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Protein

NPC intracellular cholesterol transporter 1

Gene

NPC1

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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 (By similarity).By similarity

Sites

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
NPC intracellular cholesterol transporter 1By similarity
Alternative name(s):
Niemann-Pick C1 protein1 Publication
Gene namesi
Name:NPC1By similarity
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 677LumenalSequence analysis3
Transmembranei678 – 698HelicalSequence analysisAdd BLAST21
Topological domaini699 – 734CytoplasmicSequence analysisAdd BLAST36
Transmembranei735 – 755HelicalSequence analysisAdd BLAST21
Topological domaini756 – 759LumenalSequence analysis4
Transmembranei760 – 780HelicalSequence analysisAdd BLAST21
Topological domaini781 – 832CytoplasmicSequence analysisAdd BLAST52
Transmembranei833 – 853HelicalSequence analysisAdd BLAST21
Topological domaini854 – 1097LumenalSequence analysisAdd BLAST244
Transmembranei1098 – 1118HelicalSequence analysisAdd BLAST21
Topological domaini1119 – 1123CytoplasmicSequence analysis5
Transmembranei1124 – 1144HelicalSequence analysisAdd BLAST21
Topological domaini1145LumenalSequence analysis1
Transmembranei1146 – 1166HelicalSequence analysisAdd BLAST21
Topological domaini1167 – 1194CytoplasmicSequence analysisAdd BLAST28
Transmembranei1195 – 1215HelicalSequence analysisAdd BLAST21
Topological domaini1216 – 1226LumenalSequence analysisAdd BLAST11
Transmembranei1227 – 1247HelicalSequence analysisAdd BLAST21
Topological domaini1248 – 1277CytoplasmicSequence analysisAdd BLAST30

Keywords - Cellular componenti

Endosome, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000002326323 – 1277NPC intracellular cholesterol transporter 1Add BLAST1255

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi25 ↔ 74By similarity
Disulfide bondi31 ↔ 42By similarity
Disulfide bondi63 ↔ 109By similarity
Glycosylationi70N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi75 ↔ 113By similarity
Disulfide bondi97 ↔ 238By similarity
Disulfide bondi100 ↔ 160By similarity
Glycosylationi122N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi135N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi177 ↔ 184By similarity
Glycosylationi185N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi222N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi227 ↔ 243By similarity
Disulfide bondi240 ↔ 247By similarity
Glycosylationi415N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi452N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi459N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi478N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi898N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi916N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi931N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi961N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi968N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1028N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1063N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP56941
PeptideAtlasiP56941
PRIDEiP56941

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000004014

Structurei

3D structure databases

ProteinModelPortaliP56941
SMRiP56941
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.By similarity

Sequence similaritiesi

Belongs to the patched family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1933 Eukaryota
ENOG410XR54 LUCA
HOGENOMiHOG000036674
HOVERGENiHBG003913
InParanoidiP56941
KOiK12385

Family and domain databases

InterProiView protein in InterPro
IPR004765 NPC1-like
IPR032190 NPC1_N
IPR003392 Ptc/Disp
IPR000731 SSD
PfamiView protein in Pfam
PF16414 NPC1_N, 1 hit
PF02460 Patched, 1 hit
PF12349 Sterol-sensing, 1 hit
TIGRFAMsiTIGR00917 2A060601, 1 hit
PROSITEiView protein in PROSITE
PS50156 SSD, 1 hit

Sequencei

Sequence statusi: Complete.

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

P56941-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSARGPAFGL LLLLLCPVQV FSQSCVWYGE CGIASGDKRY NCRYSGPPKP
60 70 80 90 100
LPEDGYDLVQ ELCPGFFFGN VSLCCDVQQL RTLKDNLQLP LQFLSRCPSC
110 120 130 140 150
FYNLMNLFCE LTCSPRQSQF LNVTATEDYV DPVTNQTKTN VKELEYYVGE
160 170 180 190 200
TFANAMYNAC RDVEAPSSNE KALGLLCGRE AQACNATNWI EYMFNKDNGQ
210 220 230 240 250
APFTITPIFS DLPTHGMEPM NNATKGCDES VDEVTGPCSC QDCSIVCGPK
260 270 280 290 300
PQPPPPPVPW RILGLDAMYV IMWSSYMAFL IVFFGAFFAV WCYRKRYFVS
310 320 330 340 350
EYTPIDGNIA FSVNSSDKGQ AFCCDPLGAA FERGLRRLFA QWGAFCVRHP
360 370 380 390 400
GCVVFFSLAF IVACSSGLVF IRVTTDPVDL WSAPGSQARR EKEYFDTHFG
410 420 430 440 450
PFFRMEQLII RATNNQSHIY HPYPAGADVP FGPPLSRDIL HQVLDLQTAI
460 470 480 490 500
ENITASYNNE TVTLQDICLA PLSPYNKNCT ILSVLNYFQN SHSVLDHQVG
510 520 530 540 550
DFFFVYADYH THFLYCVRAP ASLNDASLLH DPCLGTFGGP VFPWLVLGGY
560 570 580 590 600
DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWESEFINF VKNYKNPNLT
610 620 630 640 650
ISFMAERSIE DELNRESNSD LFTILISYAI MFLYISIALG HIKSCSRLLV
660 670 680 690 700
DSKISLGIAG ILIVLSSVAC SLGIFSYIGV PLTLIVIEVI PFLVLAVGVD
710 720 730 740 750
NIFILVQTYQ RDERLQGETL DQQLGRVLGE VAPSMFLSSF SETVAFFLGG
760 770 780 790 800
LSVVPAVHTF SLFAGMAVLI DFLLQITCFV SLLGLDIKRQ EKNRLDVVCC
810 820 830 840 850
VQGAEDGAGV QASESCLFRF FKNSYAPLLL KDWMRPIVIA VFVGVLSFSI
860 870 880 890 900
AVLNKVEIGL DQSLSMPDDS YVMDYFQSLS RYLHAGPPVY FVVEEGHNYT
910 920 930 940 950
SLKGQNMVCG GLGCNNDSLV QQIFTAAQLD NYTRIGFAPS SWIDDYFDWI
960 970 980 990 1000
KPQSSCCRVY NSTDQFCNAS VVDPTCIRCR PLTSEGKQRP QGEDFMRFLP
1010 1020 1030 1040 1050
MFLSDNPNPK CGKGGHAAYS SAVNILGNGS GVGATYFMTY HTVLQASADF
1060 1070 1080 1090 1100
IDAMQKARLI ASNITRTMGL EASSYRVFPY SVFYVFYEQY LTVIDDTIFN
1110 1120 1130 1140 1150
LGVSLGAIFL VTVVLMGCEL WATVIMCVTI AMILVNMFGV MWLWGISLNA
1160 1170 1180 1190 1200
VSLVNLVMSC GISVEFCSHI TRAFTLSTKG SRVDRAEEAL AHMGSSVFSG
1210 1220 1230 1240 1250
ITLTKFGGIV VLAFAKSQIF QIFYFRMYLA IVLLGATHGL IFLPVLLSYI
1260 1270
GPSINKAKSL ATQERYKGTE REQLLNF
Length:1,277
Mass (Da):141,963
Last modified:May 30, 2000 - v1
Checksum:i2C80D300889F02EB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169635 mRNA Translation: AAD47090.1
RefSeqiNP_999487.1, NM_214322.1
UniGeneiSsc.1533

Genome annotation databases

GeneIDi397591
KEGGissc:397591

Similar proteinsi

Entry informationi

Entry nameiNPC1_PIG
AccessioniPrimary (citable) accession number: P56941
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: April 25, 2018
This is version 92 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health