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UniProtKB/Swiss-Prot entry O15118

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name NPC1_HUMAN
Primary accession number O15118
Secondary accession number Q9P130
Integrated into Swiss-Prot on May 30, 2000
Sequence was last modified on May 10, 2005 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 90)
Name and origin of the protein
Protein name Niemann-Pick C1 protein [Precursor]
Synonyms None
Gene name
Name: NPC1
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-642, AND VARIANTS NPC1.
DOI=10.1126/science.277.5323.228; PubMed=9211849 [NCBI, ExPASy, EBI, Israel, Japan]
Carstea E.D., Morris J.A., Coleman K.G., Loftus S.K., Zhang D., Cummings C., Gu J., Rosenfeld M.A., Pavan W.J., Krizman D.B., Nagle J., Polymeropoulos M.H., Sturley S.L., Ioannou Y.A., Higgins M.E., Comly M., Cooney A., Brown A., Kaneski C.R., Blanchette-Mackie E.J., Dwyer N.K., Neufeld E.B., Chang T.-Y., Liscum L., Strauss J.F. III, Ohno K., Zeigler M., Carmi R., Sokol J., Markie D., O'Neill R.R., van Diggelen O.P., Elleder M., Patterson M.C., Brady R.O., Vanier M.T., Pentchev P.G., Tagle D.A.;
"Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.";
Science 277:228-231(1997).
[2]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS.
DOI=10.1006/bbrc.1999.1070; PubMed=10425213 [NCBI, ExPASy, EBI, Israel, Japan]
Morris J.A., Zhang D., Coleman K.G., Nagle J., Pentchev P.G., Carstea E.D.;
"The genomic organization and polymorphism analysis of the human Niemann-Pick C1 gene.";
Biochem. Biophys. Res. Commun. 261:493-498(1999).
[3]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS NPC1 ARG-512; TRP-670; CYS-825; ILE-849; VAL-874; TYR-948; LEU-954; LEU-958; ALA-1007 AND THR-1061, AND VARIANTS ARG-215; ILE-642; VAL-858; GLY-971 AND VAL-1049.
DOI=10.1002/humu.10016; PubMed=11754101 [NCBI, ExPASy, EBI, Israel, Japan]
Bauer P., Knoblich R., Bauer C., Finckh U., Hufen A., Kropp J., Braun S., Kustermann-Kuhn B., Schmidt D., Harzer K., Rolfs A.;
"NPC1: complete genomic sequence, mutation analysis, and characterization of haplotypes.";
Hum. Mutat. 19:30-38(2002).
[4]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLY-151 AND ILE-642.
TISSUE=Placenta;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
 CHARACTERIZATION.
DOI=10.1073/pnas.96.3.805; PubMed=9927649 [NCBI, ExPASy, EBI, Israel, Japan]
Watari H., Blanchette-Mackie E.J., Dwyer N.K., Glick J.M., Patel S., Neufeld E.B., Brady R.O., Pentchev P.G., Strauss J.F. III;
"Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization.";
Proc. Natl. Acad. Sci. U.S.A. 96:805-810(1999).
[6]
 GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-135 AND ASN-524, AND MASS SPECTROMETRY.
TISSUE=Liver;
DOI=10.1021/pr8008012; PubMed=19159218 [NCBI, ExPASy, EBI, Israel, Japan]
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.";
J. Proteome Res. 8:651-661(2009).
[7]
 VARIANT NPD TRP-992.
DOI=10.1086/301931; PubMed=9634529 [NCBI, ExPASy, EBI, Israel, Japan]
Greer W.L., Riddell D.C., Gillan T.L., Girouard G.S., Sparrow S.M., Byers D.M., Dobson M.J., Neumann P.E.;
"The Nova Scotia (type D) form of Niemann-Pick disease is caused by a G3097-->T transversion in NPC1.";
Am. J. Hum. Genet. 63:52-54(1998).
[8]
 VARIANTS NPC1 GLN-934; LEU-940; ASN-948; LEU-954; TRP-992; ALA-1007; THR-1061 AND VAL-1213.
DOI=10.1086/302620; PubMed=10521290 [NCBI, ExPASy, EBI, Israel, Japan]
Greer W.L., Dobson M.J., Girouard G.S., Byers D.M., Riddell D.C., Neumann P.E.;
"Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain.";
Am. J. Hum. Genet. 65:1252-1260(1999).
[9]
 VARIANT NPC1 THR-1061.
DOI=10.1086/302626; PubMed=10521297 [NCBI, ExPASy, EBI, Israel, Japan]
Millat G., Marcais C., Rafi M.A., Yamamoto T., Morris J.A., Pentchev P.G., Ohno K., Wenger D.A., Vanier M.T.;
"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. 65:1321-1329(1999).
[10]
 VARIANTS NPC1, AND VARIANTS ARG-215; VAL-858 AND GLN-1266.
DOI=10.1007/s004390051057; PubMed=10480349 [NCBI, ExPASy, EBI, Israel, Japan]
