| IED ID | IndEnz0002019060 |
| Enzyme Type ID | protease019060 |
| Protein Name |
Disintegrin and metalloproteinase domain-containing protein 17 ADAM 17 EC 3.4.24.86 Snake venom-like protease TNF-alpha convertase TNF-alpha-converting enzyme CD antigen CD156b |
| Gene Name | ADAM17 CSVP TACE |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQSPKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEC |
| Enzyme Length | 824 |
| Uniprot Accession Number | P78536 |
| Absorption | |
| Active Site | ACT_SITE 406; /evidence="ECO:0000255|PROSITE-ProRule:PRU00276, ECO:0000255|PROSITE-ProRule:PRU10095, ECO:0000269|PubMed:9520379" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=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). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.; EC=3.4.24.86; Evidence={ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:24227843}; |
| DNA Binding | |
| EC Number | 3.4.24.86 |
| Enzyme Function | 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). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells. {ECO:0000250|UniProtKB:Q9Z0F8, ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:24226769, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:24337742, ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:28060820, ECO:0000269|PubMed:9034191}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (1); Beta strand (19); Chain (1); Compositional bias (3); Disulfide bond (7); Domain (2); Glycosylation (9); Helix (11); Metal binding (4); Modified residue (5); Motif (3); Natural variant (2); Propeptide (1); Region (2); Sequence conflict (4); Signal peptide (1); Topological domain (2); Transmembrane (1); Turn (5) |
| Keywords | 3D-structure;Alternative splicing;Cleavage on pair of basic residues;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Metal-binding;Metalloprotease;Notch signaling pathway;Phosphoprotein;Protease;Reference proteome;SH3-binding;Signal;Transmembrane;Transmembrane helix;Zinc;Zymogen |
| Interact With | Q12959; P05556; Q13257; Q80WQ6 |
| Induction | INDUCTION: In arthritis-affected cartilage. |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. |
| Modified Residue | MOD_RES 735; /note="Phosphothreonine; by MAPK14"; /evidence="ECO:0000269|PubMed:12058067, ECO:0000269|PubMed:20188673"; MOD_RES 761; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 767; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:Q9Z1K9"; MOD_RES 791; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 819; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:12621058" |
| Post Translational Modification | PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.; PTM: Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding. {ECO:0000269|PubMed:12058067, ECO:0000269|PubMed:12621058, ECO:0000269|PubMed:20188673}. |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000250|UniProtKB:Q9Z1K9 |
| Structure 3D | NMR spectroscopy (1); X-ray crystallography (22) |
| Cross Reference PDB | 1BKC; 1ZXC; 2A8H; 2DDF; 2FV5; 2FV9; 2I47; 2M2F; 2OI0; 3B92; 3CKI; 3E8R; 3EDZ; 3EWJ; 3G42; 3KMC; 3KME; 3L0T; 3L0V; 3LE9; 3LEA; 3LGP; 3O64; |
| Mapped Pubmed ID | 10066432; 10497257; 10527948; 10601018; 10744726; 10882063; 11108241; 11823465; 12135369; 12207026; 12354787; 12356719; 12403792; 12668732; 12755693; 12843241; 12869563; 12913006; 14623079; 15556967; 15701642; 15923650; 16054021; 16084720; 16426848; 16459338; 16738328; 16762314; 17064892; 17170699; 17289381; 17401372; 18054488; 18187448; 1831692; 18638486; 18722532; 18835710; 19054672; 19124506; 19176481; 19410464; 19726682; 20022498; 20172725; 20638281; 20663669; 20711500; 20807704; 21458257; 21570469; 21664575; 22246777; 22246778; 22384041; 22413019; 22479555; 23118222; 23375636; 23521534; 24275664; 24338472; 25241761; 25795784; 26496610; 29045841; 30297396; 30833304; 32197276; 32319605; 33260349; 9244301; 9620803; 9774383; |
| Motif | MOTIF 182..189; /note=Cysteine switch; /evidence=ECO:0000250; MOTIF 731..738; /note=SH3-binding; /evidence=ECO:0000255; MOTIF 741..748; /note=SH3-binding; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 93,021 |
| Kinetics | |
| Metal Binding | METAL 184; /note=Zinc; in inhibited form; /evidence=ECO:0000250; METAL 405; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:9520379; METAL 409; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:9520379; METAL 415; /note=Zinc; catalytic; /evidence=ECO:0000269|PubMed:9520379 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.24.86; |