| IED ID | IndEnz0002014580 |
| Enzyme Type ID | protease014580 |
| Protein Name |
A disintegrin and metalloproteinase with thrombospondin motifs 12 ADAM-TS 12 ADAM-TS12 ADAMTS-12 EC 3.4.24.- |
| Gene Name | ADAMTS12 UNQ1918/PRO4389 |
| 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 | MPCAQRSWLANLSVVAQLLNFGALCYGRQPQPGPVRFPDRRQEHFIKGLPEYHVVGPVRVDASGHFLSYGLHYPITSSRRKRDLDGSEDWVYYRISHEEKDLFFNLTVNQGFLSNSYIMEKRYGNLSHVKMMASSAPLCHLSGTVLQQGTRVGTAALSACHGLTGFFQLPHGDFFIEPVKKHPLVEGGYHPHIVYRRQKVPETKEPTCGLKDSVNISQKQELWREKWERHNLPSRSLSRRSISKERWVETLVVADTKMIEYHGSENVESYILTIMNMVTGLFHNPSIGNAIHIVVVRLILLEEEEQGLKIVHHAEKTLSSFCKWQKSINPKSDLNPVHHDVAVLLTRKDICAGFNRPCETLGLSHLSGMCQPHRSCNINEDSGLPLAFTIAHELGHSFGIQHDGKENDCEPVGRHPYIMSRQLQYDPTPLTWSKCSEEYITRFLDRGWGFCLDDIPKKKGLKSKVIAPGVIYDVHHQCQLQYGPNATFCQEVENVCQTLWCSVKGFCRSKLDAAADGTQCGEKKWCMAGKCITVGKKPESIPGGWGRWSPWSHCSRTCGAGVQSAERLCNNPEPKFGGKYCTGERKRYRLCNVHPCRSEAPTFRQMQCSEFDTVPYKNELYHWFPIFNPAHPCELYCRPIDGQFSEKMLDAVIDGTPCFEGGNSRNVCINGICKMVGCDYEIDSNATEDRCGVCLGDGSSCQTVRKMFKQKEGSGYVDIGLIPKGARDIRVMEIEGAGNFLAIRSEDPEKYYLNGGFIIQWNGNYKLAGTVFQYDRKGDLEKLMATGPTNESVWIQLLFQVTNPGIKYEYTIQKDGLDNDVEQQMYFWQYGHWTECSVTCGTGIRRQTAHCIKKGRGMVKATFCDPETQPNGRQKKCHEKACPPRWWAGEWEACSATCGPHGEKKRTVLCIQTMVSDEQALPPTDCQHLLKPKTLLSCNRDILCPSDWTVGNWSECSVSCGGGVRIRSVTCAKNHDEPCDVTRKPNSRALCGLQQCPSSRRVLKPNKGTISNGKNPPTLKPVPPPTSRPRMLTTPTGPESMSTSTPAISSPSPTTASKEGDLGGKQWQDSSTQPELSSRYLISTGSTSQPILTSQSLSIQPSEENVSSSDTGPTSEGGLVATTTSGSGLSSSRNPITWPVTPFYNTLTKGPEMEIHSGSGEEREQPEDKDESNPVIWTKIRVPGNDAPVESTEMPLAPPLTPDLSRESWWPPFSTVMEGLLPSQRPTTSETGTPRVEGMVTEKPANTLLPLGGDHQPEPSGKTANRNHLKLPNNMNQTKSSEPVLTEEDATSLITEGFLLNASNYKQLTNGHGSAHWIVGNWSECSTTCGLGAYWRRVECSTQMDSDCAAIQRPDPAKRCHLRPCAGWKVGNWSKCSRNCSGGFKIREIQCVDSRDHRNLRPFHCQFLAGIPPPLSMSCNPEPCEAWQVEPWSQCSRSCGGGVQERGVFCPGGLCDWTKRPTSTMSCNEHLCCHWATGNWDLCSTSCGGGFQKRTVQCVPSEGNKTEDQDQCLCDHKPRPPEFKKCNQQACKKSADLLCTKDKLSASFCQTLKAMKKCSVPTVRAECCFSCPQTHITHTQRQRRQRLLQKSKEL |
| Enzyme Length | 1594 |
| Uniprot Accession Number | P58397 |
| Absorption | |
| Active Site | ACT_SITE 393; /evidence="ECO:0000255|PROSITE-ProRule:PRU00276, ECO:0000255|PROSITE-ProRule:PRU10095" |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by alpha-2 macroglobulin. {ECO:0000269|PubMed:18485748}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.24.- |
| Enzyme Function | FUNCTION: Metalloprotease that may play a role in the degradation of COMP. Cleaves also alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties. {ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:17895370, ECO:0000269|PubMed:18485748}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is between 7.5 and 9.5 with COMP for substrate. {ECO:0000269|PubMed:16611630}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (3); Chain (1); Compositional bias (6); Disulfide bond (11); Domain (11); Glycosylation (14); Metal binding (4); Motif (1); Natural variant (5); Propeptide (1); Region (5); Sequence conflict (1); Signal peptide (1) |
| Keywords | Alternative splicing;Cleavage on pair of basic residues;Disulfide bond;Extracellular matrix;Glycoprotein;Hydrolase;Metal-binding;Metalloprotease;Protease;Reference proteome;Repeat;Secreted;Signal;Zinc;Zymogen |
| Interact With | P49747; B4DJ51; P50222; P60660; Q9R0G6; P38432; Q8IYA8; Q05BL1; Q14142 |
| Induction | INDUCTION: By IFN-alpha and by IL1B/interleukin-1 beta. Up-regulated in articular cartilage and synovium from arthritis patients. Up-regulared in chondrocytes. {ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:18485748}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: The precursor is cleaved by a furin endopeptidase.; PTM: Subjected to an intracellular maturation process yielding a 120 kDa N-terminal fragment containing the metalloproteinase, disintegrin, one TSP type-1 and the Cys-rich domains and a 83 kDa C-terminal fragment containing the spacer 2 and four TSP type-1 domains.; PTM: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..25; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11067851; 16464858; 18720094; 19098927; 19151918; 19638407; 19796186; 20379614; 20400778; 21494557; 21559743; 22247065; 22322903; 22505177; 22588082; 23019333; 23889335; 24876675; 25416956; 25544610; 26363034; 28005267; 29135310; 34198725; |
| Motif | MOTIF 208..213; /note=Cysteine switch; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 177,676 |
| Kinetics | |
| Metal Binding | METAL 208; /note=Zinc; in inhibited form; /evidence=ECO:0000250; METAL 392; /note=Zinc; catalytic; /evidence=ECO:0000250; METAL 396; /note=Zinc; catalytic; /evidence=ECO:0000250; METAL 402; /note=Zinc; catalytic; /evidence=ECO:0000250 |
| Rhea ID | |
| Cross Reference Brenda |