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 M.T., Morris J.A., Pentchev P.G., Ohno K.;
"NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C.";
Hum. Genet. 105:10-16(1999).
[11]
 VARIANTS NPC1 GLY-177; SER-237; PRO-473; PRO-510; GLN-518; SER-703; MET-889; LEU-954; TYR-956; ARG-996; THR-1061; CYS-1088; ARG-1205; PHE-1213 AND GLU-1236, AND VARIANT ALA-873.
DOI=10.1136/jmg.37.9.707; PubMed=11182931 [NCBI, ExPASy, EBI, Israel, Japan]
Yamamoto T., Ninomiya H., Matsumoto M., Ohta Y., Nanba E., Tsutsumi Y., Yamakawa K., Millat G., Vanier M.T., Pentchev P.G., Ohno K.;
"Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts.";
J. Med. Genet. 37:707-712(2000).
[12]
 VARIANTS NPC1 ARG-92; MET-137; SER-237; ASN-242; VAL-248; THR-401; GLN-404; ASP-612; TRP-652; CYS-789; CYS-825; VAL-874; SER-888; PRO-929; LEU-940; ASN-944; ASN-948; GLN-958; ARG-976; CYS-978; LEU-1004; ALA-1007; GLY-1023; THR-1061; LYS-1089; THR-1142; LYS-1150; SER-1156; MET-1165; HIS-1186 AND GLY-1189.
DOI=10.1086/320599; PubMed=11349231 [NCBI, ExPASy, EBI, Israel, Japan]
Sun X., Marks D.L., Park W.D., Wheatley C.L., Puri V., O'Brien J.F., Kraft D.L., Lundquist P.A., Patterson M.C., Pagano R.E., Snow K.;
"Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1.";
Am. J. Hum. Genet. 68:1361-1372(2001).
[13]
 VARIANTS NPC1 SER-237; HIS-242; ARG-272; ALA-378; GLN-404; GLN-518; VAL-605; ARG-631; PRO-724; PRO-775; CYS-825; VAL-874; GLN-934; MET-943; ASN-944; MET-950; SER-986; ARG-992; ALA-1007; THR-1054; THR-1061; THR-1142; TYR-1168 AND HIS-1186.
DOI=10.1086/320606; PubMed=11333381 [NCBI, ExPASy, EBI, Israel, Japan]
Millat G., Marcais C., Tomasetto C., Chikh K., Fensom A.H., Harzer K., Wenger D.A., Ohno K., Vanier M.T.;
"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. 68:1373-1385(2001).
[14]
 VARIANTS NPC1 ARG-63; GLN-404; VAL-927; TRP-992; ASP-1012 AND SER-1156.
DOI=10.1097/00125817-200109000-00003; PubMed=11545687 [NCBI, ExPASy, EBI, Israel, Japan]
Meiner V., Shpitzen S., Mandel H., Klar A., Ben-Neriah Z., Zlotogora J., Sagi M., Lossos A., Bargal R., Sury V., Carmi R., Leitersdorf E., Zeigler M.;
"Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C.";
Genet. Med. 3:343-348(2001).
[15]
 VARIANTS NPC1 ARG-92; TYR-177; TRP-518; CYS-942; CYS-978; ALA-1007 VAL-1035 AND THR-1061, AND VARIANTS ARG-215; ILE-642 AND VAL-858.
DOI=10.1007/s004390100531; PubMed=11479732 [NCBI, ExPASy, EBI, Israel, Japan]
Ribeiro I., Marcao A., Amaral O., Sa Miranda M.C., Vanier M.T., Millat G.;
"Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations.";
Hum. Genet. 109:24-32(2001).
[16]
 VARIANTS NPC1 GLY-231; SER-237; VAL-874 ASN-948 AND THR-1094, AND VARIANTS CYS-381 AND ILE-642.
DOI=10.1023/A:1020151801060; PubMed=12408188 [NCBI, ExPASy, EBI, Israel, Japan]
Kaminski W.E., Kluenemann H.H., Ibach B., Aslanidis C., Klein H.E., Schmitz G.;
"Identification of novel mutations in the NPC1 gene in German patients with Niemann-Pick C disease.";
J. Inherit. Metab. Dis. 25:385-389(2002).
[17]
 VARIANTS NPC1 LYS-451; LEU-474; CYS-890; ASP-899; SER-910; TRP-992; ALA-1007; THR-1061 AND SER-1156, AND VARIANTS ARG-215; ILE-642 AND VAL-858.
DOI=10.1194/jlr.M200203-JLR200; PubMed=12401890 [NCBI, ExPASy, EBI, Israel, Japan]
Tarugi P., Ballarini G., Bembi B., Battisti C., Palmeri S., Panzani F., Di Leo E., Martini C., Federico A., Calandra S.;
"Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts.";
J. Lipid Res. 43:1908-1919(2002).
[18]
 VARIANT NPC1 ARG-113, VARIANT SER-273, CHARACTERIZATION OF VARIANT NPC1 ARG-113, AND CHARACTERIZATION OF VARIANT SER-273.
DOI=10.1093/hmg/ddg025; PubMed=12554680 [NCBI, ExPASy, EBI, Israel, Japan]
Blom T.S., Linder M.D., Snow K., Pihko H., Hess M.W., Jokitalo E., Veckman V., Syvaenen A.-C., Ikonen E.;
"Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease.";
Hum. Mol. Genet. 12:257-272(2003).
[19]
 VARIANTS NPC1 TYR-74; SER-166; SER-222; TYR-247; PHE-380; PRO-388; CYS-389; TRP-404; LEU-433; SER-509; SER-521; LEU-543; CYS-615; ARG-640; SER-660; MET-664; VAL-673; PHE-684; LEU-691; VAL-695; ASN-700; ILE-734; LYS-742; GLU-745; VAL-767; GLY-789; ASN-945; ARG-1016; GLN-1059; LEU-1087; ILE-1137; VAL-1140; LYS-1205 AND GLY-1249, AND VARIANTS ARG-215; SER-237; SER-434 AND GLN-1266.
