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

    Gene ID: 5596, updated on 10-Dec-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
    mouse all
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    Genomic context

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    See MAPK4 in Genome Data Viewer
    Location:
    18q21.1-q21.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (50559612..50731826)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (50761375..50933569)
    RS_2024_09 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. Mitogen-activated protein kinase pathways. Robinson MJ, et al. Curr Opin Cell Biol, 1997 Apr. PMID 9069255
    2. 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
    3. Evolutionary history of the vertebrate mitogen activated protein kinases family. Li M, et al. PLoS One, 2011. PMID 22046431, Free PMC Article
    4. 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
    5. 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

    See all (36) 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)

    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 JUN kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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 JNK cascade 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_2024_08

    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

      UniProtKB/TrEMBL
      B4E104

    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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