Human ADAM-12L DNA spans 373186 bp and ADAM-12S DNA spans 347114 bp. Both sequences are composed of 19 exons.

The full-length ADAM-12L cDNA spans 5048 nucleotides, including a 311- nucleotides 5-untranslated region, an open reading frame of 2727 nucleotides encoding 909 aa, a TGA stop codon, and a 3-untranslated region of 2006 nucleotides. Full-length ADAM-12S cDNA has a 2214 nucleotides open reading frame that is identical to ADAM-12L up to nucleotide 2426, whereupon it diverges. The final 102 nucleotides of the ADAM-12S open reading frame encode a 34-aa carboxyl terminus, followed by a TGA stop codon and a 3-end untranslated region of 788 nucleotides. The 3-untranslated regions are different in the two human ADAM-12 forms.

ADAM-12 seems to be encoded by a single copy gene which is located on chromosome 10q26. No pseudogenes reported.

Full-length ADAM-12L: 909 amino acids; Mr: 99,641. There are two isoforms of ADAM-12 resulting from an alternative splicing: mature membrane-bound ADAM-12 (ADAM-12L) (881 amino acids, Mr: 96,917) and a secreted form (ADAM-12S) (718 amino acids, Mr: 77,775).

The open reading frame begins at the translation initiation codon ATG at nucleotide 312. Residues 1-28 encode the signal peptide. The mature human ADAM-12L contains 881 aa with an Mr of about 96,9 and that of ADAM-12S contains 718 aa with an Mr of 77,8. Five potential N-linked glycosylation sites are present. These five sites are also found at the same position in mouse ADAM-12, whereas three additional sites present in mouse are not found in human ADAM-12. The human ADAM-12 metalloproteinase domain contains the highly conserved zinc-binding motif HEXGHXXGXXHD which is regulated by a potential "cysteine switch" in the prodomain.

Highly expressed in placenta and in lower amounts in skeletal muscle, heart, prostate, uterus, colon, small intestine, bladder, stomach. In prostate, uterus, colon, small intestine, bladder, stomach, the source of ADAM-12 may be the smooth muscle cells. ADAM-12 is also expressed by activated hepatic stellate cells (LePabic et al, 2003). ADAM-12 is present in higher amounts in maternal serum during pregnancy (Laigaard et al, 2006).

Membrane-bound for ADAM-12L, extracellular localization for ADAM-12S.

ADAM-12 is a catalytic active protein and functions ascribed to ADAM-12 in the literature are mostly related to its catalytic activity. Indeed, ADAM-12 is able to cleave Insulin-like Growth Factor Binding Protein-3 and-5 (IGFBP-3 and IGFBP-5). The release of increasing concentrations of bioavailable IGF through IGFBP cleavage is important during pregnancy for foetal growth (Laigaard et al, 2006). ADAM-12 is also able to cleave membrane-bound Heparin-binding EGF-like Growth Factor (HB-EGF) (Asakura et al, 2002).

Human version of ADAM-12 shares 84% overall amino acid identity with its mouse homolog. Homology is highest in cysteine-rich, metalloproteinase, and disintegrin domains and lower in the pro- and cytoplasmic domains. Human ADAM-12 shares about 83% with the rat homolog, 68% with zebra fish ADAM-12 and 99% with chimpanzees. Human ADAM-12 shares 45% overall amino acid similarity with ADAM-8, ADAM-9 and ADAM-15.

Three somatic mutations in ADAM-12 have been observed at significant frequencies in breast cancers (Dyczynska et al, 2008).

D301H, G479E and L792F: the first two mutations involve highly conserved residues in ADAM-12 which inhibit its proteolytic processing and activation. These mutants are retained inside of the cell and are not transported to the cell surface (Dyczynska et al, 2008).