DOI=10.1002/humu.10255; PubMed=12955717 [NCBI, ExPASy, EBI, Israel, Japan]
Park W.D., O'Brien J.F., Lundquist P.A., Kraft D.L., Vockley C.W., Karnes P.S., Patterson M.C., Snow K.;
"Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1.";
Hum. Mutat. 22:313-325(2003).
[20]
 VARIANTS NPC1 MET-137; TYR-177; TRP-372; LEU-434; LEU-474; TYR-479; ARG-576; MET-664; PHE-727; LYS-754; PRO-775; LEU-865; THR-926; CYS-942; ASN-944; HIS-948; GLU-959; 961-ASN--PHE-966 DELINS SER; ALA-1007; VAL-1035; LYS-1036; THR-1061; ASN-1066; ILE-1156; SER-1156 AND LEU-1224, AND VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266.
DOI=10.1111/j.1399-0004.2005.00490.x; PubMed=16098014 [NCBI, ExPASy, EBI, Israel, Japan]
Fernandez-Valero E.M., Ballart A., Iturriaga C., Lluch M., Macias J., Vanier M.T., Pineda M., Coll M.J.;
"Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations.";
Clin. Genet. 68:245-254(2005).
[21]
 VARIANTS NPC1 SER-968; VAL-1015; ARG-1034 AND LEU-1212, AND VARIANTS ARG-215; ILE-642; VAL-858 AND GLN-1266.
DOI=10.1136/jnnp.2004.046045; PubMed=15774455 [NCBI, ExPASy, EBI, Israel, Japan]
Yang C.-C., Su Y.-N., Chiou P.-C., Fietz M.J., Yu C.-L., Hwu W.-L., Lee M.-J.;
"Six novel NPC1 mutations in Chinese patients with Niemann-Pick disease type C.";
J. Neurol. Neurosurg. Psych. 76:592-595(2005).
[22]
 VARIANTS NPC1 SER-166; TYR-177; PRO-404; LEU-537; LEU-543; LEU-615; ARG-631; LEU-763; CYS-825; LEU-862; LEU-865; CYS-871; TYR-917; GLN-934; LEU-940; MET-950; SER-968; ALA-992; ARG-992; TRP-992; ALA-1007; MET-1036; THR-1061; VAL-1062; ASN-1097; VAL-1174; HIS-1186; VAL-1216 AND ARG-1240, AND VARIANT MET-511.
DOI=10.1016/j.ymgme.2005.07.007; PubMed=16126423 [NCBI, ExPASy, EBI, Israel, Japan]
Millat G., Baielo N., Molinero S., Rodriguez C., Chikh K., Vanier M.T.;
"Niemann-Pick C disease: use of denaturing high performance liquid chromatography for the detection of NPC1 and NPC2 genetic variations and impact on management of patients and families.";
Mol. Genet. Metab. 86:220-232(2005).
[23]
 VARIANTS NPC1 ASN-666 AND SER-961.
DOI=10.1007/s10545-006-0330-z; PubMed=16802107 [NCBI, ExPASy, EBI, Israel, Japan]
Dvorakova L., Sikora J., Hrebicek M., Hulkova H., Bouckova M., Stolnaja L., Elleder M.;
"Subclinical course of adult visceral Niemann-Pick type C1 disease. A rare or underdiagnosed disorder?";
J. Inherit. Metab. Dis. 29:591-591(2006).
Comments
  • FUNCTION: Involved in the intracellular trafficking of cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals.
  • SUBCELLULAR LOCATION: Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein.
  • DOMAIN: A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes.
  • PTM: Glycosylated.
  • DISEASE: Defects in NPC1 are the cause of Niemann-Pick disease type C1 (NPC1) [MIM:257220]. NPC1 is an autosomal recessive lipid storage disorder, which affects particularly the brain, liver and spleen, and which is characterized by lysosomal accumulation of low density lipoprotein derived cholesterol. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood.
  • DISEASE: Defects in NPC1 are the cause of Niemann-Pick disease type D (NPD) [MIM:257220]; also known as Niemann-Pick disease without sphingomyelinase deficiency, or Nova Scotian type. Because of evidence from biochemical changes, lack of complementation, and linkage mapping to the same chromosome site, NPD and NPC1 are considered to be allelic disorders.
  • SIMILARITY: Belongs to the patched family.
  • SIMILARITY: Contains 1 SSD (sterol-sensing) domain.
