MGP Database

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MGP006056

UniProt Annotations

Entry Information
Gene NameADAM metallopeptidase with thrombospondin type 1 motif, 12
Protein EntryATS12_HUMAN
UniProt IDP58397
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P58397-1; Sequence=Displayed; Name=2; IsoId=P58397-2; Sequence=VSP_013141, VSP_013142; Name=3; IsoId=P58397-3; Sequence=VSP_038151; Note=No experimental confirmation available.;
Biophysicochemical PropertiespH dependence: Optimum pH is between 7.5 and 9.5 with COMP for substrate. {ECO:0000269|PubMed:16611630};
CofactorName=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
DomainThe conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
DomainThe C-terminal four TSP1-like repeats are necessary and sufficient for binding COMP.
DomainThe spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix. {ECO:0000250}.
Enzyme RegulationInhibited by alpha-2 macroglobulin. {ECO:0000269|PubMed:18485748}.
FunctionMetalloprotease 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}.
InductionBy 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}.
InteractionP49747:COMP; NbExp=3; IntAct=EBI-9028051, EBI-2531022; Q9R0G6:Comp (xeno); NbExp=3; IntAct=EBI-9028051, EBI-9028018;
PtmGlycosylated. 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}.
PtmSubjected 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.
PtmThe precursor is cleaved by a furin endopeptidase.
SimilarityContains 1 disintegrin domain. {ECO:0000305}.
SimilarityContains 1 peptidase M12B domain. {ECO:0000255|PROSITE-ProRule:PRU00276}.
SimilarityContains 1 PLAC domain. {ECO:0000255|PROSITE- ProRule:PRU00233}.
SimilarityContains 8 TSP type-1 domains. {ECO:0000255|PROSITE- ProRule:PRU00210}.
Subcellular LocationSecreted, extracellular space, extracellular matrix {ECO:0000250}.
SubunitInteracts with COMP. {ECO:0000269|PubMed:16611630}.
Tissue SpecificityExpressed in skeletal muscle and fat. Detected at significant levels in fetal lung. Widely expressed in gastric carcinomas and in cancer cells of diverse origin. {ECO:0000269|PubMed:11279086, ECO:0000269|PubMed:16611630}.
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