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Protein

Niemann-Pick C1-like protein 1

Gene

Npc1l1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption (By similarity). Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (By similarity).By similarity1 Publication

GO - Molecular functioni

  • drug binding Source: RGD
  • hedgehog receptor activity Source: InterPro
  • lipid transporter activity Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

ReactomeiR-RNO-265473. Trafficking of dietary sterols.

Names & Taxonomyi

Protein namesi
Recommended name:
Niemann-Pick C1-like protein 1
Gene namesi
Name:Npc1l1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 14

Organism-specific databases

RGDi1303135. Npc1l1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 282262ExtracellularSequence analysisAdd
BLAST
Transmembranei283 – 30321Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini304 – 35249CytoplasmicSequence analysisAdd
BLAST
Transmembranei353 – 37321Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini374 – 632259ExtracellularSequence analysisAdd
BLAST
Transmembranei633 – 65321Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini654 – 66512CytoplasmicSequence analysisAdd
BLAST
Transmembranei666 – 68621Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini687 – 69610ExtracellularSequence analysis
Transmembranei697 – 71721Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini718 – 74225CytoplasmicSequence analysisAdd
BLAST
Transmembranei743 – 76321Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini764 – 77613ExtracellularSequence analysisAdd
BLAST
Transmembranei777 – 79721Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini798 – 84649CytoplasmicSequence analysisAdd
BLAST
Transmembranei847 – 86721Helical; Name=8Sequence analysisAdd
BLAST
Topological domaini868 – 1113246ExtracellularSequence analysisAdd
BLAST
Transmembranei1114 – 113421Helical; Name=9Sequence analysisAdd
BLAST
Topological domaini1135 – 11428CytoplasmicSequence analysis
Transmembranei1143 – 116321Helical; Name=10Sequence analysisAdd
BLAST
Topological domaini1164 – 11652ExtracellularSequence analysis
Transmembranei1166 – 118621Helical; Name=11Sequence analysisAdd
BLAST
Topological domaini1187 – 120620CytoplasmicSequence analysisAdd
BLAST
Transmembranei1207 – 122721Helical; Name=12Sequence analysisAdd
BLAST
Topological domaini1228 – 124215ExtracellularSequence analysisAdd
BLAST
Transmembranei1243 – 126321Helical; Name=13Sequence analysisAdd
BLAST
Topological domaini1264 – 133168CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • brush border membrane Source: RGD
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL5161.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Chaini21 – 13311311Niemann-Pick C1-like protein 1PRO_0000023268Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi32 ↔ 90By similarity
Disulfide bondi38 ↔ 56By similarity
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence analysis
Disulfide bondi77 ↔ 125By similarity
Glycosylationi85 – 851N-linked (GlcNAc...)Sequence analysis
Disulfide bondi91 ↔ 129By similarity
Disulfide bondi113 ↔ 254By similarity
Disulfide bondi116 ↔ 172By similarity
Glycosylationi138 – 1381N-linked (GlcNAc...)Sequence analysis
Disulfide bondi189 ↔ 197By similarity
Disulfide bondi243 ↔ 259By similarity
Glycosylationi244 – 2441N-linked (GlcNAc...)Sequence analysis
Disulfide bondi256 ↔ 263By similarity
Glycosylationi416 – 4161N-linked (GlcNAc...)Sequence analysis
Glycosylationi431 – 4311N-linked (GlcNAc...)Sequence analysis
Glycosylationi464 – 4641N-linked (GlcNAc...)Sequence analysis
Glycosylationi479 – 4791N-linked (GlcNAc...)Sequence analysis
Glycosylationi497 – 4971N-linked (GlcNAc...)Sequence analysis
Glycosylationi506 – 5061N-linked (GlcNAc...)Sequence analysis
Glycosylationi606 – 6061N-linked (GlcNAc...)Sequence analysis
Glycosylationi626 – 6261N-linked (GlcNAc...)Sequence analysis
Glycosylationi909 – 9091N-linked (GlcNAc...)Sequence analysis
Glycosylationi917 – 9171N-linked (GlcNAc...)Sequence analysis
Glycosylationi996 – 9961N-linked (GlcNAc...)Sequence analysis
Glycosylationi1038 – 10381N-linked (GlcNAc...)Sequence analysis
Glycosylationi1076 – 10761N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Highly glycosylated.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6T3U3.
PRIDEiQ6T3U3.

