Disintegrin and metalloproteinase domain-containing protein 17 (P78536)

Uniprot ID	P78536
Protein Name	Disintegrin and metalloproteinase domain-containing protein 17
Gene Name	ADAM17
Species	Homo sapiens (Human)

Signal peptide^(a)	N	Secretome P^(b)	0.113
Function	Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). 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, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). .
GO - Molecular function	endopeptidase activity : IMP:UniProtKB integrin binding : IPI:BHF-UCL interleukin-6 receptor binding : IPI:BHF-UCL metal ion binding : IEA:UniProtKB-KW metalloendopeptidase activity : IDA:UniProtKB metallopeptidase activity : IDA:BHF-UCL Notch binding : IDA:UniProtKB PDZ domain binding : IPI:BHF-UCL peptidase activity : TAS:ARUK-UCL SH3 domain binding : IEA:UniProtKB-KW
GO - Biological process	B cell differentiation : ISS:BHF-UCL cell adhesion : IDA:BHF-UCL cell adhesion mediated by integrin : IDA:BHF-UCL cell motility : ISS:BHF-UCL cellular response to high density lipoprotein particle stimulus : IDA:BHF-UCL defense response to Gram-positive bacterium : IMP:BHF-UCL epidermal growth factor receptor signaling pathway : IDA:BHF-UCL germinal center formation : ISS:BHF-UCL membrane protein ectodomain proteolysis : IDA:BHF-UCL membrane protein intracellular domain proteolysis : TAS:Reactome negative regulation of cold-induced thermogenesis : ISS:YuBioLab negative regulation of transforming growth factor beta receptor signaling pathway : IMP:UniProtKB neutrophil mediated immunity : IC:BHF-UCL Notch receptor processing : IDA:UniProtKB Notch signaling pathway : IBA:GO_Central PMA-inducible membrane protein ectodomain proteolysis : IDA:BHF-UCL positive regulation of blood vessel endothelial cell migration : IDA:BHF-UCL positive regulation of cell growth : IMP:BHF-UCL positive regulation of cell migration : IMP:BHF-UCL positive regulation of cell population proliferation : IMP:BHF-UCL positive regulation of cellular component movement : ISS:BHF-UCL positive regulation of chemokine production : IMP:BHF-UCL positive regulation of cyclin-dependent protein serine/threonine kinase activity : IMP:BHF-UCL positive regulation of epidermal growth factor-activated receptor activity : IDA:BHF-UCL positive regulation of G1/S transition of mitotic cell cycle : IMP:BHF-UCL positive regulation of leukocyte chemotaxis : IC:BHF-UCL positive regulation of protein phosphorylation : IMP:BHF-UCL positive regulation of T cell chemotaxis : IMP:BHF-UCL positive regulation of transforming growth factor beta receptor signaling pathway : ISS:BHF-UCL positive regulation of tumor necrosis factor-mediated signaling pathway : IMP:BHF-UCL positive regulation of vascular endothelial cell proliferation : IDA:BHF-UCL proteolysis : IDA:UniProtKB receptor transactivation : IMP:BHF-UCL regulation of mast cell apoptotic process : ISS:BHF-UCL response to drug : ISS:BHF-UCL response to hypoxia : IDA:BHF-UCL response to lipopolysaccharide : IDA:BHF-UCL spleen development : ISS:BHF-UCL T cell differentiation in thymus : ISS:BHF-UCL tumor necrosis factor-mediated signaling pathway : TAS:Reactome wound healing, spreading of epidermal cells : IEP:BHF-UCL

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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.}