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Aliases for MAP3K7 Gene

Aliases for MAP3K7 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 7 2 3
  • TAK1 3 4 6
  • Transforming Growth Factor-Beta-Activated Kinase 1 3 4
  • TGF-Beta-Activated Kinase 1 3 4
  • EC 2.7.11.25 4 63
  • TGF-Beta Activated Kinase 1 3
  • EC 2.7.11 63
  • MEKK7 3
  • TGF1a 3

External Ids for MAP3K7 Gene

Previous HGNC Symbols for MAP3K7 Gene

  • TAK1

Previous GeneCards Identifiers for MAP3K7 Gene

  • GC06M091171
  • GC06M091220
  • GC06M091282
  • GC06M088444

Summaries for MAP3K7 Gene

Entrez Gene Summary for MAP3K7 Gene

  • The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

GeneCards Summary for MAP3K7 Gene

MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7) is a Protein Coding gene. Among its related pathways are PI-3K cascade and MAPK signaling pathway. GO annotations related to this gene include protein serine/threonine kinase activity and protein kinase activity. An important paralog of this gene is MAP3K9.

UniProtKB/Swiss-Prot for MAP3K7 Gene

  • Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.

Gene Wiki entry for MAP3K7 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP3K7 Gene

Genomics for MAP3K7 Gene

Regulatory Elements for MAP3K7 Gene

Transcription factor binding sites by QIAGEN in the MAP3K7 gene promoter:

Genomic Location for MAP3K7 Gene

Start:
90,513,573 bp from pter
End:
90,587,301 bp from pter
Size:
73,729 bases
Orientation:
Minus strand

Genomic View for MAP3K7 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MAP3K7 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K7 Gene

Proteins for MAP3K7 Gene

  • Protein details for MAP3K7 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43318-M3K7_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 7
    Protein Accession:
    O43318
    Secondary Accessions:
    • B2RE27
    • E1P523
    • O43317
    • O43319
    • Q5TDN2
    • Q5TDN3
    • Q5TDT7
    • Q9NTR3
    • Q9NZ70

    Protein attributes for MAP3K7 Gene

    Size:
    606 amino acids
    Molecular mass:
    67196 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3. Identified in the TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2. Interacts with PPM1L and PPM1B/PP2CB. Interaction with PP2A and PPP6C leads to its repressed activity. Interacts with TRAF6 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with TAOK1 and TAOK2; interaction with TAOK2 interferes with MAP3K7 interaction with IKKA, thus preventing NF-kappa-B activation. Interacts with WDR34 (via WD domains). Interacts with CYLD and RBCK1. Interacts with TGFBR1; induces MAP3K7/TAK1 activation by TRAF6. Interacts with MAPK8IP1 and SMAD6 (By similarity). Interacts with isoform 1 of VRK2. Interacts with DAB2; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation. Interacts with TRIM5.

    Three dimensional structures from OCA and Proteopedia for MAP3K7 Gene

    Alternative splice isoforms for MAP3K7 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K7 Gene

Proteomics data for MAP3K7 Gene at MOPED

Selected DME Specific Peptides for MAP3K7 Gene

Post-translational modifications for MAP3K7 Gene

  • Association with TAB1/MAP3K7IP1 promotes autophosphorylation at Ser-192 and subsequent activation. Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7. Dephosphorylation at Ser-192 by PPM1B/PP2CB and at Thr-187 by PP2A and PPP6C leads to inactivation.
  • Lys-48-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation. Requires Lys-63-linked polyubiquitination for autophosphorylation and subsequent activation. Lys-63-linked ubiquitination does not lead to proteasomal degradation. Deubiquitinated by CYLD, a protease that selectively cleaves Lys-63-linked ubiquitin chains. Deubiquitinated by Y.enterocolitica YopP.
  • Ubiquitination at Lys72 and Lys547
  • Modification sites at PhosphoSitePlus

Other Protein References for MAP3K7 Gene

Domains for MAP3K7 Gene

Gene Families for MAP3K7 Gene

HGNC:
  • MAP3K :Mitogen-activated protein kinase cascade / Kinase kinase kinases
IUPHAR :

Suggested Antigen Peptide Sequences for MAP3K7 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O43318

UniProtKB/Swiss-Prot:

