Recombinant Human SorCS2 Protein, CF

SorCS2 is a type I transmembrane glycoprotein receptor that belongs to the mammalian Vps10p (vacuolar protein-sorting 10 protein) family (1, 2). Family receptors include sortilin, SorLA, and three SorCS proteins. All SorCS proteins are predominantly expressed in the brain, especially during development, but vary in other locations (1 - 3). SorCS2 mRNA has also been found in the kidney, lung, testis and heart (1, 2). SorCS2 presumably mediates endocytosis, but its ligands are not well-defined. However, the other SorCS proteins have been shown to bind NGF and PDGF-BB (4 - 6). Human SorCS2 is synthesized as a 1159 amino acid (aa) prepro form with a 50 aa signal sequence and a potential furin-type proteolytic processing site at aa 119. This would produce a mature SorCS2 protein of 1040 aa with a 959 aa extracellular/lumenal domain (ECD), a 21 aa transmembrane domain and a 60 aa cytoplasmic domain. The ECD contains an imperfect leucine-rich repeat (LRR) and a Vps10p domain (2). Within the ECD, human SorCS2 shares 89%, 88%, 88% and 79% aa identity with mouse, rat, equine and canine SorCS2, respectively. It also shares 46% aa identity with the ECD of both SorCS1 and SorCS3. Unlike other SorCS, shedding of the SorCS2 ECD occurs very slowly and is mainly independent of the metalloproteinase TACE/ADAM17 (4).