Q6T3U3 · NPCL1_RAT
- ProteinNPC1-like intracellular cholesterol transporter 1
- GeneNpc1l1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1331 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a major role in cholesterol homeostasis (PubMed:17135346).
Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:17135346).
Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (PubMed:17135346).
Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption and is approved for the treatment of hypercholesterolemia (PubMed:15928087).
May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (By similarity).
May be involved in caveolin trafficking from the plasma membrane (By similarity).
Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (By similarity).
Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:17135346).
Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (PubMed:17135346).
Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption and is approved for the treatment of hypercholesterolemia (PubMed:15928087).
May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (By similarity).
May be involved in caveolin trafficking from the plasma membrane (By similarity).
Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (By similarity).
Catalytic activity
- cholesterol(in) = cholesterol(out)
- sitosterol(out) = sitosterol(in)
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | apical plasma membrane | |
Cellular Component | brush border membrane | |
Cellular Component | plasma membrane | |
Molecular Function | cholesterol binding | |
Molecular Function | heterocyclic compound binding | |
Molecular Function | lipid transporter activity | |
Molecular Function | myosin V binding | |
Molecular Function | protein homodimerization activity | |
Molecular Function | small GTPase binding | |
Molecular Function | vitamin E binding | |
Biological Process | cellular response to sterol depletion | |
Biological Process | cholesterol biosynthetic process | |
Biological Process | cholesterol homeostasis | |
Biological Process | cholesterol import | |
Biological Process | cholesterol transport | |
Biological Process | intestinal cholesterol absorption | |
Biological Process | lipoprotein metabolic process | |
Biological Process | response to muscle activity | |
Biological Process | response to xenobiotic stimulus | |
Biological Process | vitamin E metabolic process | |
Biological Process | vitamin transport |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNPC1-like intracellular cholesterol transporter 1
- Short namesNpc1l1
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ6T3U3
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Multi-pass membrane protein
Cell membrane ; Multi-pass membrane protein
Note: Subfractionation of brush border membranes from proximal enterocytes suggests considerable association with the apical membrane fraction. Exists as a predominantly cell surface membrane expressed protein.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 21-282 | Extracellular | ||||
Sequence: ELYTPKHEAGVCTFYEECGKNPELSGGLTSLSNVSCLSNTPARHVTGEHLALLQRICPRLYNGPNTTFACCSTKQLLSLESSMSITKALLTRCPACSDNFVSLHCHNTCSPDQSLFINVTRVVERGAGEPPAVVAYEAFYQRSFAEKAYESCSQVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALPDGIQPLNGKIAPCNESQGDDSAVCSCQDCAASCPVIPPPEALRPSFYMGRMP | ||||||
Transmembrane | 283-303 | Helical; Name=1 | ||||
Sequence: GWLALIIIFTAVFVLLSAVLV | ||||||
Topological domain | 304-352 | Cytoplasmic | ||||
Sequence: RLRVVSNRNKNKAEGPQEAPKLPHKHKLSPHTILGRFFQNWGTRVASWP | ||||||
Transmembrane | 353-373 | Helical; Name=2 | ||||
Sequence: LTVLALSFIVVIALAAGLTFI | ||||||
Topological domain | 374-632 | Extracellular | ||||
Sequence: ELTTDPVELWSAPKSQARKEKSFHDEHFGPFFRTNQIFVTARNRSSYKYDSLLLGSKNFSGILSLDFLLELLELQERLRHLQVWSPEAERNISLQDICYAPLNPYNTSLSDCCVNSLLQYFQNNRTLLMLTANQTLNGQTSLVDWKDHFLYCANAPLTFKDGTSLALSCMADYGAPVFPFLAVGGYQGTDYSEAEALIITFSLNNYPADDPRMAQAKLWEEAFLKEMESFQRNTSDKFQVAFSAERSLEDEINRTTIQD | ||||||
Transmembrane | 633-653 | Helical; Name=3 | ||||
Sequence: LPVFAVSYIIVFLYISLALGS | ||||||
