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: Protease; Motility/polarity/chemotaxis; Membrane protein, integral; EC 3.4.24.86
Chromosomal Location of Human Ortholog: 2p25
Cellular Component: focal adhesion; cell surface; membrane; integral to plasma membrane; apical plasma membrane; cytoplasm; plasma membrane; intercellular junction; lipid raft; actin cytoskeleton
Molecular Function: integrin binding; protein binding; interleukin-6 receptor binding; metallopeptidase activity; zinc ion binding; metalloendopeptidase activity; Notch binding; SH3 domain binding; PDZ domain binding
Biological Process: extracellular matrix organization and biogenesis; nerve growth factor receptor signaling pathway; cell motility involved in cell locomotion; T cell differentiation in the thymus; neutrophil mediated immunity; positive regulation of leukocyte chemotaxis; response to lipopolysaccharide; proteolysis; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; extracellular matrix disassembly; positive regulation of epidermal growth factor receptor activity; positive regulation of cell proliferation; germinal center formation; negative regulation of interleukin-8 production; cell adhesion; spleen development; response to drug; epidermal growth factor receptor signaling pathway; Notch signaling pathway; membrane protein intracellular domain proteolysis; response to high density lipoprotein stimulus; membrane protein ectodomain proteolysis; positive regulation of transforming growth factor beta receptor signaling pathway; Notch receptor processing; positive regulation of cell motility; positive regulation of cell growth; positive regulation of chemokine production; collagen catabolic process; regulation of mast cell apoptosis; PMA-inducible membrane protein ectodomain proteolysis; B cell differentiation; response to hypoxia; cell adhesion mediated by integrin; positive regulation of protein amino acid phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of cell migration; wound healing, spreading of epidermal cells
Disease: Inflammatory Skin And Bowel Disease, Neonatal, 1
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