M3K7_HUMAN :
  • O43318
Domain:
  • Contains 1 protein kinase domain.
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 MAP3K7: view

Function for MAP3K7 Gene

Molecular function for MAP3K7 Gene

GENATLAS Biochemistry: mitogen activated protein (MAP/ERK) kinase kinase kinase 7,widely expressed,activated by MAP4K4 (see symbol) in JNK signaling pathway,involved in the BMP signaling through binding with API3 (XIAP)3,also associating with TRAF6 during IL-1 signaling and activating NFKB
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by proinflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation. Activated by Lys-63-linked polyubiquitination and by autophosphorylation. Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation.
UniProtKB/Swiss-Prot Function: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity.

Enzyme Numbers (IUBMB) for MAP3K7 Gene

Gene Ontology (GO) - Molecular Function for MAP3K7 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IEA --
GO:0004672 protein kinase activity IDA 10094049
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004708 MAP kinase kinase activity IEA --
GO:0004709 MAP kinase kinase kinase activity IDA 11460167
genes like me logo Genes that share ontologies with MAP3K7: view
genes like me logo Genes that share phenotypes with MAP3K7: view

Animal Models for MAP3K7 Gene

MGI Knock Outs for MAP3K7:

No data available for Transcription Factor Targeting and HOMER Transcription for MAP3K7 Gene

Localization for MAP3K7 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K7 Gene

Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Although the majority of MAP3K7/TAK1 is found in the cytosol, when complexed with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2, it is also localized at the cell membrane.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP3K7 Gene COMPARTMENTS Subcellular localization image for MAP3K7 gene
Compartment Confidence
plasma membrane 5
cytosol 4
endosome 4
nucleus 4

Gene Ontology (GO) - Cellular Components for MAP3K7 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005671 Ada2/Gcn5/Ada3 transcription activator complex IDA 18838386
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MAP3K7: view

Pathways for MAP3K7 Gene

genes like me logo Genes that share pathways with MAP3K7: view

Gene Ontology (GO) - Biological Process for MAP3K7 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade --
GO:0000186 activation of MAPKK activity IDA 8663074
GO:0000187 activation of MAPK activity TAS --
GO:0001525 angiogenesis IEA --
GO:0001841 neural tube formation IEA --
genes like me logo Genes that share ontologies with MAP3K7: view

Compounds for MAP3K7 Gene

(3) HMDB Compounds for MAP3K7 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(13) Novoseek inferred chemical compound relationships for MAP3K7 Gene

Compound -log(P) Hits PubMed IDs
tab-1 97.8 84
tab-2 97.3 85
threonine 46.5 4
sb 203580 42.1 2
serine 34.1 6
genes like me logo Genes that share compounds with MAP3K7: view

Transcripts for MAP3K7 Gene

Unigene Clusters for MAP3K7 Gene

Mitogen-activated protein kinase kinase kinase 7:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K7 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ·
SP1: - -
SP2: - - -
SP3: -
SP4: -
SP5: -
SP6:
SP7: - - - - - -

ExUns: 19c
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:

Relevant External Links for MAP3K7 Gene

GeneLoc Exon Structure for
MAP3K7
ECgene alternative splicing isoforms for
MAP3K7

Expression for MAP3K7 Gene

mRNA expression in normal human tissues for MAP3K7 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP3K7 Gene

SOURCE GeneReport for Unigene cluster for MAP3K7 Gene Hs.594838

mRNA Expression by UniProt/SwissProt for MAP3K7 Gene

O43318-M3K7_HUMAN
Tissue specificity: Isoform 1A is the most abundant in ovary, skeletal muscle, spleen and blood mononuclear cells. Isoform 1B is highly expressed in brain, kidney and small intestine. Isoform 1C is the major form in prostate. Isoform 1D is the less abundant form.
genes like me logo Genes that share expressions with MAP3K7: view

No data available for mRNA differential expression in normal tissues for MAP3K7 Gene

Orthologs for MAP3K7 Gene

This gene was present in the common ancestor of animals.

