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    MAPK6 mitogen-activated protein kinase 6 [ Homo sapiens (human) ]

    Gene ID: 5597, updated on 10-Dec-2024

    Summary

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    Official Symbol
    MAPK6provided by HGNC
    Official Full Name
    mitogen-activated protein kinase 6provided by HGNC
    Primary source
    HGNC:HGNC:6879
    See related
    Ensembl:ENSG00000069956 MIM:602904; AllianceGenome:HGNC:6879
    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; PRKM6; p97MAPK; HsT17250
    Summary
    The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 25.2), brain (RPKM 20.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAPK6 in Genome Data Viewer
    Location:
    15q21.2
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (51971825..52067375)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (49779463..49875996)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (52311416..52359572)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC112268148 Neighboring gene LEO1 homolog, Paf1/RNA polymerase II complex component pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9408 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9409 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:52239187-52239400 Neighboring gene LEO1 homolog, Paf1/RNA polymerase II complex component Neighboring gene H3K27ac hESC enhancers GRCh37_chr15:52263092-52263668 and GRCh37_chr15:52263669-52264244 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9411 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9412 Neighboring gene Sharpr-MPRA regulatory region 2333 Neighboring gene Sharpr-MPRA regulatory region 7002 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9414 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6442 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6443 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9415 Neighboring gene MAPK6 divergent transcript Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:52317121-52317701 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9416 Neighboring gene MPRA-validated peak2339 silencer Neighboring gene uncharacterized LOC112268150 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9417 Neighboring gene uncharacterized LOC124903494 Neighboring gene MAPK6-RPS13P8 intergenic CAGE-defined mid-level expression enhancer Neighboring gene ReSE screen-validated silencer GRCh37_chr15:52386957-52387157 Neighboring gene ribosomal protein S13 pseudogene 8

    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. Proteasome- and p38-dependent regulation of ERK3 expression. Zimmermann J, et al. J Biol Chem, 2001 Apr 6. PMID 11148204
    2. CircRNA_100395 protects breast carcinoma deterioration by targeting MAPK6. Yu XP, et al. Eur Rev Med Pharmacol Sci, 2020 Dec. PMID 33336740
    3. Crystal Structure and Inhibitor Identifications Reveal Targeting Opportunity for the Atypical MAPK Kinase ERK3. Schröder M, et al. Int J Mol Sci, 2020 Oct 26. PMID 33114754, Free PMC Article
    4. ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis. Bogucka K, et al. Cancer Gene Ther, 2021 May. PMID 33070159
    5. Molecular cloning, isolation and characterisation of ERK3 gene from chewing-tobacco induced oral squamous cell carcinoma. Rai R, et al. Oral Oncol, 2004 Aug. PMID 15172640

    See all (78) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The circ_0003928/miR-31-5p/MAPK6 cascade affects high glucose-induced inflammatory response, fibrosis and oxidative stress in HK-2 cells.
      Title: The circ_0003928/miR-31-5p/MAPK6 cascade affects high glucose-induced inflammatory response, fibrosis and oxidative stress in HK-2 cells.
    2. Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma.
      Title: Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma.
    3. ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization.
      Title: ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization.
    4. miR-128-3p inhibits the inflammation by targeting MAPK6 in penicillin-induced astrocytes.
      Title: miR-128-3p inhibits the inflammation by targeting MAPK6 in penicillin-induced astrocytes.
    5. LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway.
      Title: LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway.
    6. ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis.
      Title: ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis.
    7. CircRNA_100395 protects breast carcinoma deterioration by targeting MAPK6.
      Title: CircRNA_100395 protects breast carcinoma deterioration by targeting MAPK6.
    8. ERK3 is transcriptionally upregulated by Np63alpha and mediates the role of Np63alpha in suppressing cell migration in non-melanoma skin cancers.
      Title: ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers.
    9. miR6535p suppresses the growth and migration of breast cancer cells by targeting MAPK6.
      Title: miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6.
    10. let7f5p attenuates inflammatory injury in in vitro pneumonia models by targeting MAPK6.
      Title: let7f‑5p attenuates inflammatory injury in in vitro pneumonia models by targeting MAPK6.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    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

