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O35604 (NPC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Niemann-Pick C1 protein
Gene names
Name:Npc1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1277 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than 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.

Subunit structure

Interacts with TMEM97 By similarity. Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner. Ref.6

Subcellular location

Late endosome membrane; Multi-pass membrane protein. Lysosome membrane; Multi-pass membrane protein Ref.4 Ref.6.

Tissue specificity

Expressed predominantly in perisynaptic astrocytic glial processes. Also expressed in heart, spleen, lung, liver, skeletal muscle, kidney, testis.

Induction

Activated by the drugs progesterone and U-18666A which block cholesterol transport out of lysosomes and by the lysosomotropic agent NAH4CL.

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.

Sequence similarities

Belongs to the patched family.

Contains 1 SSD (sterol-sensing) domain.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Steroid metabolism
Sterol metabolism
   Cellular componentEndosome
Lysosome
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from genetic interaction PubMed 19074461. Source: MGI

autophagy

Inferred from sequence orthology PubMed 19074461. Source: MGI

bile acid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to low-density lipoprotein particle stimulus

Inferred from direct assay PubMed 10787428. Source: MGI

cellular response to steroid hormone stimulus

Inferred from direct assay PubMed 10787428. Source: MGI

cholesterol efflux

Inferred from mutant phenotype PubMed 17148552. Source: MGI

cholesterol homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

cholesterol transport

Inferred from sequence or structural similarity. Source: UniProtKB

endocytosis

Inferred from mutant phenotype PubMed 15078881. Source: MGI

lysosomal transport

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell death

Inferred from electronic annotation. Source: Ensembl

negative regulation of macroautophagy

Inferred from mutant phenotype PubMed 17468177. Source: MGI

protein glycosylation

Inferred from direct assay Ref.6. Source: UniProtKB

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from direct assay PubMed 10787428. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 10787428. Source: MGI

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

endosome

Inferred from direct assay PubMed 10787428PubMed 16757520. Source: MGI

extracellular region

Inferred from direct assay Ref.6. Source: UniProtKB

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

late endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Inferred from direct assay Ref.6. Source: UniProtKB

membrane

Inferred from direct assay PubMed 10787428. Source: MGI

membrane raft

Inferred from direct assay PubMed 10787428. Source: MGI

nuclear envelope

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 10787428. Source: MGI

vesicle

Inferred from direct assay PubMed 10787428. Source: MGI

   Molecular_functioncholesterol binding

Inferred from sequence or structural similarity. Source: UniProtKB

hedgehog receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 12771255Niemann-Pick C1 protein
PRO_0000023262

Regions

Topological domain23 – 269247Lumenal Potential
Transmembrane270 – 29021Helical; Potential
Topological domain291 – 35060Cytoplasmic Potential
Transmembrane351 – 37121Helical; Potential
Topological domain372 – 621250Lumenal Potential
Transmembrane622 – 64221Helical; Potential
Topological domain643 – 65311Cytoplasmic Potential
Transmembrane654 – 67421Helical; Potential
Topological domain675 – 6839Lumenal Potential
Transmembrane684 – 70421Helical; Potential
Topological domain705 – 73026Cytoplasmic Potential
Transmembrane731 – 75121Helical; Potential
Topological domain752 – 7598Lumenal Potential
Transmembrane760 – 78021Helical; Potential
Topological domain781 – 83252Cytoplasmic Potential
Transmembrane833 – 85321Helical; Potential
Topological domain854 – 1076223Lumenal Potential
Transmembrane1077 – 109418Helical; Potential
Topological domain1095 – 10973Cytoplasmic Potential
Transmembrane1098 – 111821Helical; Potential
Topological domain1119 – 11235Lumenal Potential
Transmembrane1124 – 114421Helical; Potential
Topological domain11451Cytoplasmic Potential
Transmembrane1146 – 116621Helical; Potential
Topological domain1167 – 119428Lumenal Potential
Transmembrane1195 – 121521Helical; Potential
Topological domain1216 – 122611Cytoplasmic Potential
Transmembrane1227 – 124721Helical; Potential
Topological domain1248 – 127730Lumenal Potential
Domain620 – 785166SSD
Region175 – 20531Important for cholesterol binding and cholesterol transfer from NPC1 to liposomes By similarity
Motif1274 – 12774Di-leucine motif
Compositional bias249 – 25911Poly-Pro

Sites

Binding site411Cholesterol By similarity
Binding site791Cholesterol By similarity
Site1081Important for cholesterol binding By similarity

