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MAPK10 mitogen-activated protein kinase 10 [ Homo sapiens (human) ]

Gene ID: 5602, updated on 3-Apr-2024

Summary

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Official Symbol
MAPK10provided by HGNC
Official Full Name
mitogen-activated protein kinase 10provided by HGNC
Primary source
HGNC:HGNC:6872
See related
Ensembl:ENSG00000109339 MIM:602897; AllianceGenome:HGNC:6872
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
JNK3; JNK3A; PRKM10; SAPK1b; p493F12; p54bSAPK
Summary
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]
Expression
Biased expression in brain (RPKM 15.3), fat (RPKM 4.4) and 11 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
4q21.3
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (86010405..86594074, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (89339877..89923587, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (86931558..87374348, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene Rho GTPase activating protein 24 Neighboring gene uncharacterized LOC105377319 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:86587778-86588977 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21694 Neighboring gene uncharacterized LOC124900728 Neighboring gene Sharpr-MPRA regulatory region 4363 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:86694939-86695479 Neighboring gene NANOG hESC enhancer GRCh37_chr4:86709821-86710322 Neighboring gene microRNA 4451 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:86747140-86747682 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:86996696-86997266 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:86997267-86997836 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:87056245-87056789 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:87055698-87056244 Neighboring gene MAPK10 antisense RNA 1 Neighboring gene RN7SK pseudogene 96 Neighboring gene NANOG hESC enhancer GRCh37_chr4:87353806-87354348 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:87374354-87374902 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:87393729-87394298 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:87398123-87398623 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:87403957-87404713 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21695 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:87468519-87469019 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:87515119-87515705 Neighboring gene microRNA 4452 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15548 Neighboring gene protein tyrosine phosphatase non-receptor type 13 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:87651683-87652182 Neighboring gene solute carrier family 10 member 6

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. Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes. Tsai YC, et al. Life Sci, 2021 Jun 15. PMID 33774030
  2. JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases. Musi CA, et al. Cells, 2020 Sep 28. PMID 32998477, Free PMC Article
  3. Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10. Li H, et al. Eur Rev Med Pharmacol Sci, 2020 Jun. PMID 32572915
  4. Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay. Rajan RK, et al. J Comput Aided Mol Des, 2020 Jun. PMID 32040807
  5. Dysregulated miR-27a-3p promotes nasopharyngeal carcinoma cell proliferation and migration by targeting Mapk10. Li L, et al. Oncol Rep, 2017 May. PMID 28393229, Free PMC Article

See all (124) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases.
    Title: The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases.
  2. Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay.
    Title: Identification and neuroprotective evaluation of a potential c-Jun N-terminal kinase 3 inhibitor through structure-based virtual screening and in-vitro assay.
  3. MicroRNA-4516-mediated regulation of MAPK10 relies on 3' UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease.
    Title: MicroRNA-4516-mediated regulation of MAPK10 relies on 3' UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease.
  4. JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases.
    Title: JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases.
  5. Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes.
    Title: Genetic variants in MAPK10 modify renal cell carcinoma susceptibility and clinical outcomes.
  6. Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10.
    Title: Circ_0000515 drives the progression of hepatocellular carcinoma by regulating MAPK10.
  7. Propofol suppresses the progression of nonsmall cell lung cancer via downregulation of the miR215p/MAPK10 axis.
    Title: Propofol suppresses the progression of non‑small cell lung cancer via downregulation of the miR‑21‑5p/MAPK10 axis.
  8. Structural mechanisms of the arrestin-3/JNK3 interactions have been reported.
    Title: Structural Mechanism of the Arrestin-3/JNK3 Interaction.
  9. the present study identified a novel significant association between the increased expression levels of MAPK10, TUBB2B and RASL11B, and neuroblastoma cells.
    Title: Upregulation of MAPK10, TUBB2B and RASL11B may contribute to the development of neuroblastoma.
  10. phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3
    Title: Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification.
Submit: New GeneRIF Correction See all GeneRIFs (32)

