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Niemann Pick C1

OverviewProducts

Domain

A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes.

Function

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.

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

N-glycosylated.

Sequence similarities

Belongs to the patched family.

Cellular localization

  • Late endosome membrane
  • Multi-pass membrane protein
  • Lysosome membrane
  • Multi-pass membrane protein

Alternative names

  • NPC intracellular cholesterol transporter 1
  • Niemann-Pick C1 protein
  • NPC1

Database links

Target type

Proteins

Molecular weight

142167Da