Disintegrin and metalloproteinase domain-containing protein 10 (O14672)

Uniprot ID O14672
Protein Name Disintegrin and metalloproteinase domain-containing protein 10
Gene Name ADAM10
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b) 0.117
Function Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' to its mature soluble form. 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 heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:26686862, PubMed:11786905, PubMed:29224781). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:24990881). Involved in the development and maturation of glomerular and coronary vasculature (By similarity). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity). May regulate the EFNA5-EPHA3 signaling (PubMed:16239146). .(Microbial infection) Promotes the cytotoxic activity of S.aureus hly by binding to the toxin at zonula adherens and promoting formation of toxin pores. {ECO:0000269|PubMed:20624979, ECO:0000269|PubMed:30463011}.
GO - Molecular function
  • endopeptidase activity : IMP:UniProtKB
  • integrin binding : NAS:UniProtKB
  • metal ion binding : IEA:UniProtKB-KW
  • metalloendopeptidase activity : IMP:UniProtKB
  • metalloendopeptidase activity involved in amyloid precursor protein catabolic process : IMP:UniProtKB
  • metallopeptidase activity : IDA:UniProtKB
  • protein homodimerization activity : ISS:UniProtKB
  • protein kinase binding : ISS:UniProtKB
  • SH3 domain binding : IEA:UniProtKB-KW
  • signaling receptor binding : NAS:UniProtKB
GO - Biological process
  • amyloid precursor protein catabolic process : IMP:UniProtKB
  • amyloid-beta formation : IEA:Ensembl
  • cell-cell signaling : NAS:UniProtKB
  • cellular protein metabolic process : TAS:Reactome
  • cochlea development : IEA:Ensembl
  • constitutive protein ectodomain proteolysis : IDA:UniProtKB
  • extracellular matrix disassembly : TAS:Reactome
  • in utero embryonic development : ISS:UniProtKB
  • integrin-mediated signaling pathway : NAS:UniProtKB
  • membrane protein ectodomain proteolysis : IDA:UniProtKB
  • monocyte activation : IMP:BHF-UCL
  • negative regulation of cell adhesion : IDA:UniProtKB
  • neutrophil degranulation : TAS:Reactome
  • Notch receptor processing, ligand-dependent : TAS:Reactome
  • Notch signaling pathway : ISS:UniProtKB
  • PMA-inducible membrane protein ectodomain proteolysis : IMP:BHF-UCL
  • pore complex assembly : IMP:UniProtKB
  • positive regulation of apoptotic process : IEA:Ensembl
  • 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 T cell chemotaxis : IMP:BHF-UCL
  • post-translational protein modification : TAS:Reactome
  • postsynapse organization : IEA:Ensembl
  • protein phosphorylation : ISS:UniProtKB
  • protein processing : IEA:Ensembl
  • regulation of dendritic spine morphogenesis : IEA:Ensembl
  • regulation of neurotransmitter receptor localization to postsynaptic specialization membrane : IEA:Ensembl
  • regulation of Notch signaling pathway : IEA:Ensembl
  • regulation of vasculature development : IEA:Ensembl
  • response to antineoplastic agent : IEA:Ensembl
  • response to tumor necrosis factor : IDA:BHF-UCL
  • spermatogenesis : IEA:Ensembl
  • toxin transport : IMP:UniProtKB
Back
(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.