InterPro domain: IPR031777

This domain is the C-terminal cytoplasmic tail of sortilin, a Vps10p domain-containing family of proteins [ 1 , 2 ]. Most sortilin is expressed within intracellular compartments, where it chaperones diverse ligands, including proBDNF and acid hydrolases. The sortilin cytoplasmic tail is homologous to mannose 6-phosphate receptor and is required for the intracellular trafficking of cargo proteins via interactions with distinct adaptor molecules [ 3 , 4 ]. In addition to mediating lysosomal targeting of specific acid hydrolases, the sortilin cytoplasmic tail also directs trafficking of BDNF to the secretory pathway in neurons, where it can be released in response to depolarisation to modulate cell survival and synaptic plasticity [ 5 ].

1. Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. J. Biol. Chem. 272, 3599-605
2. The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. J. Biol. Chem. 273, 26273-6
3. Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J. Biol. Chem. 274, 8832-6
4. The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J. 20, 2180-90
5. Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain. Nat. Struct. Mol. Biol. 16, 96-8