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Protein

Niemann-Pick C1 protein

Gene

Npc1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei41CholesterolBy similarity1
Binding sitei79CholesterolBy similarity1
Sitei108Important for cholesterol bindingBy similarity1

GO - Molecular functioni

GO - Biological processi

  • adult walking behavior Source: MGI
  • autophagy Source: MGI
  • bile acid metabolic process Source: UniProtKB
  • cellular response to low-density lipoprotein particle stimulus Source: MGI
  • cellular response to steroid hormone stimulus Source: MGI
  • cholesterol efflux Source: MGI
  • cholesterol homeostasis Source: UniProtKB
  • cholesterol metabolic process Source: UniProtKB-KW
  • cholesterol transport Source: UniProtKB
  • endocytosis Source: MGI
  • establishment of protein localization to membrane Source: MGI
  • lysosomal transport Source: UniProtKB
  • membrane raft organization Source: MGI
  • negative regulation of cell death Source: Ensembl
  • negative regulation of macroautophagy Source: MGI
  • positive regulation of cholesterol homeostasis Source: MGI
  • protein glycosylation Source: UniProtKB
  • response to cadmium ion Source: Ensembl
  • response to drug Source: MGI
  • viral entry into host cell Source: CACAO
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Chemistry databases

SwissLipidsiSLP:000000479.

Names & Taxonomyi

Protein namesi
Recommended name:
Niemann-Pick C1 protein
Gene namesi
Name:Npc1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:1097712. Npc1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 269LumenalSequence analysisAdd BLAST247
Transmembranei270 – 290HelicalSequence analysisAdd BLAST21
Topological domaini291 – 350CytoplasmicSequence analysisAdd BLAST60
Transmembranei351 – 371HelicalSequence analysisAdd BLAST21
Topological domaini372 – 621LumenalSequence analysisAdd BLAST250
Transmembranei622 – 642HelicalSequence analysisAdd BLAST21
Topological domaini643 – 653CytoplasmicSequence analysisAdd BLAST11
Transmembranei654 – 674HelicalSequence analysisAdd BLAST21
Topological domaini675 – 683LumenalSequence analysis9
Transmembranei684 – 704HelicalSequence analysisAdd BLAST21
Topological domaini705 – 730CytoplasmicSequence analysisAdd BLAST26
Transmembranei731 – 751HelicalSequence analysisAdd BLAST21
Topological domaini752 – 759LumenalSequence analysis8
Transmembranei760 – 780HelicalSequence analysisAdd BLAST21
Topological domaini781 – 832CytoplasmicSequence analysisAdd BLAST52
Transmembranei833 – 853HelicalSequence analysisAdd BLAST21
Topological domaini854 – 1076LumenalSequence analysisAdd BLAST223
Transmembranei1077 – 1094HelicalSequence analysisAdd BLAST18
Topological domaini1095 – 1097CytoplasmicSequence analysis3
Transmembranei1098 – 1118HelicalSequence analysisAdd BLAST21
Topological domaini1119 – 1123LumenalSequence analysis5
Transmembranei1124 – 1144HelicalSequence analysisAdd BLAST21
Topological domaini1145CytoplasmicSequence analysis1
Transmembranei1146 – 1166HelicalSequence analysisAdd BLAST21
Topological domaini1167 – 1194LumenalSequence analysisAdd BLAST28
Transmembranei1195 – 1215HelicalSequence analysisAdd BLAST21
Topological domaini1216 – 1226CytoplasmicSequence analysisAdd BLAST11
Transmembranei1227 – 1247HelicalSequence analysisAdd BLAST21
Topological domaini1248 – 1277LumenalSequence analysisAdd BLAST30

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endosome Source: MGI
  • extracellular exosome Source: MGI
  • extracellular region Source: UniProtKB
  • Golgi apparatus Source: MGI
  • integral component of plasma membrane Source: UniProtKB
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: MGI
  • lysosome Source: UniProtKB
  • membrane Source: MGI
  • membrane raft Source: MGI
  • nuclear envelope Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: MGI
  • vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2321610.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000002326223 – 1277Niemann-Pick C1 proteinAdd BLAST1255

