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A disintegrin & metalloproteinase domain 12; meltrin alpha (ADAM12, MLTN, UNQ346/PRO545)
Function:
- role in skeletal muscle regeneration, specifically at the onset of cell fusion
- also involved in macrophage-derived giant cells & osteoclast formation from mononuclear precursors (putative)
- interacts with alpha-actinin-2 & with syndecans
- interacts with SH3PXD2A
- cytoplasmic domain interacts with src
- precursor is cleaved by a furin endopeptidase
Cofactor: binds 1 Zn+2 per subunit
Structure:
- cysteine-rich domain supports cell adhesion through syndecans & triggers signaling events that lead to beta-1 integrin-dependent cell spreading
- conserved Cys present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme
- dissociation of Cyst from the Zn+2 upon activation- peptide release activates the enzyme
- contains 1 disintegrin domain
- contains 1 EGF-like domain
- contains 1 peptidase M12B domain
Compartment:
- isoform 1: cell membrane
- isoforms 2,3,4: secreted
Alternative splicing: named isoforms=4
Expression:
- isoform 1 is expressed in placenta, skeletal muscle, cardiac muscle, & smooth muscle
- isoform 2 seems to be expressed only in placenta or in embryo & fetus
- both forms were expressed in some tumor cells lines
- not detected in brain, lung, liver, kidney or pancreas
Pathology:
- in carcinomas cell, binding of cysteine-rich domain to syndecans does not allow integrin-mediated cell spreading
General
ADAM (A disintegrin & metalloproteinase domain); MDC (metalloproteinase, disintegrin, cysteine-rich) protein
Properties
SIZE: MW = 100 kD
entity length = 909 aa
MOTIF: N-glycosylation site {N111}
N-glycosylation site {N149}
metalloprotease domain {208-416}
MOTIF: cysteine residue {C325}
MODIFICATION: cysteine residue {C411}
active site
SITE: E351
N-glycosylation site {N381}
cysteine residue {C411}
MODIFICATION: cysteine residue {C325}
disintegrin domain {417-512}
MOTIF: N-glycosylation site {N452}
cysteine residue {C482}
MODIFICATION: cysteine residue {C495}
cysteine residue {C495}
MODIFICATION: cysteine residue {C482}
cysteine-rich region {514-649}
EGF domain {656-688}
MOTIF: cysteine residue {C660}
MODIFICATION: cysteine residue {C670}
cysteine residue {C664}
MODIFICATION: cysteine residue {C676}
cysteine residue {C670}
MODIFICATION: cysteine residue {C660}
cysteine residue {C676}
MODIFICATION: cysteine residue {C664}
cysteine residue {C678}
MODIFICATION: cysteine residue {C687}
cysteine residue {C687}
MODIFICATION: cysteine residue {C678}
transmembrane domain {709-729}
src homology 3 [SH3] domain
SITE: 834-840
src homology 3 [SH3] domain
SITE: 885-891
src homology 3 [SH3] domain
SITE: 890-896
Database Correlations
OMIM 602714
UniProt O43184
PFAM correlations
Entrez Gene 8038
Kegg hsa:8038
References
- Yong VW et al
Metalloproteinases in biology and pathology of the nervous
system.
Nat Rev Neurosci. 2001 Jul;2(7):502-11. Review.
PMID: 11433375
- UniProt :accession O43184