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    MAP3K15 mitogen-activated protein kinase kinase kinase 15 [ Homo sapiens (human) ]

    Gene ID: 389840, updated on 2-May-2024

    Summary

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    Official Symbol
    MAP3K15provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 15provided by HGNC
    Primary source
    HGNC:HGNC:31689
    See related
    Ensembl:ENSG00000180815 MIM:300820; AllianceGenome:HGNC:31689
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ASK3; bA723P2.3
    Summary
    The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAPK) family. These family members function in a protein kinase signal transduction cascade, where an activated MAPK kinase kinase (MAP3K) phosphorylates and activates a specific MAPK kinase (MAP2K), which then activates a specific MAPK. This MAP3K protein plays an essential role in apoptotic cell death triggered by cellular stresses. [provided by RefSeq, Jul 2010]
    Expression
    Ubiquitous expression in adrenal (RPKM 7.5), heart (RPKM 3.2) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MAP3K15 in Genome Data Viewer
    Location:
    Xp22.12
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (19360059..19515508, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (18942795..19098393, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (19378177..19533626, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 48, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:19002034-19002534 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29461 Neighboring gene uncharacterized LOC101928415 Neighboring gene phosphorylase kinase regulatory subunit alpha 2 Neighboring gene adhesion G protein-coupled receptor G2 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:19125111-19125740 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:19182810-19182961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29462 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:19278446-19278946 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:19309116-19309616 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:19309617-19310117 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:19391289-19392229 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29463 Neighboring gene pyruvate dehydrogenase E1 subunit alpha 1 Neighboring gene eukaryotic translation initiation factor 5 pseudogene 2 Neighboring gene SH3 domain containing kinase binding protein 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chrX:19643274-19644473 Neighboring gene uncharacterized LOC124905255 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:19740595-19741095 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29464 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29465 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29466 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29467 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20687 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20688 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:19820680-19821600 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29468 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20689 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29469 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29470 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29471 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:19880674-19881280 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29472 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29473 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29474 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29475 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20690 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20691 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20692 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29476 Neighboring gene uncharacterized LOC124905256 Neighboring gene BCLAF1 and THRAP3 family member 3

    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. Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes. Nag A, et al. Sci Adv, 2022 Nov 18. PMID 36383675, Free PMC Article
    2. Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway. Maruyama J, et al. Sci Rep, 2016 Jan 6. PMID 26732173, Free PMC Article
    3. ASK3, a novel member of the apoptosis signal-regulating kinase family, is essential for stress-induced cell death in HeLa cells. Kaji T, et al. Biochem Biophys Res Commun, 2010 Apr 30. PMID 20362554
    4. ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney. Naguro I, et al. Nat Commun, 2012. PMID 23250415
    5. Structure-based mechanism of preferential complex formation by apoptosis signal-regulating kinases. Trevelyan SJ, et al. Sci Signal, 2020 Mar 10. PMID 32156783

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes.
      Title: Human genetics uncovers MAP3K15 as an obesity-independent therapeutic target for diabetes.
    2. Structure-based mechanism of preferential complex formation by apoptosis signal-regulating kinases.
      Title: Structure-based mechanism of preferential complex formation by apoptosis signal-regulating kinases.
    3. Macromolecular crowding induces liquid-demixing condensates of ASK3 under hyperosmotic stress, which transduce osmosensing signal into ASK3 inactivation.
      Title: Cells recognize osmotic stress through liquid-liquid phase separation lubricated with poly(ADP-ribose).
    4. ASK3 controls both RVD and RVI under osmotic stress.
      Title: A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress.
    5. "ASK3 gene" is a novel member of apoptosis signal-regulating kinases and that it plays a pivotal role in the signal transduction pathway implicated in apoptotic cell death triggered by cellular stresses.
      Title: ASK3, a novel member of the apoptosis signal-regulating kinase family, is essential for stress-induced cell death in HeLa cells.
    Submit: New GeneRIF Correction

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ16518

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables MAP kinase kinase kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables MAP kinase kinase kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to stress IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 15
    Names
    MAPK/ERK kinase kinase 15
    MEK kinase 15
    MEKK 15
    apoptosis signal-regulating kinase 3
    NP_001001671.3
    XP_011543809.4
    XP_011543810.4
    XP_011543812.1
    XP_011543813.1
    XP_047298056.1
    XP_054183012.1
    XP_054183013.1
    XP_054183014.1
    XP_054183015.1
    XP_054183016.1

    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.

    Genomic

    1. NG_021184.1 RefSeqGene

      Range
      4754..160203
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001001671.4 → NP_001001671.3  mitogen-activated protein kinase kinase kinase 15

      See identical proteins and their annotated locations for NP_001001671.3

      Status: VALIDATED

      Source sequence(s)
      AL732326, AL732423
      Consensus CDS
      CCDS35212.2
      UniProtKB/Swiss-Prot
      A2AI49, A2AI50, A6NJ61, Q5JPR4, Q6ZMV3, Q6ZN16
      Related
      ENSP00000345629.4, ENST00000338883.9
      Conserved Domains (3) summary
      smart00220
      Location:657 → 908
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06624
      Location:643 → 908
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
      pfam13281
      Location:136 → 514
      DUF4071; Domain of unknown function (DUF4071)

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      19360059..19515508 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011545508.4 → XP_011543810.4  mitogen-activated protein kinase kinase kinase 15 isoform X2

    2. XM_011545507.4 → XP_011543809.4  mitogen-activated protein kinase kinase kinase 15 isoform X1

    3. XM_011545510.3 → XP_011543812.1  mitogen-activated protein kinase kinase kinase 15 isoform X3

      Conserved Domains (3) summary
      smart00220
      Location:215 → 466
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06624
      Location:201 → 466
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase
      pfam13281
      Location:1 → 72
      DUF4071; Domain of unknown function (DUF4071)

    4. XM_011545511.2 → XP_011543813.1  mitogen-activated protein kinase kinase kinase 15 isoform X5

      See identical proteins and their annotated locations for XP_011543813.1

      UniProtKB/Swiss-Prot
      Q6ZN16
      Conserved Domains (2) summary
      smart00220
      Location:92 → 343
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd06624
      Location:78 → 343
      STKc_ASK; Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase

    5. XM_047442100.1 → XP_047298056.1  mitogen-activated protein kinase kinase kinase 15 isoform X4

    RNA

    1. XR_007068188.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      18942795..19098393 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327038.1 → XP_054183013.1  mitogen-activated protein kinase kinase kinase 15 isoform X2

    2. XM_054327037.1 → XP_054183012.1  mitogen-activated protein kinase kinase kinase 15 isoform X1

    3. XM_054327039.1 → XP_054183014.1  mitogen-activated protein kinase kinase kinase 15 isoform X3

    4. XM_054327041.1 → XP_054183016.1  mitogen-activated protein kinase kinase kinase 15 isoform X5

    5. XM_054327040.1 → XP_054183015.1  mitogen-activated protein kinase kinase kinase 15 isoform X4

    RNA

    1. XR_008485479.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6ZN16.2 GenPept UniProtKB/Swiss-Prot:Q6ZN16

    Gene LinkOut

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