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    MAP3K10 mitogen-activated protein kinase kinase kinase 10 [ Homo sapiens (human) ]

    Gene ID: 4294, updated on 10-Dec-2024

    Summary

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    Official Symbol
    MAP3K10provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 10provided by HGNC
    Primary source
    HGNC:HGNC:6849
    See related
    Ensembl:ENSG00000130758 MIM:600137; AllianceGenome:HGNC:6849
    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
    MST; MLK2; MEKK10
    Summary
    The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase has been shown to activate MAPK8/JNK and MKK4/SEK1, and this kinase itself can be phoshorylated, and thus activated by JNK kinases. This kinase functions preferentially on the JNK signaling pathway, and is reported to be involved in nerve growth factor (NGF) induced neuronal apoptosis. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in brain (RPKM 11.1), testis (RPKM 4.1) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAP3K10 in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (40191426..40215575)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (43011933..43036086)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (40697333..40721482)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904803 Neighboring gene MPRA-validated peak3482 silencer Neighboring gene vomeronasal 1 receptor 96 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14639 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14640 Neighboring gene Sharpr-MPRA regulatory region 5792 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14641 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10616 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10617 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:40711899-40712419 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:40723159-40723749 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr19:40725328-40726527 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr19:40729726-40730925 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10618 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:40732430-40732983 Neighboring gene tetratricopeptide repeat domain 9B Neighboring gene cyclin P

    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. DNA methylation of the MAP3K10 gene may participate in the development of intracranial aneurysm. Zhao J, et al. Gene, 2023 Jan 30. PMID 36341729
    2. Cloning and characterization of MST, a novel (putative) serine/threonine kinase with SH3 domain. Katoh M, et al. Oncogene, 1995 Apr 6. PMID 7731697
    3. Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2. Hirai S, et al. J Biol Chem, 1998 Mar 27. PMID 9516438
    4. Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2. Dorow DS, et al. Eur J Biochem, 1995 Dec 1. PMID 8536694
    5. Mixed lineage kinase 2 and hippocalcin are localized in Lewy bodies of Parkinson's disease. Nagao M, et al. J Neurol Sci, 2009 Jun 15. PMID 19332348

    See all (47) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. DNA methylation of the MAP3K10 gene may participate in the development of intracranial aneurysm.
      Title: DNA methylation of the MAP3K10 gene may participate in the development of intracranial aneurysm.
    2. DNA methylationregulated miR1555p depresses sensitivity of esophageal carcinoma cells to radiation and multiple chemotherapeutic drugs via suppression of MAP3K10.
      Title: DNA methylation‑regulated miR‑155‑5p depresses sensitivity of esophageal carcinoma cells to radiation and multiple chemotherapeutic drugs via suppression of MAP3K10.
    3. MST interaction with MOB1 is not essential for development and tissue growth control.
      Title: Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.
    4. We identified a direct target of miR-155 as MAP3K10 in osteosarcoma
      Title: MicroRNA-155 targets MAP3K10 and regulates osteosarcoma cell growth.
    5. MAP3K4 is sufficiently mediate the TGFbeta-induced phosphorylation of p38 MAPK in MEFs and HaCaT cells.
      Title: The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1.
    6. A novel and important role for MAP3K10 in the proliferation and chemoresistance of pancreatic ductal adenocarcinoma.
      Title: MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2.
    7. This study showed that show that RUNX3 is a principal and evolutionarily conserved component of the MST pathway.
      Title: Identification of RUNX3 as a component of the MST/Hpo signaling pathway.
    8. Mechanism of MAP kinase activation by TNF requires Src-dependent activation of Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site on MLK3.
      Title: TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway.
    9. Mechanism of MAP kinase activation by TNF requires Src-dependent activation of Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site on MLK2 and 3.
      Title: TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway.
    10. Data show that miR-181b contributed to proliferation of AML cells by targeting MLK2.
      Title: microRNA-181b targets MLK2 in HL-60 cells.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    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)

    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 kinase kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables JUN kinase kinase kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables bHLH transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription corepressor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in JNK cascade TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of DNA-binding transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-threonine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of JNK cascade IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of JUN kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in smoothened signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 10
    Names
    MKN28 derived nonreceptor_type serine/threonine kinase
    MKN28 kinase
    mixed lineage kinase 2
    protein kinase MST
    NP_002437.2
    XP_011525283.1
    XP_011525284.1
    XP_047294800.1
    XP_047294801.1
    XP_054177013.1
    XP_054177014.1
    XP_054177015.1
    XP_054177016.1

    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_002446.4 → NP_002437.2  mitogen-activated protein kinase kinase kinase 10

      See identical proteins and their annotated locations for NP_002437.2

      Status: REVIEWED

      Source sequence(s)
      AC011496, BF594729, BU633407, X90846, Z48615
      Consensus CDS
      CCDS12549.1
      UniProtKB/Swiss-Prot
      Q02779, Q12761, Q14871
      Related
      ENSP00000253055.2, ENST00000253055.8
      Conserved Domains (3) summary
      smart00219
      Location:98 → 357
      TyrKc; Tyrosine kinase, catalytic domain
      cd12059
      Location:20 → 76
      SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
      cd14148
      Location:103 → 360
      STKc_MLK2; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      40191426..40215575
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011526981.3 → XP_011525283.1  mitogen-activated protein kinase kinase kinase 10 isoform X1

      Conserved Domains (3) summary
      smart00219
      Location:98 → 365
      TyrKc; Tyrosine kinase, catalytic domain
      cd12059
      Location:20 → 76
      SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
      cl21453
      Location:103 → 368
      PKc_like; Protein Kinases, catalytic domain

    2. XM_011526982.4 → XP_011525284.1  mitogen-activated protein kinase kinase kinase 10 isoform X2

      Conserved Domains (3) summary
      smart00219
      Location:98 → 365
      TyrKc; Tyrosine kinase, catalytic domain
      cd12059
      Location:20 → 76
      SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
      cl21453
      Location:103 → 368
      PKc_like; Protein Kinases, catalytic domain

    3. XM_047438844.1 → XP_047294800.1  mitogen-activated protein kinase kinase kinase 10 isoform X3

    4. XM_047438845.1 → XP_047294801.1  mitogen-activated protein kinase kinase kinase 10 isoform X4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      43011933..43036086
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321038.1 → XP_054177013.1  mitogen-activated protein kinase kinase kinase 10 isoform X1

    2. XM_054321039.1 → XP_054177014.1  mitogen-activated protein kinase kinase kinase 10 isoform X2

    3. XM_054321040.1 → XP_054177015.1  mitogen-activated protein kinase kinase kinase 10 isoform X3

    4. XM_054321041.1 → XP_054177016.1  mitogen-activated protein kinase kinase kinase 10 isoform X4

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q02779.3 GenPept UniProtKB/Swiss-Prot:Q02779

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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