TAK1 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. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. 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. 4 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.

Protein type: ASK subfamily; EC 2.7.11.25; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; STE group; STE11 family

Chromosomal Location of human Ortholog: 6q15

Cellular Component: ATAC complex; cytoplasm; cytosol; endosome membrane; plasma membrane

Molecular Function: ATP binding; DNA-binding transcription factor binding; histone kinase activity; identical protein binding; linear polyubiquitin binding; magnesium ion binding; MAP kinase activity; MAP kinase kinase kinase activity; MAP kinase kinase kinase kinase activity; protein binding; protein kinase activity; protein serine kinase activity; protein serine/threonine kinase activity; protein serine/threonine kinase binding; receptor tyrosine kinase binding; scaffold protein binding; transcription coactivator binding; type II transforming growth factor beta receptor binding; ubiquitin protein ligase binding

Biological Process: activation of NF-kappaB-inducing kinase activity; anoikis; cellular response to angiotensin; cellular response to oxygen-glucose deprivation; cellular response to tumor necrosis factor; chromatin remodeling; cytosolic pattern recognition receptor signaling pathway; Fc-epsilon receptor signaling pathway; histone H3 acetylation; I-kappaB kinase/NF-kappaB signaling; I-kappaB phosphorylation; immune response; inflammatory response; interleukin-1-mediated signaling pathway; interleukin-17A-mediated signaling pathway; JNK cascade; MAPK cascade; MyD88-dependent toll-like receptor signaling pathway; negative regulation of gene expression; negative regulation of voltage-gated calcium channel activity; nucleotide-binding oligomerization domain containing signaling pathway; p38MAPK cascade; positive regulation of cell cycle; positive regulation of cell size; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of interleukin-2 production; positive regulation of JUN kinase activity; positive regulation of macroautophagy; positive regulation of NF-kappaB transcription factor activity; positive regulation of T cell cytokine production; positive regulation of vascular associated smooth muscle cell migration; positive regulation of vascular associated smooth muscle cell proliferation; response to hypoxia; stimulatory C-type lectin receptor signaling pathway; stress-activated MAPK cascade; T cell receptor signaling pathway; toll-like receptor 4 signaling pathway; transforming growth factor beta receptor signaling pathway

Disease: Cardiospondylocarpofacial Syndrome; Frontometaphyseal Dysplasia 2

Reference #: O43318 (UniProtKB)

Alt. Names/Synonyms: CSCF; FMD2; M3K7; MAP3K7; MEKK7; Mitogen-activated protein kinase kinase kinase 7; TAK1; TGF-beta activated kinase 1; TGF-beta-activated kinase 1; TGF1a; Transforming growth factor-beta-activated kinase 1

Gene Symbols: MAP3K7

Molecular weight: 67,196 Da

Basal Isoelectric point: 6.69 Predict pI for various phosphorylation states

Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology^®

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TAK1

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