    Clone Names

    • DKFZp686F03189

    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 ISS
    Inferred from Sequence or Structural Similarity
    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 kinase binding IEA
    Inferred from Electronic Annotation
    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 positive regulation of dendritic spine development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in signal transduction 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 IDA
    Inferred from Direct Assay
    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
    		  
    part_of protein-containing complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in septin cytoskeleton IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase 6
    Names
    ERK-3
    MAP kinase 6
    MAPK 6
    extracellular signal-regulated kinase 3
    extracellular signal-regulated kinase, p97
    p97-MAPK
    protein kinase, mitogen-activated 5
    protein kinase, mitogen-activated 6
    NP_002739.1
    XP_005254594.1
    XP_005254595.1
    XP_011520084.1
    XP_047288803.1
    XP_047288804.1
    XP_047288805.1
    XP_047288806.1
    XP_047288807.1
    XP_047288808.1
    XP_047288809.1
    XP_047288810.1
    XP_047288811.1
    XP_054234407.1
    XP_054234408.1
    XP_054234409.1
    XP_054234410.1
    XP_054234411.1
    XP_054234412.1
    XP_054234413.1
    XP_054234414.1
    XP_054234415.1
    XP_054234416.1
    XP_054234417.1

    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_002748.4 → NP_002739.1  mitogen-activated protein kinase 6

      See identical proteins and their annotated locations for NP_002739.1

      Status: REVIEWED

      Source sequence(s)
      AC023906, BC035492, DA109756, L77964
      Consensus CDS
      CCDS10147.1
      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8
      Related
      ENSP00000261845.5, ENST00000261845.7
      Conserved Domains (1) summary
      cd07854
      Location:14 → 355
      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_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      51971825..52067375
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432852.1 → XP_047288808.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8
      Related
      ENSP00000509662.1, ENST00000691380.1

    2. XM_047432853.1 → XP_047288809.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    3. XM_005254537.4 → XP_005254594.1  mitogen-activated protein kinase 6 isoform X1

      See identical proteins and their annotated locations for XP_005254594.1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8
      Conserved Domains (1) summary
      cd07854
      Location:14 → 355
      STKc_MAPK4_6; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3)

    4. XM_005254538.3 → XP_005254595.1  mitogen-activated protein kinase 6 isoform X1

      See identical proteins and their annotated locations for XP_005254595.1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8
      Related
      ENSP00000506036.1, ENST00000681888.1
      Conserved Domains (1) summary
      cd07854
      Location:14 → 355
      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_011521782.2 → XP_011520084.1  mitogen-activated protein kinase 6 isoform X1

      See identical proteins and their annotated locations for XP_011520084.1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8
      Conserved Domains (1) summary
      cd07854
      Location:14 → 355
      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_047432855.1 → XP_047288811.1  mitogen-activated protein kinase 6 isoform X2

    7. XM_047432851.1 → XP_047288807.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    8. XM_047432847.1 → XP_047288803.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    9. XM_047432850.1 → XP_047288806.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    10. XM_047432849.1 → XP_047288805.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    11. XM_047432854.1 → XP_047288810.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    12. XM_047432848.1 → XP_047288804.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      49779463..49875996
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054378439.1 → XP_054234414.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    2. XM_054378440.1 → XP_054234415.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    3. XM_054378434.1 → XP_054234409.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    4. XM_054378432.1 → XP_054234407.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    5. XM_054378433.1 → XP_054234408.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    6. XM_054378437.1 → XP_054234412.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    7. XM_054378436.1 → XP_054234411.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    8. XM_054378435.1 → XP_054234410.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    9. XM_054378438.1 → XP_054234413.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    10. XM_054378442.1 → XP_054234417.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8

    11. XM_054378441.1 → XP_054234416.1  mitogen-activated protein kinase 6 isoform X1

      UniProtKB/Swiss-Prot
      B2R945, B5BU65, Q16659, Q68DH4, Q8IYN8
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16659.1 GenPept UniProtKB/Swiss-Prot:Q16659

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