NPC1

NPC1
ساختارهای موجود
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3GKH, 3GKI, 3GKJ, 5F1B, 5F18, 5HNS, 3JD8, 5I31, 5JNX
معین‌کننده‌ها
نام‌های دیگر	NPC1, NPC, NPC intracellular cholesterol transporter 1, SLC65A1, POGZ
شناسه‌های بیرونی	OMIM: 607623 MGI: 1097712 HomoloGene: 228 GeneCards: NPC1
Gene location (Mouse)
Chr.	Chromosome 18 (mouse)[1]
End	12,236,400 bp[1]
الگوی گسترش RNA
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• virus receptor activity; • lipid transporter activity; • sterol transporter activity; • cholesterol binding; • GO:0001948 پیوند پروتئینی; • transmembrane signaling receptor activity; • signaling receptor activity;
ترکیبات سلولی	• integral component of membrane; • ریزکیسه; • اندوزوم; • دستگاه گلژی; • nuclear envelope; • membrane; • late endosome membrane; • پوسته یاخته; • integral component of plasma membrane; • extracellular region; • شبکه آندوپلاسمی; • perinuclear region of cytoplasm; • لیپید رفت; • کافنده‌تن; • extracellular exosome; • lysosomal membrane; • integral component of lysosomal membrane;
فرایند زیستی	• cellular response to steroid hormone stimulus; • steroid metabolic process; • response to cadmium ion; • اندوسیتوز; • negative regulation of macroautophagy; • lipid metabolism; • bile acid metabolic process; • cholesterol transport; • establishment of protein localization to membrane; • cellular response to low-density lipoprotein particle stimulus; • cholesterol metabolic process; • negative regulation of cell death; • خودخواری; • protein glycosylation; • membrane raft organization; • cholesterol efflux; • lysosomal transport; • ورود ویروس; • cholesterol homeostasis; • GO:0022415 viral process; • response to drug; • adult walking behavior; • ورارسانی پیام; • low-density lipoprotein particle clearance; • intracellular cholesterol transport; • lipid transport;
	Sources:آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	4864
	18145
	ENSG00000141458
	ENSMUSG00000024413
	O15118
	O35604
	XM_005258277، XM_005258278، XM_005258279، XM_006722479، XM_017025784، XM_017025785، XM_017025786، XM_017025787 NM_000271، XM_005258277، XM_005258278، XM_005258279، XM_006722479، XM_017025784، XM_017025785، XM_017025786، XM_017025787
	XM_017317849 NM_008720، XM_017317849
	XP_005258334، XP_005258335، XP_005258336، XP_006722542، XP_016881273، XP_016881274، XP_016881275، XP_016881276 NP_000262، XP_005258334، XP_005258335، XP_005258336، XP_006722542، XP_016881273، XP_016881274، XP_016881275، XP_016881276
	XP_017173338 NP_032746، XP_017173338
	ویکی‌داده
مشاهده/ویرایش Human	View/Edit Mouse

NPC1 (انگلیسی: NPC1‎) یک پروتئین غشایی است که کارش میانجیگری در انتقال کلسترول درون‌سلولی در پستانداران است. در انسان، این پروتئین توسط ژن «NPC1» که بر روی بازوی بلند کروموزوم ۸ قرار گرفته، کدگذاری می‌شود.[4][5]

اهمیت بالینی

جهش در ژن NPC1 موجب بروز بیماری نیمن پیک، نوع سی می‌شود.
جهش در این ژن ارتباط مستحکمی با چاقی دارد.[6]
مسیرهای مرتبط با کلسترول نقش مهمی در پاتوژنز بیماری ایدز و مراحل اولیهٔ آلودگی با ویروس HIV-1 داراست و چسبندگی، دخول، ساخت و تکثیر این ویروس از طریق جایگاه‌های غنی از کلسترول در دیواره سلول موسوم به گستره چربی انجام می‌شود. در نتیجه این ژن در تولید و تکثیر درون‌سلولی ویروس HIV-1 مؤثر است.[7][8]
وجود این حامل پروتئینی کلسترول همچنین در بیماری‌زایی ویروس ابولا نقش مهمی ایفا می‌کند.[9][10]

منابع

GRCm38: Ensembl release 89: ENSMUSG00000024413 - 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.
"Entrez Gene: NPC1 Niemann-Pick disease, type C1".
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.
Meyre D, Delplanque J, Chèvre JC, Lecoeur C, Lobbens S, Gallina S, Durand E, Vatin V, Degraeve F, Proença C, Gaget S, Körner A, Kovacs P, Kiess W, Tichet J, Marre M, Hartikainen AL, Horber F, Potoczna N, Hercberg S, Levy-Marchal C, Pattou F, Heude B, Tauber M, McCarthy MI, Blakemore AI, Montpetit A, Polychronakos C, Weill J, Coin LJ, Asher J, Elliott P, Järvelin MR, Visvikis-Siest S, Balkau B, Sladek R, Balding D, Walley A, Dina C, Froguel P (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.
Tang Y, Leao IC, Coleman EM, Broughton RS, Hildreth JE (August 2009). "Deficiency of niemann-pick type C-1 protein impairs release of human immunodeficiency virus type 1 and results in Gag accumulation in late endosomal/lysosomal compartments". J. Virol. 83 (16): 7982–95. doi:10.1128/JVI.00259-09. PMC 2715784. PMID 19474101.
Coleman EM, Walker TN, Hildreth JE (January 2012). "Loss of Niemann Pick type C proteins 1 and 2 greatly enhances HIV infectivity and is associated with accumulation of HIV Gag and cholesterol in late endosomes/lysosomes". Virol J. 9 (1): 31. doi:10.1186/1743-422X-9-31. PMC 3299633. PMID 22273177.
Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR (September 2011). "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1". Nature. 477 (7364): 340–3. doi:10.1038/nature10348. PMC 3175325. PMID 21866103. Lay summary – New York Times.
Côté M, Misasi J, Ren T, Bruchez A, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J (September 2011). "Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection". Nature. 477 (7364): 344–8. doi:10.1038/nature10380. PMC 3230319. PMID 21866101. Lay summary – New York Times.