Amino acid modifications

Glycosylation701N-linked (GlcNAc...) Potential
Glycosylation1221N-linked (GlcNAc...) Potential
Glycosylation1371N-linked (GlcNAc...) Potential
Glycosylation1851N-linked (GlcNAc...) Potential
Glycosylation2221N-linked (GlcNAc...) Potential
Glycosylation2281N-linked (GlcNAc...) Potential
Glycosylation4141N-linked (GlcNAc...) Potential
Glycosylation4591N-linked (GlcNAc...) Potential
Glycosylation4781N-linked (GlcNAc...) Potential
Glycosylation5241N-linked (GlcNAc...) Potential
Glycosylation8681N-linked (GlcNAc...) Potential
Glycosylation8981N-linked (GlcNAc...) Potential
Glycosylation9161N-linked (GlcNAc...) Potential
Glycosylation9611N-linked (GlcNAc...) Potential
Glycosylation9681N-linked (GlcNAc...) Potential
Glycosylation10631N-linked (GlcNAc...) Potential
Disulfide bond25 ↔ 74 By similarity
Disulfide bond31 ↔ 42 By similarity
Disulfide bond63 ↔ 109 By similarity
Disulfide bond75 ↔ 113 By similarity
Disulfide bond97 ↔ 238 By similarity
Disulfide bond100 ↔ 160 By similarity
Disulfide bond177 ↔ 184 By similarity
Disulfide bond227 ↔ 243 By similarity
Disulfide bond240 ↔ 247 By similarity

Experimental info

Sequence conflict91G → GL in AAB63372. Ref.1
Sequence conflict1351Q → P in AAB63372. Ref.1
Sequence conflict1471F → Y in AAB63372. Ref.1
Sequence conflict4451D → N in AAB63372. Ref.1
Sequence conflict4781N → D in AAB63373. Ref.1
Sequence conflict874 – 8752DY → AN in AAB63372. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O35604 [UniParc].

Last modified February 6, 2013. Version 2.
Checksum: 3B42230AAC86764E

FASTA1,277142,885
        10         20         30         40         50         60 
MGAHHPALGL LLLLLCPAQV FSQSCVWYGE CGIATGDKRY NCKYSGPPKP LPKDGYDLVQ 

        70         80         90        100        110        120 
ELCPGLFFDN VSLCCDIQQL QTLKSNLQLP LQFLSRCPSC FYNLMTLFCE LTCSPHQSQF 

       130        140        150        160        170        180 
LNVTATEDYF DPKTQENKTN VKELEYFVGQ SFANAMYNAC RDVEAPSSNE KALGLLCGRD 

       190        200        210        220        230        240 
ARACNATNWI EYMFNKDNGQ APFTIIPVFS DLSILGMEPM RNATKGCNES VDEVTGPCSC 

       250        260        270        280        290        300 
QDCSIVCGPK PQPPPPPMPW RIWGLDAMYV IMWVTYVAFL FVFFGALLAV WCHRRRYFVS 

       310        320        330        340        350        360 
EYTPIDSNIA FSVNSSDKGE ASCCDPLGAA FDDCLRRMFT KWGAFCVRNP TCIIFFSLAF 

       370        380        390        400        410        420 
ITVCSSGLVF VQVTTNPVEL WSAPHSQARL EKEYFDKHFG PFFRTEQLII QAPNTSVHIY 

       430        440        450        460        470        480 
EPYPAGADVP FGPPLNKEIL HQVLDLQIAI ESITASYNNE TVTLQDICVA PLSPYNKNCT 

       490        500        510        520        530        540 
IMSVLNYFQN SHAVLDSQVG DDFYIYADYH THFLYCVRAP ASLNDTSLLH GPCLGTFGGP 

       550        560        570        580        590        600 
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTERLQRA WAWEKEFISF VKNYKNPNLT 

       610        620        630        640        650        660 
ISFTAERSIE DELNRESNSD VFTVIISYVV MFLYISLALG HIQSCSRLLV DSKISLGIAG 

       670        680        690        700        710        720 
ILIVLSSVAC SLGIFSYMGM PLTLIVIEVI PFLVLAVGVD NIFILVQTYQ RDERLQEETL 

       730        740        750        760        770        780 
DQQLGRILGE VAPTMFLSSF SETSAFFFGA LSSMPAVHTF SLFAGMAVLI DFLLQITCFV 

       790        800        810        820        830        840 
SLLGLDIKRQ EKNHLDILCC VRGADDGQGS HASESYLFRF FKNYFAPLLL KDWLRPIVVA 

