Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001343
UniProt IDP04035
Primary gene name(s)HMGCR
Synonym gene name(s)unknown
Protein name3-hydroxy-3-methylglutaryl-coenzyme A reductase
Protein functionTransmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
Subcellular locationEndoplasmic reticulum membrane;
Multi-pass membrane protein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P04035
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
cholesterol biosynthetic process [GO:0006695];
coenzyme A metabolic process [GO:0015936];
isoprenoid biosynthetic process [GO:0008299];
myoblast differentiation [GO:0045445];
negative regulation of insulin secretion involved in cellular response to glucose stimulus [GO:0061179];
negative regulation of MAP kinase activity [GO:0043407];
negative regulation of striated muscle cell apoptotic process [GO:0010664];
negative regulation of vasodilation [GO:0045908];
negative regulation of wound healing [GO:0061045];
positive regulation of cardiac muscle cell apoptotic process [GO:0010666];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of skeletal muscle tissue development [GO:0048643];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of stress-activated MAPK cascade [GO:0032874];
protein tetramerization [GO:0051262];
response to ethanol [GO:0045471];
response to nutrient [GO:0007584];
ubiquinone metabolic process [GO:0006743];
visual learning [GO:0008542]
Gene Ontology
(Molecular Function)
Complete annatation
coenzyme binding [GO:0050662];
hydroxymethylglutaryl-CoA reductase, NADPH activity [GO:0004420];
hydroxymethylglutaryl-CoA reductase activity [GO:0042282];
NADPH binding [GO:0070402]
Gene Ontology
(Cellular Component)
Complete annatation
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
integral component of membrane [GO:0016021];
peroxisomal membrane [GO:0005778]
Protein-protein interaction109399
Phylogenetic treeP04035
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD30.6291350645257860.2859135248105570.402661992706476
AZA vs. DISU0.0005979216716072950.9981164551934720.999458001306287
AZA vs. IL70.1487942625252690.5625313243265010.999311006273513
AZA vs. SAHA-0.426712640518480.08091978424736480.354009323573951
DISU vs. CD3-0.6406067975907720.2745925614511910.40351383165006
DISU vs. IL70.138909667509850.5826215915120550.868574020178424
DISU vs. SAHA-0.4262372341257270.144000651442820.487629464528577
DMSO vs. AZA-0.02348483647555990.9082646789559761
DMSO vs. CD3-0.6628699439432390.2612851309705310.368532508614518
DMSO vs. DISU-0.0256606680320930.9162863966642770.988576460318632
DMSO vs. IL70.1794516216584840.4770558437307270.88048675007664
DMSO vs. SAHA-0.4099811469238770.08259520496419070.334891669092095
HIV vs. Mock in Activation0.1541476605306050.9020178408273320.999983755607037
HIV vs. Mock in Latency0.02644609755868720.8733635362777270.999834320637052
IL7 vs. CD3-0.4731384633535450.4280048221554560.564123529586323
SAHA vs. CD3-1.07970166408640.06386821589501770.121327872625478
SAHA vs. IL7-0.5786323859077310.01806968545961310.0940871981410043
(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 0.142141 0.384488
(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
1.048 1.009 0.887 0.636 0.64
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00227 Lovastatin approved, investigational yes inhibitor
DB00439 Cerivastatin withdrawn yes inhibitor
DB00641 Simvastatin approved yes inhibitor
DB01076 Atorvastatin approved yes inhibitor
DB01098 Rosuvastatin approved yes inhibitor
DB00157 NADH nutraceutical unknown unknown
DB01992 Coenzyme A nutraceutical unknown unknown
DB03169 (S)-Hmg-Coa experimental unknown unknown
DB03461 2&,39;-Monophosphoadenosine 5&,39;-Diphosphoribose experimental unknown unknown
DB04377 3-Hydroxy-3-Methyl-Glutaric Acid experimental unknown unknown
DB04447 1,4-Dithiothreitol experimental unknown unknown
DB01095 Fluvastatin approved yes inhibitor
DB00175 Pravastatin approved yes inhibitor
DB05317 TAK-475 investigational unknown unknown
DB05342 SP-01A investigational unknown unknown
DB06693 Mevastatin experimental yes inhibitor
DB06846 7-[3-(4-FLUORO-PHENYL)-1-ISOPROPYL-1H-INDOL-2-YL]-3,5-DIHYDROXY-HEPTANOIC ACID experimental unknown unknown
DB08860 Pitavastatin approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1DQ8 X-ray 2.1Å A/B/C/D=426-888.
1DQ9 X-ray 2.8Å A/B/C/D=426-888.
1DQA X-ray 2.0Å A/B/C/D=426-888.
1HW8 X-ray 2.1Å A/B/C/D=426-888.
1HW9 X-ray 2.3Å A/B/C/D=426-888.
1HWI X-ray 2.3Å A/B/C/D=426-888.
1HWJ X-ray 2.2Å A/B/C/D=426-888.
1HWK X-ray 2.2Å A/B/C/D=426-888.
1HWL X-ray 2.1Å A/B/C/D=426-888.
2Q1L X-ray 2.0Å A/B/C/D=441-875.
2Q6B X-ray 2.0Å A/B/C/D=441-875.
2Q6C X-ray 2.0Å A/B/C/D=441-875.
2R4F X-ray 1.7Å A/B/C/D=441-875.
3BGL X-ray 2.2Å A/B/C/D=441-875.
3CCT X-ray 2.1Å A/B/C/D=441-875.
3CCW X-ray 2.1Å A/B/C/D=441-875.
3CCZ X-ray 1.7Å A/B/C/D=441-875.
3CD0 X-ray 2.4Å A/B/C/D=441-875.
3CD5 X-ray 2.3Å A/B/C/D=441-875.
3CD7 X-ray 2.0Å A/B/C/D=441-875.
3CDA X-ray 2.0Å A/B/C/D=441-875.
3CDB X-ray 2.3Å A/B/C/D=441-875.

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

HIV Partner Interaction Type PubMed
Nef modulates 16014965
16515720

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00900 Terpenoid backbone biosynthesis - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04976 Bile secretion - Homo sapiens (human)
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