  • WEB RESOURCE: Name=Niemann-Pick type C disease gene variation database; URL="http://npc.fzk.de";.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=NPC1";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF002020; AAB63982.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157379; AAD48006.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157365; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157366; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157367; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157368; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157369; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157370; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157371; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157372; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157373; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157374; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157375; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157376; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157377; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF157378; AAD48006.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF338230; AAK25791.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF123046; AAF28875.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF123045; AAF28875.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC063302; AAH63302.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00005107; -.
RefSeq NP_000262.1; -.
UniGene Hs.464779
3D structure databases
ModBase O15118.
Protein family/group databases
TCDB 2.A.6.6.1; resistance-nodulation-cell division (RND) superfamily.
Organism-specific databases
GeneCards GC18M019365; -.
HGNC HGNC:7897; NPC1.
GenAtlas NPC1.
MIM 257220; phenotype. [NCBI / EBI]
607623; gene. [NCBI / EBI]
Orphanet 646; Niemann-Pick disease, type C.
PharmGKB PA26398; -.
Gene expression databases
Bgee O15118; -.
CleanEx HS_NPC1; -.
GermOnline ENSG00000141458; Homo sapiens.
Ontologies
GO
GO:0005783; Cellular component: endoplasmic reticulum (inferred from direct assay from UniProtKB).
GO:0005887; Cellular component: integral to plasma membrane (inferred from direct assay from UniProtKB).
GO:0031902; Cellular component: late endosome membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005765; Cellular component: lysosomal membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005635; Cellular component: nuclear envelope (inferred from direct assay from UniProtKB).
GO:0048471; Cellular component: perinuclear region of cytoplasm (inferred from direct assay from UniProtKB).
GO:0008158; Molecular function: hedgehog receptor activity (inferred from electronic annotation from InterPro).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0015248; Molecular function: sterol transporter activity (traceable author statement from ProtInc).
GO:0008206; Biological process: bile acid metabolic process (inferred from sequence or structural similarity from UniProtKB).
GO:0042632; Biological process: cholesterol homeostasis (inferred from direct assay from UniProtKB).
GO:0007041; Biological process: lysosomal transport (inferred from sequence or structural similarity from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR004765; NP_C_type.
IPR003392; Patched.
IPR000731; SSD_5TM.
Graphical view of domain structure.
Pfam PF02460; Patched; 1.
Pfam graphical view of domain structure.
TIGRFAMs TIGR00917; 2A060601; 1.
PROSITE PS50156; SSD; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PeptideAtlas O15118; -.
PRIDE O15118; -.
Genome annotation databases
Ensembl ENSG00000141458; Homo sapiens. [Contig view]
GeneID 4864; -.
KEGG hsa:4864; -.
NMPDR fig|9606.3.peg.14865; -.
Phylogenomic databases
HOVERGEN O15118; -.
OMA O15118; VGATYFM.
Other
NextBio 18738; -.
SOURCE NPC1; Homo sapiens.
ProtoNet O15118.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Disease mutation; Endosome; Glycoprotein; Lysosome; Membrane; Polymorphism; Signal; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
SIGNAL   1     22  22     Potential. 
CHAIN   23   1278  1256     Niemann-Pick C1 protein. PRO_0000023261
TRANSMEM   270    290  21     Potential. 
TRANSMEM   351    371  21     Potential. 
TRANSMEM   622    642  21     Potential. 
TRANSMEM   655    675  21     Potential. 
TRANSMEM   678    698  21     Potential. 
