NPC1_HUMAN
ID NPC1_HUMAN Reviewed; 1278 AA.
AC O15118; B4DET3; Q9P130;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=NPC intracellular cholesterol transporter 1 {ECO:0000312|HGNC:HGNC:7897};
DE AltName: Full=Niemann-Pick C1 protein {ECO:0000303|PubMed:9211849};
DE Flags: Precursor;
GN Name=NPC1 {ECO:0000312|HGNC:HGNC:7897};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANT ILE-642, AND
RP VARIANTS NPC1.
RX PubMed=9211849; DOI=10.1126/science.277.5323.228;
RA Carstea E.D., Morris J.A., Coleman K.G., Loftus S.K., Zhang D.,
RA Cummings C., Gu J., Rosenfeld M.A., Pavan W.J., Krizman D.B., Nagle J.,
RA Polymeropoulos M.H., Sturley S.L., Ioannou Y.A., Higgins M.E., Comly M.,
RA Cooney A., Brown A., Kaneski C.R., Blanchette-Mackie E.J., Dwyer N.K.,
RA Neufeld E.B., Chang T.-Y., Liscum L., Strauss J.F. III, Ohno K.,
RA Zeigler M., Carmi R., Sokol J., Markie D., O'Neill R.R., van Diggelen O.P.,
RA Elleder M., Patterson M.C., Brady R.O., Vanier M.T., Pentchev P.G.,
RA Tagle D.A.;
RT "Niemann-Pick C1 disease gene: homology to mediators of cholesterol
RT homeostasis.";
RL Science 277:228-231(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS.
RX PubMed=10425213; DOI=10.1006/bbrc.1999.1070;
RA Morris J.A., Zhang D., Coleman K.G., Nagle J., Pentchev P.G., Carstea E.D.;
RT "The genomic organization and polymorphism analysis of the human Niemann-
RT Pick C1 gene.";
RL Biochem. Biophys. Res. Commun. 261:493-498(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS NPC1 ARG-512; TRP-670; CYS-825;
RP ILE-849; VAL-874; TYR-948; LEU-954; LEU-958; ALA-1007 AND THR-1061, AND
RP VARIANTS ARG-215; ILE-642; VAL-858; GLY-971 AND VAL-1049.
RX PubMed=11754101; DOI=10.1002/humu.10016;
RA Bauer P., Knoblich R., Bauer C., Finckh U., Hufen A., Kropp J., Braun S.,
RA Kustermann-Kuhn B., Schmidt D., Harzer K., Rolfs A.;
RT "NPC1: complete genomic sequence, mutation analysis, and characterization
RT of haplotypes.";
RL Hum. Mutat. 19:30-38(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-151
RP AND ILE-642.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF CYS-63;
RP 74-CYS-CYS-75; CYS-97 AND 1275-LEU--PHE-1278.
RX PubMed=9927649; DOI=10.1073/pnas.96.3.805;
RA Watari H., Blanchette-Mackie E.J., Dwyer N.K., Glick J.M., Patel S.,
RA Neufeld E.B., Brady R.O., Pentchev P.G., Strauss J.F. III;
RT "Niemann-Pick C1 protein: obligatory roles for N-terminal domains and
RT lysosomal targeting in cholesterol mobilization.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:805-810(1999).
RN [8]
RP FUNCTION, TOPOLOGY, AND GLYCOSYLATION.
RX PubMed=10821832; DOI=10.1074/jbc.m002184200;
RA Davies J.P., Ioannou Y.A.;
RT "Topological analysis of Niemann-Pick C1 protein reveals that the membrane
RT orientation of the putative sterol-sensing domain is identical to those of
RT 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element
RT binding protein cleavage-activating protein.";
RL J. Biol. Chem. 275:24367-24374(2000).
RN [9]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [10]
RP FUNCTION, INTERACTION WITH NPC2, AND CATALYTIC ACTIVITY.
RX PubMed=18772377; DOI=10.1073/pnas.0807328105;
RA Infante R.E., Wang M.L., Radhakrishnan A., Kwon H.J., Brown M.S.,
RA Goldstein J.L.;
RT "NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and
RT lipid bilayers, a step in cholesterol egress from lysosomes.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15287-15292(2008).
RN [11]
RP INTERACTION WITH TMEM97.
RX PubMed=19583955; DOI=10.1016/j.cmet.2009.05.009;
RA Bartz F., Kern L., Erz D., Zhu M., Gilbert D., Meinhof T., Wirkner U.,
RA Erfle H., Muckenthaler M., Pepperkok R., Runz H.;
RT "Identification of cholesterol-regulating genes by targeted RNAi
RT screening.";
RL Cell Metab. 10:63-75(2009).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135 AND ASN-524.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP REVIEW ON FUNCTION.
RX PubMed=18832164; DOI=10.1073/pnas.0808256105;
RA Subramanian K., Balch W.E.;
RT "NPC1/NPC2 function as a tag team duo to mobilize cholesterol.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15223-15224(2008).
RN [14]
RP REVIEW ON FUNCTION.
RX PubMed=20674853; DOI=10.1016/j.cmet.2010.07.004;
RA Vance J.E.;
RT "Transfer of cholesterol by the NPC team.";
RL Cell Metab. 12:105-106(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP REVIEW ON FUNCTION.
RX PubMed=21412152; DOI=10.1097/mol.0b013e3283453e69;
RA Vance J.E., Peake K.B.;
RT "Function of the Niemann-Pick type C proteins and their bypass by
RT cyclodextrin.";
RL Curr. Opin. Lipidol. 22:204-209(2011).
RN [17]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH EBOLAVIRUS
RP GLYCOPROTEIN.
RX PubMed=21866103; DOI=10.1038/nature10348;
RA Carette J.E., Raaben M., Wong A.C., Herbert A.S., Obernosterer G.,
RA Mulherkar N., Kuehne A.I., Kranzusch P.J., Griffin A.M., Ruthel G.,
RA Dal Cin P., Dye J.M., Whelan S.P., Chandran K., Brummelkamp T.R.;
RT "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.";
RL Nature 477:340-343(2011).
RN [18]
RP INTERACTION WITH TIM1, AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=25855742; DOI=10.1128/jvi.03156-14;
RA Kuroda M., Fujikura D., Nanbo A., Marzi A., Noyori O., Kajihara M.,
RA Maruyama J., Matsuno K., Miyamoto H., Yoshida R., Feldmann H., Takada A.;
RT "Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of
RT Ebola Virus.";
RL J. Virol. 89:6481-6493(2015).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [20]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=32855215; DOI=10.1126/science.abb3753;
RA Bruchez A., Sha K., Johnson J., Chen L., Stefani C., McConnell H.,
RA Gaucherand L., Prins R., Matreyek K.A., Hume A.J., Muehlberger E.,
RA Schmidt E.V., Olinger G.G., Stuart L.M., Lacy-Hulbert A.;
RT "MHC class II transactivator CIITA induces cell resistance to Ebola virus
RT and SARS-like coronaviruses.";
RL Science 370:241-247(2020).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 23-252 OF MUTANT GLN-70; GLN-122
RP AND GLN-185 IN COMPLEX WITH CHOLESTEROL, FUNCTION, DISULFIDE BONDS,
RP GLYCOSYLATION AT ASN-158 AND ASN-222, AND MUTAGENESIS OF 26-VAL-TRP-27;
RP 39-ARG--ASN-41; ASN-41; ASN-70; 82-THR-LEU-83; 101-PHE-TYR-102;
RP 106-ASN--PHE-108; 110-GLU--THR-112; ASN-122; 144-LEU-GLN-145;
RP 146-TYR-TYR-147; 175-LEU-LEU-176; 180-ASP--ASP-182; ASN-185;
RP 187-TYR-ASN-188; 191-GLU-TYR-192; 195-ASN-LYS-196; 197-ASP-ASN-198;
RP 199-GLY-GLN-200; 202-PRO-PHE-203; 204-THR-ILE-205 AND GLY-660.
RX PubMed=19563754; DOI=10.1016/j.cell.2009.03.049;
RA Kwon H.J., Abi-Mosleh L., Wang M.L., Deisenhofer J., Goldstein J.L.,
RA Brown M.S., Infante R.E.;
RT "Structure of N-terminal domain of NPC1 reveals distinct subdomains for
RT binding and transfer of cholesterol.";
RL Cell 137:1213-1224(2009).
RN [22] {ECO:0007744|PDB:5F18, ECO:0007744|PDB:5F1B}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 374-620 IN COMPLEX WITH
RP EBOLAVIRUS GLYCOPROTEIN GP, INTERACTION WITH EBOLAVIRUS GLYCOPROTEIN GP
RP (MICROBIAL INFECTION), MUTAGENESIS OF 423-TYR-PRO-424; PHE-503; PHE-504 AND
RP TYR-506, AND DISULFIDE BONDS.
RX PubMed=26771495; DOI=10.1016/j.cell.2015.12.044;
RA Wang H., Shi Y., Song J., Qi J., Lu G., Yan J., Gao G.F.;
RT "Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick
RT C1.";
RL Cell 164:258-268(2016).
RN [23] {ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.43 ANGSTROMS), FUNCTION, INTERACTION
RP WITH NPC2 AND WITH EBOLAVIRUS GLYCOPROTEIN GP, TOPOLOGY, GLYCOSYLATION AT
RP ASN-122; ASN-135; ASN-158; ASN-185; ASN-222; ASN-524; ASN-572; ASN-598 AND
RP ASN-1064, DISULFIDE BONDS, CHARACTERIZATION OF VARIANT NPC1 TRP-518, AND
RP MUTAGENESIS OF 25-CYS--PRO-257; 175-LEU-LEU-176; 202-PRO-PHE-203 AND
RP 249-PRO--PRO-257.
RX PubMed=27238017; DOI=10.1016/j.cell.2016.05.022;
RA Gong X., Qian H., Zhou X., Wu J., Wan T., Cao P., Huang W., Zhao X.,
RA Wang X., Wang P., Shi Y., Gao G.F., Zhou Q., Yan N.;
RT "Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol
RT Transfer and Ebola Infection.";
RL Cell 165:1467-1478(2016).
RN [24] {ECO:0007744|PDB:5HNS}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 387-618, GLYCOSYLATION AT
RP ASN-478; ASN-524; ASN-557; ASN-572 AND ASN-598, AND DISULFIDE BONDS.
RX PubMed=26846330; DOI=10.1002/1873-3468.12089;
RA Zhao Y., Ren J., Harlos K., Stuart D.I.;
RT "Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2
RT and Ebola virus interactions.";
RL FEBS Lett. 590:605-612(2016).
RN [25] {ECO:0007744|PDB:5KWY}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 374-620 IN COMPLEX WITH NPC2, AND
RP DISULFIDE BONDS.
RX PubMed=27551080; DOI=10.1073/pnas.1611956113;
RA Li X., Saha P., Li J., Blobel G., Pfeffer S.R.;
RT "Clues to the mechanism of cholesterol transfer from the structure of NPC1
RT middle lumenal domain bound to NPC2.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:10079-10084(2016).
RN [26] {ECO:0007744|PDB:5U73, ECO:0007744|PDB:5U74}
RP X-RAY CRYSTALLOGRAPHY (3.33 ANGSTROMS) OF 334-1278, FUNCTION, TOPOLOGY,
RP GLYCOSYLATION AT ASN-452; ASN-459; ASN-478; ASN-524; ASN-557; ASN-598;
RP ASN-916; ASN-931; ASN-961; ASN-968 AND ASN-1064, MUTAGENESIS OF
RP 230-SER--VAL-234; PRO-691 AND 909-CYS--ASP-917, AND DISULFIDE BONDS.
RX PubMed=28784760; DOI=10.1073/pnas.1711716114;
RA Li X., Lu F., Trinh M.N., Schmiege P., Seemann J., Wang J., Blobel G.;
RT "3.3 A structure of Niemann-Pick C1 protein reveals insights into the
RT function of the C-terminal luminal domain in cholesterol transport.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:9116-9121(2017).
RN [27]
RP VARIANT NPC1 TRP-992.
RX PubMed=9634529; DOI=10.1086/301931;
RA Greer W.L., Riddell D.C., Gillan T.L., Girouard G.S., Sparrow S.M.,
RA Byers D.M., Dobson M.J., Neumann P.E.;
RT "The Nova Scotia (type D) form of Niemann-Pick disease is caused by a
RT G3097-->T transversion in NPC1.";
RL Am. J. Hum. Genet. 63:52-54(1998).
RN [28]
RP VARIANTS NPC1 GLN-934; LEU-940; ASN-948; LEU-954; TRP-992; ALA-1007;
RP THR-1061 AND VAL-1213.
RX PubMed=10521290; DOI=10.1086/302620;
RA Greer W.L., Dobson M.J., Girouard G.S., Byers D.M., Riddell D.C.,
RA Neumann P.E.;
RT "Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich
RT domain.";
RL Am. J. Hum. Genet. 65:1252-1260(1999).
RN [29]
RP VARIANT NPC1 THR-1061.
RX PubMed=10521297; DOI=10.1086/302626;
RA Millat G., Marcais C., Rafi M.A., Yamamoto T., Morris J.A., Pentchev P.G.,
RA Ohno K., Wenger D.A., Vanier M.T.;
RT "Niemann-Pick C1 disease: the I1061T substitution is a frequent mutant
RT allele in patients of Western European descent and correlates with a
RT classic juvenile phenotype.";
RL Am. J. Hum. Genet. 65:1321-1329(1999).
RN [30]
RP VARIANTS NPC1, AND VARIANTS ARG-215; VAL-858 AND GLN-1266.
RX PubMed=10480349; DOI=10.1007/s004399900059;
RA Yamamoto T., Nanba E., Ninomiya H., Higaki K., Taniguchi M., Zhang H.,
RA Akaboshi S., Watanabe Y., Takeshima T., Inui K., Okada S., Tanaka A.,
RA Sakuragawa N., Millat G., Vanier M.T., Morris J.A., Pentchev P.G., Ohno K.;
RT "NPC1 gene mutations in Japanese patients with Niemann-Pick disease type
RT C.";
RL Hum. Genet. 105:10-16(1999).
RN [31]
RP VARIANTS NPC1 GLY-177; PRO-473; PRO-510; GLN-518; SER-703; MET-889;
RP LEU-954; TYR-956; ARG-996; THR-1061; CYS-1088; ARG-1205; PHE-1213 AND
RP GLU-1236, AND VARIANTS SER-237 AND ALA-873.
RX PubMed=11182931; DOI=10.1136/jmg.37.9.707;
RA Yamamoto T., Ninomiya H., Matsumoto M., Ohta Y., Nanba E., Tsutsumi Y.,
RA Yamakawa K., Millat G., Vanier M.T., Pentchev P.G., Ohno K.;
RT "Genotype-phenotype relationship of Niemann-Pick disease type C: a possible
RT correlation between clinical onset and levels of NPC1 protein in isolated
RT skin fibroblasts.";
RL J. Med. Genet. 37:707-712(2000).
RN [32]
RP VARIANTS NPC1 ARG-92; MET-137; ASN-242; VAL-248; THR-401; GLN-404; ASP-612;
RP TRP-652; CYS-789; CYS-825; VAL-874; SER-888; PRO-929; LEU-940; ASN-944;
RP ASN-948; GLN-958; ARG-976; CYS-978; LEU-1004; ALA-1007; GLY-1023; THR-1061;
RP LYS-1089; THR-1142; LYS-1150; SER-1156; MET-1165; HIS-1186 AND GLY-1189,
RP AND VARIANT SER-237.
RX PubMed=11349231; DOI=10.1086/320599;
RA Sun X., Marks D.L., Park W.D., Wheatley C.L., Puri V., O'Brien J.F.,
RA Kraft D.L., Lundquist P.A., Patterson M.C., Pagano R.E., Snow K.;
RT "Niemann-Pick C variant detection by altered sphingolipid trafficking and
RT correlation with mutations within a specific domain of NPC1.";
RL Am. J. Hum. Genet. 68:1361-1372(2001).
RN [33]
RP VARIANTS NPC1 HIS-242; ARG-272; ALA-378; GLN-404; GLN-518; VAL-605;
RP ARG-631; PRO-724; PRO-775; CYS-825; VAL-874; GLN-934; MET-943; ASN-944;
RP MET-950; SER-986; ARG-992; ALA-1007; THR-1054; THR-1061; THR-1142; TYR-1168
RP AND HIS-1186, AND VARIANT SER-237.
RX PubMed=11333381; DOI=10.1086/320606;
RA Millat G., Marcais C., Tomasetto C., Chikh K., Fensom A.H., Harzer K.,
RA Wenger D.A., Ohno K., Vanier M.T.;
RT "Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of
RT NPC1 protein, and phenotypes emphasize the functional significance of the
RT putative sterol-sensing domain and of the cysteine-rich luminal loop.";
RL Am. J. Hum. Genet. 68:1373-1385(2001).
RN [34]
RP VARIANTS NPC1 ARG-63; GLN-404; VAL-927; TRP-992; ASP-1012 AND SER-1156.
RX PubMed=11545687; DOI=10.1097/00125817-200109000-00003;
RA Meiner V., Shpitzen S., Mandel H., Klar A., Ben-Neriah Z., Zlotogora J.,
RA Sagi M., Lossos A., Bargal R., Sury V., Carmi R., Leitersdorf E.,
RA Zeigler M.;
RT "Clinical-biochemical correlation in molecularly characterized patients
RT with Niemann-Pick type C.";
RL Genet. Med. 3:343-348(2001).
RN [35]
RP VARIANTS NPC1 ARG-92; TYR-177; TRP-518; CYS-942; CYS-978; ALA-1007 VAL-1035
RP AND THR-1061, AND VARIANTS ARG-215; ILE-642 AND VAL-858.
RX PubMed=11479732; DOI=10.1007/s004390100531;
RA Ribeiro I., Marcao A., Amaral O., Sa Miranda M.C., Vanier M.T., Millat G.;
RT "Niemann-Pick type C disease: NPC1 mutations associated with severe and
RT mild cellular cholesterol trafficking alterations.";
RL Hum. Genet. 109:24-32(2001).
RN [36]
RP VARIANTS NPC1 GLY-231; VAL-874 ASN-948 AND THR-1094, AND VARIANTS SER-237;
RP CYS-381 AND ILE-642.
RX PubMed=12408188; DOI=10.1023/a:1020151801060;
RA Kaminski W.E., Kluenemann H.H., Ibach B., Aslanidis C., Klein H.E.,
RA Schmitz G.;
RT "Identification of novel mutations in the NPC1 gene in German patients with
RT Niemann-Pick C disease.";
RL J. Inherit. Metab. Dis. 25:385-389(2002).