       850        860        870        880        890        900 
VFVGVLSFSV AVVNKVDIGL DQSLSMPNDS YVIDYFKSLA QYLHSGPPVY FVLEEGYNYS 

       910        920        930        940        950        960 
SRKGQNMVCG GMGCDNDSLV QQIFNAAELD TYTRVGFAPS SWIDDYFDWV SPQSSCCRLY 

       970        980        990       1000       1010       1020 
NVTHQFCNAS VMDPTCVRCR PLTPEGKQRP QGKEFMKFLP MFLSDNPNPK CGKGGHAAYG 

      1030       1040       1050       1060       1070       1080 
SAVNIVGDDT YIGATYFMTY HTILKTSADY TDAMKKARLI ASNITETMRS KGSDYRVFPY 

      1090       1100       1110       1120       1130       1140 
SVFYVFYEQY LTIIDDTIFN LSVSLGSIFL VTLVVLGCEL WSAVIMCITI AMILVNMFGV 

      1150       1160       1170       1180       1190       1200 
MWLWGISLNA VSLVNLVMSC GISVEFCSHI TRAFTMSTKG SRVSRAEEAL AHMGSSVFSG 

      1210       1220       1230       1240       1250       1260 
ITLTKFGGIV VLAFAKSQIF EIFYFRMYLA MVLLGATHGL IFLPVLLSYI GPSVNKAKRH 

      1270 
TTYERYRGTE RERLLNF 

« Hide

References

« Hide 'large scale' references
[1]"Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene."
Loftus S.K., Morris J.A., Carstea E.D., Gu J.Z., Cummings C., Brown A., Ellison J., Ohno K., Rosenfeld M.A., Tagle D.A., Pentchev P.G., Pavan W.J.
Science 277:232-235(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Localization of Niemann-Pick C1 protein in astrocytes: implications for neuronal degeneration in Niemann-Pick type C disease."
Patel S.C., Suresh S., Kumar U., Hu C.Y., Cooney A., Blanchette-Mackie E.J., Neufeld E.B., Patel R.C., Brady R.O., Patel Y.C., Pentchev P.G., Ong W.-Y.
Proc. Natl. Acad. Sci. U.S.A. 96:1657-1662(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[5]"Function of the Niemann-Pick type C proteins and their bypass by cyclodextrin."
Vance J.E., Peake K.B.
Curr. Opin. Lipidol. 22:204-209(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[6]"Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding."
Deffieu M.S., Pfeffer S.R.
Proc. Natl. Acad. Sci. U.S.A. 108:18932-18936(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NPC2, SUBCELLULAR LOCATION, GLYCOSYLATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF003348 mRNA. Translation: AAB63372.1.
AF003349 Genomic DNA. Translation: AAB63373.1.
AC102096 Genomic DNA. No translation available.
AC102248 Genomic DNA. No translation available.
CH466622 Genomic DNA. Translation: EDL01560.1.
PIRT30188.
RefSeqNP_032746.2. NM_008720.2.
UniGeneMm.3484.

3D structure databases

ProteinModelPortalO35604.
SMRO35604. Positions 16-249.
ModBaseSearch...
MobiDBSearch...

Chemistry

ChEMBLCHEMBL2321610.

PTM databases

PhosphoSiteO35604.

Proteomic databases

PaxDbO35604.
PRIDEO35604.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000025279; ENSMUSP00000025279; ENSMUSG00000024413.
GeneID18145.
KEGGmmu:18145.
UCSCuc008ecb.1. mouse.

Organism-specific databases

CTD4864.
MGIMGI:1097712. Npc1.

Phylogenomic databases

eggNOGNOG149152.
GeneTreeENSGT00680000099777.
HOGENOMHOG000036674.
HOVERGENHBG003913.
InParanoidO35604.
KOK12385.
OMAITRAFTM.
OrthoDBEOG7QRQT0.
TreeFamTF300416.

Gene expression databases

CleanExMM_NPC1.
GenevestigatorO35604.

Family and domain databases

InterProIPR004765. NP_C_type.
IPR003392. Patched.
IPR000731. SSD.
[Graphical view]
PfamPF02460. Patched. 1 hit.
[Graphical view]
TIGRFAMsTIGR00917. 2A060601. 1 hit.
PROSITEPS50156. SSD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNPC1. mouse.
NextBio293400.
PROO35604.
SOURCESearch...

Entry information

Entry nameNPC1_MOUSE
AccessionPrimary (citable) accession number: O35604
Secondary accession number(s): G3X8W9, O35605
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 6, 2013
Last modified: April 16, 2014
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot