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Protein

Niemann-Pick C1-like protein 1

Gene

Npc1l1

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

Functioni

Plays a major role in cholesterol homeostasis. Is critical for the uptake of both phytosterol and cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption (By similarity). The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. 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 similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
Niemann-Pick C1-like protein 1
Gene namesi
Name:Npc1l1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:2685089. Npc1l1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 284264ExtracellularSequence analysisAdd
BLAST
Transmembranei285 – 30521Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini306 – 35247CytoplasmicSequence 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 – 133370CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice have multiple lipid transport defects and have a protective effect against diet-induced hyperlipidemia. They have also a deregulation of CAV1 transport and localization, suggesting that the observed lipid transport defect may be the indirect result of an inability of cells to properly target and/or regulate CAV1 expression.1 Publication

Chemistry

ChEMBLiCHEMBL1075296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Chaini21 – 13331313Niemann-Pick C1-like protein 1PRO_0000023267Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi32 ↔ 90By similarity
Disulfide bondi38 ↔ 56By similarity
Disulfide bondi77 ↔ 125By similarity
Disulfide bondi91 ↔ 129By similarity
Disulfide bondi113 ↔ 254By similarity
Disulfide bondi116 ↔ 172By similarity
Disulfide bondi189 ↔ 197By similarity
Disulfide bondi243 ↔ 259By similarity
Disulfide bondi256 ↔ 263By similarity

Post-translational modificationi

Highly glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ6T3U4.
PaxDbiQ6T3U4.
PRIDEiQ6T3U4.

PTM databases

PhosphoSiteiQ6T3U4.

Expressioni

Tissue specificityi

Expressed in small intestine, stomach and muscle, along with detectable expression in lung, heart, gall bladder, brain, testis, skin and liver. Expression in liver is extremely low.2 Publications

Inductioni

Cholesterol/cholate feeding resulted in down-regulation of intestinal expression. Expression is decreased by 35% in the jejunum upon PPARD activation.2 Publications

Gene expression databases

BgeeiQ6T3U4.
CleanExiMM_NPC1L1.

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000004505.

Chemistry

BindingDBiQ6T3U4.

Structurei

3D structure databases

ProteinModelPortaliQ6T3U4.
SMRiQ6T3U4. Positions 21-264.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi267 – 2704Poly-Pro
Compositional biasi500 – 5034Poly-Leu

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.
HOGENOMiHOG000036674.
HOVERGENiHBG003913.
InParanoidiQ6T3U4.
PhylomeDBiQ6T3U4.
TreeFamiTF300416.

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.