مشارکت‌کنندگان ویکی‌پدیا. «NPC1». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۲۵ مارس ۲۰۱۸.

بیشتر بخوانید

Vanier MT, Suzuki K (January 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 (April 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 (December 1998). "Niemann-Pick C disease: cholesterol handling gone awry". Mol Med Today. 4 (12): 525–31. doi:10.1016/S1357-4310(98)01374-4. PMID 9866822.
Garver WS, Heidenreich RA (August 2002). "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.
Greer WL, Riddell DC, Byers DM, Welch JP, Girouard GS, Sparrow SM, Gillan TL, Neumann PE (July 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.
Greer WL, Riddell DC, Gillan TL, Girouard GS, Sparrow SM, Byers DM, Dobson MJ, Neumann PE (July 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.
Watari H, Blanchette-Mackie EJ, Dwyer NK, Glick JM, Patel S, Neufeld EB, Brady RO, Pentchev PG, Strauss JF (February 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.
Patel SC, Suresh S, Kumar U, Hu CY, Cooney A, Blanchette-Mackie EJ, Neufeld EB, Patel RC, Brady RO, Patel YC, Pentchev PG, Ong WY (February 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.
Morris JA, Zhang D, Coleman KG, Nagle J, Pentchev PG, Carstea ED (August 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, Higaki K, Taniguchi M, Zhang H, Akaboshi S, Watanabe Y, Takeshima T, Inui K, Okada S, Tanaka A, Sakuragawa N, Millat G, Vanier MT, Morris JA, Pentchev PG, Ohno K (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, Byers DM, Riddell DC, Neumann PE (November 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.
Millat G, Marçais C, Rafi MA, Yamamoto T, Morris JA, Pentchev PG, Ohno K, Wenger DA, Vanier MT (November 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.
Davies JP, Ioannou YA (August 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, Chikh K, Fensom AH, Harzer K, Wenger DA, Ohno K, Vanier MT (June 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.
Sun X, Marks DL, Park WD, Wheatley CL, Puri V, O'Brien JF, Kraft DL, Lundquist PA, Patterson MC, Pagano RE, Snow K (June 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.

پیوند به بیرون

NPC1 protein, human در سرعنوان‌های موضوعی پزشکی (MeSH) در کتابخانهٔ ملی پزشکی ایالات متحدهٔ آمریکا

در ویکی‌انبار پرونده‌هایی دربارهٔ NPC1 موجود است.

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[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000024413 - Ensembl, May 2017

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

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

[entrez-4] "Entrez Gene: NPC1 Niemann-Pick disease, type C1".

[pmid8446622-5] 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.

[pmid19151714-6] Meyre D, Delplanque J, Chèvre JC, Lecoeur C, Lobbens S, Gallina S, Durand E, Vatin V, Degraeve F, Proença C, Gaget S, Körner A, Kovacs P, Kiess W, Tichet J, Marre M, Hartikainen AL, Horber F, Potoczna N, Hercberg S, Levy-Marchal C, Pattou F, Heude B, Tauber M, McCarthy MI, Blakemore AI, Montpetit A, Polychronakos C, Weill J, Coin LJ, Asher J, Elliott P, Järvelin MR, Visvikis-Siest S, Balkau B, Sladek R, Balding D, Walley A, Dina C, Froguel P (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.

[pmid19474101-7] Tang Y, Leao IC, Coleman EM, Broughton RS, Hildreth JE (August 2009). "Deficiency of niemann-pick type C-1 protein impairs release of human immunodeficiency virus type 1 and results in Gag accumulation in late endosomal/lysosomal compartments". J. Virol. 83 (16): 7982–95. doi:10.1128/JVI.00259-09. PMC 2715784. PMID 19474101.

[pmid22273177-8] Coleman EM, Walker TN, Hildreth JE (January 2012). "Loss of Niemann Pick type C proteins 1 and 2 greatly enhances HIV infectivity and is associated with accumulation of HIV Gag and cholesterol in late endosomes/lysosomes". Virol J. 9 (1): 31. doi:10.1186/1743-422X-9-31. PMC 3299633. PMID 22273177.

[Carette_2011-9] Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR (September 2011). "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1". Nature. 477 (7364): 340–3. doi:10.1038/nature10348. PMC 3175325. PMID 21866103. Lay summary – New York Times.

[Côté_2011-10] Côté M, Misasi J, Ren T, Bruchez A, Lee K, Filone CM, Hensley L, Li Q, Ory D, Chandran K, Cunningham J (September 2011). "Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection". Nature. 477 (7364): 344–8. doi:10.1038/nature10380. PMC 3230319. PMID 21866101. Lay summary – New York Times.