NPC1

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

Niemann-Pick disease, type C1

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:9211849, PubMed:9927649, PubMed:10821832, PubMed:18772377, PubMed:27238017, PubMed:12554680).
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:9211849, PubMed:9927649, PubMed:18772377, PubMed:19563754, PubMed:27238017, PubMed:28784760).
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).
(Microbial infection) Acts as an endosomal entry receptor for ebolavirus.

Adult walking behaviorIEA:Ensembl
AutophagyManual Assertion Based On ExperimentIGI:MGI
Bile acid metabolic processISS:UniProtKB
Cellular response to low-density lipoprotein particle stimulusIEA:Ensembl
Cellular response to steroid hormone stimulusIEA:Ensembl
Cholesterol effluxManual Assertion Based On ExperimentIDA:BHF-UCL
Cholesterol homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
Cholesterol metabolic processIEA:UniProtKB-KW
Cholesterol transportManual Assertion Based On ExperimentIDA:UniProtKB
EndocytosisIEA:Ensembl
Establishment of protein localization to membraneManual Assertion Based On ExperimentIDA:UniProtKB
Gene expressionIEA:Ensembl
Intracellular cholesterol transportManual Assertion Based On ExperimentIMP:UniProtKB
Lysosomal transportISS:UniProtKB
Membrane raft organizationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of cell deathIEA:Ensembl
Negative regulation of macroautophagyIEA:Ensembl
Protein glycosylationManual Assertion Based On ExperimentIDA:UniProtKB
Response to cadmium ionIEA:Ensembl
Response to xenobiotic stimulusIEA:Ensembl
Viral entry into host cellManual Assertion Based On ExperimentIMP:CACAO

Late endosome membrane
Lysosome membrane

Niemann-Pick disease C1 (NPC1):
A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C1 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. An allelic variant of Niemann-Pick disease type C1 is found in people with Nova Scotia ancestry. Patients with the Nova Scotian clinical variant are less severely affected.

Lumenal: 23-261
Helical: 262-282
Cytoplasmic: 283-350
Helical: 351-371
Lumenal: 372-620
Helical: 621-641
Cytoplasmic: 642-653
Helical: 654-675
Lumenal: 676-685
Helical: 686-706
Cytoplasmic: 707-730
Helical: 731-751
Lumenal: 752-759
Helical: 760-783
Cytoplasmic: 784-832
Helical: 833-853
Lumenal: 854-1097
Helical: 1098-1118
Cytoplasmic: 1119-1124
Helical: 1125-1145
Lumenal: 1146-1150
Helical: 1151-1171
Cytoplasmic: 1172-1194
Helical: 1195-1215
Lumenal: 1216-1223
Helical: 1224-1244
Cytoplasmic: 1245-1278

N-glycosylated.