Expressioni

Tissue specificityi

Small intestine showed the highest level of expression. Expression in other tissues including gall bladder, liver, testis and stomach is also observed. Along the duodenum-ileum axis, the levels vary in different segments of the intestine with peak expression in the proximal jejunum. Protein expression is confined to the enterocyte. Discrete localization to the epithelial layer bordering the luminal space along the crypt-villus axis. Protein expression in the enterocyte is observed closest to the luminal space. Expression in enterocytes from the proximal (jejunum) but not in the distal (ileum) region.1 Publication

Interactioni

Subunit structurei

Interacts with RAB11A, MYO5B and RAB11FIP2. Interaction with RAB11A, MYO5B and RAB11FIP2 is required for proper transport to the plasma membrane upon cholesterol depletion (By similarity). Interacts with NPC2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000065524.

Chemistry

BindingDBiQ6T3U3.

Structurei

3D structure databases

ProteinModelPortaliQ6T3U3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini632 – 797166SSDPROSITE-ProRule annotationAdd
BLAST

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.
HOVERGENiHBG003913.
InParanoidiQ6T3U3.
KOiK14461.
OMAiLCLVPTF.
OrthoDBiEOG7QRQT0.
PhylomeDBiQ6T3U3.

Family and domain databases

InterProiIPR004765. NP_C_type.
IPR032190. NPC1_N.
IPR003392. Patched.
IPR000731. SSD.
[Graphical view]
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.

Q6T3U3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAWLGWLL WALLLSAAQG ELYTPKHEAG VCTFYEECGK NPELSGGLTS
60 70 80 90 100
LSNVSCLSNT PARHVTGEHL ALLQRICPRL YNGPNTTFAC CSTKQLLSLE
110 120 130 140 150
SSMSITKALL TRCPACSDNF VSLHCHNTCS PDQSLFINVT RVVERGAGEP
160 170 180 190 200
PAVVAYEAFY QRSFAEKAYE SCSQVRIPAA ASLAVGSMCG VYGSALCNAQ
210 220 230 240 250
RWLNFQGDTG NGLAPLDITF HLLEPGQALP DGIQPLNGKI APCNESQGDD
260 270 280 290 300
SAVCSCQDCA ASCPVIPPPE ALRPSFYMGR MPGWLALIII FTAVFVLLSA
310 320 330 340 350
VLVRLRVVSN RNKNKAEGPQ EAPKLPHKHK LSPHTILGRF FQNWGTRVAS
360 370 380 390 400
WPLTVLALSF IVVIALAAGL TFIELTTDPV ELWSAPKSQA RKEKSFHDEH
410 420 430 440 450
FGPFFRTNQI FVTARNRSSY KYDSLLLGSK NFSGILSLDF LLELLELQER
460 470 480 490 500
LRHLQVWSPE AERNISLQDI CYAPLNPYNT SLSDCCVNSL LQYFQNNRTL
510 520 530 540 550
LMLTANQTLN GQTSLVDWKD HFLYCANAPL TFKDGTSLAL SCMADYGAPV
560 570 580 590 600
FPFLAVGGYQ GTDYSEAEAL IITFSLNNYP ADDPRMAQAK LWEEAFLKEM
610 620 630 640 650
ESFQRNTSDK FQVAFSAERS LEDEINRTTI QDLPVFAVSY IIVFLYISLA
660 670 680 690 700
LGSYSRCSRV AVESKATLGL GGVIVVLGAV LAAMGFYSYL GVPSSLVIIQ
710 720 730 740 750
VVPFLVLAVG ADNIFIFVLE YQRLPRMPGE QREAHIGRTL GSVAPSMLLC
760 770 780 790 800
SLSEAICFFL GALTPMPAVR TFALTSGLAI ILDFLLQMTA FVALLSLDSK
810 820 830 840 850
RQEASRPDVL CCFSTRKLPP PKEKEGLLLR FFRKIYAPFL LHRFIRPVVM
860 870 880 890 900
LLFLTLFGAN LYLMCNINVG LDQELALPKD SYLIDYFLFL NRYLEVGPPV
910 920 930 940 950
YFVTTSGFNF SSEAGMNATC SSAGCKSFSL TQKIQYASEF PDQSYVAIAA
960 970 980 990 1000
SSWVDDFIDW LTPSSSCCRL YIRGPHKDEF CPSTDTSFNC LKNCMNRTLG
1010 1020 1030 1040 1050
PVRPTAEQFH KYLPWFLNDP PNIRCPKGGL AAYRTSVNLS SDGQVIASQF
1060 1070 1080 1090 1100
MAYHKPLRNS QDFTEALRAS RLLAANITAD LRKVPGTDPN FEVFPYTISN
1110 1120 1130 1140 1150
VFYQQYLTVL PEGIFTLALC FVPTFVVCYL LLGLDMCSGI LNLLSIIMIL
1160 1170 1180 1190 1200
VDTIGLMAVW GISYNAVSLI NLVTAVGMSV EFVSHITRSF AVSTKPTRLE
1210 1220 1230 1240 1250
RAKDATVFMG SAVFAGVAMT NFPGILILGF AQAQLIQIFF FRLNLLITLL
1260 1270 1280 1290 1300
GLLHGLVFLP VVLSYLGPDV NQALVQEEKL ASEAAVAPEP SCPQYPSPAD
1310 1320 1330
ADANVNYGFA PELAHGANAA RSSLPKSDQK F
Length:1,331
Mass (Da):146,415
Last modified:July 5, 2004 - v1
Checksum:i2E10EF2E3A337F70
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY437867 mRNA. Translation: AAR97888.1.
RefSeqiNP_001002025.1. NM_001002025.1.
UniGeneiRn.123563.

