Identification and characterization of SorCS, a third member of a novel receptor family

A novel receptor, SorCS, was isolated from murine brain. It shows homology to the mosaic receptor SorLA and the neurotensin receptor sortilin based on a common VPS10 domain which is the hallmark of this new receptor family. In the N-terminus of SorCS two putative cleavage sites for the convertase furin mark the beginning of the VPS10 domain, followed by a module of imperfect leucine-rich repeats and a transmembrane domain. The short intracellular C-terminus contains consensus signals for rapid internalization. The identified putative binding motifs for SH2 and SH3 domains are unique in the family of VPS10 domain receptors. SorCS is predominantly expressed in brain, but also in heart, liver, and kidney. SorCS transcripts detected by in situ hybridization in the murine central nervous system point to a neuronal expression.