Topological domain | 654-665 | Cytoplasmic | ||||
Sequence: YSRCSRVAVESK | ||||||
Transmembrane | 666-686 | Helical; Name=4 | ||||
Sequence: ATLGLGGVIVVLGAVLAAMGF | ||||||
Topological domain | 687-696 | Extracellular | ||||
Sequence: YSYLGVPSSL | ||||||
Transmembrane | 697-717 | Helical; Name=5 | ||||
Sequence: VIIQVVPFLVLAVGADNIFIF | ||||||
Topological domain | 718-742 | Cytoplasmic | ||||
Sequence: VLEYQRLPRMPGEQREAHIGRTLGS | ||||||
Transmembrane | 743-763 | Helical; Name=6 | ||||
Sequence: VAPSMLLCSLSEAICFFLGAL | ||||||
Topological domain | 764-776 | Extracellular | ||||
Sequence: TPMPAVRTFALTS | ||||||
Transmembrane | 777-797 | Helical; Name=7 | ||||
Sequence: GLAIILDFLLQMTAFVALLSL | ||||||
Topological domain | 798-846 | Cytoplasmic | ||||
Sequence: DSKRQEASRPDVLCCFSTRKLPPPKEKEGLLLRFFRKIYAPFLLHRFIR | ||||||
Transmembrane | 847-867 | Helical; Name=8 | ||||
Sequence: PVVMLLFLTLFGANLYLMCNI | ||||||
Topological domain | 868-1113 | Extracellular | ||||
Sequence: NVGLDQELALPKDSYLIDYFLFLNRYLEVGPPVYFVTTSGFNFSSEAGMNATCSSAGCKSFSLTQKIQYASEFPDQSYVAIAASSWVDDFIDWLTPSSSCCRLYIRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTAEQFHKYLPWFLNDPPNIRCPKGGLAAYRTSVNLSSDGQVIASQFMAYHKPLRNSQDFTEALRASRLLAANITADLRKVPGTDPNFEVFPYTISNVFYQQYLTVLPEG | ||||||
Transmembrane | 1114-1134 | Helical; Name=9 | ||||
Sequence: IFTLALCFVPTFVVCYLLLGL | ||||||
Topological domain | 1135-1142 | Cytoplasmic | ||||
Sequence: DMCSGILN | ||||||
Transmembrane | 1143-1163 | Helical; Name=10 | ||||
Sequence: LLSIIMILVDTIGLMAVWGIS | ||||||
Topological domain | 1164-1165 | Extracellular | ||||
Sequence: YN | ||||||
Transmembrane | 1166-1186 | Helical; Name=11 | ||||
Sequence: AVSLINLVTAVGMSVEFVSHI | ||||||
Topological domain | 1187-1206 | Cytoplasmic | ||||
Sequence: TRSFAVSTKPTRLERAKDAT | ||||||
Transmembrane | 1207-1227 | Helical; Name=12 | ||||
Sequence: VFMGSAVFAGVAMTNFPGILI | ||||||
Topological domain | 1228-1242 | Extracellular | ||||
Sequence: LGFAQAQLIQIFFFR | ||||||
Transmembrane | 1243-1263 | Helical; Name=13 | ||||
Sequence: LNLLITLLGLLHGLVFLPVVL | ||||||
Topological domain | 1264-1331 | Cytoplasmic | ||||
Sequence: SYLGPDVNQALVQEEKLASEAAVAPEPSCPQYPSPADADANVNYGFAPELAHGANAARSSLPKSDQKF |
Keywords
- Cellular component
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1 variant from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MAAAWLGWLLWALLLSAAQG | ||||||
Chain | PRO_0000023268 | 21-1331 | NPC1-like intracellular cholesterol transporter 1 | |||
Sequence: ELYTPKHEAGVCTFYEECGKNPELSGGLTSLSNVSCLSNTPARHVTGEHLALLQRICPRLYNGPNTTFACCSTKQLLSLESSMSITKALLTRCPACSDNFVSLHCHNTCSPDQSLFINVTRVVERGAGEPPAVVAYEAFYQRSFAEKAYESCSQVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALPDGIQPLNGKIAPCNESQGDDSAVCSCQDCAASCPVIPPPEALRPSFYMGRMPGWLALIIIFTAVFVLLSAVLVRLRVVSNRNKNKAEGPQEAPKLPHKHKLSPHTILGRFFQNWGTRVASWPLTVLALSFIVVIALAAGLTFIELTTDPVELWSAPKSQARKEKSFHDEHFGPFFRTNQIFVTARNRSSYKYDSLLLGSKNFSGILSLDFLLELLELQERLRHLQVWSPEAERNISLQDICYAPLNPYNTSLSDCCVNSLLQYFQNNRTLLMLTANQTLNGQTSLVDWKDHFLYCANAPLTFKDGTSLALSCMADYGAPVFPFLAVGGYQGTDYSEAEALIITFSLNNYPADDPRMAQAKLWEEAFLKEMESFQRNTSDKFQVAFSAERSLEDEINRTTIQDLPVFAVSYIIVFLYISLALGSYSRCSRVAVESKATLGLGGVIVVLGAVLAAMGFYSYLGVPSSLVIIQVVPFLVLAVGADNIFIFVLEYQRLPRMPGEQREAHIGRTLGSVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAIILDFLLQMTAFVALLSLDSKRQEASRPDVLCCFSTRKLPPPKEKEGLLLRFFRKIYAPFLLHRFIRPVVMLLFLTLFGANLYLMCNINVGLDQELALPKDSYLIDYFLFLNRYLEVGPPVYFVTTSGFNFSSEAGMNATCSSAGCKSFSLTQKIQYASEFPDQSYVAIAASSWVDDFIDWLTPSSSCCRLYIRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTAEQFHKYLPWFLNDPPNIRCPKGGLAAYRTSVNLSSDGQVIASQFMAYHKPLRNSQDFTEALRASRLLAANITADLRKVPGTDPNFEVFPYTISNVFYQQYLTVLPEGIFTLALCFVPTFVVCYLLLGLDMCSGILNLLSIIMILVDTIGLMAVWGISYNAVSLINLVTAVGMSVEFVSHITRSFAVSTKPTRLERAKDATVFMGSAVFAGVAMTNFPGILILGFAQAQLIQIFFFRLNLLITLLGLLHGLVFLPVVLSYLGPDVNQALVQEEKLASEAAVAPEPSCPQYPSPADADANVNYGFAPELAHGANAARSSLPKSDQKF | ||||||
Disulfide bond | 32↔90 | |||||
Sequence: CTFYEECGKNPELSGGLTSLSNVSCLSNTPARHVTGEHLALLQRICPRLYNGPNTTFAC | ||||||
Disulfide bond | 38↔56 | |||||
Sequence: CGKNPELSGGLTSLSNVSC | ||||||
