TACE: a type I membrane protein with disintegrin and metalloprotease activity. An ubiquitously expressed ectoenzyme of peptidase family M12B. Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Possesses a narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha) to its mature soluble form. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, and the amyloid precursor protein. Also involved in the activation of Notch pathway. Binds 1 zinc ion per subunit. Two splice variant isoforms have been described.
Protein type: EC 3.4.24.86; Membrane protein, integral; Motility/polarity/chemotaxis; Protease
Chromosomal Location of Human Ortholog: 2p25.1
Cellular Component: actin cytoskeleton; apical plasma membrane; cell surface; cytoplasm; cytosol; focal adhesion; integral component of plasma membrane; intercellular junction; membrane; membrane raft; plasma membrane
Molecular Function: integrin binding; interleukin-6 receptor binding; metal ion binding; metalloendopeptidase activity; metallopeptidase activity; Notch binding; PDZ domain binding; protein binding; SH3 domain binding
Biological Process: B cell differentiation; cell adhesion; cell adhesion mediated by integrin; cell motility; defense response to Gram-positive bacterium; epidermal growth factor receptor signaling pathway; germinal center formation; membrane protein ectodomain proteolysis; membrane protein intracellular domain proteolysis; negative regulation of transforming growth factor beta receptor signaling pathway; neutrophil mediated immunity; Notch receptor processing; Notch signaling pathway; PMA-inducible membrane protein ectodomain proteolysis; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of cellular component movement; positive regulation of chemokine production; positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; positive regulation of epidermal growth factor-activated receptor activity; positive regulation of leukocyte chemotaxis; positive regulation of protein phosphorylation; positive regulation of T cell chemotaxis; positive regulation of transforming growth factor beta receptor signaling pathway; proteolysis; regulation of mast cell apoptotic process; response to drug; response to high density lipoprotein stimulus; response to hypoxia; response to lipopolysaccharide; spleen development; T cell differentiation in thymus; tumor necrosis factor-mediated signaling pathway; wound healing, spreading of epidermal cells
Disease: Inflammatory Skin And Bowel Disease, Neonatal, 1
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