NPC1

Niemann-Pick disease, type C1
Rendering based on PDB 3GKH.
Available structures PDB 3GKH, 3GKI, 3GKJ
Identifiers
Symbols	NPC1; FLJ98532; NPC
External IDs	OMIM: 607623 MGI: 1097712 HomoloGene: 228 GeneCards: NPC1 Gene
Gene Ontology Molecular function • receptor activity • transmembrane receptor activity • protein binding • hedgehog receptor activity • sterol transporter activity Cellular component • membrane fraction • nuclear envelope • lysosome • lysosomal membrane • endosome • endoplasmic reticulum • Golgi apparatus • plasma membrane • integral to plasma membrane • integral to membrane • late endosome membrane • vesicle • membrane raft • perinuclear region of cytoplasm Biological process • endocytosis • autophagy • lysosomal transport • adult walking behavior • bile acid metabolic process • sterol transport • negative regulation of macroautophagy • cholesterol efflux • response to drug • cholesterol homeostasis • cholesterol homeostasis • response to cadmium ion • cellular response to steroid hormone stimulus • cellular response to low-density lipoprotein particle stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4864	18145
Ensembl	ENSG00000141458	ENSMUSG00000024413
UniProt	O15118	Q3U2B2
RefSeq (mRNA)	NM_000271.4	NM_008720.2
RefSeq (protein)	NP_000262.2	NP_032746.2
Location (UCSC)	Chr 18: 21.11 – 21.17 Mb	Chr 18: 12.35 – 12.39 Mb
PubMed search	[1]	[2]

Niemann-Pick disease, type C1 also known as NPC1 is a protein which in humans is encoded by the NPC1 gene.^[1][2]

NPC1 was identified as the gene that when mutated, results in Niemann-Pick disease, type C. NPC1 encodes a putative integral membrane protein containing sequence motifs consistent with a role in intracellular transport of cholesterol to post-lysosomal destinations.^[1][3]

It has been associated with obesity.^[4]

Mice carrying a mutation in this gene are resistant to infection by the Ebola virus (it is not yet known whether this mutated gene might offer similar protection against Ebola's cousin in the filovirus group, the Marburg virus). Agents that can cause a short-term alteration (permanent alterations normally cause Niemann-Pick disease, a disorder of cholesterol metabolism) in this cellular protein similar to this scenario might be tolerated long enough to be a potential treatment for the as-yet virtually untreatable and very deadly hemorrhagic virus. Research and development of such agents is now actively being pursued. This is being done with the assistance of personnel and resources from the Harvard University Medical School-based National Small Molecule Screening Laboratory, the Whitehead Institute for Biomedical Research, Harvard affiliate Brigham and Women's Hospital, the Albert Einstein College of Medicine, and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID). These findings, reported in September 2011, build on a 2005 paper that found that Ebola exploits the cathepsin B protein, apparently in order to subsequently bind with normal NPC1.^[5]

References

1. ^ ^{a b} "Entrez Gene: NPC1 Niemann-Pick disease, type C1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4864. 
2. ^ Carstea ED, Polymeropoulos MH, Parker CC, Detera-Wadleigh SD, O'Neill RR, Patterson MC, Goldin E, Xiao H, Straub RE, Vanier MT (March 1993). "Linkage of Niemann-Pick disease type C to human chromosome 18". Proc. Natl. Acad. Sci. U.S.A. 90 (5): 2002–4. doi:10.1073/pnas.90.5.2002. PMC 46008. PMID 8446622. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8446622. 
3. ^ Carstea ED, Morris JA, Coleman KG, Loftus SK, Zhang D, Cummings C, Gu J, Rosenfeld MA, Pavan WJ, Krizman DB, Nagle J, Polymeropoulos MH, Sturley SL, Ioannou YA, Higgins ME, Comly M, Cooney A, Brown A, Kaneski CR, Blanchette-Mackie EJ, Dwyer NK, Neufeld EB, Chang TY, Liscum L, Strauss JF 3rd, Ohno K, Zeigler M, Carmi R, Sokol J, Markie D, O'Neill RR, van Diggelen OP, Elleder M, Patterson MC, Brady RO, Vanier MT, Pentchev PG, Tagle DA (July 1997). "Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis". Science 277 (5323): 228–31. doi:10.1126/science.277.5323.228. PMID 9211849. 
4. ^ Meyre D, Delplanque J, Chèvre JC et al. (February 2009). "Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations". Nat. Genet. 41 (2): 157–9. doi:10.1038/ng.301. PMID 19151714. 
5. ^ http://www.focushms.com/features/protein-essential-for-ebola-virus-infection-is-a-promising-target/

