Recombinant Human MAGP-2/MFAP5 Protein, CF

MAGP-2 (Microfibril-associated glycoprotein 2), also called MFAP5 (microfibril associated protein 5) is a secreted, cell-associated 25 kDa mammalian member of the MFAP family of proteins (1). Human MAGP-2 cDNA encodes 173 amino acids (aa) including a 21 aa signal sequence, an RDG motif (aa 30‑32; absent in MAGP-1) and a central cysteine‑rich binding domain (aa 84‑140) (1‑3). One potential splice variant shows a 10 aa deletion between aa 73‑82 that includes the only potential glycosylation site (4). Mature human MAGP-2 shares 80%, 82%, 82%, 84% and 85% aa identity with mouse, rat, bovine, porcine and canine MAGP-2, respectively. Both MAGP-1 and MAGP-2 bind and covalently crosslink fibrillins 1 and 2  through the binding domain, but MAGP-2 has more limited distribution and binds a more limited set of extracellular matrix proteins (1‑3). However, the MAGP-2 RGD motif binds to the integrin alphav beta3, allowing cell attachment to microfibrils (5). MAGP‑2 is thought to facilitate microfibril assembly and induce elastin fiber formation (1‑3, 6). Through its binding to EGF repeats, MAGP-2 mediates the metalloproteinase-dependent release of Jagged1 and the metalloproteinase-independent release of Notch extracellular domains (7, 8). In endothelial cells, MAGP-2 promotes angiogenic sprouting through inhibiting Notch signaling, binding integrin  alphav beta3 (which then enhances VEGF signaling), and/or enhancing endothelial cell response to FGF basic and EGF (9, 10). In ovarian cancer, MAGP-2 expression is associated with cancer cell survival, increased microvessel density, and poor prognosis (11). Skin MAGP-2 expression is increased in human scleroderma and the tight skin (TSK) mouse; MAGP‑2 may contribute to abnormal collagen accumulation in these conditions by increasing the half-life of type I collagen (12, 13). Fibrillin-1 mutations within the region that binds MAGP-2 can be found in Marfan syndrome (6).