Mitogen-activated protein kinase kinase kinase 7 (O43318)

Uniprot ID	O43318
Protein Name	Mitogen-activated protein kinase kinase kinase 7
Gene Name	MAP3K7
Species	Homo sapiens (Human)

Signal peptide^(a)	N	Secretome P^(b)	0.591
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. .
GO - Molecular function	ATP binding : IEA:UniProtKB-KW identical protein binding : IPI:UniProtKB magnesium ion binding : IEA:InterPro MAP kinase kinase kinase activity : IDA:UniProtKB protein kinase activity : IDA:UniProtKB protein serine/threonine kinase activity : EXP:Reactome receptor tyrosine kinase binding : IPI:WormBase scaffold protein binding : IDA:MGI
GO - Biological process	activation of MAPK activity : IDA:UniProtKB activation of MAPKK activity : IDA:UniProtKB activation of NF-kappaB-inducing kinase activity : IMP:UniProtKB anoikis : ISS:BHF-UCL Fc-epsilon receptor signaling pathway : TAS:Reactome histone H3 acetylation : IDA:BHF-UCL I-kappaB kinase/NF-kappaB signaling : TAS:Reactome I-kappaB phosphorylation : IDA:UniProtKB interleukin-1-mediated signaling pathway : TAS:Reactome JNK cascade : IDA:UniProtKB MyD88-dependent toll-like receptor signaling pathway : TAS:Reactome nucleotide-binding oligomerization domain containing signaling pathway : TAS:Reactome positive regulation of I-kappaB kinase/NF-kappaB signaling : IMP:UniProtKB positive regulation of interleukin-2 production : IMP:UniProtKB positive regulation of JUN kinase activity : IDA:UniProtKB positive regulation of macroautophagy : ISS:BHF-UCL positive regulation of NF-kappaB transcription factor activity : TAS:Reactome positive regulation of T cell cytokine production : IMP:UniProtKB protein deubiquitination : TAS:Reactome stimulatory C-type lectin receptor signaling pathway : TAS:Reactome stress-activated MAPK cascade : IDA:UniProtKB T cell receptor signaling pathway : TAS:Reactome transcription, DNA-templated : IEA:UniProtKB-KW transforming growth factor beta receptor signaling pathway : TAS:ProtInc viral process : IEA:UniProtKB-KW Wnt signaling pathway, calcium modulating pathway : TAS:Reactome

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^{(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.}
^{(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.}