Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001992
UniProt IDO15118
Primary gene name(s)NPC1
Synonym gene name(s)unknown
Protein nameNiemann-Pick C1 protein
Protein functionIntracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo', TTD to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome, LE to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals. {ECO:0000269|PubMed:18772377, ECO:0000269|PubMed:19563754}.; FUNCTION:, Microbial infection Acts as an endosomal entry receptor for ebolavirus. {ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:25855742}.
Subcellular locationLate endosome membrane {ECO:0000269|PubMed:17897319};
Multi-pass membrane protein {ECO:0000269|PubMed:17897319}. Lysosome membrane {ECO:0000269|PubMed:17897319};
Multi-pass membrane protein {ECO:0000269|PubMed:17897319}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O15118
Gene Ontology
(Biological Process)
Complete annatation
adult walking behavior [GO:0007628];
autophagy [GO:0006914];
bile acid metabolic process [GO:0008206];
cellular response to low-density lipoprotein particle stimulus [GO:0071404];
cellular response to steroid hormone stimulus [GO:0071383];
cholesterol efflux [GO:0033344];
cholesterol homeostasis [GO:0042632];
cholesterol metabolic process [GO:0008203];
cholesterol transport [GO:0030301];
endocytosis [GO:0006897];
establishment of protein localization to membrane [GO:0090150];
lysosomal transport [GO:0007041];
membrane raft organization [GO:0031579];
negative regulation of cell death [GO:0060548];
negative regulation of macroautophagy [GO:0016242];
positive regulation of cholesterol homeostasis [GO:2000189];
protein glycosylation [GO:0006486];
response to cadmium ion [GO:0046686];
response to drug [GO:0042493];
viral entry into host cell [GO:0046718]
Gene Ontology
(Molecular Function)
Complete annatation
cholesterol binding [GO:0015485];
hedgehog receptor activity [GO:0008158];
receptor activity [GO:0004872];
sterol transporter activity [GO:0015248];
transmembrane signaling receptor activity [GO:0004888];
virus receptor activity [GO:0001618]
Gene Ontology
(Cellular Component)
Complete annatation
endoplasmic reticulum [GO:0005783];
extracellular exosome [GO:0070062];
extracellular region [GO:0005576];
Golgi apparatus [GO:0005794];
integral component of membrane [GO:0016021];
integral component of plasma membrane [GO:0005887];
late endosome membrane [GO:0031902];
lysosomal membrane [GO:0005765];
lysosome [GO:0005764];
membrane [GO:0016020];
membrane raft [GO:0045121];
nuclear envelope [GO:0005635];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction110925
Phylogenetic treeO15118
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.7072227180978570.03219079607988380.0690772767778917
AZA vs. DISU0.7710053911878660.002598009280769250.130107614280119
AZA vs. IL7-0.3548589034598730.06848435377637150.744779700195706
AZA vs. SAHA0.164713183180020.5020400294453910.821867007369659
DISU vs. CD31.464138695157927.86818711970838e-050.000458820319700132
DISU vs. IL7-1.135014580236619.40727924370055e-060.000839140441412934
DISU vs. SAHA-0.603965584089810.04036834051791070.246912037315516
DMSO vs. AZA0.06932288246251080.6829863189715261
DMSO vs. CD30.7632731281330590.01794346176082850.0408334437674549
DMSO vs. DISU-0.7040586484678910.004264583649849160.141438899965727
DMSO vs. IL7-0.416674302650610.02221243448467030.304411987392303
DMSO vs. SAHA0.08981711126307140.7048180539805180.911473561999346
HIV vs. Mock in Activation0.1537425580295450.8055268558569450.999983755607037
HIV vs. Mock in Latency0.07395540897230390.6585742255531870.999834320637052
IL7 vs. CD30.3588087501665370.2664214741280890.400535695145889
SAHA vs. CD30.8476017911516280.0175914300613970.0413319069262944
SAHA vs. IL70.5163070750871920.03584102787002560.146652457685333
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.0639008 0.742886
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.106 1.275 1.401 1.597 1.298
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3GKH X-ray 1.8Å A=23-252.
3GKI X-ray 1.8Å A=23-252.
3GKJ X-ray 1.6Å A=23-252.
3JD8 EM 4.4Å A=1-1267.
5F18 X-ray 2.0Å A=374-620.
5F1B X-ray 2.3Å C=374-620.
5HNS X-ray 2.4Å A/B=387-618.
5I31 X-ray 3.3Å A=341-1246.
5JNX EM 6.5Å A=1-1278.
5KWY X-ray 2.4Å A/B=374-620.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Pr55(Gag) interacts with 19474101

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04142 Lysosome - Homo sapiens (human)