Q6T3U4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAWQGWLL WALLLNSAQG ELYTPTHKAG FCTFYEECGK NPELSGGLTS
60 70 80 90 100
LSNISCLSNT PARHVTGDHL ALLQRVCPRL YNGPNDTYAC CSTKQLVSLD
110 120 130 140 150
SSLSITKALL TRCPACSENF VSIHCHNTCS PDQSLFINVT RVVQRDPGQL
160 170 180 190 200
PAVVAYEAFY QRSFAEKAYE SCSRVRIPAA ASLAVGSMCG VYGSALCNAQ
210 220 230 240 250
RWLNFQGDTG NGLAPLDITF HLLEPGQALA DGMKPLDGKI TPCNESQGED
260 270 280 290 300
SAACSCQDCA ASCPVIPPPP ALRPSFYMGR MPGWLALIII FTAVFVLLSV
310 320 330 340 350
VLVYLRVASN RNKNKTAGSQ EAPNLPRKRR FSPHTVLGRF FESWGTRVAS
360 370 380 390 400
WPLTVLALSF IVVIALSVGL TFIELTTDPV ELWSAPKSQA RKEKAFHDEH
410 420 430 440 450
FGPFFRTNQI FVTAKNRSSY KYDSLLLGPK NFSGILSLDL LQELLELQER
460 470 480 490 500
LRHLQVWSHE AQRNISLQDI CYAPLNPHNT SLTDCCVNSL LQYFQNNHTL
510 520 530 540 550
LLLTANQTLN GQTSLVDWKD HFLYCANAPL TYKDGTALAL SCIADYGAPV
560 570 580 590 600
FPFLAVGGYQ GTDYSEAEAL IITFSINNYP ADDPRMAHAK LWEEAFLKEM
610 620 630 640 650
QSFQRSTADK FQIAFSAERS LEDEINRTTI QDLPVFAISY LIVFLYISLA
660 670 680 690 700
LGSYSRWSRV AVDSKATLGL GGVAVVLGAV VAAMGFYSYL GVPSSLVIIQ
710 720 730 740 750
VVPFLVLAVG ADNIFIFVLE YQRLPRMPGE QREAHIGRTL GSVAPSMLLC
760 770 780 790 800
SLSEAICFFL GALTSMPAVR TFALTSGLAI IFDFLLQMTA FVALLSLDSK
810 820 830 840 850
RQEASRPDVV CCFSSRNLPP PKQKEGLLLC FFRKIYTPFL LHRFIRPVVL
860 870 880 890 900
LLFLVLFGAN LYLMCNISVG LDQDLALPKD SYLIDYFLFL NRYLEVGPPV
910 920 930 940 950
YFDTTSGYNF STEAGMNAIC SSAGCESFSL TQKIQYASEF PNQSYVAIAA
960 970 980 990 1000
SSWVDDFIDW LTPSSSCCRI YTRGPHKDEF CPSTDTSFNC LKNCMNRTLG
1010 1020 1030 1040 1050
PVRPTTEQFH KYLPWFLNDT PNIRCPKGGL AAYRTSVNLS SDGQIIASQF
1060 1070 1080 1090 1100
MAYHKPLRNS QDFTEALRAS RLLAANITAE LRKVPGTDPN FEVFPYTISN
1110 1120 1130 1140 1150
VFYQQYLTVL PEGIFTLALC FVPTFVVCYL LLGLDIRSGI LNLLSIIMIL
1160 1170 1180 1190 1200
VDTIGLMAVW GISYNAVSLI NLVTAVGMSV EFVSHITRSF AVSTKPTRLE
1210 1220 1230 1240 1250
RAKDATIFMG SAVFAGVAMT NFPGILILGF AQAQLIQIFF FRLNLLITLL
1260 1270 1280 1290 1300
GLLHGLVFLP VVLSYLGPDV NQALVLEEKL ATEAAMVSEP SCPQYPFPAD
1310 1320 1330
ANTSDYVNYG FNPEFIPEIN AASSSLPKSD QKF
Length:1,333
Mass (Da):147,132
Last modified:July 5, 2004 - v1
Checksum:i7771520D9B352735
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti476 – 4761N → K in CAI24395 (PubMed:19468303).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY437866 mRNA. Translation: AAR97887.1.
AL607152 Genomic DNA. Translation: CAI24395.1.
CCDSiCCDS24413.1.
UniGeneiMm.212492.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY437866 mRNA. Translation: AAR97887.1.
AL607152 Genomic DNA. Translation: CAI24395.1.
CCDSiCCDS24413.1.
UniGeneiMm.212492.

3D structure databases

ProteinModelPortaliQ6T3U4.
SMRiQ6T3U4. Positions 21-264.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000004505.

Chemistry

BindingDBiQ6T3U4.
ChEMBLiCHEMBL1075296.

PTM databases

PhosphoSiteiQ6T3U4.

Proteomic databases

MaxQBiQ6T3U4.
PaxDbiQ6T3U4.
PRIDEiQ6T3U4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:2685089. Npc1l1.

Phylogenomic databases

eggNOGiKOG1933. Eukaryota.
ENOG410XR54. LUCA.
HOGENOMiHOG000036674.
HOVERGENiHBG003913.
InParanoidiQ6T3U4.
PhylomeDBiQ6T3U4.
TreeFamiTF300416.

Miscellaneous databases

NextBioi383428.
PROiQ6T3U4.
SOURCEiSearch...

Gene expression databases

BgeeiQ6T3U4.
CleanExiMM_NPC1L1.

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

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Strain: C57BL/6J.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis."
    Davis H.R. Jr., Zhu L.-J., Hoos L.M., Tetzloff G., Maguire M., Liu J., Yao X., Iyer S.P.N., Lam M.-H., Lund E.G., Detmers P.A., Graziano M.P., Altmann S.W.
    J. Biol. Chem. 279:33586-33592(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  4. "Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia."
    Davies J.P., Scott C., Oishi K., Liapis A., Ioannou Y.A.
    J. Biol. Chem. 280:12710-12720(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, FUNCTION, DISRUPTION PHENOTYPE.
  5. "Reduced cholesterol absorption upon PPARdelta activation coincides with decreased intestinal expression of NPC1L1."
    van der Veen J.N., Kruit J.K., Havinga R., Baller J.F.W., Chimini G., Lestavel S., Staels B., Groot P.H.E., Groen A.K., Kuipers F.
    J. Lipid Res. 46:526-534(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.

Entry informationi

Entry nameiNPCL1_MOUSE
AccessioniPrimary (citable) accession number: Q6T3U4
Secondary accession number(s): Q5SVX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: July 5, 2004
Last modified: May 11, 2016
This is version 93 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. 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.