RN [37]
RP VARIANTS NPC1 LYS-451; LEU-474; CYS-890; ASP-899; SER-910; TRP-992;
RP ALA-1007; THR-1061 AND SER-1156, AND VARIANTS ARG-215; ILE-642 AND VAL-858.
RX PubMed=12401890; DOI=10.1194/jlr.m200203-jlr200;
RA Tarugi P., Ballarini G., Bembi B., Battisti C., Palmeri S., Panzani F.,
RA Di Leo E., Martini C., Federico A., Calandra S.;
RT "Niemann-Pick type C disease: mutations of NPC1 gene and evidence of
RT abnormal expression of some mutant alleles in fibroblasts.";
RL J. Lipid Res. 43:1908-1919(2002).
RN [38]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT NPC1 ARG-113, VARIANT SER-237,
RP CHARACTERIZATION OF VARIANT NPC1 ARG-113, AND CHARACTERIZATION OF VARIANT
RP SER-237.
RX PubMed=12554680; DOI=10.1093/hmg/ddg025;
RA Blom T.S., Linder M.D., Snow K., Pihko H., Hess M.W., Jokitalo E.,
RA Veckman V., Syvaenen A.-C., Ikonen E.;
RT "Defective endocytic trafficking of NPC1 and NPC2 underlying infantile
RT Niemann-Pick type C disease.";
RL Hum. Mol. Genet. 12:257-272(2003).
RN [39]
RP VARIANTS NPC1 TYR-74; SER-166; SER-222; TYR-247; PHE-380; PRO-388; CYS-389;
RP TRP-404; LEU-433; SER-509; SER-521; LEU-543; CYS-615; ARG-640; SER-660;
RP MET-664; VAL-673; PHE-684; LEU-691; VAL-695; ASN-700; ILE-734; LYS-742;
RP GLU-745; VAL-767; GLY-789; ASN-945; ARG-1016; GLN-1059; LEU-1087; ILE-1137;
RP VAL-1140; LYS-1205 AND GLY-1249, AND VARIANTS ARG-215; SER-237; SER-434 AND
RP GLN-1266.
RX PubMed=12955717; DOI=10.1002/humu.10255;
RA Park W.D., O'Brien J.F., Lundquist P.A., Kraft D.L., Vockley C.W.,
RA Karnes P.S., Patterson M.C., Snow K.;
RT "Identification of 58 novel mutations in Niemann-Pick disease type C:
RT correlation with biochemical phenotype and importance of PTC1-like domains
RT in NPC1.";
RL Hum. Mutat. 22:313-325(2003).
RN [40]
RP VARIANTS NPC1 MET-137; TYR-177; TRP-372; LEU-434; LEU-474; TYR-479;
RP ARG-576; MET-664; PHE-727; LYS-754; PRO-775; LEU-865; THR-926; CYS-942;
RP ASN-944; HIS-948; GLU-959; 961-ASN--PHE-966 DELINS SER; ALA-1007; VAL-1035;
RP LYS-1036; THR-1061; ASN-1066; ILE-1156; SER-1156 AND LEU-1224, AND VARIANTS
RP ARG-215; ILE-642; VAL-858 AND GLN-1266.
RX PubMed=16098014; DOI=10.1111/j.1399-0004.2005.00490.x;
RA Fernandez-Valero E.M., Ballart A., Iturriaga C., Lluch M., Macias J.,
RA Vanier M.T., Pineda M., Coll M.J.;
RT "Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick
RT type C patients: genotype-phenotype correlations.";
RL Clin. Genet. 68:245-254(2005).
RN [41]
RP VARIANTS NPC1 SER-968; VAL-1015; ARG-1034 AND LEU-1212, AND VARIANTS
RP ARG-215; ILE-642; VAL-858 AND GLN-1266.
RX PubMed=15774455; DOI=10.1136/jnnp.2004.046045;
RA Yang C.-C., Su Y.-N., Chiou P.-C., Fietz M.J., Yu C.-L., Hwu W.-L.,
RA Lee M.-J.;
RT "Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease
RT type C.";
RL J. Neurol. Neurosurg. Psych. 76:592-595(2005).
RN [42]
RP VARIANTS NPC1 SER-166; TYR-177; PRO-404; LEU-537; LEU-543; LEU-615;
RP ARG-631; LEU-763; CYS-825; LEU-862; LEU-865; CYS-871; TYR-917; GLN-934;
RP LEU-940; MET-950; SER-968; ALA-992; ARG-992; TRP-992; ALA-1007; MET-1036;
RP THR-1061; VAL-1062; ASN-1097; VAL-1174; HIS-1186; VAL-1216 AND ARG-1240,
RP AND VARIANT MET-511.
RX PubMed=16126423; DOI=10.1016/j.ymgme.2005.07.007;
RA Millat G., Baielo N., Molinero S., Rodriguez C., Chikh K., Vanier M.T.;
RT "Niemann-Pick C disease: use of denaturing high performance liquid
RT chromatography for the detection of NPC1 and NPC2 genetic variations and
RT impact on management of patients and families.";
RL Mol. Genet. Metab. 86:220-232(2005).
RN [43]
RP VARIANTS NPC1 ASN-666 AND SER-961.
RX PubMed=16802107; DOI=10.1007/s10545-006-0330-z;
RA Dvorakova L., Sikora J., Hrebicek M., Hulkova H., Bouckova M., Stolnaja L.,
RA Elleder M.;
RT "Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare
RT or underdiagnosed disorder?";
RL J. Inherit. Metab. Dis. 29:591-591(2006).
RN [44]
RP VARIANT NCP1 MET-137.
RX PubMed=23453666; DOI=10.1016/j.ajhg.2013.02.004;
RA Akizu N., Shembesh N.M., Ben-Omran T., Bastaki L., Al-Tawari A., Zaki M.S.,
RA Koul R., Spencer E., Rosti R.O., Scott E., Nickerson E., Gabriel S.,
RA da Gente G., Li J., Deardorff M.A., Conlin L.K., Horton M.A., Zackai E.H.,
RA Sherr E.H., Gleeson J.G.;
RT "Whole-exome sequencing identifies mutated c12orf57 in recessive corpus
RT callosum hypoplasia.";
RL Am. J. Hum. Genet. 92:392-400(2013).
CC -!- FUNCTION: Intracellular cholesterol transporter which acts in concert
CC with NPC2 and plays an important role in the egress of cholesterol from
CC the endosomal/lysosomal compartment (PubMed:9211849, PubMed:9927649,
CC PubMed:10821832, PubMed:18772377, PubMed:27238017, PubMed:12554680).
CC Unesterified cholesterol that has been released from LDLs in the lumen
CC of the late endosomes/lysosomes is transferred by NPC2 to the
CC cholesterol-binding pocket in the N-terminal domain of NPC1
CC (PubMed:9211849, PubMed:9927649, PubMed:18772377, PubMed:19563754,
CC PubMed:27238017, PubMed:28784760). Cholesterol binds to NPC1 with the
CC hydroxyl group buried in the binding pocket (PubMed:19563754). Binds
CC oxysterol with higher affinity than cholesterol. May play a role in
CC vesicular trafficking in glia, a process that may be crucial for
CC maintaining the structural and functional integrity of nerve terminals
CC (Probable). {ECO:0000269|PubMed:10821832, ECO:0000269|PubMed:12554680,
CC ECO:0000269|PubMed:18772377, ECO:0000269|PubMed:19563754,
CC ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760,
CC ECO:0000269|PubMed:9211849, ECO:0000269|PubMed:9927649, ECO:0000305}.
CC -!- FUNCTION: (Microbial infection) Acts as an endosomal entry receptor for
CC ebolavirus. {ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:25855742,
CC ECO:0000269|PubMed:32855215}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000269|PubMed:18772377};
CC -!- SUBUNIT: Interacts (via the second lumenal domain) with NPC2
CC (PubMed:18772377, PubMed:27238017, PubMed:27551080). Interacts with
CC TMEM97 (PubMed:19583955). Interacts with TIM1 (PubMed:25855742).
CC {ECO:0000269|PubMed:18772377, ECO:0000269|PubMed:19583955,
CC ECO:0000269|PubMed:25855742, ECO:0000269|PubMed:27238017,
CC ECO:0000269|PubMed:27551080}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus glycoprotein.
CC {ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:26771495,
CC ECO:0000269|PubMed:27238017}.
CC -!- INTERACTION:
CC O15118; Q03135: CAV1; NbExp=3; IntAct=EBI-2368710, EBI-603614;
CC O15118; P61916: NPC2; NbExp=3; IntAct=EBI-2368710, EBI-2368946;
CC O15118; P87666: GP; Xeno; NbExp=3; IntAct=EBI-2368710, EBI-22015020;
CC O15118; X5HMX4: GP; Xeno; NbExp=3; IntAct=EBI-2368710, EBI-13643336;
CC O15118; P0DTC9: N; Xeno; NbExp=3; IntAct=EBI-2368710, EBI-25475856;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:12554680}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10821832, ECO:0000269|PubMed:27238017,
CC ECO:0000269|PubMed:28784760}. Lysosome membrane
CC {ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:9927649}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10821832,
CC ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15118-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15118-2; Sequence=VSP_056431, VSP_056432, VSP_056433;
CC -!- DOMAIN: A cysteine-rich N-terminal domain and a C-terminal domain
CC containing a di-leucine motif necessary for lysosomal targeting are
CC critical for mobilization of cholesterol from lysosomes.