Further reading

• Vanier MT, Suzuki K (1998). "Recent advances in elucidating Niemann-Pick C disease". Brain Pathol. 8 (1): 163–74. doi:10.1111/j.1750-3639.1998.tb00143.x. PMID 9458174. 
• Liscum L, Klansek JJ (1998). "Niemann-Pick disease type C". Curr. Opin. Lipidol. 9 (2): 131–5. doi:10.1097/00041433-199804000-00009. PMID 9559270. 
• Morris JA, Carstea ED (1999). "Niemann-Pick C disease: cholesterol handling gone awry". Molecular medicine today 4 (12): 525–31. doi:10.1016/S1357-4310(98)01374-4. PMID 9866822. 
• Garver WS, Heidenreich RA (2003). "The Niemann-Pick C proteins and trafficking of cholesterol through the late endosomal/lysosomal system". Curr. Mol. Med. 2 (5): 485–505. doi:10.2174/1566524023362375. PMID 12125814. 
• Carstea ED, Polymeropoulos MH, Parker CC et al. (1993). "Linkage of Niemann-Pick disease type C to human chromosome 18". Proc. Natl. Acad. Sci. U.S.A. 90 (5): 2002–4. doi:10.1073/pnas.90.5.2002. PMC 46008. PMID 8446622. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46008. 
• Carstea ED, Morris JA, Coleman KG et al. (1997). "Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis". Science 277 (5323): 228–31. doi:10.1126/science.277.5323.228. PMID 9211849. 
• Greer WL, Riddell DC, Byers DM et al. (1997). "Linkage of Niemann-Pick disease type D to the same region of human chromosome 18 as Niemann-Pick disease type C". Am. J. Hum. Genet. 61 (1): 139–42. doi:10.1086/513899. PMC 1715879. PMID 9245994. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1715879. 
• Greer WL, Riddell DC, Gillan TL et al. (1998). "The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1". Am. J. Hum. Genet. 63 (1): 52–4. doi:10.1086/301931. PMC 1377252. PMID 9634529. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1377252. 
• Watari H, Blanchette-Mackie EJ, Dwyer NK et al. (1999). "Niemann-Pick C1 protein: Obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization". Proc. Natl. Acad. Sci. U.S.A. 96 (3): 805–10. doi:10.1073/pnas.96.3.805. PMC 15306. PMID 9927649. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15306. 
• Patel SC, Suresh S, Kumar U et al. (1999). "Localization of Niemann–Pick C1 protein in astrocytes: Implications for neuronal degeneration in Niemann– Pick type C disease". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1657–62. doi:10.1073/pnas.96.4.1657. PMC 15549. PMID 9990080. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15549. 
• Morris JA, Zhang D, Coleman KG et al. (1999). "The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene". Biochem. Biophys. Res. Commun. 261 (2): 493–8. doi:10.1006/bbrc.1999.1070. PMID 10425213. 
• Yamamoto T, Nanba E, Ninomiya H et al. (1999). "NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C". Hum. Genet. 105 (1–2): 10–6. doi:10.1007/s004390051057. PMID 10480349. 
• Greer WL, Dobson MJ, Girouard GS et al. (1999). "Mutations in NPC1 Highlight a Conserved NPC1-Specific Cysteine-Rich Domain". Am. J. Hum. Genet. 65 (5): 1252–60. doi:10.1086/302620. PMC 1288277. PMID 10521290. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1288277. 
• Millat G, Marçais C, Rafi MA et al. (1999). "Niemann-Pick C1 Disease: The I1061T Substitution Is a Frequent Mutant Allele in Patients of Western European Descent and Correlates with a Classic Juvenile Phenotype". Am. J. Hum. Genet. 65 (5): 1321–9. doi:10.1086/302626. PMC 1288284. PMID 10521297. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1288284. 
• Davies JP, Ioannou YA (2000). "Topological analysis of Niemann-Pick C1 protein reveals that the membrane orientation of the putative sterol-sensing domain is identical to those of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein cleavage-activating protein". J. Biol. Chem. 275 (32): 24367–74. doi:10.1074/jbc.M002184200. PMID 10821832. 
• Millat G, Marçais C, Tomasetto C et al. (2001). "Niemann-Pick C1 Disease: Correlations between NPC1 Mutations, Levels of NPC1 Protein, and Phenotypes Emphasize the Functional Significance of the Putative Sterol-Sensing Domain and of the Cysteine-Rich Luminal Loop". Am. J. Hum. Genet. 68 (6): 1373–85. doi:10.1086/320606. PMC 1226124. PMID 11333381. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1226124. 
• Sun X, Marks DL, Park WD et al. (2001). "Niemann-Pick C Variant Detection by Altered Sphingolipid Trafficking and Correlation with Mutations within a Specific Domain of NPC1". Am. J. Hum. Genet. 68 (6): 1361–72. doi:10.1086/320599. PMC 1226123. PMID 11349231. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1226123. 

External links

• MeSH NPC1+protein,+human
• Hide & Seek Foundation for Lysosomal Disease Research

This article incorporates text from the United States National Library of Medicine, which is in the public domain.