TRANSMEM   760    780  21     Potential. 
TRANSMEM   833    853  21     Potential. 
TRANSMEM   1099   1119  21     Potential. 
TRANSMEM   1125   1145  21     Potential. 
TRANSMEM   1196   1216  21     Potential. 
TRANSMEM   1228   1248  21     Potential. 
DOMAIN   620    785  166     SSD. 
MOTIF   1275   1278  4     Di-leucine motif. 
COMPBIAS   249    259  11     Poly-Pro. 
CARBOHYD   70     70        N-linked (GlcNAc...) (Potential). 
CARBOHYD   122    122        N-linked (GlcNAc...) (Potential). 
CARBOHYD   135    135        N-linked (GlcNAc...). 
CARBOHYD   185    185        N-linked (GlcNAc...) (Potential). 
CARBOHYD   222    222        N-linked (GlcNAc...) (Potential). 
CARBOHYD   452    452        N-linked (GlcNAc...) (Potential). 
CARBOHYD   459    459        N-linked (GlcNAc...) (Potential). 
CARBOHYD   478    478        N-linked (GlcNAc...) (Potential). 
CARBOHYD   524    524        N-linked (GlcNAc...). 
CARBOHYD   916    916        N-linked (GlcNAc...) (Potential). 
VARIANT   63     63  1     C -> R (in NPC1). VAR_043172 
VARIANT   74     74  1     C -> Y (in NPC1). VAR_043173 
VARIANT   92     92  1     Q -> R (in NPC1). VAR_043174 
VARIANT   113    113  1     C -> R (in NPC1; partially mislocalized from late endocytic organelles diffusely to the cell periphery; localizes to the endoplasmic reticulum Rab7-negative endosomes and the cell surface; does not clears the lysosomal cholesterol accumulation in NPC1-deficient cells). VAR_043175 
VARIANT   137    137  1     T -> M (in NPC1). VAR_043176 
VARIANT   151    151  1     S -> G (in dbSNP:rs17855819 [NCBI]). VAR_043177 
VARIANT   166    166  1     P -> S (in NPC1). VAR_043178 
VARIANT   177    177  1     C -> G (in NPC1; late infantile form). VAR_008815 
VARIANT   177    177  1     C -> Y (in NPC1). VAR_015561 
VARIANT   215    215  1     H -> R (common polymorphism in Japanese; dbSNP:rs1805081 [NCBI]). VAR_008816 
VARIANT   222    222  1     N -> S (in NPC1). VAR_043179 
VARIANT   231    231  1     V -> G (in NPC1). VAR_043180 
VARIANT   237    237  1     P -> S (in NPC1; late infantile form). VAR_008817 
VARIANT   242    242  1     D -> H (in NPC1). VAR_043181 
VARIANT   242    242  1     D -> N (in NPC1). VAR_043182 
VARIANT   247    247  1     C -> Y (in NPC1). VAR_043183 
VARIANT   248    248  1     G -> V (in NPC1). VAR_043184 
VARIANT   272    272  1     M -> R (in NPC1). VAR_043185 
VARIANT   273    273  1     W -> S (colocalizes with the wild-type protein with Rab7-positive late endosomes; clears the lysosomal cholesterol accumulation in NPC1-deficient cells). VAR_043186 
VARIANT   333    333  1     G -> D. VAR_008818 
VARIANT   372    372  1     R -> W (in NPC1). VAR_043187 
VARIANT   378    378  1     V -> A (in NPC1). VAR_015562 
VARIANT   380    380  1     L -> F (in NPC1). VAR_043188 
VARIANT   381    381  1     W -> C. VAR_043189 
VARIANT   388    388  1     A -> P (in NPC1). VAR_043190 
VARIANT   389    389  1     R -> C (in NPC1). VAR_043191 
VARIANT   401    401  1     P -> T (in NPC1). VAR_043192 
VARIANT   404    404  1     R -> P (in NPC1). VAR_043193 
VARIANT   404    404  1     R -> Q (in NPC1). VAR_043194 
VARIANT   404    404  1     R -> W (in NPC1). VAR_043195 
VARIANT   433    433  1     P -> L (in NPC1). VAR_043196 
VARIANT   434    434  1     P -> L (in NPC1). VAR_043197 
VARIANT   434    434  1     P -> S. VAR_043198 
VARIANT   451    451  1     E -> K (in NPC1). VAR_043199 
VARIANT   472    472  1     L -> P. VAR_008819 
VARIANT   473    473  1     S -> P (in NPC1; late infantile form). VAR_008820 
VARIANT   474    474  1     P -> L (in NPC1). VAR_043200 
VARIANT   479    479  1     C -> Y (in NPC1). VAR_043201 
VARIANT   509    509  1     Y -> S (in NPC1). VAR_043202 
VARIANT   510    510  1     H -> P (in NPC1; late infantile form). VAR_008821 
VARIANT   511    511  1     T -> M (in dbSNP:rs13381670 [NCBI]). VAR_043203 
VARIANT   512    512  1     H -> R (in NPC1). VAR_043204 
VARIANT   518    518  1     R -> Q (in NPC1; late infantile form; Common in Japanese). VAR_008822 
