EL's+Milestone+-+What+is+NPC+protein?

b. What is NPC protein? NPC 1 protein predominantly localized to late endosomes, and only transiently associates with lysosomes and the trans-Golgi network. [Higgins et al., 1999] And NPC1 protein does not show obvious similarity to other proteins except in transmembrane domains 3-7. The general function of the sterol-sensing domain (SSD) can be inferred from its common involvement in cholesterol homeostasis [Kuwabara et al., 2002], but different types of proteins employ the SSD in different ways. Also, NPC 1 protein also has some similarity to the prokaryotic permeates of the resistance-nodulation-division (RND) family.
 * NPC ||
 * Niemann-Pick C disease is a genetic, pediatric, neurodegenerative disorder that is inherited in an autosomal recessive manner. This disease is characterized by an accumulation of cholesterol and other lipids in cells, particularly those of major organs, such as the liver, spleen and the central nervous system. It mutates to NPC 1 protein and NPC 2 protein. Little is known about the physiologically relevant activities of these proteins or the precise mechanisms of this disease. ||
 * NPC 1 ||
 * NPC 1 encodes a 1278 amino acid multi-transmembrane protein, and maps to chromosome 18q11-12 [Carstea et al., 1997; Carstear et al., 1993]. Its topology was found to have 13 transmemrane domains, with three large luminal loops and several small loops in the lumen and cytoplasm. There are more than 170 mutations in NPC1 that have been found to be associated with NPC1 disease.
 * NPC 1 encodes a 1278 amino acid multi-transmembrane protein, and maps to chromosome 18q11-12 [Carstea et al., 1997; Carstear et al., 1993]. Its topology was found to have 13 transmemrane domains, with three large luminal loops and several small loops in the lumen and cytoplasm. There are more than 170 mutations in NPC1 that have been found to be associated with NPC1 disease.

↑ Topological model for NPC 1 (ccr.coriell.org/Images/npc.gif) || Many studies identified NPC 2 as a cholesterol-biding protein with submicromolar affinity at neutral and acidic PH. It facilitates cholesterol egress from the endosomal/lysosomal compartment. A recent study found that NPC 2 not only binds cholesterol, but also binds a range of cholesterol-related molecules, such as plant sterols, oxysterols, cholesterol sulfate, etc [Liou et al., 2006] ||
 * NPC 2 ||
 * MPC 2 protein is a small soluble glycoprotein of the endosome/lysosome system, and it is mapped to chromosome 14q24.3 [Naureckiene et al., 2000] It forms several adjacent small cavities, which have the ability to specifically bind cholestro with affinity Kd=30-50nM [Ko et al., 2003].
 * MPC 2 protein is a small soluble glycoprotein of the endosome/lysosome system, and it is mapped to chromosome 14q24.3 [Naureckiene et al., 2000] It forms several adjacent small cavities, which have the ability to specifically bind cholestro with affinity Kd=30-50nM [Ko et al., 2003].