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Protein

NPC1-like intracellular cholesterol transporter 1

Gene

Npc1l1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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
  • lipid transporter activity Source: InterPro
  • myosin V binding Source: Ensembl
  • Rab GTPase binding Source: Ensembl

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-RNO-8963678 Intestinal lipid absorption

Names & Taxonomyi

Protein namesi
Recommended name:
NPC1-like intracellular cholesterol transporter 1Imported
Alternative name(s):
Niemann-Pick C1-like protein 11 Publication
Gene namesi
Name:Npc1l1Imported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 14

Organism-specific databases

RGDi1303135 Npc1l1

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 domaini21 – 282ExtracellularSequence analysisAdd BLAST262
Transmembranei283 – 303Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini304 – 352CytoplasmicSequence analysisAdd BLAST49
Transmembranei353 – 373Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini374 – 632ExtracellularSequence analysisAdd BLAST259
Transmembranei633 – 653Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini654 – 665CytoplasmicSequence analysisAdd BLAST12
Transmembranei666 – 686Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini687 – 696ExtracellularSequence analysis10
Transmembranei697 – 717Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini718 – 742CytoplasmicSequence analysisAdd BLAST25
Transmembranei743 – 763Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini764 – 776ExtracellularSequence analysisAdd BLAST13
Transmembranei777 – 797Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini798 – 846CytoplasmicSequence analysisAdd BLAST49
Transmembranei847 – 867Helical; Name=8Sequence analysisAdd BLAST21
Topological domaini868 – 1113ExtracellularSequence analysisAdd BLAST246
Transmembranei1114 – 1134Helical; Name=9Sequence analysisAdd BLAST21
Topological domaini1135 – 1142CytoplasmicSequence analysis8
Transmembranei1143 – 1163Helical; Name=10Sequence analysisAdd BLAST21
Topological domaini1164 – 1165ExtracellularSequence analysis2
Transmembranei1166 – 1186Helical; Name=11Sequence analysisAdd BLAST21
Topological domaini1187 – 1206CytoplasmicSequence analysisAdd BLAST20
Transmembranei1207 – 1227Helical; Name=12Sequence analysisAdd BLAST21
Topological domaini1228 – 1242ExtracellularSequence analysisAdd BLAST15
Transmembranei1243 – 1263Helical; Name=13Sequence analysisAdd BLAST21
Topological domaini1264 – 1331CytoplasmicSequence analysisAdd BLAST68

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5161

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000002326821 – 1331NPC1-like intracellular cholesterol transporter 1Add BLAST1311

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 90By similarity
Disulfide bondi38 ↔ 56By similarity
Glycosylationi53N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi77 ↔ 125By similarity
Glycosylationi85N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi91 ↔ 129By similarity
Disulfide bondi113 ↔ 254By similarity
Disulfide bondi116 ↔ 172By similarity
Glycosylationi138N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi189 ↔ 197By similarity
Disulfide bondi243 ↔ 259By similarity
Glycosylationi244N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi256 ↔ 263By similarity
Glycosylationi416N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi431N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi464N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi479N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi497N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi506N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi606N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi626N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi909N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi917N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi996N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1038N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1076N-linked (GlcNAc...) asparagineSequence analysis1

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

Gene expression databases

BgeeiENSRNOG00000049955

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

STRINGi10116.ENSRNOP00000065524

Chemistry databases

BindingDBiQ6T3U3

Structurei

3D structure databases

ProteinModelPortaliQ6T3U3
SMRiQ6T3U3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini632 – 797SSDPROSITE-ProRule annotationAdd BLAST166

Sequence similaritiesi

Belongs to the patched family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1933 Eukaryota
ENOG410XR54 LUCA
GeneTreeiENSGT00900000140845
HOVERGENiHBG003913
InParanoidiQ6T3U3
KOiK14461
OMAiKDEFCPS
OrthoDBiEOG091G00JD
PhylomeDBiQ6T3U3

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.

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

Similar proteinsi

Entry informationi

Entry nameiNPCL1_RAT
AccessioniPrimary (citable) accession number: Q6T3U3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: July 5, 2004
Last modified: May 23, 2018
This is version 89 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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