Orthologs for MAP3K7 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP3K7 35
  • 99.61 (n)
  • 100 (a)
MAP3K7 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MAP3K7 35
  • 94.8 (n)
  • 99.47 (a)
MAP3K7 36
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LOC102156745 35
  • 97.08 (n)
  • 100 (a)
MAP3K7 36
  • 100 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map3k7 16
Map3k7 36
  • 99 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP3K7 36
  • 98 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 81 (a)
OneToMany
-- 36
  • 96 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Map3k7 35
  • 91.86 (n)
  • 99.01 (a)
chicken
(Gallus gallus)
Aves MAP3K7 35
  • 85.17 (n)
  • 92.36 (a)
MAP3K7 36
  • 89 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP3K7 36
  • 89 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.274 35
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k7 35
  • 83.15 (n)
  • 96.34 (a)
Str.3144 35
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.12347 35
zebrafish
(Danio rerio)
Actinopterygii Dr.17131 35
map3k7 36
  • 76 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Tak1 36
  • 31 (a)
OneToMany
Takl1 36
  • 33 (a)
OneToMany
Takl2 36
  • 42 (a)
OneToMany
Takl1 37
  • 31 (a)
Tak1 37
  • 54 (a)
Takl2 37
  • 40 (a)
worm
(Caenorhabditis elegans)
Secernentea mom-4 37
  • 32 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 50 (a)
OneToOne
Species with no ortholog for MAP3K7:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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)
  • wheat (Triticum aestivum)

Evolution for MAP3K7 Gene

ENSEMBL:
Gene Tree for MAP3K7 (if available)
TreeFam:
Gene Tree for MAP3K7 (if available)

Paralogs for MAP3K7 Gene

Selected SIMAP similar genes for MAP3K7 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with MAP3K7: view

Variants for MAP3K7 Gene

Sequence variations from dbSNP and Humsavar for MAP3K7 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs9396 -- 90,515,792(-) AAGAT(A/T)TTTAA utr-variant-3-prime
rs10894 -- 90,513,901(-) TTTAC(A/G)GATGT utr-variant-3-prime
rs150117 -- 90,558,630(+) GAAGG(A/T)TATAT intron-variant
rs150123 -- 90,531,770(-) TCACC(A/C)TGTTG intron-variant
rs150124 -- 90,529,781(-) TTTTG(A/G)AGAGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K7 Gene

Variant ID Type Subtype PubMed ID
nsv523939 CNV Gain 19592680
esv2449643 CNV Deletion 19546169
esv1987764 CNV Deletion 18987734
esv3668 CNV Deletion 18987735
esv2732413 CNV Deletion 23290073
esv992475 CNV Deletion 20482838
esv5848 CNV Loss 19470904
esv1333350 CNV Deletion 17803354

Relevant External Links for MAP3K7 Gene

HapMap Linkage Disequilibrium report
MAP3K7
Locus Specific Mutation Databases (LSDB)
MAP3K7

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K7 Gene

Disorders for MAP3K7 Gene

(14) Novoseek inferred disease relationships for MAP3K7 Gene

Disease -log(P) Hits PubMed IDs
necrosis 51.4 21
tumors 35.8 21
inflammation 22.8 2
adenocarcinoma lung 8.3 1
cancer 3.73 2

Relevant External Links for MAP3K7

Genetic Association Database (GAD)
MAP3K7
Human Genome Epidemiology (HuGE) Navigator
MAP3K7
genes like me logo Genes that share disorders with MAP3K7: view

No data available for UniProtKB/Swiss-Prot for MAP3K7 Gene

Publications for MAP3K7 Gene

  1. TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. (PMID: 8638164) Shibuya H. … Matsumoto K. (Science 1996) 3 4 23
  2. A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. (PMID: 8663074) Moriguchi T. … Hagiwara M. (J. Biol. Chem. 1996) 3 4 23
  3. TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. (PMID: 9079627) Shirakabe K. … Nishida E. (J. Biol. Chem. 1997) 3 4 23
  4. Molecular cloning of human TAK1 and its mutational analysis in human lung cancer. (PMID: 9466656) Kondo M. … Takahashi T. (Int. J. Cancer 1998) 2 3 23
  5. TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism. (PMID: 9480845) Sakurai H. … Sugita T. (Biochem. Biophys. Res. Commun. 1998) 3 4 23

Products for MAP3K7 Gene

Sources for MAP3K7 Gene

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