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

Gene ID: 389840, updated on 5-Mar-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
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Genomic context

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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
  
involved_in phosphorylation IEA
Inferred from Electronic Annotation
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

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