Tchem NPC1 NPC intracellular cholesterol transporter 1

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• O15118
• B4DET3
• Q9P130

Gene Name

• NPC1

Ensembl ID

• ENST00000269228
• ENSP00000269228
• ENSG00000141458

Symbol

• NPC
• POGZ
• SLC65A1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
cellular component	0.98
disease perturbation	0.96
transcription factor perturbation	0.94
virus perturbation	0.92
biological process	0.91

Protein Classes

DTO Classes

Protein / Transporter / Slc Superfamily Of Solute Carriers / Slc65 Npc-type Cholesterol Transporters / Niemann-pick C1 Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 878.24   (req: < 5)

Gene RIFs: 166   (req: <= 3)

Antibodies: 356   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 878.24   (req: >= 5)

Gene RIFs: 166   (req: > 3)

Antibodies: 356   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0