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 ... See more...

Aliases for MAP3K15 Gene

Aliases for MAP3K15 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 15 2 3 4 5
  • ASK3 2 3 4
  • Apoptosis Signal-Regulating Kinase 3 3 4
  • MAPK/ERK Kinase Kinase 15 3 4
  • MEK Kinase 15 3 4
  • EC 2.7.11.25 4 51
  • BA723P2.3 2 3
  • MEKK 15 3 4
  • EC 2.7.11 51
  • FLJ16518 2
  • MAP3K15 5

External Ids for MAP3K15 Gene

Previous GeneCards Identifiers for MAP3K15 Gene

  • GC0XM019138
  • GC0XM019288
  • GC0XM017127

Summaries for MAP3K15 Gene

Entrez Gene Summary for MAP3K15 Gene

  • 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]

GeneCards Summary for MAP3K15 Gene

MAP3K15 (Mitogen-Activated Protein Kinase Kinase Kinase 15) is a Protein Coding gene. Diseases associated with MAP3K15 include Pyruvate Dehydrogenase E1-Alpha Deficiency and Neuropathy, Hereditary Sensory And Autonomic, Type Iia. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP3K5.

UniProtKB/Swiss-Prot Summary for MAP3K15 Gene

  • May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis.

Additional gene information for MAP3K15 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP3K15 Gene

Genomics for MAP3K15 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MAP3K15 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ019514 Promoter 0.9 Ensembl 600.7 +0.2 161 2.6 PRDM10 ZNF692 ZIC2 RBFOX2 PATZ1 CTCF MGA ZBTB20 ZNF10 RNF2 MAP3K15 piR-41838-036 BCLAF3 piR-40110-716 PDHA1
GH0XJ019566 Enhancer 0.9 Ensembl ENCODE 0.2 -50.4 -50440 4.2 GATAD2A REST ZNF7 NR2C1 HDAC1 GABPA SOX6 PKNOX1 CEBPA EP300 SH3KBP1 BCLAF3 RF00017-8203 5MWI_A-186 MAP3K15
GH0XJ019544 Enhancer 0.7 Ensembl ENCODE 0.3 -29.4 -29422 1 CTCF FOXA1 REST RAD21 RUNX3 ZNF444 SMC3 ZNF654 RF00017-8203 hsa-miR-5095-527 MAP3K15 SH3KBP1
GH0XJ019342 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 0.1 +171.0 170960 3.4 SP1 CREB1 ZNF629 SOX13 ZNF692 POLR2A ZNF7 MTA2 RBFOX2 MTA1 PDHA1 HE855935 RF00017-8200 PHKA2 PHKA2-AS1 MAP3K15
GH0XJ019554 Enhancer 0.7 Ensembl ENCODE 0.3 -40.0 -39980 1.5 RELA IKZF2 EED RELB RUNX3 IKZF1 JUNB SPI1 BATF MTA2 RF00017-8203 hsa-miR-5095-527 MAP3K15 SH3KBP1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP3K15 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MAP3K15

Top Transcription factor binding sites by QIAGEN in the MAP3K15 gene promoter:
  • AML1a
  • HTF
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • PPAR-gamma1
  • PPAR-gamma2
  • RP58
  • RSRFC4
  • STAT3

Genomic Locations for MAP3K15 Gene

Genomic Locations for MAP3K15 Gene
chrX:19,360,056-19,515,261
(GRCh38/hg38)
Size:
155,206 bases
Orientation:
Minus strand
chrX:19,378,174-19,533,379
(GRCh37/hg19)
Size:
155,206 bases
Orientation:
Minus strand

Genomic View for MAP3K15 Gene

Genes around MAP3K15 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K15 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP3K15 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K15 Gene

Proteins for MAP3K15 Gene

  • Protein details for MAP3K15 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6ZN16-M3K15_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 15
    Protein Accession:
    Q6ZN16
    Secondary Accessions:
    • A2AI49
    • A2AI50
    • A6NJ61
    • Q5JPR4
    • Q6ZMV3

    Protein attributes for MAP3K15 Gene

    Size:
    1313 amino acids
    Molecular mass:
    147437 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for MAP3K15 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K15 Gene

