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: 6q16
Cellular Component: actin cytoskeleton; apical plasma membrane; cell surface; cytoplasm; cytosol; extracellular space; focal adhesion; integral component of membrane; 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; 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; integrin-mediated signaling pathway; membrane protein ectodomain proteolysis; negative regulation of apoptosis; negative regulation of neuron projection development; negative regulation of transforming growth factor beta receptor signaling pathway; 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 protein phosphorylation; positive regulation of T cell chemotaxis; positive regulation of transforming growth factor beta receptor signaling pathway; production of molecular mediator of acute inflammatory response; proteolysis; regulation of axon regeneration; regulation of mast cell apoptotic process; regulation of neuron migration; response to drug; response to high density lipoprotein stimulus; response to hypoxia; response to lipopolysaccharide; spleen development; T cell differentiation in thymus; wound healing, spreading of epidermal cells
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