1 producer cells is able to activate virion-associated MAPK in trans, and the activated MAPK facilitates efficient disengagement of the HIV-1 reverse transcription complex from the cell membrane and subsequent nuclear translocation 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

    Potential readthrough

    Included gene: HDAC10

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in MAPK cascade TAS
    Traceable Author Statement
    more info
    		  
    involved_in intracellular signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in muscle organ development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in myoblast differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-serine phosphorylation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of muscle cell differentiation TAS
    Traceable Author Statement
    more info
    		  
    involved_in positive regulation of peptidase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of cell cycle TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction in response to DNA damage TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase 12
    Names
    MAP kinase 12
    MAP kinase p38 gamma
    extracellular signal-regulated kinase 6
    mitogen-activated protein kinase 3
    mitogen-activated protein kinase p38 gamma
    stress-activated protein kinase 3
    NP_001290181.1
    NP_002960.2

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_001303252.3 → NP_001290181.1  mitogen-activated protein kinase 12 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region compared to variant 1. This difference results in a shorter isoform (2), compared to isoform 1.
      Source sequence(s)
      BC015741, BX640648, CB123561, N94360, U66243, Y10487
      Consensus CDS
      CCDS77688.1
      UniProtKB/TrEMBL
      Q6N076
      Related
      ENSP00000479972.1, ENST00000622558.4
      Conserved Domains (2) summary
      cd07880
      Location:11 → 343
      STKc_p38gamma; Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12)
      smart00220
      Location:27 → 301
      S_TKc; Serine/Threonine protein kinases, catalytic domain

    2. NM_002969.6 → NP_002960.2  mitogen-activated protein kinase 12 isoform 1

      See identical proteins and their annotated locations for NP_002960.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      BC015741, CB123561, N94360, U66243, Y10487
      Consensus CDS
      CCDS14089.1
      UniProtKB/Swiss-Prot
      P53778, Q14260, Q6IC53, Q99588, Q99672
      UniProtKB/TrEMBL
      Q6N076
      Related
      ENSP00000215659.8, ENST00000215659.13
      Conserved Domains (1) summary
      cd07880
      Location:11 → 353
      STKc_p38gamma; Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12)

    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_000022.11 Reference GRCh38.p14 Primary Assembly

      Range
      50252901..50261683 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060946.1 Alternate T2T-CHM13v2.0

      Range
      50759904..50768686 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P53778.3 GenPept UniProtKB/Swiss-Prot:P53778

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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