Q6T3U3 · NPCL1_RAT

  • Protein
    NPC1-like intracellular cholesterol transporter 1
  • Gene
    Npc1l1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbrush border membrane
Cellular Componentplasma membrane
Molecular Functioncholesterol binding
Molecular Functionheterocyclic compound binding
Molecular Functionlipid transporter activity
Molecular Functionmyosin V binding
Molecular Functionprotein homodimerization activity
Molecular Functionsmall GTPase binding
Molecular Functionvitamin E binding
Biological Processcellular response to sterol depletion
Biological Processcholesterol biosynthetic process
Biological Processcholesterol homeostasis
Biological Processcholesterol import
Biological Processcholesterol transport
Biological Processintestinal cholesterol absorption
Biological Processlipoprotein metabolic process
Biological Processresponse to muscle activity
Biological Processresponse to xenobiotic stimulus
Biological Processvitamin E metabolic process
Biological Processvitamin transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    NPC1-like intracellular cholesterol transporter 1
  • Short names
    Npc1l1
  • Alternative names
    • Niemann-Pick C1-like protein 1

Gene names

    • Name
      Npc1l1

Organism names

  • Taxonomic identifier
  • Strain
    • Sprague-Dawley
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q6T3U3

Proteomes

Organism-specific databases

Subcellular Location

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.

TypeIDPosition(s)Description
Topological domain21-282Extracellular
Transmembrane283-303Helical; Name=1
Topological domain304-352Cytoplasmic
Transmembrane353-373Helical; Name=2
Topological domain374-632Extracellular
Transmembrane633-653Helical; Name=3
Topological domain654-665Cytoplasmic
Transmembrane666-686Helical; Name=4
Topological domain687-696Extracellular
Transmembrane697-717Helical; Name=5
Topological domain718-742Cytoplasmic
Transmembrane743-763Helical; Name=6
Topological domain764-776Extracellular
Transmembrane777-797Helical; Name=7
Topological domain798-846Cytoplasmic
Transmembrane847-867Helical; Name=8
Topological domain868-1113Extracellular
Transmembrane1114-1134Helical; Name=9
Topological domain1135-1142Cytoplasmic
Transmembrane1143-1163Helical; Name=10
Topological domain1164-1165Extracellular
Transmembrane1166-1186Helical; Name=11
Topological domain1187-1206Cytoplasmic
Transmembrane1207-1227Helical; Name=12
Topological domain1228-1242Extracellular
Transmembrane1243-1263Helical; Name=13
Topological domain1264-1331Cytoplasmic

Keywords

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.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for signal, chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
Signal1-20
ChainPRO_000002326821-1331NPC1-like intracellular cholesterol transporter 1
Disulfide bond32↔90
Disulfide bond38↔56
Glycosylation53N-linked (GlcNAc...) asparagine
Disulfide bond77↔125
Glycosylation85N-linked (GlcNAc...) asparagine
Disulfide bond91↔129
Disulfide bond113↔254
Disulfide bond116↔172
Glycosylation138N-linked (GlcNAc...) asparagine
Disulfide bond189↔197
Disulfide bond243↔259
Glycosylation244N-linked (GlcNAc...) asparagine
Disulfide bond256↔263
Glycosylation416N-linked (GlcNAc...) asparagine
Glycosylation431N-linked (GlcNAc...) asparagine
Glycosylation464N-linked (GlcNAc...) asparagine
Disulfide bond471↔485
Glycosylation479N-linked (GlcNAc...) asparagine
Glycosylation497N-linked (GlcNAc...) asparagine
Glycosylation506N-linked (GlcNAc...) asparagine
Disulfide bond525↔542
Glycosylation606N-linked (GlcNAc...) asparagine
Glycosylation626N-linked (GlcNAc...) asparagine
Glycosylation909N-linked (GlcNAc...) asparagine
Glycosylation917N-linked (GlcNAc...) asparagine
Disulfide bond920↔925
Disulfide bond967↔1025
Disulfide bond981↔990
Glycosylation996N-linked (GlcNAc...) asparagine
Glycosylation1038N-linked (GlcNAc...) asparagine
Glycosylation1076N-linked (GlcNAc...) asparagine

Post-translational modification

Highly glycosylated.

Keywords

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).

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).

Protein-protein interaction databases

Chemistry

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain632-797SSD

Sequence similarities

Belongs to the patched family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    1,331
  • Mass (Da)
    146,415
  • Last updated
    2004-07-05 v1
  • Checksum
    2E10EF2E3A337F70
MAAAWLGWLLWALLLSAAQGELYTPKHEAGVCTFYEECGKNPELSGGLTSLSNVSCLSNTPARHVTGEHLALLQRICPRLYNGPNTTFACCSTKQLLSLESSMSITKALLTRCPACSDNFVSLHCHNTCSPDQSLFINVTRVVERGAGEPPAVVAYEAFYQRSFAEKAYESCSQVRIPAAASLAVGSMCGVYGSALCNAQRWLNFQGDTGNGLAPLDITFHLLEPGQALPDGIQPLNGKIAPCNESQGDDSAVCSCQDCAASCPVIPPPEALRPSFYMGRMPGWLALIIIFTAVFVLLSAVLVRLRVVSNRNKNKAEGPQEAPKLPHKHKLSPHTILGRFFQNWGTRVASWPLTVLALSFIVVIALAAGLTFIELTTDPVELWSAPKSQARKEKSFHDEHFGPFFRTNQIFVTARNRSSYKYDSLLLGSKNFSGILSLDFLLELLELQERLRHLQVWSPEAERNISLQDICYAPLNPYNTSLSDCCVNSLLQYFQNNRTLLMLTANQTLNGQTSLVDWKDHFLYCANAPLTFKDGTSLALSCMADYGAPVFPFLAVGGYQGTDYSEAEALIITFSLNNYPADDPRMAQAKLWEEAFLKEMESFQRNTSDKFQVAFSAERSLEDEINRTTIQDLPVFAVSYIIVFLYISLALGSYSRCSRVAVESKATLGLGGVIVVLGAVLAAMGFYSYLGVPSSLVIIQVVPFLVLAVGADNIFIFVLEYQRLPRMPGEQREAHIGRTLGSVAPSMLLCSLSEAICFFLGALTPMPAVRTFALTSGLAIILDFLLQMTAFVALLSLDSKRQEASRPDVLCCFSTRKLPPPKEKEGLLLRFFRKIYAPFLLHRFIRPVVMLLFLTLFGANLYLMCNINVGLDQELALPKDSYLIDYFLFLNRYLEVGPPVYFVTTSGFNFSSEAGMNATCSSAGCKSFSLTQKIQYASEFPDQSYVAIAASSWVDDFIDWLTPSSSCCRLYIRGPHKDEFCPSTDTSFNCLKNCMNRTLGPVRPTAEQFHKYLPWFLNDPPNIRCPKGGLAAYRTSVNLSSDGQVIASQFMAYHKPLRNSQDFTEALRASRLLAANITADLRKVPGTDPNFEVFPYTISNVFYQQYLTVLPEGIFTLALCFVPTFVVCYLLLGLDMCSGILNLLSIIMILVDTIGLMAVWGISYNAVSLINLVTAVGMSVEFVSHITRSFAVSTKPTRLERAKDATVFMGSAVFAGVAMTNFPGILILGFAQAQLIQIFFFRLNLLITLLGLLHGLVFLPVVLSYLGPDVNQALVQEEKLASEAAVAPEPSCPQYPSPADADANVNYGFAPELAHGANAARSSLPKSDQKF

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY437867
EMBL· GenBank· DDBJ
AAR97888.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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