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NPC1 NPC intracellular cholesterol transporter 1 [ Homo sapiens (human) ]

Gene ID: 4864, updated on 12-Aug-2018

Summary

Official Symbol
NPC1provided by HGNC
Official Full Name
NPC intracellular cholesterol transporter 1provided by HGNC
Primary source
HGNC:HGNC:7897
See related
Ensembl:ENSG00000141458 MIM:607623; Vega:OTTHUMG00000131873
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
NPC; POGZ; SLC65A1
Summary
This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
Expression
Ubiquitous expression in adrenal (RPKM 13.9), brain (RPKM 10.0) and 24 other tissues See more
Orthologs

Genomic context

See NPC1 in Genome Data Viewer
Location:
18q11.2
Exon count:
28
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 18 NC_000018.10 (23506184..23586617, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (21086148..21166581, complement)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene Cdk5 and Abl enzyme substrate 1 Neighboring gene transmembrane protein 241 Neighboring gene RIO kinase 3 Neighboring gene regulator of MON1-CCZ1 Neighboring gene ankyrin repeat domain 29 Neighboring gene ribosomal protein S10 pseudogene 27

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Niemann-Pick disease type C1
MedGen: C3179455 OMIM: 257220 GeneReviews: Niemann-Pick Disease Type C
Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag NPC2-deficient cells exhibit Gag accumulation in late endosomal/lysosomal (LE/L) compartments of these cells as well as decreased NPC1 expression after HIV infection PubMed
gag Niemann-Pick type C-1 (NPC1)-deficient (NPCD) cells exhibit few HIV-1 budding events. HIV-1 Gag accumulates in late endosomal/lysosomal (LE/L) compartments in NPCD cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Irinotecan Pathway, organism-specific biosystem (from WikiPathways)
    Irinotecan Pathway, organism-specific biosystemThis pathway shows the biotransformation of the chemotherapy prodrug irinotecan to form the active metabolite SN-38, an inhibitor of DNA topoisomerase I. SN-38 is primarily metabolized to the inactiv...
  • LDL-mediated lipid transport, organism-specific biosystem (from REACTOME)
    LDL-mediated lipid transport, organism-specific biosystemLDL (low density lipoproteins) are complexes of a single molecule of apoprotein B-100 (apoB-100) non-covalently associated with triacylglycerol, free cholesterol, cholesterol esters, and phospholipid...
  • Lipid digestion, mobilization, and transport, organism-specific biosystem (from REACTOME)
    Lipid digestion, mobilization, and transport, organism-specific biosystemProcesses annotated here include the digestion of dietary lipids, sterol uptake, the formation and turnover of lipoproteins (chylomicrons, VLDL, LDL, and HDL), and the mobilization of fatty acids thr...
  • Lipoprotein metabolism, organism-specific biosystem (from REACTOME)
    Lipoprotein metabolism, organism-specific biosystemBecause of their hydrophobicity, lipids are found in the extracellular spaces of the human body primarily in the form of lipoprotein complexes. Chylomicrons form in the small intestine and transport ...
  • Lysosome, organism-specific biosystem (from KEGG)
    Lysosome, organism-specific biosystemLysosomes are membrane-delimited organelles in animal cells serving as the cell's main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than...
  • Lysosome, conserved biosystem (from KEGG)
    Lysosome, conserved biosystemLysosomes are membrane-delimited organelles in animal cells serving as the cell's main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than...
  • Metabolism, organism-specific biosystem (from REACTOME)
    Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
  • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
    Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • FLJ98532

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cholesterol binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
signaling receptor activity TAS
Traceable Author Statement
more info
PubMed 
sterol transporter activity TAS
Traceable Author Statement
more info
PubMed 
transmembrane signaling receptor activity TAS
Traceable Author Statement
more info
PubMed 
virus receptor activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
adult walking behavior IEA
Inferred from Electronic Annotation
more info
 
autophagy IGI
Inferred from Genetic Interaction
more info
PubMed 
bile acid metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to low-density lipoprotein particle stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to steroid hormone stimulus IEA
Inferred from Electronic Annotation
more info
 
cholesterol efflux IDA
Inferred from Direct Assay
more info
PubMed 
cholesterol homeostasis IDA
Inferred from Direct Assay
more info
PubMed 
cholesterol homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
cholesterol homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
 
