ADAM1bca12An ADAMs family protein encoded by ADAM12 on chromosome 10q26.3, which has two forms—ADAM12S (short secreted form) and ADAM12L (long membrane-bound form)—generated by alternative splicing. It is synthesized as a proenzyme in which the pro domain maintains the metalloprotease domain in a latent form. After activation, ADAM12’s metalloprotease domain is catalytically active. It is involved in myogenesis, required for myotube formation, expressed largely in mesenchymal cells that give rise to skeletal muscle, bones and viscera, may play a role in osteoblast differentiation and activity, and has been linked to obesity and adipogenic cell proliferation. Secreted ADAM12, which is highly expressed in placental tissues, binds to insulin-like growth factor-binding protein-3 (IGFBP-3).
Activities, ADAM12 Degrades gelatin, collagen IV, fibronectin, IGFBP3, a2-macroglobulin. It interacts with integrin-alpha-9/integrin-beta-1. The cytoplasmic tail of ADAM12 mediates interactions with the nonreceptor protein tyrosine kinase Src through the SH3 domain. It is inhibited by TIMP-3.
Abnormal expression Haematologic malignancy—e.g., leukaemia, erythroleukemia, lymphoma, and myeloma. It is found in the urine of breast cancer patients; the levels correlate with cancer progression. Likewise, in liver cancer, ADAM12 expression correlates with tumour aggressiveness and progression.