Genome annotation databases

EnsembliENSRNOT00000075827; ENSRNOP00000065524; ENSRNOG00000049955.
GeneIDi432367.
KEGGirno:432367.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY437867 mRNA. Translation: AAR97888.1.
RefSeqiNP_001002025.1. NM_001002025.1.
UniGeneiRn.123563.

3D structure databases

ProteinModelPortaliQ6T3U3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000065524.

Chemistry

BindingDBiQ6T3U3.
ChEMBLiCHEMBL5161.

Proteomic databases

PaxDbiQ6T3U3.
PRIDEiQ6T3U3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000075827; ENSRNOP00000065524; ENSRNOG00000049955.
GeneIDi432367.
KEGGirno:432367.

Organism-specific databases

CTDi29881.
RGDi1303135. Npc1l1.

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
GeneTreeiENSGT00800000124043.
HOVERGENiHBG003913.
InParanoidiQ6T3U3.
KOiK14461.
OMAiLCLVPTF.
OrthoDBiEOG7QRQT0.
PhylomeDBiQ6T3U3.

Enzyme and pathway databases

ReactomeiR-RNO-265473. Trafficking of dietary sterols.

Miscellaneous databases

NextBioi696855.
PROiQ6T3U3.

Family and domain databases

InterProiIPR004765. NP_C_type.
IPR032190. NPC1_N.
IPR003392. Patched.
IPR000731. SSD.
[Graphical view]
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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Strain: Sprague-Dawley.
  2. "Characterization of the putative native and recombinant rat sterol transporter Niemann-Pick C1 Like 1 (NPC1L1) protein."
    Iyer S.P.N., Yao X., Crona J.H., Hoos L.M., Tetzloff G., Davis H.R. Jr., Graziano M.P., Altmann S.W.
    Biochim. Biophys. Acta 1722:282-292(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, CHARACTERIZATION.
  3. Cited for: FUNCTION.

Entry informationi

Entry nameiNPCL1_RAT
AccessioniPrimary (citable) accession number: Q6T3U3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: July 5, 2004
Last modified: May 11, 2016
This is version 76 of the entry and version 1 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. 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.