cholesterol metabolic process IEA
Inferred from Electronic Annotation
more info
 
cholesterol transport IDA
Inferred from Direct Assay
more info
PubMed 
endocytosis IEA
Inferred from Electronic Annotation
more info
 
establishment of protein localization to membrane IDA
Inferred from Direct Assay
more info
PubMed 
intracellular cholesterol transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
low-density lipoprotein particle clearance TAS
Traceable Author Statement
more info
 
lysosomal transport ISS
Inferred from Sequence or Structural Similarity
more info
 
membrane raft organization IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell death IEA
Inferred from Electronic Annotation
more info
 
negative regulation of macroautophagy IEA
Inferred from Electronic Annotation
more info
 
protein glycosylation IDA
Inferred from Direct Assay
more info
PubMed 
response to cadmium ion IEA
Inferred from Electronic Annotation
more info
 
response to drug IEA
Inferred from Electronic Annotation
more info
 
viral entry into host cell IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
extracellular region ISS
Inferred from Sequence or Structural Similarity
more info
 
integral component of lysosomal membrane IDA
Inferred from Direct Assay
more info
PubMed 
integral component of membrane TAS
Traceable Author Statement
more info
PubMed 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
late endosome membrane IEA
Inferred from Electronic Annotation
more info
 
lysosomal membrane HDA PubMed 
lysosomal membrane TAS
Traceable Author Statement
more info
 
lysosome ISS
Inferred from Sequence or Structural Similarity
more info
 
membrane HDA PubMed 
membrane raft IEA
Inferred from Electronic Annotation
more info
 
nuclear envelope IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
NPC intracellular cholesterol transporter 1
Names
Niemann-Pick C1 protein
truncated Niemann-Pick C1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012795.1 RefSeqGene

    Range
    5001..60119
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000271.4NP_000262.2  NPC intracellular cholesterol transporter 1 precursor

    See identical proteins and their annotated locations for NP_000262.2

    Status: REVIEWED

    Source sequence(s)
    AB209048, AF002020, BC063302, DR159421
    Consensus CDS
    CCDS11878.1
    UniProtKB/Swiss-Prot
    O15118
    Related
    ENSP00000269228.4, OTTHUMP00000162699, ENST00000269228.9, OTTHUMT00000254823
    Conserved Domains (3) summary
    TIGR00917
    Location:251252
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:649802
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:23267
    NPC1_N; Niemann-Pick C1 N terminus

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p12 Primary Assembly

    Range
    23506184..23586617 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005258277.1XP_005258334.1  NPC intracellular cholesterol transporter 1 isoform X1

    Conserved Domains (3) summary
    TIGR00917
    Location:251268
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:666819
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:23267
    NPC1_N; Niemann-Pick C1 N terminus
  2. XM_005258279.2XP_005258336.1  NPC intracellular cholesterol transporter 1 isoform X3

    Conserved Domains (3) summary
    TIGR00917
    Location:251251
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:649802
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:23267
    NPC1_N; Niemann-Pick C1 N terminus
  3. XM_017025787.1XP_016881276.1  NPC intracellular cholesterol transporter 1 isoform X8

  4. XM_006722479.3XP_006722542.1  NPC intracellular cholesterol transporter 1 isoform X5

    Conserved Domains (3) summary
    TIGR00917
    Location:251269
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:666819
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:23267
    NPC1_N; Niemann-Pick C1 N terminus
  5. XM_017025785.1XP_016881274.1  NPC intracellular cholesterol transporter 1 isoform X6

  6. XM_017025784.1XP_016881273.1  NPC intracellular cholesterol transporter 1 isoform X4

  7. XM_017025786.1XP_016881275.1  NPC intracellular cholesterol transporter 1 isoform X7

  8. XM_005258278.5XP_005258335.1  NPC intracellular cholesterol transporter 1 isoform X2

    Conserved Domains (3) summary
    TIGR00917
    Location:251269
    2A060601; Niemann-Pick C type protein family
    pfam12349
    Location:666819
    Sterol-sensing; Sterol-sensing domain of SREBP cleavage-activation
    pfam16414
    Location:23267
    NPC1_N; Niemann-Pick C1 N terminus
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