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A disintegrin & metalloproteinase with thrombospondin type 1 motif 12; ADAMTS-12; ADAM-TS 12; ADAM-TS12; (ADAMTS12)
Function:
- interaction with the extracellular matrix
- precursor is cleaved by a furin endopeptidase
- subjected to an intracellular maturation process yielding a 120 kD N-terminal fragment containing the metalloproteinase, disintegrin, one TSP type-1 domain & the Cys-rich domains & a 83 kD C-terminal fragment containing the spacer 2 & four TSP type-1 domains
Cofactor: binds 1 Zn+2 per subunit (putative)
Structure:
- spacer domain & TSP type-1 domains are important for a tight interaction with the extracellular matrix
- conserved cysteine present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme
- dissociation of Cys from Zn+2 upon the activation- peptide release activates the enzyme
- contains 1 disintegrin domain
- contains 1 peptidase M12B domain
- contains 1 PLAC domain
- contains 8 TSP type-1 domains
Compartment:
- secreted, extracellular space, extracellular matrix (putative)
Alternative splicing: named isoforms=2
Expression: expressed exclusively in fetal lung
Pathology:
- expressed in gastric carcinomas & in cancer cells of diverse origin
General
A disintegrin & metalloproteinase with thrombospondin type 1 motif (ADAMTS)
glycoprotein
phosphoprotein
Properties
SIZE: entity length = 1593 aa
MW = 178 kD
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-25}
N-glycosylation site {N105}
N-glycosylation site {N125}
Cysteine switch {208-213}
MOTIF: Zn+2-binding site
SITE: 208-208
N-glycosylation site {N215}
Ser phosphorylation site {S234}
Ser phosphorylation site {S236}
Peptidase M12B {246-456}
MOTIF: glutamate-rich region {302-305}
MOTIF: glutamate residue (SEVERAL)
cysteine residue {C370}
MODIFICATION: cysteine residue {C451}
Zn+2-binding site
SITE: 392-392
glutamate residue {E393}
Zn+2-binding site
SITE: 396-396
Zn+2-binding site
SITE: 402-402
cysteine residue {C409}
MODIFICATION: cysteine residue {C435}
cysteine residue {C435}
MODIFICATION: cysteine residue {C409}
cysteine residue {C451}
MODIFICATION: cysteine residue {C370}
disintegrin domain {465-544}
MOTIF: N-glycosylation site {N485}
TSP1 module {542-597}
MOTIF: cysteine residue {C554}
MODIFICATION: cysteine residue {C591}
cysteine residue {C558}
MODIFICATION: cysteine residue {C596}
cysteine residue {C569}
MODIFICATION: cysteine residue {C581}
cysteine residue {C581}
MODIFICATION: cysteine residue {C569}
cysteine residue {C591}
MODIFICATION: cysteine residue {C554}
cysteine residue {C596}
MODIFICATION: cysteine residue {C558}
cysteine-rich region {597-700}
MOTIF: N-glycosylation site {N685}
Spacer 1 {701-826}
MOTIF: N-glycosylation site {N790}
TSP1 module {823-882}
TSP1 module {886-942}
TSP1 module {943-996}
MOTIF: N-glycosylation site {N951}
Thr phosphorylation site {T981}
Spacer 2 {996-1315}
MOTIF: N-glycosylation site {N1104}
N-glycosylation site {N1275}
N-glycosylation site {N1300}
TSP1 module {1312-1365}
MOTIF: N-glycosylation site {N1320}
TSP1 module {1367-1421}
MOTIF: N-glycosylation site {N1371}
N-glycosylation site {N1378}
TSP1 module {1422-1470}
TSP1 module {1471-1531}
MOTIF: N-glycosylation site {N1503}
PLAC {1534-1574}
Database Correlations
OMIM 606184
UniProt P58397
PFAM correlations
Entrez Gene 81792
Kegg hsa:81792
References
UniProt :accession P58397