VARIANT   518    518  1     R -> W (in NPC1). VAR_043205 
VARIANT   521    521  1     A -> S (in NPC1). VAR_043206 
VARIANT   537    537  1     F -> L (in NPC1). VAR_043207 
VARIANT   543    543  1     P -> L (in NPC1). VAR_043208 
VARIANT   574    574  1     T -> K (in NPC1). VAR_043209 
VARIANT   576    576  1     K -> R (in NPC1). VAR_043210 
VARIANT   605    605  1     A -> V (in NPC1). VAR_043211 
VARIANT   612    612  1     E -> D (in NPC1). VAR_043212 
VARIANT   615    615  1     R -> C (in NPC1). VAR_043213 
VARIANT   615    615  1     R -> L (in NPC1). VAR_043214 
VARIANT   631    631  1     M -> R (in NPC1). VAR_043215 
VARIANT   640    640  1     G -> R (in NPC1). VAR_043216 
VARIANT   642    642  1     M -> I (in dbSNP:rs1788799 [NCBI]). VAR_008823 
VARIANT   652    652  1     S -> W (in NPC1). VAR_043217 
VARIANT   660    660  1     G -> S (in NPC1). VAR_043218 
VARIANT   664    664  1     V -> M (in NPC1). VAR_043219 
VARIANT   666    666  1     S -> N (in NPC1). VAR_043220 
VARIANT   670    670  1     C -> W (in NPC1). VAR_043221 
VARIANT   673    673  1     G -> V (in NPC1). VAR_043222 
VARIANT   684    684  1     L -> F (in NPC1). VAR_043223 
VARIANT   691    691  1     P -> L (in NPC1). VAR_043224 
VARIANT   695    695  1     L -> V (in NPC1). VAR_043225 
VARIANT   700    700  1     D -> N (in NPC1). VAR_043226 
VARIANT   703    703  1     F -> S (in NPC1). VAR_043227 
VARIANT   724    724  1     L -> P (in NPC1). VAR_043228 
VARIANT   727    727  1     V -> F (in NPC1). VAR_043229 
VARIANT   734    734  1     S -> I (in NPC1). VAR_043230 
VARIANT   742    742  1     E -> K (in NPC1). VAR_043231 
VARIANT   745    745  1     A -> E (in NPC1). VAR_043232 
VARIANT   754    754  1     M -> K (in NPC1). VAR_043233 
VARIANT   757    757  1     V -> A. VAR_008824 
VARIANT   763    763  1     F -> L (in NPC1). VAR_043234 
VARIANT   767    767  1     A -> V (in NPC1). VAR_043235 
VARIANT   775    775  1     Q -> P (in NPC1). VAR_043236 
VARIANT   789    789  1     R -> C (in NPC1). VAR_043237 
VARIANT   789    789  1     R -> G (in NPC1). VAR_043238 
VARIANT   825    825  1     Y -> C (in NPC1). VAR_043239 
VARIANT   849    849  1     S -> I (in NPC1). VAR_043240 
VARIANT   858    858  1     I -> V (common polymorphism in Japanese; dbSNP:rs1805082 [NCBI]). VAR_008825 
VARIANT   862    862  1     Q -> L (in NPC1). VAR_043241 
VARIANT   865    865  1     S -> L (in NPC1). VAR_043242 
VARIANT   871    871  1     Y -> C (in NPC1). VAR_043243 
VARIANT   873    873  1     V -> A. VAR_043244 
VARIANT   874    874  1     D -> V (in NPC1). VAR_043245 
VARIANT   888    888  1     P -> S (in NPC1). VAR_043246 
VARIANT   889    889  1     V -> M (in NPC1; adult form). VAR_008826 
VARIANT   890    890  1     Y -> C (in NPC1). VAR_043247 
VARIANT   899    899  1     Y -> D (in NPC1). VAR_043248 
VARIANT   910    910  1     G -> S (in NPC1). VAR_043249 
VARIANT   917    917  1     D -> Y (in NPC1). VAR_043250 
VARIANT   926    926  1     A -> T (in NPC1). VAR_043251 
VARIANT   927    927  1     A -> V (in NPC1). VAR_043252 
VARIANT   928    928  1     Q -> P (in NPC1; dbSNP:rs28940897 [NCBI]). VAR_008827 
VARIANT   929    929  1     L -> P (in NPC1). VAR_043253 
VARIANT   934    934  1     R -> Q (in NPC1). VAR_008828 
VARIANT   940    940  1     S -> L (in NPC1). VAR_008829 
VARIANT   942    942  1     W -> C (in NPC1). VAR_043254 
VARIANT   943    943  1     I -> M (in NPC1). VAR_043255 
VARIANT   944    944  1     D -> N (in NPC1). VAR_043256 
VARIANT   945    945  1     D -> N (in NPC1). VAR_043257 
VARIANT   948    948  1     D -> H (in NPC1). VAR_043258 
VARIANT   948    948  1     D -> N (in NPC1). VAR_008830 
VARIANT   948    948  1     D -> Y (in NPC1). VAR_043259 
VARIANT   950    950  1     V -> M (in NPC1; adult form). VAR_015563 
VARIANT   954    954  1     S -> L (in NPC1). VAR_008831 
VARIANT   956    956  1     C -> Y (in NPC1; late infantile form). VAR_008832 
VARIANT   958    958  1     R -> L (in NPC1). VAR_043260 