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
Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines.
EBI GWAS Catalog
Genome wide association study identifies a novel putative mammographic density locus at 1q12-q21.
EBI GWAS Catalog
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.
EBI GWAS Catalog
The ATXN2-SH2B3 locus is associated with peripheral arterial disease: an electronic medical record-based genome-wide association study.
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 activates NMDA receptor directly and phosphorylates JNK through a gp120-mediated apoptotic pathway in human neuroblastoma cells PubMed
env CCR5 and CXCR4 coreceptor engagement by HIV-1 gp120 in primary macrophages activates 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase and p38 MAPK PubMed
env Pretreatment of CD4+ T cells with HIV-1 gp120 followed by stimulation with jacalin results in marked inhibition of phosphorylation of ERK2 as well as JNK PubMed
env HIV-1 gp120 activates c-Jun N-terminal kinase (JNK) and p42 extracellular-regulated kinase (ERK) in primary human central nervous system (CNS) cells with an early peak of activation at 2 to 5 minutes PubMed
Envelope surface glycoprotein gp160, precursor env The activation of mitogen-activated protein kinases (MAPKs, including ERK, JNK, and p38MAPK) is induced by incubation of HIV-1 gp160 with CD4+complement receptor type 2 (CR2)+ cells PubMed
env Pre-incubation of CD4+ T lymphocytes with anti-CD4 mAb or HIV-1 gp160 inhibits the activation of c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinase 2 (ERK2) in response to phorbol 12-myristate 13-acetate and ionomycin 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

  • FLJ12099, FLJ33785, MGC50974

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables JUN kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables JUN kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
enables JUN kinase activity TAS
Traceable Author Statement
more info
  
enables MAP kinase kinase activity TAS
Traceable Author Statement
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
  
Process Evidence Code Pubs
involved_in Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
  
involved_in JNK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in JNK cascade ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in cellular senescence TAS
Traceable Author Statement
more info
  
involved_in protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of circadian rhythm ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in response to light stimulus ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in rhythmic process IEA
Inferred from Electronic Annotation
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 TAS
Traceable Author Statement
more info
  
located_in mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
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 plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
mitogen-activated protein kinase 10
Names
JNK3 alpha protein kinase
MAP kinase 10
MAP kinase p49 3F12
c-Jun N-terminal kinase 3
stress activated protein kinase beta
stress-activated protein kinase 1b
stress-activated protein kinase JNK3
NP_001304996.1
NP_001304997.1
NP_001304998.1
NP_001338553.1
NP_001338554.1
NP_001350586.1
NP_002744.1
NP_620446.1
NP_620448.1
XP_047271920.1
XP_047271921.1
XP_047271922.1
XP_047271923.1
XP_047271924.1
XP_054206482.1
XP_054206483.1
XP_054206484.1
XP_054206485.1

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.

Genomic

  1. NG_013325.3 RefSeqGene

    Range
    239021..588669
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001318067.1 → NP_001304996.1  mitogen-activated protein kinase 10 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) contains an alternate in-frame coding exon compared to variant 1. The resulting isoform (5) is the same length; however, contains a different 23 aa protein segment compared to isoform 1.
    Source sequence(s)
    AC104059, AF052141, AK225974, BC035057
    Consensus CDS
    CCDS87243.1
    UniProtKB/TrEMBL
    A0A286YF97, A0A286YFA6
    Related
    ENSP00000493344.1, ENST00000641718.1
    Conserved Domains (1) summary
    cd07850
    Location:63 → 398
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  2. NM_001318068.1 → NP_001304997.1  mitogen-activated protein kinase 10 isoform 6

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) contains an alternate 5' terminal exon, lacks an internal exon and contains an alternate in-frame coding exon compared to variant 1. These differences result in translation initiation from an in-frame, downstream start codon, and an isoform (6) with a shorter N-terminus and containing a different 23 aa protein segment compared to isoform 1.
    Source sequence(s)
    AC104059, AF052141, AK057723, BC035057, BC051731
    UniProtKB/TrEMBL
    B7Z1Z1, Q499Y8
    Conserved Domains (1) summary
    cl21453
    Location:1 → 253
    PKc_like; Protein Kinases, catalytic domain

