This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
GeneCards Summary for NPC1 Gene
NPC1 (NPC Intracellular Cholesterol Transporter 1) is a Protein Coding gene. Diseases associated with NPC1 include Niemann-Pick Disease, Type C1 and Niemann-Pick Disease, Type C2. Among its related pathways are Plasma lipoprotein assembly, remodeling, and clearance and Cholesterol and Sphingolipids transport / Distribution to the intracellular membrane compartments (normal and CF). Gene Ontology (GO) annotations related to this gene include signaling receptor activity and cholesterol binding. An important paralog of this gene is NPC1L1.
UniProtKB/Swiss-Prot Summary for NPC1 Gene
Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:10821832, 12554680, 18772377, 27238017, 9211849, 9927649). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1 (PubMed:18772377, 19563754, 27238017, 27378690, 28784760, 9211849, 9927649). Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (PubMed:19563754). Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals (Probable). Inhibits cholesterol-mediated mTORC1 activation throught its interaction with SLC38A9 (PubMed:28336668). ( NPC1_HUMAN,O15118 )
(Microbial infection) Acts as an endosomal entry receptor for ebolavirus. ( NPC1_HUMAN,O15118 )