Glycosylation | 53 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 77↔125 | |||||
Sequence: CPRLYNGPNTTFACCSTKQLLSLESSMSITKALLTRCPACSDNFVSLHC | ||||||
Glycosylation | 85 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 91↔129 | |||||
Sequence: CSTKQLLSLESSMSITKALLTRCPACSDNFVSLHCHNTC | ||||||
Disulfide bond | 113↔254 | |||||
Sequence: CPACSDNFVSLHCHNTCSPDQSLFINVTRVVERGAGEPPAVVAYEAFYQRSFAEKAYESCSQVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALPDGIQPLNGKIAPCNESQGDDSAVC | ||||||
Disulfide bond | 116↔172 | |||||
Sequence: CSDNFVSLHCHNTCSPDQSLFINVTRVVERGAGEPPAVVAYEAFYQRSFAEKAYESC | ||||||
Glycosylation | 138 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 189↔197 | |||||
Sequence: CGVYGSALC | ||||||
Disulfide bond | 243↔259 | |||||
Sequence: CNESQGDDSAVCSCQDC | ||||||
Glycosylation | 244 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 256↔263 | |||||
Sequence: CQDCAASC | ||||||
Glycosylation | 416 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 431 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 464 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 471↔485 | |||||
Sequence: CYAPLNPYNTSLSDC | ||||||
Glycosylation | 479 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 497 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 506 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 525↔542 | |||||
Sequence: CANAPLTFKDGTSLALSC | ||||||
Glycosylation | 606 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 626 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 909 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 917 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 920↔925 | |||||
Sequence: CSSAGC | ||||||
Disulfide bond | 967↔1025 | |||||
Sequence: CCRLYIRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTAEQFHKYLPWFLNDPPNIRC | ||||||
Disulfide bond | 981↔990 | |||||
Sequence: CPSTDTSFNC | ||||||
Glycosylation | 996 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 1038 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 1076 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Highly glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Small intestine showed the highest level of expression (PubMed:14976318).
Expression in other tissues including gall bladder, liver, testis and stomach is also observed (PubMed:14976318).
Along the duodenum-ileum axis, the levels vary in different segments of the intestine with peak expression in the proximal jejunum (PubMed:14976318).
Protein expression is confined to the enterocyte (PubMed:14976318).
Discrete localization to the epithelial layer bordering the luminal space along the crypt-villus axis (PubMed:14976318).
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 (PubMed:14976318).
Expression in other tissues including gall bladder, liver, testis and stomach is also observed (PubMed:14976318).
Along the duodenum-ileum axis, the levels vary in different segments of the intestine with peak expression in the proximal jejunum (PubMed:14976318).
Protein expression is confined to the enterocyte (PubMed:14976318).
Discrete localization to the epithelial layer bordering the luminal space along the crypt-villus axis (PubMed:14976318).
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 (PubMed:14976318).
Gene expression databases
Interaction
Subunit
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).
Interacts with LIMA1 (By similarity).
Interacts with NPC2 (By similarity).
Interacts with LIMA1 (By similarity).
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 632-797 | SSD | ||||
Sequence: DLPVFAVSYIIVFLYISLALGSYSRCSRVAVESKATLGLGGVIVVLGAVLAAMGFYSYLGVPSSLVIIQVVPFLVLAVGADNIFIFVLEYQRLPRMPGEQREAHIGRTLGSVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAIILDFLLQMTAFVALLSL |
Sequence similarities
Belongs to the patched family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length1,331
- Mass (Da)146,415
- Last updated2004-07-05 v1
- Checksum2E10EF2E3A337F70
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY437867 EMBL· GenBank· DDBJ | AAR97888.1 EMBL· GenBank· DDBJ | mRNA |