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi25 ↔ 74By similarity
Disulfide bondi31 ↔ 42By similarity
Disulfide bondi63 ↔ 109By similarity
Glycosylationi70N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi75 ↔ 113By similarity
Disulfide bondi97 ↔ 238By similarity
Disulfide bondi100 ↔ 160By similarity
Glycosylationi122N-linked (GlcNAc...)Sequence analysis1
Glycosylationi137N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi177 ↔ 184By similarity
Glycosylationi185N-linked (GlcNAc...)Sequence analysis1
Glycosylationi222N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi227 ↔ 243By similarity
Glycosylationi228N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi240 ↔ 247By similarity
Glycosylationi414N-linked (GlcNAc...)Sequence analysis1
Glycosylationi459N-linked (GlcNAc...)Sequence analysis1
Glycosylationi478N-linked (GlcNAc...)Sequence analysis1
Glycosylationi524N-linked (GlcNAc...)Sequence analysis1
Glycosylationi868N-linked (GlcNAc...)Sequence analysis1
Glycosylationi898N-linked (GlcNAc...)Sequence analysis1
Glycosylationi916N-linked (GlcNAc...)Sequence analysis1
Glycosylationi961N-linked (GlcNAc...)Sequence analysis1
Glycosylationi968N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1063N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO35604.
MaxQBiO35604.
PaxDbiO35604.
PeptideAtlasiO35604.
PRIDEiO35604.

PTM databases

iPTMnetiO35604.
PhosphoSitePlusiO35604.
SwissPalmiO35604.

Expressioni

Tissue specificityi

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

Inductioni

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

Gene expression databases

BgeeiENSMUSG00000024413.
CleanExiMM_NPC1.
GenevisibleiO35604. MM.

Interactioni

Subunit structurei

Interacts with TMEM97 (By similarity). Interacts (via the second lumenal domain) with NPC2 in a cholestrol-dependent manner.By similarity1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025279.

Structurei

3D structure databases

ProteinModelPortaliO35604.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini620 – 785SSDPROSITE-ProRule annotationAdd BLAST166

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni175 – 205Important for cholesterol binding and cholesterol transfer from NPC1 to liposomesBy similarityAdd BLAST31

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1274 – 1277Di-leucine motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi249 – 259Poly-ProAdd BLAST11

Domaini

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 similaritiesi

Belongs to the patched family.Curated
Contains 1 SSD (sterol-sensing) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
GeneTreeiENSGT00800000124043.
HOGENOMiHOG000036674.
HOVERGENiHBG003913.
InParanoidiO35604.
KOiK12385.
OMAiITRAFTM.
OrthoDBiEOG091G00JD.
TreeFamiTF300416.

Family and domain databases

InterProiIPR004765. NP_C_type.
IPR032190. NPC1_N.
IPR003392. Ptc/Disp.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10796:SF116. PTHR10796:SF116. 1 hit.
PfamiPF16414. NPC1_N. 1 hit.
PF02460. Patched. 1 hit.
PF12349. Sterol-sensing. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00917. 2A060601. 1 hit.
PROSITEiPS50156. SSD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O35604-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAHHPALGL LLLLLCPAQV FSQSCVWYGE CGIATGDKRY NCKYSGPPKP
60 70 80 90 100
LPKDGYDLVQ ELCPGLFFDN VSLCCDIQQL QTLKSNLQLP LQFLSRCPSC
110 120 130 140 150
FYNLMTLFCE LTCSPHQSQF LNVTATEDYF DPKTQENKTN VKELEYFVGQ
160 170 180 190 200
SFANAMYNAC RDVEAPSSNE KALGLLCGRD ARACNATNWI EYMFNKDNGQ
210 220 230 240 250
APFTIIPVFS DLSILGMEPM RNATKGCNES VDEVTGPCSC QDCSIVCGPK
260 270 280 290 300
PQPPPPPMPW RIWGLDAMYV IMWVTYVAFL FVFFGALLAV WCHRRRYFVS
310 320 330 340 350
EYTPIDSNIA FSVNSSDKGE ASCCDPLGAA FDDCLRRMFT KWGAFCVRNP
360 370 380 390 400
TCIIFFSLAF ITVCSSGLVF VQVTTNPVEL WSAPHSQARL EKEYFDKHFG
410 420 430 440 450
PFFRTEQLII QAPNTSVHIY EPYPAGADVP FGPPLNKEIL HQVLDLQIAI
460 470 480 490 500
ESITASYNNE TVTLQDICVA PLSPYNKNCT IMSVLNYFQN SHAVLDSQVG
510 520 530 540 550
DDFYIYADYH THFLYCVRAP ASLNDTSLLH GPCLGTFGGP VFPWLVLGGY
560 570 580 590 600
DDQNYNNATA LVITFPVNNY YNDTERLQRA WAWEKEFISF VKNYKNPNLT
610 620 630 640 650
ISFTAERSIE DELNRESNSD VFTVIISYVV MFLYISLALG HIQSCSRLLV
660 670 680 690 700
DSKISLGIAG ILIVLSSVAC SLGIFSYMGM PLTLIVIEVI PFLVLAVGVD
710 720 730 740 750
NIFILVQTYQ RDERLQEETL DQQLGRILGE VAPTMFLSSF SETSAFFFGA
760 770 780 790 800
LSSMPAVHTF SLFAGMAVLI DFLLQITCFV SLLGLDIKRQ EKNHLDILCC
810 820 830 840 850
VRGADDGQGS HASESYLFRF FKNYFAPLLL KDWLRPIVVA VFVGVLSFSV
860 870 880 890 900
AVVNKVDIGL DQSLSMPNDS YVIDYFKSLA QYLHSGPPVY FVLEEGYNYS
910 920 930 940 950
SRKGQNMVCG GMGCDNDSLV QQIFNAAELD TYTRVGFAPS SWIDDYFDWV
960 970 980 990 1000
SPQSSCCRLY NVTHQFCNAS VMDPTCVRCR PLTPEGKQRP QGKEFMKFLP
1010 1020 1030 1040 1050
MFLSDNPNPK CGKGGHAAYG SAVNIVGDDT YIGATYFMTY HTILKTSADY
1060 1070 1080 1090 1100
TDAMKKARLI ASNITETMRS KGSDYRVFPY SVFYVFYEQY LTIIDDTIFN
1110 1120 1130 1140 1150
LSVSLGSIFL VTLVVLGCEL WSAVIMCITI AMILVNMFGV MWLWGISLNA
1160 1170 1180 1190 1200
VSLVNLVMSC GISVEFCSHI TRAFTMSTKG SRVSRAEEAL AHMGSSVFSG
1210 1220 1230 1240 1250
ITLTKFGGIV VLAFAKSQIF EIFYFRMYLA MVLLGATHGL IFLPVLLSYI
1260 1270
GPSVNKAKRH TTYERYRGTE RERLLNF
Length:1,277
Mass (Da):142,885
Last modified:February 6, 2013 - v2
Checksum:i3B42230AAC86764E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9G → GL in AAB63372 (PubMed:9211850).Curated1
Sequence conflicti135Q → P in AAB63372 (PubMed:9211850).Curated1
Sequence conflicti147F → Y in AAB63372 (PubMed:9211850).Curated1
Sequence conflicti445D → N in AAB63372 (PubMed:9211850).Curated1
Sequence conflicti478N → D in AAB63373 (PubMed:9211850).Curated1
Sequence conflicti874 – 875DY → AN in AAB63372 (PubMed:9211850).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29064.1.
PIRiT30188.
RefSeqiNP_032746.2. NM_008720.2.
UniGeneiMm.3484.

