Top ▲

NPC1 like intracellular cholesterol transporter 1

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 2629

Nomenclature: NPC1 like intracellular cholesterol transporter 1

Systematic Nomenclature: SLC65A2

Family: SLC65 NPC-type cholesterol transporters

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 13 1359 7p13 NPC1L1 NPC1 like intracellular cholesterol transporter 1
Mouse 13 1333 11 A1 Npc1l1 NPC1 like intracellular cholesterol transporter 1
Rat 13 1331 14q21 Npc1l1 NPC1 like intracellular cholesterol transporter 1
Previous and Unofficial Names Click here for help
Niemann-Pick C1-like protein 1 | NPC1-like 1 | NPC1 like 1
Database Links Click here for help
Specialist databases
RESOLUTE NPC1L1 (Hs)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  The structure of the NPC1L1 N-terminal domain in a closed conformation.
PDB Id:  3QNT
Resolution:  2.83Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-EM structure of NPC1L1 in apo form.
PDB Id:  6V3F
Resolution:  3.7Å
Species:  Rat
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Structure of NPC1-like intracellular cholesterol transporter 1 (NPC1L1) in complex with an ezetimibe analog
PDB Id:  6V3H
Resolution:  3.5Å
Species:  Rat
References:  4
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
Cholesterol N/A - - 1

Download all structure-activity data for this target as a CSV file go icon to follow link

Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ezetimibe Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.7 pKd 2
pKd 6.7 (Kd 2.2x10-7 M) [2]
Description: Measure of ezetimibe glucuronide binding to NPC1L1
Functional Assays Click here for help
In vitro 3H-cholesterol uptake assay.
Species:  Human
Tissue:  Madin-Darby Canine Kidney II (MDCKII) cells stably expressing human NPC1L1
Response measured:  Increase in intracellular 3H-cholesterol.
References:  3
Clinically-Relevant Mutations and Pathophysiology Comments
Two rare polymorphisms in the NPC1L1 gene are associated with a non-reponse to ezetimibe in hyperlipidemia patients. For more details see the OMIM entry linked to from this target page.
General Comments
NPC1L1 acts in the gut epithelium to allow the accumulation of dietary cholesterol through a clathrin-dependent mechanism. Ezetimibe is used to reduce cholesterol absorption through inhibition of NPC1L1. Analysis of cryo-EM structures reveals how NPC1L1 transports cholesterol and the mechanism of ezetimibe inhibition [3].

References

Show »

1. Altmann SW, Davis Jr HR, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M et al.. (2004) Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science, 303 (5661): 1201-4. [PMID:14976318]

2. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis Jr HR, Dean DC, Detmers PA et al.. (2005) The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci USA, 102 (23): 8132-7. [PMID:15928087]

3. Huang CS, Yu X, Fordstrom P, Choi K, Chung BC, Roh SH, Chiu W, Zhou M, Min X, Wang Z. (2020) Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition. Sci Adv, 6 (25): eabb1989. DOI: 10.1126/sciadv.abb1989 [PMID:32596471]

4. Huang CS, Yu X, Fordstrom P, Choi K, Chung BC, Roh SH, Chiu W, Zhou M, Min X, Wang Z. (2020) Cryo-EM structures of NPC1L1 reveal mechanisms of cholesterol transport and ezetimibe inhibition. Sci Adv, 6 (25): eabb1989. [PMID:32596471]

5. Kwon HJ, Palnitkar M, Deisenhofer J. (2011) The structure of the NPC1L1 N-terminal domain in a closed conformation. PLoS ONE, 6 (4): e18722. [PMID:21525977]

How to cite this page

SLC65 NPC-type cholesterol transporters: NPC1 like intracellular cholesterol transporter 1. Last modified on 02/07/2020. Accessed on 28/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2629.