Tclin NPC1L1 NPC1-like intracellular cholesterol transporter 1

Protein Summary

Description

Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption. Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation. The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• Q9UHC9
• A4D2J7
• B7ZLE6
• D3DVK9
• Q17RV5
• Q6R3Q4
• Q9UHC8

Gene Name

• NPC1L1

Ensembl ID

• ENST00000289547
• ENSP00000289547
• ENSG00000015520
• ENST00000423141
• ENSP00000404670

Symbol

• LDLCQ7
• NPC11L1
• SLC65A2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.81
cellular component	0.65
biological term	0.64
molecular function	0.63
tissue sample	0.61

Protein Classes

DTO Classes

Protein / Transporter / Slc Superfamily Of Solute Carriers / Slc65 Npc-type Cholesterol Transporters / Niemann-pick C1-like Protein 1

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: 366.96   (req: < 5)

Gene RIFs: 96   (req: <= 3)

Antibodies: 182   (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: 366.96   (req: >= 5)

Gene RIFs: 96   (req: > 3)

Antibodies: 182   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

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

Active Ligands: 20

Tclin

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

Active Drug: 1