CC {ECO:0000269|PubMed:9927649}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10821832,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19563754}.
CC -!- DISEASE: Niemann-Pick disease C1 (NPC1) [MIM:257220]: A lysosomal
CC storage disorder that affects the viscera and the central nervous
CC system. It is due to defective intracellular processing and transport
CC of low-density lipoprotein derived cholesterol. It causes accumulation
CC of cholesterol in lysosomes, with delayed induction of cholesterol
CC homeostatic reactions. Niemann-Pick disease type C1 has a highly
CC variable clinical phenotype. Clinical features include variable
CC hepatosplenomegaly and severe progressive neurological dysfunction such
CC as ataxia, dystonia and dementia. The age of onset can vary from
CC infancy to late adulthood. An allelic variant of Niemann-Pick disease
CC type C1 is found in people with Nova Scotia ancestry. Patients with the
CC Nova Scotian clinical variant are less severely affected.
CC {ECO:0000269|PubMed:10480349, ECO:0000269|PubMed:10521290,
CC ECO:0000269|PubMed:10521297, ECO:0000269|PubMed:11182931,
CC ECO:0000269|PubMed:11333381, ECO:0000269|PubMed:11349231,
CC ECO:0000269|PubMed:11479732, ECO:0000269|PubMed:11545687,
CC ECO:0000269|PubMed:11754101, ECO:0000269|PubMed:12401890,
CC ECO:0000269|PubMed:12408188, ECO:0000269|PubMed:12554680,
CC ECO:0000269|PubMed:12955717, ECO:0000269|PubMed:15774455,
CC ECO:0000269|PubMed:16098014, ECO:0000269|PubMed:16126423,
CC ECO:0000269|PubMed:16802107, ECO:0000269|PubMed:27238017,
CC ECO:0000269|PubMed:9211849, ECO:0000269|PubMed:9634529}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; AF002020; AAB63982.1; -; mRNA.
DR EMBL; AF157379; AAD48006.1; -; Genomic_DNA.
DR EMBL; AF157365; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157366; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157367; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157368; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157369; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157370; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157371; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157372; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157373; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157374; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157375; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157376; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157377; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF157378; AAD48006.1; JOINED; Genomic_DNA.
DR EMBL; AF338230; AAK25791.1; -; Genomic_DNA.
DR EMBL; AH009108; AAF28875.1; -; Genomic_DNA.
DR EMBL; AK293779; BAG57194.1; -; mRNA.
DR EMBL; AC010853; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026634; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC063302; AAH63302.1; -; mRNA.
DR CCDS; CCDS11878.1; -. [O15118-1]
DR RefSeq; NP_000262.2; NM_000271.4. [O15118-1]
DR PDB; 3GKH; X-ray; 1.81 A; A=23-252.
DR PDB; 3GKI; X-ray; 1.80 A; A=23-252.
DR PDB; 3GKJ; X-ray; 1.60 A; A=23-252.
DR PDB; 3JD8; EM; 4.43 A; A=1-1278.
DR PDB; 5F18; X-ray; 2.00 A; A=374-620.
DR PDB; 5F1B; X-ray; 2.30 A; C=374-620.
DR PDB; 5HNS; X-ray; 2.45 A; A/B=387-618.
DR PDB; 5JNX; EM; 6.56 A; A=1-1278.
DR PDB; 5KWY; X-ray; 2.40 A; A/B=374-620.
DR PDB; 5U73; X-ray; 3.35 A; A=1-1278.
DR PDB; 5U74; X-ray; 3.33 A; A=1-1278.
DR PDB; 6UOX; EM; 4.13 A; A=1-1278.
DR PDB; 6W5R; EM; 3.60 A; A=1-1278.
DR PDB; 6W5S; EM; 3.00 A; A=1-1278.
DR PDB; 6W5T; EM; 3.70 A; A=1-1278.
DR PDB; 6W5U; EM; 3.90 A; A=1-1278.
DR PDB; 6W5V; EM; 4.00 A; A=1-1278.
DR PDBsum; 3GKH; -.
DR PDBsum; 3GKI; -.
DR PDBsum; 3GKJ; -.
DR PDBsum; 3JD8; -.
DR PDBsum; 5F18; -.
DR PDBsum; 5F1B; -.
DR PDBsum; 5HNS; -.
DR PDBsum; 5JNX; -.
DR PDBsum; 5KWY; -.
DR PDBsum; 5U73; -.
DR PDBsum; 5U74; -.
DR PDBsum; 6UOX; -.
DR PDBsum; 6W5R; -.
DR PDBsum; 6W5S; -.
DR PDBsum; 6W5T; -.
DR PDBsum; 6W5U; -.
DR PDBsum; 6W5V; -.
DR AlphaFoldDB; O15118; -.
DR SMR; O15118; -.
DR BioGRID; 110925; 386.
DR DIP; DIP-53217N; -.
DR ELM; O15118; -.
DR IntAct; O15118; 19.
DR MINT; O15118; -.
DR STRING; 9606.ENSP00000269228; -.
DR BindingDB; O15118; -.
DR ChEMBL; CHEMBL1293277; -.
DR SwissLipids; SLP:000000478; -.
DR TCDB; 2.A.6.6.1; the resistance-nodulation-cell division (rnd) superfamily.
DR GlyConnect; 1571; 3 N-Linked glycans (2 sites).
DR GlyGen; O15118; 26 sites, 3 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
DR iPTMnet; O15118; -.
DR PhosphoSitePlus; O15118; -.
DR SwissPalm; O15118; -.
DR BioMuta; NPC1; -.
DR EPD; O15118; -.
DR jPOST; O15118; -.
DR MassIVE; O15118; -.
DR MaxQB; O15118; -.
DR PaxDb; O15118; -.
DR PeptideAtlas; O15118; -.
DR PRIDE; O15118; -.
DR ProteomicsDB; 3980; -.
DR ProteomicsDB; 48453; -. [O15118-1]
DR Antibodypedia; 7463; 418 antibodies from 39 providers.
DR DNASU; 4864; -.
DR Ensembl; ENST00000269228.10; ENSP00000269228.4; ENSG00000141458.13. [O15118-1]
DR GeneID; 4864; -.
DR KEGG; hsa:4864; -.
DR MANE-Select; ENST00000269228.10; ENSP00000269228.4; NM_000271.5; NP_000262.2.
DR UCSC; uc002kum.5; human. [O15118-1]
DR CTD; 4864; -.
DR DisGeNET; 4864; -.
DR GeneCards; NPC1; -.
DR GeneReviews; NPC1; -.
DR HGNC; HGNC:7897; NPC1.
DR HPA; ENSG00000141458; Tissue enhanced (brain).
DR MalaCards; NPC1; -.
DR MIM; 257220; phenotype.
DR MIM; 607623; gene.
DR neXtProt; NX_O15118; -.
DR OpenTargets; ENSG00000141458; -.
DR Orphanet; 216986; Niemann-Pick disease type C, adult neurologic onset.
DR Orphanet; 216981; Niemann-Pick disease type C, juvenile neurologic onset.
DR Orphanet; 216978; Niemann-Pick disease type C, late infantile neurologic onset.
DR Orphanet; 216975; Niemann-Pick disease type C, severe early infantile neurologic onset.
DR Orphanet; 216972; Niemann-Pick disease type C, severe perinatal form.
DR PharmGKB; PA31698; -.
DR VEuPathDB; HostDB:ENSG00000141458; -.
DR eggNOG; KOG1933; Eukaryota.
DR GeneTree; ENSGT00940000156182; -.
DR InParanoid; O15118; -.
DR OMA; CPDNGLA; -.
DR OrthoDB; 731120at2759; -.
DR PhylomeDB; O15118; -.
DR TreeFam; TF300416; -.
DR PathwayCommons; O15118; -.
DR Reactome; R-HSA-8964038; LDL clearance.
DR SignaLink; O15118; -.
DR BioGRID-ORCS; 4864; 50 hits in 1096 CRISPR screens.
DR ChiTaRS; NPC1; human.
DR EvolutionaryTrace; O15118; -.
DR GeneWiki; NPC1; -.
DR GenomeRNAi; 4864; -.
DR Pharos; O15118; Tchem.
DR PRO; PR:O15118; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O15118; protein.
DR Bgee; ENSG00000141458; Expressed in secondary oocyte and 194 other tissues.
DR ExpressionAtlas; O15118; baseline and differential.
DR Genevisible; O15118; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:1905103; C:integral component of lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0015248; F:sterol transporter activity; TAS:ProtInc.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IGI:MGI.
DR GO; GO:0008206; P:bile acid metabolic process; ISS:UniProtKB.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEA:Ensembl.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0033344; P:cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0042632; P:cholesterol homeostasis; IDA:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030301; P:cholesterol transport; IDA:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:Ensembl.
DR GO; GO:0090150; P:establishment of protein localization to membrane; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IBA:GO_Central.
DR GO; GO:0032367; P:intracellular cholesterol transport; IMP:UniProtKB.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IEA:Ensembl.
DR GO; GO:0031579; P:membrane raft organization; IMP:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IEA:Ensembl.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IEA:Ensembl.
DR GO; GO:0006486; P:protein glycosylation; IDA:UniProtKB.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR GO; GO:0046718; P:viral entry into host cell; IMP:CACAO.
DR InterPro; IPR004765; NPC1-like.
