Anti-ADAM 12 Antibody, clone 6E6 clone 6E6, from mouse

Disintegrin and metalloproteinase domain-containing protein 12 (UniProt: O43184, also known as ADAM 12, Meltrin-alpha) is encoded by the ADAM12 (also known as MLTN, UNQ346/PRO545) gene (Gene ID: 8038) in human. ADAM (A disintegrin and metalloprotease) family consists of multidomain cell-surface proteins that are synthesized in their proform. Four isoforms of ADAM12 have been described that are produced by alternative splicing. Isoform 1 is a single-pass transmembrane protein and isoforms 2,3, and 4 are secreted proteins. ADM12 is synthesized with a signal peptide (aa 1-28) and a propeptide (aa 29-207), which are subsequently cleaved off in the mature form. Isoform 1 shown to be expressed in placenta and in skeletal, cardiac, and smooth muscle. Isoform 2 is reported to be expressed only in placenta or in embryo and fetus. ADAM12 contains a cysteine rich domain (aa 514-649) that support cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. However, in carcinoma cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. Dissociation of the cysteine from the zinc ion activates the enzyme. Upregulation of ADAM12 has been reported in malignant tumors. In human breast cancer cells expressing ADAM12, MMP-14 is shown to be recruited to the cell surface which results in ADAM12 activation and accelerates tumor progression. ADAM12 does not affect tumor cell proliferation, but it causes a diminution in tumor cell apoptosis and increases stromal cell apoptosis. (Ref.: Sundberg, C., et al. (2004). J. Biol. Chem. 279(49); 51601 51611; Albrechtsen, R., et al. (2013). J. Cell Sci. 126(20); 4707 4720; Kveiborg, M., et al. (2005). Cancer Res. 65(11); 4754-4761).