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MAPK4 mitogen-activated protein kinase 4 [ Homo sapiens (human) ]

Gene ID: 5596, updated on 3-Apr-2024

Summary

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Official Symbol
MAPK4provided by HGNC
Official Full Name
mitogen-activated protein kinase 4provided by HGNC
Primary source
HGNC:HGNC:6878
See related
Ensembl:ENSG00000141639 MIM:176949; AllianceGenome:HGNC:6878
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
ERK4; ERK-4; PRKM4; p63MAPK; p63-MAPK
Summary
Mitogen-activated protein kinase 4 is a member of the mitogen-activated protein kinase family. Tyrosine kinase growth factor receptors activate mitogen-activated protein kinases which then translocate into the nucleus and phosphorylate nuclear targets. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
Expression
Biased expression in adrenal (RPKM 3.2), brain (RPKM 3.1) and 11 other tissues See more
Orthologs
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Genomic context

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Location:
18q21.1-q21.2
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (50559612..50731826)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (50761375..50933569)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (48086457..48258196)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372115 Neighboring gene CRISPRi-validated cis-regulatory element chr18.1136 Neighboring gene ribosomal protein lateral stalk subunit P0 pseudogene 11 Neighboring gene uncharacterized LOC124904302 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:48247846-48248346 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr18:48248347-48248847 Neighboring gene uncharacterized LOC105372116 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr18:48302541-48303248 Neighboring gene heterogeneous nuclear ribonucleoprotein A3 pseudogene 16 Neighboring gene maestro

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
  • 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. Promotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors. Guan W, et al. Thorac Cancer, 2022 Oct. PMID 36073321, Free PMC Article
  2. MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade. Wang W, et al. Nat Commun, 2022 Jan 11. PMID 35017531, Free PMC Article
  3. MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer. Tian S, et al. J Exp Clin Cancer Res, 2020 Jul 25. PMID 32711558, Free PMC Article
  4. Tumour promoting and suppressing roles of the atypical MAP kinase signalling pathway ERK3/4-MK5. Kostenko S, et al. J Mol Signal, 2012 Jul 16. PMID 22800433, Free PMC Article
  5. Evolutionary history of the vertebrate mitogen activated protein kinases family. Li M, et al. PLoS One, 2011. PMID 22046431, Free PMC Article

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis.
    Title: Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis.
  2. LINC00467 enhanced the proliferative, migratory and invasive ability of breast cancer cells by targeting miR-18a/b-5p/MAPK4 axis.
    Title: LINC00467 enhanced the proliferative, migratory and invasive ability of breast cancer cells by targeting miR-18a/b-5p/MAPK4 axis.
  3. Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy.
    Title: Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy.
  4. Promotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors.
    Title: Promotor methylation status of MAPK4 is a novel epigenetic biomarker for prognosis of recurrence in patients with thymic epithelial tumors.
  5. MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade.
    Title: MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade.
  6. MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT.
    Title: MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT.
  7. MiR-127-3p inhibits proliferation of ovarian cancer in rats through down-regulating MAPK4.
    Title: MiR-127-3p inhibits proliferation of ovarian cancer in rats through down-regulating MAPK4.
  8. MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer.
    Title: MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer.
  9. MAPK4 can promote cancer by activating the AKT/mTOR signaling pathway and that targeting MAPK4 may provide a novel therapeutic approach for cancer.
    Title: MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling.
  10. Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway.
    Title: Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway.
Submit: New GeneRIF Correction See all GeneRIFs (12)

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

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

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

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 protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein heterodimerization activity IEA
Inferred from Electronic Annotation
more info
  
enables protein homodimerization activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein kinase binding ISS
Inferred from Sequence or Structural Similarity
more info
  
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 TAS
Traceable Author Statement
more info
  
Process Evidence Code Pubs
involved_in MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in cell cycle IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein phosphorylation 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 cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
mitogen-activated protein kinase 4
Names
Erk3-related
MAPK 4
extracellular signal-regulated kinase 4
NP_001278968.1
NP_001278969.1
NP_002738.2
XP_005258356.1
XP_011524376.1
XP_011524377.1
XP_011524378.1
XP_011524379.1
XP_011524380.1
XP_016881328.1
XP_047293581.1
XP_054174781.1
XP_054174782.1
XP_054174783.1
XP_054174784.1
XP_054174785.1
XP_054174786.1
XP_054174787.1
XP_054174788.1