Selected DME Specific Peptides for MAP3K15 Gene

Q6ZN16:
  • LFGFQDAVN
  • YGIVYAGRDLSNQVRIAIKEIPERD
  • KISDFGTSK
  • VPGGSLS
  • NLLLSYRD

Post-translational modifications for MAP3K15 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MAP3K15 Gene

Antibody Products

  • Abcam antibodies for MAP3K15
  • Boster Bio Antibodies for MAP3K15
  • Santa Cruz Biotechnology (SCBT) Antibodies for MAP3K15

Domains & Families for MAP3K15 Gene

Gene Families for MAP3K15 Gene

Suggested Antigen Peptide Sequences for MAP3K15 Gene

GenScript: Design optimal peptide antigens:
  • MAPK/ERK kinase kinase 15 (M3K15_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6ZN16

UniProtKB/Swiss-Prot:

M3K15_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with MAP3K15: view

Function for MAP3K15 Gene

Molecular function for MAP3K15 Gene

UniProtKB/Swiss-Prot Function:
May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.25; Evidence={ECO:0000269|PubMed:20362554};.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.25; Evidence={ECO:0000269|PubMed:20362554};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-812, inhibited by phosphorylation at Ser-924 and Ser-994 (By similarity).

Enzyme Numbers (IUBMB) for MAP3K15 Gene

Phenotypes From GWAS Catalog for MAP3K15 Gene

Gene Ontology (GO) - Molecular Function for MAP3K15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IBA 21873635
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004709 MAP kinase kinase kinase activity IBA 21873635
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with MAP3K15: view
genes like me logo Genes that share phenotypes with MAP3K15: view

Animal Models for MAP3K15 Gene

MGI Knock Outs for MAP3K15:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K15

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for MAP3K15 Gene

Localization for MAP3K15 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP3K15 gene
Compartment Confidence
nucleus 2
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Gene Ontology (GO) - Cellular Components for MAP3K15 Gene

Pathways & Interactions for MAP3K15 Gene

PathCards logo

SuperPathways for MAP3K15 Gene

No Data Available

Gene Ontology (GO) - Biological Process for MAP3K15 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000186 activation of MAPKK activity IBA 21873635
GO:0006468 protein phosphorylation IEA --
GO:0016310 phosphorylation IEA --
GO:0033554 cellular response to stress IBA 21873635
genes like me logo Genes that share ontologies with MAP3K15: view

No data available for Pathways by source and SIGNOR curated interactions for MAP3K15 Gene

Drugs & Compounds for MAP3K15 Gene

(2) Drugs for MAP3K15 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
genes like me logo Genes that share compounds with MAP3K15: view

Transcripts for MAP3K15 Gene

mRNA/cDNA for MAP3K15 Gene

1 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP3K15

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K15 Gene

No ASD Table

Relevant External Links for MAP3K15 Gene

GeneLoc Exon Structure for
MAP3K15

Expression for MAP3K15 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MAP3K15 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP3K15 Gene

This gene is overexpressed in Adrenal Gland (x35.0).

Protein differential expression in normal tissues from HIPED for MAP3K15 Gene

This gene is overexpressed in Serum (35.8), Adrenal (23.9), and Peripheral blood mononuclear cells (7.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for MAP3K15 Gene



Protein tissue co-expression partners for MAP3K15 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MAP3K15

SOURCE GeneReport for Unigene cluster for MAP3K15 Gene:

Hs.713701

mRNA Expression by UniProt/SwissProt for MAP3K15 Gene:

Q6ZN16-M3K15_HUMAN
Tissue specificity: Isoform 2 and isoform 3 are widely expressed. Isoform 2 highest levels are observed in fetal brain, and isoform 3 highest levels in pancreas, peripheral blood leukocytes, fetal brain and spleen.