DR InterPro; IPR032190; NPC1_N.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF16414; NPC1_N; 1.
DR Pfam; PF02460; Patched; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR TIGRFAMs; TIGR00917; 2A060601; 1.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cholesterol metabolism;
KW Disease variant; Disulfide bond; Endosome; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction;
KW Lipid metabolism; Lipid transport; Lysosome; Membrane;
KW Niemann-Pick disease; Receptor; Reference proteome; Signal;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1278
FT /note="NPC intracellular cholesterol transporter 1"
FT /id="PRO_0000023261"
FT TOPO_DOM 23..261
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:27238017"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27238017"
FT TOPO_DOM 283..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27238017"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760"
FT TOPO_DOM 372..620
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760"
FT TRANSMEM 621..641
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760"
FT TOPO_DOM 642..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 654..675
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 676..685
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 707..730
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 731..751
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 752..759
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 760..783
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 784..832
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 833..853
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 854..1097
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 1098..1118
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 1119..1124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 1125..1145
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 1146..1150
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 1151..1171
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 1172..1194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 1195..1215
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 1216..1223
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TRANSMEM 1224..1244
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28784760"
FT TOPO_DOM 1245..1278
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28784760"
FT DOMAIN 620..785
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 175..205
FT /note="Important for cholesterol binding and cholesterol
FT transfer from NPC1 to liposomes"
FT REGION 1275..1278
FT /note="Required for location in lysosomes"
FT /evidence="ECO:0000269|PubMed:9927649"
FT MOTIF 1275..1278
FT /note="Di-leucine motif"
FT /evidence="ECO:0000305"
FT BINDING 41
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000305|PubMed:27238017, ECO:0007744|PDB:3GKI,
FT ECO:0007744|PDB:3GKJ"
FT BINDING 79
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000305|PubMed:27238017, ECO:0007744|PDB:3GKI,
FT ECO:0007744|PDB:3GKJ"
FT SITE 108
FT /note="Important for cholesterol binding"
FT /evidence="ECO:0000269|PubMed:19563754"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:10821832"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27238017,
FT ECO:0000305|PubMed:10821832, ECO:0007744|PDB:3JD8"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3JD8"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine; atypical"
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKI,
FT ECO:0007744|PDB:3GKJ, ECO:0007744|PDB:3JD8"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27238017,
FT ECO:0000305|PubMed:10821832, ECO:0007744|PDB:3JD8"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKI,
FT ECO:0007744|PDB:3GKJ, ECO:0007744|PDB:3JD8"
FT CARBOHYD 452
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26846330,
FT ECO:0000269|PubMed:28784760, ECO:0007744|PDB:5HNS,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:26846330, ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760, ECO:0007744|PDB:3JD8,
FT ECO:0007744|PDB:5HNS, ECO:0007744|PDB:5U74"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26846330,
FT ECO:0000269|PubMed:28784760, ECO:0007744|PDB:5HNS,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26846330,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3JD8,
FT ECO:0007744|PDB:5HNS"
FT CARBOHYD 598
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:26846330,
FT ECO:0000269|PubMed:27238017, ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5HNS,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 916
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 931
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 961
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 968
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 1064
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760, ECO:0007744|PDB:3JD8,
FT ECO:0007744|PDB:5U74"
FT CARBOHYD 1072
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..74
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 31..42
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 63..109
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 75..113
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 97..238
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 100..160
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 177..184
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 227..243
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017, ECO:0007744|PDB:3GKH,
FT ECO:0007744|PDB:3GKI, ECO:0007744|PDB:3GKJ,
FT ECO:0007744|PDB:3JD8, ECO:0007744|PDB:5JNX"
FT DISULFID 240..247
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0007744|PDB:3GKH, ECO:0007744|PDB:3GKI,
FT ECO:0007744|PDB:3GKJ"
FT DISULFID 468..479
FT /evidence="ECO:0000269|PubMed:26771495,
FT ECO:0000269|PubMed:26846330, ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760, ECO:0007744|PDB:3JD8,
FT ECO:0007744|PDB:5F18, ECO:0007744|PDB:5F1B,
FT ECO:0007744|PDB:5HNS, ECO:0007744|PDB:5JNX,
FT ECO:0007744|PDB:5KWY, ECO:0007744|PDB:5U73,
FT ECO:0007744|PDB:5U74"
FT DISULFID 516..533
FT /evidence="ECO:0000269|PubMed:26771495,
FT ECO:0000269|PubMed:26846330, ECO:0000269|PubMed:27238017,
FT ECO:0000269|PubMed:28784760, ECO:0007744|PDB:3JD8,
FT ECO:0007744|PDB:5F18, ECO:0007744|PDB:5F1B,
FT ECO:0007744|PDB:5HNS, ECO:0007744|PDB:5JNX,
FT ECO:0007744|PDB:5KWY, ECO:0007744|PDB:5U73,
FT ECO:0007744|PDB:5U74"
FT DISULFID 909..914
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U73, ECO:0007744|PDB:5U74"
FT DISULFID 956..1011
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U73, ECO:0007744|PDB:5U74"
FT DISULFID 957..979
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U73, ECO:0007744|PDB:5U74"
FT DISULFID 967..976
FT /evidence="ECO:0000269|PubMed:28784760,
FT ECO:0007744|PDB:5U73, ECO:0007744|PDB:5U74"
FT VAR_SEQ 1..267
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056431"
FT VAR_SEQ 318
FT /note="K -> KGTAWLLTSTFPSSPVLP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056432"
FT VAR_SEQ 519..586
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056433"
FT VARIANT 63
FT /note="C -> R (in NPC1; dbSNP:rs747049347)"
FT /evidence="ECO:0000269|PubMed:11545687"
FT /id="VAR_043172"
FT VARIANT 74
FT /note="C -> Y (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043173"
FT VARIANT 92
FT /note="Q -> R (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:11479732"
FT /id="VAR_043174"
FT VARIANT 113
FT /note="C -> R (in NPC1; partially mislocalized from late
FT endocytic organelles diffusely to the cell periphery;
FT localizes to the endoplasmic reticulum Rab7-negative
FT endosomes and the cell surface; does not clears the
FT lysosomal cholesterol accumulation in NPC1-deficient cells;
FT dbSNP:rs120074136)"
FT /evidence="ECO:0000269|PubMed:12554680"
FT /id="VAR_043175"
FT VARIANT 137
FT /note="T -> M (in NPC1; dbSNP:rs372947142)"
FT /evidence="ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:16098014, ECO:0000269|PubMed:23453666"
FT /id="VAR_043176"
FT VARIANT 151
FT /note="S -> G (in dbSNP:rs17855819)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043177"
FT VARIANT 166
FT /note="P -> S (in NPC1; dbSNP:rs866966704)"
FT /evidence="ECO:0000269|PubMed:12955717,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_043178"
FT VARIANT 177
FT /note="C -> G (in NPC1; late infantile form)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008815"
FT VARIANT 177
FT /note="C -> Y (in NPC1; dbSNP:rs80358252)"
FT /evidence="ECO:0000269|PubMed:11479732,
FT ECO:0000269|PubMed:16098014, ECO:0000269|PubMed:16126423"
FT /id="VAR_015561"
FT VARIANT 215
FT /note="H -> R (in dbSNP:rs1805081)"
FT /evidence="ECO:0000269|PubMed:10480349,
FT ECO:0000269|PubMed:11479732, ECO:0000269|PubMed:11754101,
FT ECO:0000269|PubMed:12401890, ECO:0000269|PubMed:12955717,
FT ECO:0000269|PubMed:15774455, ECO:0000269|PubMed:16098014"
FT /id="VAR_008816"
FT VARIANT 222
FT /note="N -> S (in NPC1; dbSNP:rs55680026)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043179"
FT VARIANT 231
FT /note="V -> G (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12408188"
FT /id="VAR_043180"
FT VARIANT 237
FT /note="P -> S (no effect on function; colocalizes with the
FT wild-type protein with Rab7-positive late endosomes; clears
FT the lysosomal cholesterol accumulation in NPC1-deficient
FT cells; dbSNP:rs80358251)"
FT /evidence="ECO:0000269|PubMed:11182931,
FT ECO:0000269|PubMed:11333381, ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:12408188, ECO:0000269|PubMed:12554680,
FT ECO:0000269|PubMed:12955717"
FT /id="VAR_008817"
FT VARIANT 242
FT /note="D -> H (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043181"
FT VARIANT 242
FT /note="D -> N (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043182"
FT VARIANT 247
FT /note="C -> Y (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043183"
