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A disintegrin & metalloproteinase domain 15; metalloproteinase-like, disintegrin-like, & cysteine-rich protein 15; MDC-15; metalloprotease RGD disintegrin protein; metargidin (ADAM15, MDC15)
Function:
- may be involved in cell-surface proteolysis, cell adhesion or intracellular protein maturation
- interacts with ITAGV-ITGB3 (vitronectin receptor), PACSIN3 & SNX9; PACSIN3 & SNX9 preferentially bind the precursor but not the processed form of ADAM15, suggesting that the interaction occurs in a secretory pathway compartment prior to the medial Golgi (putative)
- interacts specifically with Src family proteins
- interacts with SH3PXD2A
- cytoplasmic domain interacts with SH3 domain of endophilin 1 & sorting nexin 9 (putative)
- interacts with MAD2L2
- precursor is cleaved by a furin endopeptidase
- phosphorylation increases association with PTKs
Cofactor: binds 1 Zn+2 per subunit (putative)
Structure:
- desintegrin domain binds to integrin alphaV-beta3
- conserved Cys 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 EGF-like domain
- contains 1 peptidase M12B domain
Compartment: membrane
Expression:
- ubiquitously expressed
- constitutively expressed in cultured endothelium & smooth muscle.
- expressed in chondrocytes
Pathology:
- overexpressed in atherosclerotic lesions but not normal aorta
General
ADAM (A disintegrin & metalloproteinase domain); MDC (metalloproteinase, disintegrin, cysteine-rich) protein
glycoprotein
phosphoprotein
Properties
SIZE: MW = 88 kD
entity length = 814 aa
MOTIF: metalloprotease domain {207-414}
MOTIF: N-glycosylation site {N237}
cysteine residue {C323}
MODIFICATION: cysteine residue {C409}
active site
SITE: E349
N-glycosylation site {N389}
N-glycosylation site {N392}
cysteine residue {C409}
MODIFICATION: cysteine residue {C323}
disintegrin domain {421-508}
MOTIF: cysteine residue {C480}
MODIFICATION: cysteine residue {C493}
cysteine residue {C493}
MODIFICATION: cysteine residue {C480}
cysteine-rich region {509-656}
MOTIF: N-glycosylation site {N606}
N-glycosylation site {N611}
EGF domain {657-685}
MOTIF: cysteine residue {C657}
MODIFICATION: cysteine residue {C667}
cysteine residue {C661}
MODIFICATION: cysteine residue {C673}
cysteine residue {C667}
MODIFICATION: cysteine residue {C657}
cysteine residue {C673}
MODIFICATION: cysteine residue {C661}
cysteine residue {C675}
MODIFICATION: cysteine residue {C684}
cysteine residue {C684}
MODIFICATION: cysteine residue {C675}
transmembrane domain {697-717}
src homology 3 [SH3] domain
SITE: 766-772
src homology 3 [SH3] domain
SITE: 801-807
Database Correlations
OMIM 605548
UniProt Q13444
PFAM correlations
Entrez Gene 8751
Kegg hsa:8751
References
- OMIM :accession 605548
- UniProt :accession Q13444