Q6T3U4 · NPCL1_MOUSE
- ProteinNPC1-like intracellular cholesterol transporter 1
- GeneNpc1l1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1333 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a major role in cholesterol homeostasis (PubMed:14976318, PubMed:15173162, PubMed:15671032).
Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:15173162, PubMed:15671032).
Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (PubMed:15173162).
May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (PubMed:15671032).
May be involved in caveolin trafficking from the plasma membrane (PubMed:15671032).
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:15173162, PubMed:15671032).
Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (PubMed:15173162).
May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (PubMed:15671032).
May be involved in caveolin trafficking from the plasma membrane (PubMed:15671032).
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 | protein homodimerization activity | |
Biological Process | cholesterol homeostasis | |
Biological Process | cholesterol import | |
Biological Process | cholesterol metabolic process | |
Biological Process | cholesterol transport | |
Biological Process | intestinal cholesterol absorption | |
Biological Process | vitamin transport |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNPC1-like intracellular cholesterol transporter 1
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ6T3U4
- Secondary accessions
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 | 21-284 | Extracellular | ||||
Sequence: ELYTPTHKAGFCTFYEECGKNPELSGGLTSLSNISCLSNTPARHVTGDHLALLQRVCPRLYNGPNDTYACCSTKQLVSLDSSLSITKALLTRCPACSENFVSIHCHNTCSPDQSLFINVTRVVQRDPGQLPAVVAYEAFYQRSFAEKAYESCSRVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALADGMKPLDGKITPCNESQGEDSAACSCQDCAASCPVIPPPPALRPSFYMGRMPGW | ||||||
Transmembrane | 285-305 | Helical; Name=1 | ||||
Sequence: LALIIIFTAVFVLLSVVLVYL | ||||||
Topological domain | 306-352 | Cytoplasmic | ||||
Sequence: RVASNRNKNKTAGSQEAPNLPRKRRFSPHTVLGRFFESWGTRVASWP | ||||||
Transmembrane | 353-373 | Helical; Name=2 | ||||
Sequence: LTVLALSFIVVIALSVGLTFI | ||||||
Topological domain | 374-632 | Extracellular | ||||
Sequence: ELTTDPVELWSAPKSQARKEKAFHDEHFGPFFRTNQIFVTAKNRSSYKYDSLLLGPKNFSGILSLDLLQELLELQERLRHLQVWSHEAQRNISLQDICYAPLNPHNTSLTDCCVNSLLQYFQNNHTLLLLTANQTLNGQTSLVDWKDHFLYCANAPLTYKDGTALALSCIADYGAPVFPFLAVGGYQGTDYSEAEALIITFSINNYPADDPRMAHAKLWEEAFLKEMQSFQRSTADKFQIAFSAERSLEDEINRTTIQD | ||||||
Transmembrane | 633-653 | Helical; Name=3 | ||||
Sequence: LPVFAISYLIVFLYISLALGS | ||||||
Topological domain | 654-665 | Cytoplasmic | ||||
Sequence: YSRWSRVAVDSK | ||||||
Transmembrane | 666-686 | Helical; Name=4 | ||||
Sequence: ATLGLGGVAVVLGAVVAAMGF | ||||||
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: TSMPAVRTFALTS | ||||||
Transmembrane | 777-797 | Helical; Name=7 | ||||
Sequence: GLAIIFDFLLQMTAFVALLSL | ||||||
Topological domain | 798-846 | Cytoplasmic | ||||
Sequence: DSKRQEASRPDVVCCFSSRNLPPPKQKEGLLLCFFRKIYTPFLLHRFIR | ||||||
Transmembrane | 847-867 | Helical; Name=8 | ||||
Sequence: PVVLLLFLVLFGANLYLMCNI | ||||||
Topological domain | 868-1113 | Extracellular | ||||
Sequence: SVGLDQDLALPKDSYLIDYFLFLNRYLEVGPPVYFDTTSGYNFSTEAGMNAICSSAGCESFSLTQKIQYASEFPNQSYVAIAASSWVDDFIDWLTPSSSCCRIYTRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTTEQFHKYLPWFLNDTPNIRCPKGGLAAYRTSVNLSSDGQIIASQFMAYHKPLRNSQDFTEALRASRLLAANITAELRKVPGTDPNFEVFPYTISNVFYQQYLTVLPEG | ||||||
Transmembrane | 1114-1134 | Helical; Name=9 | ||||
Sequence: IFTLALCFVPTFVVCYLLLGL | ||||||
Topological domain | 1135-1142 | Cytoplasmic | ||||
Sequence: DIRSGILN | ||||||
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: IFMGSAVFAGVAMTNFPGILI | ||||||
Topological domain | 1228-1242 | Extracellular | ||||
Sequence: LGFAQAQLIQIFFFR | ||||||
Transmembrane | 1243-1263 | Helical; Name=13 | ||||
Sequence: LNLLITLLGLLHGLVFLPVVL | ||||||
Topological domain | 1264-1333 | Cytoplasmic | ||||