FT VARIANT 248
FT /note="G -> V (in NPC1; dbSNP:rs1230538609)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043184"
FT VARIANT 272
FT /note="M -> R (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043185"
FT VARIANT 333
FT /note="G -> D"
FT /id="VAR_008818"
FT VARIANT 372
FT /note="R -> W (in NPC1; dbSNP:rs1346436537)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043187"
FT VARIANT 378
FT /note="V -> A (in NPC1; dbSNP:rs120074134)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_015562"
FT VARIANT 380
FT /note="L -> F (in NPC1; dbSNP:rs1435915496)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043188"
FT VARIANT 381
FT /note="W -> C"
FT /evidence="ECO:0000269|PubMed:12408188"
FT /id="VAR_043189"
FT VARIANT 388
FT /note="A -> P (in NPC1; dbSNP:rs1555637157)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043190"
FT VARIANT 389
FT /note="R -> C (in NPC1; dbSNP:rs1053321823)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043191"
FT VARIANT 401
FT /note="P -> T (in NPC1; dbSNP:rs766301620)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043192"
FT VARIANT 404
FT /note="R -> P (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043193"
FT VARIANT 404
FT /note="R -> Q (in NPC1; dbSNP:rs139751448)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:11545687"
FT /id="VAR_043194"
FT VARIANT 404
FT /note="R -> W (in NPC1; dbSNP:rs1298238512)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043195"
FT VARIANT 433
FT /note="P -> L (in NPC1; dbSNP:rs1064793791)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043196"
FT VARIANT 434
FT /note="P -> L (in NPC1; dbSNP:rs774333145)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043197"
FT VARIANT 434
FT /note="P -> S (in dbSNP:rs61731962)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043198"
FT VARIANT 451
FT /note="E -> K (in NPC1; dbSNP:rs781065429)"
FT /evidence="ECO:0000269|PubMed:12401890"
FT /id="VAR_043199"
FT VARIANT 472
FT /note="L -> P"
FT /id="VAR_008819"
FT VARIANT 473
FT /note="S -> P (in NPC1; late infantile form)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008820"
FT VARIANT 474
FT /note="P -> L (in NPC1; dbSNP:rs372445155)"
FT /evidence="ECO:0000269|PubMed:12401890,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_043200"
FT VARIANT 479
FT /note="C -> Y (in NPC1; dbSNP:rs1555636659)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043201"
FT VARIANT 509
FT /note="Y -> S (in NPC1; dbSNP:rs1190383931)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043202"
FT VARIANT 510
FT /note="H -> P (in NPC1; late infantile form)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008821"
FT VARIANT 511
FT /note="T -> M (in dbSNP:rs13381670)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043203"
FT VARIANT 512
FT /note="H -> R (in NPC1; dbSNP:rs1567963883)"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043204"
FT VARIANT 518
FT /note="R -> Q (in NPC1; late infantile form; Common in
FT Japanese; dbSNP:rs483352886)"
FT /evidence="ECO:0000269|PubMed:11182931,
FT ECO:0000269|PubMed:11333381"
FT /id="VAR_008822"
FT VARIANT 518
FT /note="R -> W (in NPC1; decreased affinity for NPC2;
FT decreased cholesterol transfer from NPC2 to NPC1;
FT dbSNP:rs377515417)"
FT /evidence="ECO:0000269|PubMed:11479732,
FT ECO:0000269|PubMed:27238017"
FT /id="VAR_043205"
FT VARIANT 521
FT /note="A -> S (in NPC1; dbSNP:rs138184115)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043206"
FT VARIANT 537
FT /note="F -> L (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043207"
FT VARIANT 543
FT /note="P -> L (in NPC1; dbSNP:rs369368181)"
FT /evidence="ECO:0000269|PubMed:12955717,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_043208"
FT VARIANT 574
FT /note="T -> K (in NPC1)"
FT /id="VAR_043209"
FT VARIANT 576
FT /note="K -> R (in NPC1; dbSNP:rs761660695)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043210"
FT VARIANT 605
FT /note="A -> V (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043211"
FT VARIANT 612
FT /note="E -> D (in NPC1; dbSNP:rs1555634739)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043212"
FT VARIANT 615
FT /note="R -> C (in NPC1; dbSNP:rs745777805)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043213"
FT VARIANT 615
FT /note="R -> L (in NPC1; dbSNP:rs773351341)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043214"
FT VARIANT 631
FT /note="M -> R (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_043215"
FT VARIANT 640
FT /note="G -> R (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043216"
FT VARIANT 642
FT /note="M -> I (in dbSNP:rs1788799)"
FT /evidence="ECO:0000269|PubMed:11479732,
FT ECO:0000269|PubMed:11754101, ECO:0000269|PubMed:12401890,
FT ECO:0000269|PubMed:12408188, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15774455, ECO:0000269|PubMed:16098014,
FT ECO:0000269|PubMed:9211849"
FT /id="VAR_008823"
FT VARIANT 652
FT /note="S -> W (in NPC1; dbSNP:rs765652543)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043217"
FT VARIANT 660
FT /note="G -> S (in NPC1; dbSNP:rs1555634490)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043218"
FT VARIANT 664
FT /note="V -> M (in NPC1; dbSNP:rs376213990)"
FT /evidence="ECO:0000269|PubMed:12955717,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_043219"
FT VARIANT 666
FT /note="S -> N (in NPC1; dbSNP:rs750480579)"
FT /evidence="ECO:0000269|PubMed:16802107"
FT /id="VAR_043220"
FT VARIANT 670
FT /note="C -> W (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043221"
FT VARIANT 673
FT /note="G -> V (in NPC1; dbSNP:rs1555634452)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043222"
FT VARIANT 684
FT /note="L -> F (in NPC1; dbSNP:rs1057518942)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043223"
FT VARIANT 691
FT /note="P -> L (in NPC1; dbSNP:rs1555634422)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043224"
FT VARIANT 695
FT /note="L -> V (in NPC1; dbSNP:rs370323921)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043225"
FT VARIANT 700
FT /note="D -> N (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043226"
FT VARIANT 703
FT /note="F -> S (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_043227"
FT VARIANT 724
FT /note="L -> P (in NPC1; dbSNP:rs1393388896)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043228"
FT VARIANT 727
FT /note="V -> F (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043229"
FT VARIANT 734
FT /note="S -> I (in NPC1; dbSNP:rs757475924)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043230"
FT VARIANT 742
FT /note="E -> K (in NPC1; dbSNP:rs1555634202)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043231"
FT VARIANT 745
FT /note="A -> E (in NPC1; dbSNP:rs752386083)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043232"
FT VARIANT 754
FT /note="M -> K (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043233"
FT VARIANT 757
FT /note="V -> A"
FT /id="VAR_008824"
FT VARIANT 763
FT /note="F -> L (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043234"
FT VARIANT 767
FT /note="A -> V (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043235"
FT VARIANT 775
FT /note="Q -> P (in NPC1; dbSNP:rs80358253)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_043236"
FT VARIANT 789
FT /note="R -> C (in NPC1; dbSNP:rs1555633697)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043237"
FT VARIANT 789
FT /note="R -> G (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043238"
FT VARIANT 825
FT /note="Y -> C (in NPC1; dbSNP:rs550562774)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:11754101,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_043239"
FT VARIANT 849
FT /note="S -> I (in NPC1; dbSNP:rs1057519242)"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043240"
FT VARIANT 858
FT /note="I -> V (in dbSNP:rs1805082)"
FT /evidence="ECO:0000269|PubMed:10480349,
FT ECO:0000269|PubMed:11479732, ECO:0000269|PubMed:11754101,
FT ECO:0000269|PubMed:12401890, ECO:0000269|PubMed:15774455,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_008825"
FT VARIANT 862
FT /note="Q -> L (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043241"
FT VARIANT 865
FT /note="S -> L (in NPC1; dbSNP:rs1160114136)"
FT /evidence="ECO:0000269|PubMed:16098014,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_043242"
FT VARIANT 871
FT /note="Y -> C (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043243"
FT VARIANT 873
FT /note="V -> A"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_043244"
FT VARIANT 874
FT /note="D -> V (in NPC1; dbSNP:rs372030650)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:11754101"
FT /id="VAR_043245"
FT VARIANT 888
FT /note="P -> S (in NPC1; dbSNP:rs1191346899)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043246"
FT VARIANT 889
FT /note="V -> M (in NPC1; adult form; dbSNP:rs120074130)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008826"
FT VARIANT 890
FT /note="Y -> C (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12401890"
FT /id="VAR_043247"
FT VARIANT 899
FT /note="Y -> D (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12401890"
FT /id="VAR_043248"
FT VARIANT 910
FT /note="G -> S (in NPC1; dbSNP:rs768999208)"
FT /evidence="ECO:0000269|PubMed:12401890"
FT /id="VAR_043249"
FT VARIANT 917
FT /note="D -> Y (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043250"
FT VARIANT 926
FT /note="A -> T (in NPC1; dbSNP:rs564631426)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043251"
FT VARIANT 927
FT /note="A -> V (in NPC1; dbSNP:rs753768576)"
FT /evidence="ECO:0000269|PubMed:11545687"
FT /id="VAR_043252"
FT VARIANT 928
FT /note="Q -> P (in NPC1; dbSNP:rs28940897)"
FT /id="VAR_008827"
FT VARIANT 929
FT /note="L -> P (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043253"
FT VARIANT 934
FT /note="R -> Q (in NPC1; dbSNP:rs786204714)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:11333381, ECO:0000269|PubMed:16126423"