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.

mRNA and Protein(s)

  1. NM_001292039.2 → NP_001278968.1  mitogen-activated protein kinase 4 isoform 2

    See identical proteins and their annotated locations for NP_001278968.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks part of the 5' coding region and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AA771957, AC090638, AK293818, AK295058, BC040493, BC050299
    Consensus CDS
    CCDS77189.1
    UniProtKB/TrEMBL
    B4DEW2, B4E104
    Related
    ENSP00000439231.1, ENST00000540640.3
    Conserved Domains (1) summary
    cl21453
    Location:1 → 140
    PKc_like; Protein Kinases, catalytic domain

  2. NM_001292040.2 → NP_001278969.1  mitogen-activated protein kinase 4 isoform 3

    See identical proteins and their annotated locations for NP_001278969.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks two exons in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (3) has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AA771957, AC090638, BC040493, BC050299, X59727
    Consensus CDS
    CCDS77188.1
    UniProtKB/TrEMBL
    K7ELV1
    Related
    ENSP00000466233.1, ENST00000592595.5
    Conserved Domains (1) summary
    cl21453
    Location:14 → 231
    PKc_like; Protein Kinases, catalytic domain

  3. NM_002747.4 → NP_002738.2  mitogen-activated protein kinase 4 isoform 1

    See identical proteins and their annotated locations for NP_002738.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC090638, AI088913, BC040493, BC050299, X59727
    Consensus CDS
    CCDS42437.1
    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04
    Related
    ENSP00000383234.1, ENST00000400384.7
    Conserved Domains (1) summary
    cd07854
    Location:14 → 351
    STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

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_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    50559612..50731826
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017025839.3 → XP_016881328.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04
    Conserved Domains (1) summary
    cd07854
    Location:14 → 351
    STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

  2. XM_011526076.3 → XP_011524378.1  mitogen-activated protein kinase 4 isoform X1

    See identical proteins and their annotated locations for XP_011524378.1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04
    Conserved Domains (1) summary
    cd07854
    Location:14 → 351
    STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

  3. XM_047437625.1 → XP_047293581.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  4. XM_011526074.3 → XP_011524376.1  mitogen-activated protein kinase 4 isoform X1

    See identical proteins and their annotated locations for XP_011524376.1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04
    Conserved Domains (1) summary
    cd07854
    Location:14 → 351
    STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

  5. XM_005258299.4 → XP_005258356.1  mitogen-activated protein kinase 4 isoform X1

    See identical proteins and their annotated locations for XP_005258356.1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04
    Conserved Domains (1) summary
    cd07854
    Location:14 → 351
    STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

  6. XM_011526075.4 → XP_011524377.1  mitogen-activated protein kinase 4 isoform X1

    See identical proteins and their annotated locations for XP_011524377.1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04
    Conserved Domains (1) summary
    cd07854
    Location:14 → 351
    STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

  7. XM_011526077.2 → XP_011524379.1  mitogen-activated protein kinase 4 isoform X2

    UniProtKB/TrEMBL
    B4E104
    Conserved Domains (1) summary
    cl21453
    Location:8 → 176
    PKc_like; Protein Kinases, catalytic domain

  8. XM_011526078.2 → XP_011524380.1  mitogen-activated protein kinase 4 isoform X3

    Conserved Domains (1) summary
    cl21453
    Location:29 → 100
    PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    50761375..50933569
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054318810.1 → XP_054174785.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  2. XM_054318811.1 → XP_054174786.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  3. XM_054318808.1 → XP_054174783.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  4. XM_054318806.1 → XP_054174781.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  5. XM_054318807.1 → XP_054174782.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  6. XM_054318809.1 → XP_054174784.1  mitogen-activated protein kinase 4 isoform X1

    UniProtKB/Swiss-Prot
    A1A4C4, P31152, Q0VG04

  7. XM_054318812.1 → XP_054174787.1  mitogen-activated protein kinase 4 isoform X2

  8. XM_054318813.1 → XP_054174788.1  mitogen-activated protein kinase 4 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P31152.2 GenPept UniProtKB/Swiss-Prot:P31152

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