Recombinant Human MFRP Protein, CF

MFRP (membrane-type frizzled-related protein) is a 65 kDa, type II transmembrane protein related to both Tolloid proteases and frizzled-domain containing Wnt pathway proteins (1 - 4). Human MFRP is 579 amino acids (aa) in length (3, 5, 6). It contains a 69 aa cytoplasmic region, a 21 aa transmembrane segment, and a 489 aa extracellular domain (ECD). The ECD is characterized by the presence of two LDLR class A repeats, two CUB domains, and a C-terminal cysteine-rich/frizzled domain. The mRNA for MFRP is highly unusual in that it is dicistronic; that is, it contains two independent ORFs, one for MFRP and one for a functionally-related protein termed CTRP5/C1qTNF5 (4, 7). CTRP5 is a secreted, 25 kDa short-chain collagen that contains a C1q-type domain (6, 8). In prokaryotes, polycistronic transcripts exist that contain functionally-interactive molecules. This would also appear to be the case for MFRP and CTRP5. CTRP5 is suggested to bind to membrane MFRP via the C1q and CUB domains, respectively. This is positioned to generate a receptor-coreceptor complex that binds select Wnts such as Wnt-1 and/or Wnt-10b (4, 6, 7). MFRP has multiple documented mutations. In human, these are associated with hyperopia (severe farsightedness). The mutations result in premature truncations (3, 9). MFRP is expressed in retinal pigment epithelium, ciliary epithelium, and keratinocytes (4, 7, 10, 11). Human MFRP ECD is 70% aa identical to mouse ECD.