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

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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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

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