Schematics of γ-secretase substrates and the mammalian Vps10p proteins. a) Alignment of the transmembrane domains and juxtamembrane region of known γ-secretase substrates The number of additional amino acids in the cytoplasmic domain following the sequence shown is indicated by "+ aa". b) A schematic of the human Vps10p containing proteins is shown. Sortilin is a 95 kDa glycoprotein. SorCS1, 2, and 3 contain a leucine rich domain and are ~130 kDa. The largest of the homologs, SorLA is 250 kDa and contains a host of receptor binding domains including 14 different low density lipoprotein receptor sites, and EGF repeat, and a fribronectin type III repeat.