Genome annotation databases

EnsembliENSMUST00000025279; ENSMUSP00000025279; ENSMUSG00000024413.
GeneIDi18145.
KEGGimmu:18145.
UCSCiuc008ecb.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29064.1.
PIRiT30188.
RefSeqiNP_032746.2. NM_008720.2.
UniGeneiMm.3484.

3D structure databases

ProteinModelPortaliO35604.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025279.

Chemistry databases

ChEMBLiCHEMBL2321610.
SwissLipidsiSLP:000000479.

PTM databases

iPTMnetiO35604.
PhosphoSitePlusiO35604.
SwissPalmiO35604.

Proteomic databases

EPDiO35604.
MaxQBiO35604.
PaxDbiO35604.
PeptideAtlasiO35604.
PRIDEiO35604.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025279; ENSMUSP00000025279; ENSMUSG00000024413.
GeneIDi18145.
KEGGimmu:18145.
UCSCiuc008ecb.1. mouse.

Organism-specific databases

CTDi4864.
MGIiMGI:1097712. Npc1.

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
GeneTreeiENSGT00800000124043.
HOGENOMiHOG000036674.
HOVERGENiHBG003913.
InParanoidiO35604.
KOiK12385.
OMAiITRAFTM.
OrthoDBiEOG091G00JD.
TreeFamiTF300416.

Miscellaneous databases

ChiTaRSiNpc1. mouse.
PROiO35604.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024413.
CleanExiMM_NPC1.
GenevisibleiO35604. MM.

Family and domain databases

InterProiIPR004765. NP_C_type.
IPR032190. NPC1_N.
IPR003392. Ptc/Disp.
IPR000731. SSD.
[Graphical view]
PANTHERiPTHR10796:SF116. PTHR10796:SF116. 1 hit.
PfamiPF16414. NPC1_N. 1 hit.
PF02460. Patched. 1 hit.
PF12349. Sterol-sensing. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00917. 2A060601. 1 hit.
PROSITEiPS50156. SSD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNPC1_MOUSE
AccessioniPrimary (citable) accession number: O35604
Secondary accession number(s): G3X8W9, O35605
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: February 6, 2013
Last modified: November 2, 2016
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.