VARIANT   958    958  1     R -> Q (in NPC1). VAR_015564 
VARIANT   959    959  1     V -> E (in NPC1). VAR_043261 
VARIANT   961    966  6     NITDQF -> S (in NPC1). VAR_043262
VARIANT   961    961  1     N -> S (in NPC1; dbSNP:rs34084984 [NCBI]). VAR_043263 
VARIANT   968    968  1     N -> S (in NPC1). VAR_043264 
VARIANT   971    971  1     V -> G. VAR_043265 
VARIANT   976    976  1     C -> R (in NPC1). VAR_043266 
VARIANT   978    978  1     R -> C (in NPC1; dbSNP:rs28942108 [NCBI]). VAR_015565 
VARIANT   986    986  1     G -> S (in NPC1). VAR_043267 
VARIANT   992    992  1     G -> A (in NPC1). VAR_043268 
VARIANT   992    992  1     G -> R (in NPC1). VAR_015566 
VARIANT   992    992  1     G -> W (in NPD and NPC1). VAR_008833 
VARIANT   996    996  1     M -> R (in NPC1). VAR_043269 
VARIANT   1004   1004  1     S -> L (in NPC1). VAR_043270 
VARIANT   1007   1007  1     P -> A (in NPC1). VAR_008834 
VARIANT   1012   1012  1     G -> D (in NPC1). VAR_043271 
VARIANT   1015   1015  1     G -> V (in NPC1). VAR_043272 
VARIANT   1016   1016  1     H -> R (in NPC1). VAR_043273 
VARIANT   1023   1023  1     V -> G (in NPC1). VAR_043274 
VARIANT   1034   1034  1     G -> R (in NPC1). VAR_043275 
VARIANT   1035   1035  1     A -> V (in NPC1). VAR_015567 
VARIANT   1036   1036  1     T -> K (in NPC1). VAR_043276 
VARIANT   1036   1036  1     T -> M (in NPC1). VAR_008835 
VARIANT   1049   1049  1     A -> V. VAR_043277 
VARIANT   1054   1054  1     A -> T (in NPC1). VAR_043278 
VARIANT   1059   1059  1     R -> Q (in NPC1). VAR_043279 
VARIANT   1061   1061  1     I -> T (in NPC1; late infantile form). VAR_008836 
VARIANT   1062   1062  1     A -> V (in NPC1). VAR_043280 
VARIANT   1066   1066  1     T -> N (in NPC1). VAR_043281 
VARIANT   1087   1087  1     F -> L (in NPC1). VAR_043282 
VARIANT   1088   1088  1     Y -> C (in NPC1; juvenile form; dbSNP:rs28942106 [NCBI]). VAR_008837 
VARIANT   1089   1089  1     E -> K (in NPC1). VAR_043283 
VARIANT   1094   1094  1     I -> T (in NPC1). VAR_043284 
VARIANT   1097   1097  1     D -> N (in NPC1). VAR_043285 
VARIANT   1137   1137  1     N -> I (in NPC1). VAR_043286 
VARIANT   1140   1140  1     G -> V (in NPC1). VAR_043287 
VARIANT   1142   1142  1     M -> T (in NPC1). VAR_043288 
VARIANT   1150   1150  1     N -> K (in NPC1). VAR_043289 
VARIANT   1156   1156  1     N -> I (in NPC1; dbSNP:rs28942105 [NCBI]). VAR_043290 
VARIANT   1156   1156  1     N -> S (in NPC1). VAR_008838 
VARIANT   1165   1165  1     V -> M (in NPC1). VAR_043291 
VARIANT   1167   1167  1     F -> L (in NPC1). VAR_008839 
VARIANT   1168   1168  1     C -> Y (in NPC1). VAR_043292 
VARIANT   1174   1174  1     A -> V (in NPC1). VAR_043293 
VARIANT   1186   1186  1     R -> H (in NPC1). VAR_008840 
VARIANT   1189   1189  1     E -> G (in NPC1). VAR_043294 
VARIANT   1205   1205  1     T -> K (in NPC1). VAR_043295 
VARIANT   1205   1205  1     T -> R (in NPC1). VAR_043296 
VARIANT   1212   1212  1     V -> L (in NPC1). VAR_043297 
VARIANT   1213   1213  1     L -> F (in NPC1; juvenile form). VAR_008841 
VARIANT   1213   1213  1     L -> V (in NPC1). VAR_008842 
VARIANT   1216   1216  1     A -> V (in NPC1). VAR_043298 
VARIANT   1220   1220  1     I -> T. VAR_008843 
VARIANT   1224   1224  1     F -> L (in NPC1). VAR_043299 
VARIANT   1236   1236  1     G -> E (in NPC1). VAR_043300 
VARIANT   1240   1240  1     G -> R (in NPC1). VAR_043301 
VARIANT   1249   1249  1     S -> G (in NPC1). VAR_043302 
VARIANT   1266   1266  1     R -> Q (common polymorphism in Japanese; dbSNP:rs1805084 [NCBI]). VAR_008844 
MUTAGEN   63     63        C->S: Loss of function. 
MUTAGEN   97     97        C->S: Loss of function. 
Sequence information
Length: 1278 AA [This is the length of the unprocessed precursor] Molecular weight: 142167 Da [This is the MW of the unprocessed precursor] CRC64: DA1523E09822E5C7 [This is a checksum on the sequence] 
        10         20         30         40         50         60 
MTARGLALGL LLLLLCPAQV FSQSCVWYGE CGIAYGDKRY NCEYSGPPKP LPKDGYDLVQ 

