Recombinant Mouse ECM1 Protein, CF

Extracellular matrix protein-1 (ECM-1, ECM-1a) is an 85 kDa, secreted glycoprotein important in connective tissue organization (1 - 3). Of identified splice variants, the 559 amino acid (aa) form, ECM-1a is most widely expressed, with highest expression in the placenta, heart, and developing bones (3, 4). ECM-1b (434 aa) is found only in tonsil and skin, where it is associated with suprabasal keratinocytes (3, 5). Mouse ECM-1 contains a 19 aa signal peptide and a 540 aa secreted portion that includes an N-terminal proline-rich, cysteine-free region, two tandem repeat domains, and a C-terminal domain. Mature mouse ECM-1 shares 90% aa identity with rat ECM-1 and 65 - 69% aa identity with corresponding isoforms of human, equine, bovine and canine ECM-1. There are six repeats of a CC(X_{7 - 10})C motif (x = any aa) within the tandem repeat and C-terminal domains. These motifs, also found in members of the albumin family, are expected to form two (in ECM-1b) or three (in ECM-1a) “double loop” structures that are involved in ligand binding to extracellular matrix molecules such as fibulin-1, perlecan, laminin 332, and fibronectin (4 - 7). ECM-1 is over-expressed in many malignant epithelial tumors and has demonstrated angiogenic activity (8, 9). A role in regulating alkaline phosphatase during endochondral bone formation has also been suggested (4). In humans, loss of function within the tandem repeat regions due to mutation is considered causative of thickened and irregular extracellular matrix within connective tissue, called lipoid proteinosis (10). Autoantibodies in the skin disease lichen sclerosis also target these repeats (11). The phenotypes of these diseases support a role for ECM-1 as a “biological glue” in the dermis (1, 6, 7).