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

More general terms

• ADAM protease

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8038
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8038
• OMIM: https://mirror.omim.org/entry/602714
• UniProt: http://www.uniprot.org/uniprot/O43184.html