        70         80         90        100        110        120 
ELCPGFFFGN VSLCCDVRQL QTLKDNLQLP LQFLSRCPSC FYNLLNLFCE LTCSPRQSQF 

       130        140        150        160        170        180 
LNVTATEDYV DPVTNQTKTN VKELQYYVGQ SFANAMYNAC RDVEAPSSND KALGLLCGKD 

       190        200        210        220        230        240 
ADACNATNWI EYMFNKDNGQ APFTITPVFS DFPVHGMEPM NNATKGCDES VDEVTAPCSC 

       250        260        270        280        290        300 
QDCSIVCGPK PQPPPPPAPW TILGLDAMYV IMWITYMAFL LVFFGAFFAV WCYRKRYFVS 

       310        320        330        340        350        360 
EYTPIDSNIA FSVNASDKGE ASCCDPVSAA FEGCLRRLFT RWGSFCVRNP GCVIFFSLVF 

       370        380        390        400        410        420 
ITACSSGLVF VRVTTNPVDL WSAPSSQARL EKEYFDQHFG PFFRTEQLII RAPLTDKHIY 

       430        440        450        460        470        480 
QPYPSGADVP FGPPLDIQIL HQVLDLQIAI ENITASYDNE TVTLQDICLA PLSPYNTNCT 

       490        500        510        520        530        540 
ILSVLNYFQN SHSVLDHKKG DDFFVYADYH THFLYCVRAP ASLNDTSLLH DPCLGTFGGP 

       550        560        570        580        590        600 
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWEKEFINF VKNYKNPNLT 

       610        620        630        640        650        660 
ISFTAERSIE DELNRESDSD VFTVVISYAI MFLYISLALG HMKSCRRLLV DSKVSLGIAG 

       670        680        690        700        710        720 
ILIVLSSVAC SLGVFSYIGL PLTLIVIEVI PFLVLAVGVD NIFILVQAYQ RDERLQGETL 

       730        740        750        760        770        780 
DQQLGRVLGE VAPSMFLSSF SETVAFFLGA LSVMPAVHTF SLFAGLAVFI DFLLQITCFV 

       790        800        810        820        830        840 
SLLGLDIKRQ EKNRLDIFCC VRGAEDGTSV QASESCLFRF FKNSYSPLLL KDWMRPIVIA 

       850        860        870        880        890        900 
IFVGVLSFSI AVLNKVDIGL DQSLSMPDDS YMVDYFKSIS QYLHAGPPVY FVLEEGHDYT 

       910        920        930        940        950        960 
SSKGQNMVCG GMGCNNDSLV QQIFNAAQLD NYTRIGFAPS SWIDDYFDWV KPQSSCCRVD 

       970        980        990       1000       1010       1020 
NITDQFCNAS VVDPACVRCR PLTPEGKQRP QGGDFMRFLP MFLSDNPNPK CGKGGHAAYS 

      1030       1040       1050       1060       1070       1080 
SAVNILLGHG TRVGATYFMT YHTVLQTSAD FIDALKKARL IASNVTETMG INGSAYRVFP 

      1090       1100       1110       1120       1130       1140 
YSVFYVFYEQ YLTIIDDTIF NLGVSLGAIF LVTMVLLGCE LWSAVIMCAT IAMVLVNMFG 

      1150       1160       1170       1180       1190       1200 
VMWLWGISLN AVSLVNLVMS CGISVEFCSH ITRAFTVSMK GSRVERAEEA LAHMGSSVFS 

      1210       1220       1230       1240       1250       1260 
GITLTKFGGI VVLAFAKSQI FQIFYFRMYL AMVLLGATHG LIFLPVLLSY IGPSVNKAKS 

      1270 
CATEERYKGT ERERLLNF
O15118 in FASTA format

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