Sequence: SYLGPDVNQALVLEEKLATEAAMVSEPSCPQYPFPADANTSDYVNYGFNPEFIPEINAASSSLPKSDQKF |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
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.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MAAAWQGWLLWALLLNSAQG | ||||||
Chain | PRO_0000023267 | 21-1333 | NPC1-like intracellular cholesterol transporter 1 | |||
Sequence: ELYTPTHKAGFCTFYEECGKNPELSGGLTSLSNISCLSNTPARHVTGDHLALLQRVCPRLYNGPNDTYACCSTKQLVSLDSSLSITKALLTRCPACSENFVSIHCHNTCSPDQSLFINVTRVVQRDPGQLPAVVAYEAFYQRSFAEKAYESCSRVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALADGMKPLDGKITPCNESQGEDSAACSCQDCAASCPVIPPPPALRPSFYMGRMPGWLALIIIFTAVFVLLSVVLVYLRVASNRNKNKTAGSQEAPNLPRKRRFSPHTVLGRFFESWGTRVASWPLTVLALSFIVVIALSVGLTFIELTTDPVELWSAPKSQARKEKAFHDEHFGPFFRTNQIFVTAKNRSSYKYDSLLLGPKNFSGILSLDLLQELLELQERLRHLQVWSHEAQRNISLQDICYAPLNPHNTSLTDCCVNSLLQYFQNNHTLLLLTANQTLNGQTSLVDWKDHFLYCANAPLTYKDGTALALSCIADYGAPVFPFLAVGGYQGTDYSEAEALIITFSINNYPADDPRMAHAKLWEEAFLKEMQSFQRSTADKFQIAFSAERSLEDEINRTTIQDLPVFAISYLIVFLYISLALGSYSRWSRVAVDSKATLGLGGVAVVLGAVVAAMGFYSYLGVPSSLVIIQVVPFLVLAVGADNIFIFVLEYQRLPRMPGEQREAHIGRTLGSVAPSMLLCSLSEAICFFLGALTSMPAVRTFALTSGLAIIFDFLLQMTAFVALLSLDSKRQEASRPDVVCCFSSRNLPPPKQKEGLLLCFFRKIYTPFLLHRFIRPVVLLLFLVLFGANLYLMCNISVGLDQDLALPKDSYLIDYFLFLNRYLEVGPPVYFDTTSGYNFSTEAGMNAICSSAGCESFSLTQKIQYASEFPNQSYVAIAASSWVDDFIDWLTPSSSCCRIYTRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTTEQFHKYLPWFLNDTPNIRCPKGGLAAYRTSVNLSSDGQIIASQFMAYHKPLRNSQDFTEALRASRLLAANITAELRKVPGTDPNFEVFPYTISNVFYQQYLTVLPEGIFTLALCFVPTFVVCYLLLGLDIRSGILNLLSIIMILVDTIGLMAVWGISYNAVSLINLVTAVGMSVEFVSHITRSFAVSTKPTRLERAKDATIFMGSAVFAGVAMTNFPGILILGFAQAQLIQIFFFRLNLLITLLGLLHGLVFLPVVLSYLGPDVNQALVLEEKLATEAAMVSEPSCPQYPFPADANTSDYVNYGFNPEFIPEINAASSSLPKSDQKF | ||||||
Disulfide bond | 32↔90 | |||||
Sequence: CTFYEECGKNPELSGGLTSLSNISCLSNTPARHVTGDHLALLQRVCPRLYNGPNDTYAC | ||||||
Disulfide bond | 38↔56 | |||||
Sequence: CGKNPELSGGLTSLSNISC | ||||||
Disulfide bond | 77↔125 | |||||
Sequence: CPRLYNGPNDTYACCSTKQLVSLDSSLSITKALLTRCPACSENFVSIHC | ||||||
Disulfide bond | 91↔129 | |||||
Sequence: CSTKQLVSLDSSLSITKALLTRCPACSENFVSIHCHNTC | ||||||
Disulfide bond | 113↔254 | |||||
Sequence: CPACSENFVSIHCHNTCSPDQSLFINVTRVVQRDPGQLPAVVAYEAFYQRSFAEKAYESCSRVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALADGMKPLDGKITPCNESQGEDSAAC | ||||||
Disulfide bond | 116↔172 | |||||
Sequence: CSENFVSIHCHNTCSPDQSLFINVTRVVQRDPGQLPAVVAYEAFYQRSFAEKAYESC | ||||||
Disulfide bond | 189↔197 | |||||
Sequence: CGVYGSALC | ||||||
Disulfide bond | 243↔259 | |||||
Sequence: CNESQGEDSAACSCQDC | ||||||
Disulfide bond | 256↔263 | |||||
Sequence: CQDCAASC | ||||||
Disulfide bond | 471↔485 | |||||
Sequence: CYAPLNPHNTSLTDC | ||||||
Disulfide bond | 525↔542 | |||||
Sequence: CANAPLTYKDGTALALSC | ||||||
Disulfide bond | 920↔925 | |||||
Sequence: CSSAGC | ||||||
Disulfide bond | 967↔1025 | |||||
Sequence: CCRIYTRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTTEQFHKYLPWFLNDTPNIRC | ||||||
Disulfide bond | 981↔990 | |||||
Sequence: CPSTDTSFNC |
Post-translational modification
Highly glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Induction
Cholesterol/cholate feeding resulted in down-regulation of intestinal expression. Expression is decreased by 35% in the jejunum upon PPARD activation.
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 (PubMed:29880681).
Interacts with NPC2 (By similarity).
Interacts with LIMA1 (PubMed:29880681).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 632-797 | SSD | ||||
Sequence: DLPVFAISYLIVFLYISLALGSYSRWSRVAVDSKATLGLGGVAVVLGAVVAAMGFYSYLGVPSSLVIIQVVPFLVLAVGADNIFIFVLEYQRLPRMPGEQREAHIGRTLGSVAPSMLLCSLSEAICFFLGALTSMPAVRTFALTSGLAIIFDFLLQMTAFVALLSL |
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.
- Length1,333
- Mass (Da)147,132
- Last updated2004-07-05 v1
- Checksum7771520D9B352735
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Z4YJC9 | Z4YJC9_MOUSE | Npc1l1 | 1333 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 476 | in Ref. 2; CAI24395 | ||||
Sequence: N → K |
Keywords
- Technical term