FT /id="VAR_008828"
FT VARIANT 940
FT /note="S -> L (in NPC1; dbSNP:rs143124972)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:16126423"
FT /id="VAR_008829"
FT VARIANT 942
FT /note="W -> C (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11479732,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_043254"
FT VARIANT 943
FT /note="I -> M (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043255"
FT VARIANT 944
FT /note="D -> N (in NPC1; dbSNP:rs748837410)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:16098014"
FT /id="VAR_043256"
FT VARIANT 945
FT /note="D -> N (in NPC1; dbSNP:rs1428599096)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043257"
FT VARIANT 948
FT /note="D -> H (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043258"
FT VARIANT 948
FT /note="D -> N (in NPC1; dbSNP:rs1261939149)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:12408188"
FT /id="VAR_008830"
FT VARIANT 948
FT /note="D -> Y (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043259"
FT VARIANT 950
FT /note="V -> M (in NPC1; adult form; dbSNP:rs120074135)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_015563"
FT VARIANT 954
FT /note="S -> L (in NPC1; dbSNP:rs543206298)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:11182931, ECO:0000269|PubMed:11754101"
FT /id="VAR_008831"
FT VARIANT 956
FT /note="C -> Y (in NPC1; late infantile form)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008832"
FT VARIANT 958
FT /note="R -> L (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043260"
FT VARIANT 958
FT /note="R -> Q (in NPC1; dbSNP:rs120074132)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_015564"
FT VARIANT 959
FT /note="V -> E (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043261"
FT VARIANT 961..966
FT /note="NITDQF -> S (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043262"
FT VARIANT 961
FT /note="N -> S (in NPC1; dbSNP:rs34084984)"
FT /evidence="ECO:0000269|PubMed:16802107"
FT /id="VAR_043263"
FT VARIANT 968
FT /note="N -> S (in NPC1; dbSNP:rs773767253)"
FT /evidence="ECO:0000269|PubMed:15774455,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_043264"
FT VARIANT 971
FT /note="V -> G"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043265"
FT VARIANT 976
FT /note="C -> R (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043266"
FT VARIANT 978
FT /note="R -> C (in NPC1; dbSNP:rs28942108)"
FT /evidence="ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:11479732"
FT /id="VAR_015565"
FT VARIANT 986
FT /note="G -> S (in NPC1; dbSNP:rs1364834942)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043267"
FT VARIANT 992
FT /note="G -> A (in NPC1; dbSNP:rs757534240)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043268"
FT VARIANT 992
FT /note="G -> R (in NPC1; dbSNP:rs80358254)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_015566"
FT VARIANT 992
FT /note="G -> W (in NPC1; found in the Nova Scotian clinical
FT variant; dbSNP:rs80358254)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:11545687, ECO:0000269|PubMed:12401890,
FT ECO:0000269|PubMed:16126423, ECO:0000269|PubMed:9634529"
FT /id="VAR_008833"
FT VARIANT 996
FT /note="M -> R (in NPC1; dbSNP:rs1555632958)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_043269"
FT VARIANT 1004
FT /note="S -> L (in NPC1; dbSNP:rs150334966)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043270"
FT VARIANT 1007
FT /note="P -> A (in NPC1; dbSNP:rs80358257)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:11333381, ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:11754101, ECO:0000269|PubMed:12401890,
FT ECO:0000269|PubMed:16098014, ECO:0000269|PubMed:16126423"
FT /id="VAR_008834"
FT VARIANT 1012
FT /note="G -> D (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11545687"
FT /id="VAR_043271"
FT VARIANT 1015
FT /note="G -> V (in NPC1; dbSNP:rs761773567)"
FT /evidence="ECO:0000269|PubMed:15774455"
FT /id="VAR_043272"
FT VARIANT 1016
FT /note="H -> R (in NPC1; dbSNP:rs140211089)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043273"
FT VARIANT 1023
FT /note="V -> G (in NPC1)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043274"
FT VARIANT 1034
FT /note="G -> R (in NPC1)"
FT /evidence="ECO:0000269|PubMed:15774455"
FT /id="VAR_043275"
FT VARIANT 1035
FT /note="A -> V (in NPC1; dbSNP:rs28942107)"
FT /evidence="ECO:0000269|PubMed:11479732,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_015567"
FT VARIANT 1036
FT /note="T -> K (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043276"
FT VARIANT 1036
FT /note="T -> M (in NPC1; dbSNP:rs28942104)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_008835"
FT VARIANT 1049
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:11754101"
FT /id="VAR_043277"
FT VARIANT 1054
FT /note="A -> T (in NPC1; dbSNP:rs80358258)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043278"
FT VARIANT 1059
FT /note="R -> Q (in NPC1; dbSNP:rs771000314)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043279"
FT VARIANT 1061
FT /note="I -> T (in NPC1; late infantile form;
FT dbSNP:rs80358259)"
FT /evidence="ECO:0000269|PubMed:10521290,
FT ECO:0000269|PubMed:10521297, ECO:0000269|PubMed:11182931,
FT ECO:0000269|PubMed:11333381, ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:11479732, ECO:0000269|PubMed:11754101,
FT ECO:0000269|PubMed:12401890, ECO:0000269|PubMed:16098014,
FT ECO:0000269|PubMed:16126423"
FT /id="VAR_008836"
FT VARIANT 1062
FT /note="A -> V (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043280"
FT VARIANT 1066
FT /note="T -> N (in NPC1; dbSNP:rs772622214)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043281"
FT VARIANT 1087
FT /note="F -> L (in NPC1; dbSNP:rs746715353)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043282"
FT VARIANT 1088
FT /note="Y -> C (in NPC1; juvenile form; dbSNP:rs28942106)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008837"
FT VARIANT 1089
FT /note="E -> K (in NPC1; dbSNP:rs374526072)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043283"
FT VARIANT 1094
FT /note="I -> T (in NPC1; dbSNP:rs1338658857)"
FT /evidence="ECO:0000269|PubMed:12408188"
FT /id="VAR_043284"
FT VARIANT 1097
FT /note="D -> N (in NPC1; dbSNP:rs758829443)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043285"
FT VARIANT 1137
FT /note="N -> I (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043286"
FT VARIANT 1140
FT /note="G -> V (in NPC1)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043287"
FT VARIANT 1142
FT /note="M -> T (in NPC1; dbSNP:rs778878523)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:11349231"
FT /id="VAR_043288"
FT VARIANT 1150
FT /note="N -> K (in NPC1; dbSNP:rs34715591)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043289"
FT VARIANT 1156
FT /note="N -> I (in NPC1; dbSNP:rs28942105)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043290"
FT VARIANT 1156
FT /note="N -> S (in NPC1; dbSNP:rs28942105)"
FT /evidence="ECO:0000269|PubMed:11349231,
FT ECO:0000269|PubMed:11545687, ECO:0000269|PubMed:12401890,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_008838"
FT VARIANT 1165
FT /note="V -> M (in NPC1; dbSNP:rs748862167)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043291"
FT VARIANT 1167
FT /note="F -> L (in NPC1)"
FT /id="VAR_008839"
FT VARIANT 1168
FT /note="C -> Y (in NPC1; dbSNP:rs1555631998)"
FT /evidence="ECO:0000269|PubMed:11333381"
FT /id="VAR_043292"
FT VARIANT 1174
FT /note="A -> V (in NPC1; dbSNP:rs780175800)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043293"
FT VARIANT 1186
FT /note="R -> H (in NPC1; dbSNP:rs200444084)"
FT /evidence="ECO:0000269|PubMed:11333381,
FT ECO:0000269|PubMed:11349231, ECO:0000269|PubMed:16126423"
FT /id="VAR_008840"
FT VARIANT 1189
FT /note="E -> G (in NPC1; dbSNP:rs369098773)"
FT /evidence="ECO:0000269|PubMed:11349231"
FT /id="VAR_043294"
FT VARIANT 1205
FT /note="T -> K (in NPC1; dbSNP:rs758902805)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043295"
FT VARIANT 1205
FT /note="T -> R (in NPC1; dbSNP:rs758902805)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_043296"
FT VARIANT 1212
FT /note="V -> L (in NPC1; dbSNP:rs753419933)"
FT /evidence="ECO:0000269|PubMed:15774455"
FT /id="VAR_043297"
FT VARIANT 1213
FT /note="L -> F (in NPC1; juvenile form; dbSNP:rs120074131)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_008841"
FT VARIANT 1213
FT /note="L -> V (in NPC1; dbSNP:rs766178353)"
FT /evidence="ECO:0000269|PubMed:10521290"
FT /id="VAR_008842"
FT VARIANT 1216
FT /note="A -> V (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043298"
FT VARIANT 1220
FT /note="I -> T"
FT /id="VAR_008843"
FT VARIANT 1224
FT /note="F -> L (in NPC1)"
FT /evidence="ECO:0000269|PubMed:16098014"
FT /id="VAR_043299"
FT VARIANT 1236
FT /note="G -> E (in NPC1; dbSNP:rs761653115)"
FT /evidence="ECO:0000269|PubMed:11182931"
FT /id="VAR_043300"
FT VARIANT 1240
FT /note="G -> R (in NPC1; dbSNP:rs745892286)"
FT /evidence="ECO:0000269|PubMed:16126423"
FT /id="VAR_043301"
FT VARIANT 1249
FT /note="S -> G (in NPC1; dbSNP:rs1415921261)"
FT /evidence="ECO:0000269|PubMed:12955717"
FT /id="VAR_043302"
FT VARIANT 1266
FT /note="R -> Q (in dbSNP:rs1805084)"
FT /evidence="ECO:0000269|PubMed:10480349,
FT ECO:0000269|PubMed:12955717, ECO:0000269|PubMed:15774455,
FT ECO:0000269|PubMed:16098014"
FT /id="VAR_008844"
FT MUTAGEN 25..257
FT /note="Missing: Decreases affinity for NPC2. Abolishes
FT cholesterol transfer from NPC2 to NPC1."
FT /evidence="ECO:0000269|PubMed:27238017"
FT MUTAGEN 26..27
FT /note="VW->AA: Nearly abolishes 25-hydroxycholesterol
FT binding. Reduces cholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 39..41
FT /note="RYN->AAA: Strongly reduces cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 41
FT /note="N->A: Nearly abolishes cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 63
FT /note="C->S: Loss of function."
