Recombinant Human ECM1 Protein, CF

Extracellular matrix protein-1 (ECM-1) is an 85 kDa, secreted glycoprotein important in connective tissue organization (1-3). Of three identified splice variants the 540 amino acid (aa) form, ECM-1a, is the most widely expressed, with the highest expression in the placenta and heart (2). ECM-1b (415 aa) is found only in tonsil and associated with suprabasal keratinocytes (2, 4). Since ECM-1b expression is differentiation-dependent, a role in terminal keratinocyte differentiation has been suggested (4). ECM-1c (559 aa) accounts for approximately 15% of skin ECM-1 (5). Human ECM-1a contains a 19 aa signal peptide and a 521 aa secreted portion that includes an N-terminal proline-rich, cysteine-free region, two tandem repeat domains, and a C-terminal domain. 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 are involved in ligand binding to members of the albumin family, and are expected to form two (in ECM-1b) or three (in ECM-1a) “double loop” structures (2). Mature human ECM-1a shows 69%, 71%, 72% and 76% aa identity with corresponding isoforms of mouse, rat, canine, and bovine ECM-1, respectively. ECM-1 is over-expressed in many malignant epithelial tumors and has demonstrated angiogenic activity (6, 7). A variety of ECM-1 mutations, mainly within the first tandem repeat, are considered causative of lipoid proteinosis, a condition showing thickened and irregular extracellular matrix within connective tissue (8). In the autoimmune condition lichen sclerosis, auto-antibodies mainly recognize the second tandem repeat or the
C-terminus of ECM-1 (9). These domains also bind the extracellular matrix molecules fibulin-1 and perlecan (5, 10). The phenotypes of lipoid proteinosis and lichen sclerosis support a role for ECM-1 as a “biological glue” in the dermis (1).