  3. NM_001318069.2 → NP_001304998.1  mitogen-activated protein kinase 10 isoform 1x

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (1, also known as JNK3 alpha2) results from translation termination at the upstream UGA stop codon, while the longer isoform (1x) results from UGA stop codon readthrough to the downstream UGA termination codon. This RefSeq represents the longer, C-terminally extended isoform (1x). As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), the location of the upstream UGA stop codon in the longer isoform is denoted by an 'X'.
    Source sequence(s)
    AC104059, AF052141, AK057723, BC022492, BC035057
    Consensus CDS
    CCDS93556.1
    UniProtKB/TrEMBL
    A0A286YFA6, F8W9R5
    Related
    ENSP00000414469.4, ENST00000449047.8
    Conserved Domains (2) summary
    smart00220
    Location:64 → 359
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd07850
    Location:63 → 398
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  4. NM_001351624.2 → NP_001338553.1  mitogen-activated protein kinase 10 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC104059, AF052141, AK307129, BC022492, BC035057
    Consensus CDS
    CCDS3612.1
    UniProtKB/TrEMBL
    A0A286YEN5
    Related
    ENSP00000493040.1, ENST00000642015.1
    Conserved Domains (1) summary
    cd07850
    Location:25 → 360
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  5. NM_001351625.3 → NP_001338554.1  mitogen-activated protein kinase 10 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC104059, AF052141, AK307129, BC022492, BC035057, CB069160
    Consensus CDS
    CCDS87242.1
    UniProtKB/TrEMBL
    A0A286YFI3, D6RJF9
    Related
    ENSP00000352157.4, ENST00000359221.8
    Conserved Domains (1) summary
    cd07850
    Location:25 → 360
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  6. NM_001363657.3 → NP_001350586.1  mitogen-activated protein kinase 10 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC096953, AC104059, AC104827, AC108054
    Consensus CDS
    CCDS87241.1
    UniProtKB/TrEMBL
    A0A286YEQ0, A0A286YFI3
    Related
    ENSP00000492922.1, ENST00000641208.1
    Conserved Domains (1) summary
    cd07850
    Location:25 → 360
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  7. NM_002753.6 → NP_002744.1  mitogen-activated protein kinase 10 isoform 2

    See identical proteins and their annotated locations for NP_002744.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate acceptor splice site at the 3' terminal exon, which causes a frameshift compared to variant 1. The resulting isoform (2, also know as JNK3 alpha1) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC096953, AC104059, AF052141, AK057723, U07620
    Consensus CDS
    CCDS43247.1
    UniProtKB/TrEMBL
    A0A286YFJ4
    Related
    ENSP00000493237.1, ENST00000641170.1
    Conserved Domains (1) summary
    cd07850
    Location:63 → 398
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  8. NM_138980.4 → NP_620446.1  mitogen-activated protein kinase 10 isoform 3

    See identical proteins and their annotated locations for NP_620446.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate acceptor splice site in the 5' region, which results in translation initiation from an in-frame, downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AC104059, AF052141, AK057723, BC022492, BC035057, DA192997
    Consensus CDS
    CCDS3612.1
    UniProtKB/TrEMBL
    A0A286YEN5
    Related
    ENSP00000491866.1, ENST00000638225.1
    Conserved Domains (1) summary
    cd07850
    Location:25 → 360
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

  9. NM_138982.4 → NP_620448.1  mitogen-activated protein kinase 10 isoform 1

    See identical proteins and their annotated locations for NP_620448.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (1, also known as JNK3 alpha2) results from translation termination at the upstream UGA stop codon, while the longer isoform (1x) results from UGA stop codon readthrough to the downstream UGA termination codon. This RefSeq represents the shorter isoform (1).
    Source sequence(s)
    AC104059, AF052141, AK057723, BC022492, BC035057
    Consensus CDS
    CCDS34026.1
    UniProtKB/Swiss-Prot
    A6NFS3, A6NG28, B3KQ94, P53779, Q15707, Q49AP1
    UniProtKB/TrEMBL
    A0A286YFA6
    Related
    ENSP00000493435.1, ENST00000641462.2
    Conserved Domains (1) summary
    cd07850
    Location:63 → 398
    STKc_JNK; Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase

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_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    86010405..86594074 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047415964.1 → XP_047271920.1  mitogen-activated protein kinase 10 isoform X1

  2. XM_047415966.1 → XP_047271922.1  mitogen-activated protein kinase 10 isoform X3

  3. XM_047415967.1 → XP_047271923.1  mitogen-activated protein kinase 10 isoform X4

    Related
    ENSP00000422277.2, ENST00000511167.6

  4. XM_047415968.1 → XP_047271924.1  mitogen-activated protein kinase 10 isoform X4

  5. XM_047415965.1 → XP_047271921.1  mitogen-activated protein kinase 10 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    89339877..89923587 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054350507.1 → XP_054206482.1  mitogen-activated protein kinase 10 isoform X1

  2. XM_054350509.1 → XP_054206484.1  mitogen-activated protein kinase 10 isoform X3

  3. XM_054350510.1 → XP_054206485.1  mitogen-activated protein kinase 10 isoform X4

  4. XM_054350508.1 → XP_054206483.1  mitogen-activated protein kinase 10 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_138981.2: Suppressed sequence

    Description
    NM_138981.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P53779.2 GenPept UniProtKB/Swiss-Prot:P53779

Gene LinkOut

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