NPC1L1

NPC1L1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3QNT
Identifiers
Aliases	NPC1L1, NPC11L1, NPC1 like intracellular cholesterol transporter 1, SLC65A2, LDLCQ7
External IDs	OMIM: 608010 MGI: 2685089 HomoloGene: 56585 GeneCards: NPC1L1
Gene location (Human)
Chr.	Chromosome 7 (human)[1]
End	44,541,315 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	6,230,143 bp[2]
Gene ontology
Molecular function	• Rab GTPase binding; • myosin V binding; • GO:0001948 protein binding; • drug binding;
Cellular component	• membrane; • cell membrane; • brush border membrane; • apical plasma membrane; • cytoplasmic vesicle membrane; • cytoplasmic vesicle; • integral component of membrane; • spanning component of plasma membrane;
Biological process	• lipoprotein metabolic process; • steroid metabolic process; • lipid metabolism; • cholesterol transport; • cholesterol metabolic process; • intestinal cholesterol absorption; • cholesterol biosynthetic process; • response to drug; • intestinal lipid absorption; • cellular response to sterol depletion;
	Sources:Amigo / QuickGO
Orthologs
	29881
	237636
	ENSG00000015520
	ENSMUSG00000020447
	Q9UHC9
	Q6T3U4
	NM_001101648; NM_001300967; NM_013389
	NM_207242
	NP_001095118; NP_001287896; NP_037521
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract epithelial cells[5] as well as in hepatocytes.[6] Specifically, it appears to bind to a critical mediator of cholesterol absorption.

The drug ezetimibe inhibits NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of between 15-20%.[7] Polymorphic variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment.[8]

NPC1L1 has been shown to be an accessory receptor for hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy.[9]

As cancer appeared more frequently in patients treated with simvastatin-ezetimibe combination therapy in one clinical trial,[10] it had been hypothesized that NPC1L1 by ezetimibe might be associated with an increase cancer risk.[11] However a meta-analysis of ezetimibe clinical data showed no increased risk of cancer from treatment with ezetimibe.[12]

References

GRCh38: Ensembl release 89: ENSG00000015520 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000020447 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8132–7. Bibcode:2005PNAS..102.8132G. doi:10.1073/pnas.0500269102. PMC 1149415. PMID 15928087.
Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007). "Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe". The Journal of Clinical Investigation. 117 (7): 1968–78. doi:10.1172/JCI30060. PMC 1888567. PMID 17571164.
Davis HR, Veltri EP (June 2007). "Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia". Journal of Atherosclerosis and Thrombosis. 14 (3): 99–108. doi:10.5551/jat.14.99. PMID 17587760.
Universal protein resource accession number Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at UniProt.
Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012). "Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine. 18 (2): 281–5. doi:10.1038/nm.2581. PMC 3530957. PMID 22231557.
Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis". The New England Journal of Medicine. 359 (13): 1343–56. doi:10.1056/NEJMoa0804602. PMID 18765433.
Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008). "Analyses of cancer data from three ezetimibe trials". The New England Journal of Medicine. 359 (13): 1357–66. doi:10.1056/NEJMsa0806603. PMID 18765432.
Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology. 201: 247–52. doi:10.1016/j.ijcard.2015.08.103. PMID 26301648.

External links

NPC1L1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
Overview of all the structural information available in the PDB for UniProt: Q9UHC9 (Human NPC1-like intracellular cholesterol transporter 1) at the PDBe-KB.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000015520 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020447 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Garcia-Calvo2005-5] Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. (June 2005). "The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8132–7. Bibcode:2005PNAS..102.8132G. doi:10.1073/pnas.0500269102. PMC 1149415. PMID 15928087.

[Temel-6] Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L (July 2007). "Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe". The Journal of Clinical Investigation. 117 (7): 1968–78. doi:10.1172/JCI30060. PMC 1888567. PMID 17571164.

[pmid17587760-7] Davis HR, Veltri EP (June 2007). "Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia". Journal of Atherosclerosis and Thrombosis. 14 (3): 99–108. doi:10.5551/jat.14.99. PMID 17587760.

[8] Universal protein resource accession number Q9UHC9 for "Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human)" at UniProt.

[9] Sainz B, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL (January 2012). "Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine. 18 (2): 281–5. doi:10.1038/nm.2581. PMC 3530957. PMID 22231557.

[pmid18765433-10] Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. (SEAS Investigators) (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis". The New England Journal of Medicine. 359 (13): 1343–56. doi:10.1056/NEJMoa0804602. PMID 18765433.

[pmid18765432-11] Peto R, Emberson J, Landray M, Baigent C, Collins R, Clare R, Califf R (September 2008). "Analyses of cancer data from three ezetimibe trials". The New England Journal of Medicine. 359 (13): 1357–66. doi:10.1056/NEJMsa0806603. PMID 18765432.

[pmid26301648-12] Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P (December 2015). "Safety and efficacy of ezetimibe: A meta-analysis". International Journal of Cardiology. 201: 247–52. doi:10.1016/j.ijcard.2015.08.103. PMID 26301648.