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 alpha v beta 3, 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  alpha v beta 3 (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).