FT /evidence="ECO:0000269|PubMed:9927649"
FT MUTAGEN 70
FT /note="N->Q: Reduces glycosylation; when associated with Q-
FT 122 and Q-185. No effect on cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 74..75
FT /note="CC->SS: Loss of function."
FT /evidence="ECO:0000269|PubMed:9927649"
FT MUTAGEN 82..83
FT /note="TL->AA: Strongly reduces cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 88
FT /note="Q->A: Decreased affinity for NPC2 and decreased
FT cholesterol transfer from NPC2 to NPC1; when associated
FT with A-92 and A-96."
FT /evidence="ECO:0000269|PubMed:27238017"
FT MUTAGEN 92
FT /note="Q->A: Decreased affinity for NPC2 and decreased
FT cholesterol transfer from NPC2 to NPC1; when associated
FT with A-88 and A-96."
FT /evidence="ECO:0000269|PubMed:27238017"
FT MUTAGEN 96
FT /note="R->A: Decreased affinity for NPC2 and decreased
FT cholesterol transfer from NPC2 to NPC1; when associated
FT with A-88 and A-92."
FT /evidence="ECO:0000269|PubMed:27238017"
FT MUTAGEN 97
FT /note="C->S: Loss of function."
FT /evidence="ECO:0000269|PubMed:9927649"
FT MUTAGEN 101..102
FT /note="FY->AA: Strongly reduces 25-hydroxycholesterol
FT binding. No effect on cholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 106..108
FT /note="NLF->AAA: Nearly abolishes cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 110..112
FT /note="ELT->AAA: No effect on cholesterol and 25-
FT hydroxycholesterol binding and transfer."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 122
FT /note="N->Q: Reduces glycosylation; when associated with Q-
FT 70 and Q-185. No effect on cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 144..145
FT /note="LQ->AA: Strongly reduces 25-hydroxycholesterol
FT binding. No effect on cholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 146..147
FT /note="YY->AA: Strongly reduces 25-hydroxycholesterol
FT binding. No effect on cholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 175..176
FT /note="LL->AA: No effect on cholesterol or 25-
FT hydroxycholesterol binding. Decreases affinity for NPC2.
FT Strongly reduces cholesterol transfer to liposomes in a
FT NPC2-dependent manner."
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017"
FT MUTAGEN 180..182
FT /note="DAD->AAA: Strongly reduces cholesterol transfer to
FT liposomes in a NPC2-dependent manner."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 185
FT /note="N->Q: Reduces glycosylation; when associated with Q-
FT 70 and Q-122. No effect on cholesterol and 25-
FT hydroxycholesterol binding. Strongly reduces cholesterol
FT transfer to liposomes in a NPC2-dependent manner."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 187..188
FT /note="TN->AA: Strongly reduces 25-hydroxycholesterol
FT binding and cholesterol transfer to liposomes in a NPC2-
FT dependent manner."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 191..192
FT /note="EY->AA: No effect on cholesterol or 25-
FT hydroxycholesterol binding. Nearly abolishes cholesterol
FT transfer to liposomes in a NPC2-dependent manner."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 195..196
FT /note="NK->AA: Strongly reduces 25-hydroxycholesterol
FT binding. No effect on cholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 197..198
FT /note="DN->AA: Strongly reduces cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 199..200
FT /note="GQ->AA: Strongly reduces 25-hydroxycholesterol
FT binding and cholesterol transfer to liposomes in a NPC2-
FT dependent manner."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 202..203
FT /note="PF->AA: Abolishes cholesterol and 25-
FT hydroxycholesterol binding. Abolishes cholesterol transfer
FT from NPC2 to NPC1."
FT /evidence="ECO:0000269|PubMed:19563754,
FT ECO:0000269|PubMed:27238017"
FT MUTAGEN 204..205
FT /note="TI->AA: Strongly reduces cholesterol and 25-
FT hydroxycholesterol binding."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 230..234
FT /note="Missing: Decreased cholesterol transport."
FT /evidence="ECO:0000269|PubMed:28784760"
FT MUTAGEN 249..257
FT /note="Missing: Decreases affinity for NPC2. Abolishes
FT cholesterol transfer from NPC2 to NPC1."
FT /evidence="ECO:0000269|PubMed:27238017"
FT MUTAGEN 423..424
FT /note="YP->GG: Strongly reduces interaction with ebolavirus
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:26771495"
FT MUTAGEN 503
FT /note="F->A,G: Loss of interaction with ebolavirus
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:26771495"
FT MUTAGEN 504
FT /note="F->A,G: Loss of interaction with ebolavirus
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:26771495"
FT MUTAGEN 506
FT /note="Y->A: Loss of interaction with ebolavirus
FT glycoprotein."
FT /evidence="ECO:0000269|PubMed:26771495"
FT MUTAGEN 660
FT /note="G->R: Loss of function."
FT /evidence="ECO:0000269|PubMed:19563754"
FT MUTAGEN 691
FT /note="P->S: Abolishes cholesterol transport. No effect on
FT subcellular location."
FT /evidence="ECO:0000269|PubMed:28784760"
FT MUTAGEN 909..917
FT /note="CGGMGCNND->A: Abolishes cholesterol transport. No
FT effect on subcellular location."
FT /evidence="ECO:0000269|PubMed:28784760"
FT MUTAGEN 1275..1278
FT /note="Missing: Loss of location in lysosomes."
FT /evidence="ECO:0000269|PubMed:9927649"
FT STRAND 26..35
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 77..85
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 88..94
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 98..113
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 121..130
FT /evidence="ECO:0007829|PDB:3GKJ"
FT TURN 132..134
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 137..148
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 150..160
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:3GKJ"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 186..193
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 199..209
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:3GKJ"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:3GKJ"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 269..290
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 327..348
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 350..365
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 366..370
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:5KWY"
FT HELIX 385..398
FT /evidence="ECO:0007829|PDB:5F18"
FT TURN 399..402
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 403..411
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:5HNS"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 437..451
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 454..457
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 464..467
FT /evidence="ECO:0007829|PDB:5F18"
FT TURN 471..475
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 484..488
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 492..495
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 505..507
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 509..516
FT /evidence="ECO:0007829|PDB:5F18"
FT TURN 526..530
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 536..538
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 543..546
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 547..549
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 559..568
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 574..592
FT /evidence="ECO:0007829|PDB:5F18"
FT STRAND 600..603
FT /evidence="ECO:0007829|PDB:5F18"
FT HELIX 608..611
FT /evidence="ECO:0007829|PDB:5KWY"
FT TURN 617..620
FT /evidence="ECO:0007829|PDB:5U74"
FT HELIX 621..638
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 646..650
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 654..678
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 686..710
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 720..749
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 755..791
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 818..823
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 825..829
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 832..834
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 835..851
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 853..855
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 862..865
FT /evidence="ECO:0007829|PDB:5U74"
FT STRAND 868..870
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 871..882
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 887..893
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 902..906
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 911..914
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 916..918
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 919..929
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 931..933
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 943..950
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 952..954
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 958..960
FT /evidence="ECO:0007829|PDB:5U74"
FT TURN 961..963
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 969..971
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 977..980
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 984..987
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 993..1004
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 1009..1011
FT /evidence="ECO:0007829|PDB:6W5S"
FT TURN 1017..1022
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 1023..1025
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1029..1031
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 1033..1042
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1048..1069
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 1078..1081
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1085..1088
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1090..1092
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1094..1116
FT /evidence="ECO:0007829|PDB:6W5S"
FT STRAND 1117..1119
FT /evidence="ECO:0007829|PDB:5U74"
FT HELIX 1121..1145
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1153..1176
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1183..1201
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1203..1213
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1219..1224
FT /evidence="ECO:0007829|PDB:6W5S"
FT HELIX 1226..1251
FT /evidence="ECO:0007829|PDB:6W5S"
SQ SEQUENCE 1278 AA; 142167 MW; DA1523E09822E5C7 CRC64;
MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP LPKDGYDLVQ
ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC FYNLLNLFCE LTCSPRQSQF
LNVTATEDYV DPVTNQTKTN VKELQYYVGQ SFANAMYNAC RDVEAPSSND KALGLLCGKD
ADACNATNWI EYMFNKDNGQ APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC
QDCSIVCGPK PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS
EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP GCVIFFSLVF
ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG PFFRTEQLII RAPLTDKHIY
QPYPSGADVP FGPPLDIQIL HQVLDLQIAI ENITASYDNE TVTLQDICLA PLSPYNTNCT
ILSVLNYFQN SHSVLDHKKG DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT
ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV DSKVSLGIAG
ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD NIFILVQAYQ RDERLQGETL
DQQLGRVLGE VAPSMFLSSF SETVAFFLGA LSVMPAVHTF SLFAGLAVFI DFLLQITCFV
SLLGLDIKRQ EKNRLDIFCC VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA
IFVGVLSFSI AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT
SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV KPQSSCCRVD
NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP MFLSDNPNPK CGKGGHAAYS
SAVNILLGHG TRVGATYFMT YHTVLQTSAD FIDALKKARL IASNVTETMG INGSAYRVFP
YSVFYVFYEQ YLTIIDDTIF NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG
VMWLWGISLN AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS
GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY IGPSVNKAKS
CATEERYKGT ERERLLNF