Evidence on tissue expression from TISSUES for MAP3K15 Gene

  • Kidney(2.1)
genes like me logo Genes that share expression patterns with MAP3K15: view

Primer Products

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP3K15 Gene

Orthologs for MAP3K15 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP3K15 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MAP3K15 31
  • 99 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia MAP3K15 30 31
  • 87.86 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MAP3K15 30 31
  • 87.14 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Map3k15 30
  • 86.57 (n)
Mouse
(Mus musculus)
Mammalia Map3k15 30 17 31
  • 86.11 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MAP3K15 31
  • 78 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K15 31
  • 77 (a)
OneToOne
Chicken
(Gallus gallus)
Aves MAP3K15 30 31
  • 74.81 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MAP3K15 31
  • 80 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii MAP3K15 31
  • 72 (a)
OneToOne
map3k15 30
  • 70.85 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000747 30
  • 54.17 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta Pk92B 30 31
  • 53.28 (n)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea nsy-1 31
  • 34 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes STE11 31
  • 22 (a)
OneToMany
Species where no ortholog for MAP3K15 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for MAP3K15 Gene

ENSEMBL:
Gene Tree for MAP3K15 (if available)
TreeFam:
Gene Tree for MAP3K15 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP3K15: view image

Paralogs for MAP3K15 Gene

Paralogs for MAP3K15 Gene

(38) SIMAP similar genes for MAP3K15 Gene using alignment to 2 proteins:

  • M3K15_HUMAN
  • E7EWI5_HUMAN
genes like me logo Genes that share paralogs with MAP3K15: view

Variants for MAP3K15 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MAP3K15 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
770825 Benign: not provided 19,464,336(-) C/T MISSENSE_VARIANT
788841 Likely Benign: not provided 19,425,607(-) C/T MISSENSE_VARIANT
913014 Uncertain Significance: Pyruvate dehydrogenase E1-alpha deficiency 19,361,029(-) C/T THREE_PRIME_UTR_VARIANT,INTRON_VARIANT
913015 Benign: Pyruvate dehydrogenase E1-alpha deficiency 19,361,030(-) G/A THREE_PRIME_UTR_VARIANT,INTRON_VARIANT
913016 Benign: Pyruvate dehydrogenase E1-alpha deficiency 19,361,047(-) C/T THREE_PRIME_UTR_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for MAP3K15 Gene

Structural Variations from Database of Genomic Variants (DGV) for MAP3K15 Gene

Variant ID Type Subtype PubMed ID
dgv1395e199 CNV deletion 23128226
esv23814 CNV loss 19812545
esv2740000 CNV deletion 23290073
esv2740001 CNV deletion 23290073
esv3558663 CNV deletion 23714750
esv3558664 CNV deletion 23714750
esv3558667 CNV deletion 23714750
esv3573627 CNV loss 25503493
esv3573628 CNV loss 25503493
esv3573629 CNV loss 25503493
esv3573630 CNV loss 25503493
nsv1076247 CNV deletion 25765185
nsv1077221 CNV deletion 25765185
nsv1126943 CNV deletion 24896259
nsv1132237 CNV deletion 24896259
nsv1145286 CNV deletion 24896259
nsv425077 CNV insertion 16902084
nsv528469 CNV gain 19592680
nsv957810 CNV deletion 24416366

Variation tolerance for MAP3K15 Gene

Gene Damage Index Score: 3.96; 59.78% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP3K15 Gene

Human Gene Mutation Database (HGMD)
MAP3K15
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP3K15

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K15 Gene

Disorders for MAP3K15 Gene

MalaCards: The human disease database

(3) MalaCards diseases for MAP3K15 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP3K15

genes like me logo Genes that share disorders with MAP3K15: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP3K15 Gene

Publications for MAP3K15 Gene

  1. ASK3, a novel member of the apoptosis signal-regulating kinase family, is essential for stress-induced cell death in HeLa cells. (PMID: 20362554) Kaji T … Kishimoto T (Biochemical and biophysical research communications 2010) 2 3 4
  2. ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney. (PMID: 23250415) Naguro I … Ichijo H (Nature communications 2012) 2 3
  3. The DNA sequence of the human X chromosome. (PMID: 15772651) Ross MT … Bentley DR (Nature 2005) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress. (PMID: 29539411) Watanabe K … Ichijo H (Cell reports 2018) 3

Products for MAP3K15 Gene

Sources for MAP3K15 Gene