Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0011707
UniProt IDP40337
Primary gene name(s)VHL
Synonym gene name(s)unknown
Protein nameVon Hippel-Lindau disease tumor suppressor
Protein functionInvolved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor, HIF under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2. {ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355}.
Subcellular locationIsoform 1: Cytoplasm. Membrane;
Peripheral membrane protein. Nucleus. Note=Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.;
SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus and the cytoplasm but not membrane-associated.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P40337
Gene Ontology
(Biological Process)
Complete annatation
cell morphogenesis [GO:0000902];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cell proliferation [GO:0008285];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061428];
positive regulation of cell differentiation [GO:0045597];
positive regulation of transcription, DNA-templated [GO:0045893];
protein stabilization [GO:0050821];
protein ubiquitination [GO:0016567];
proteolysis [GO:0006508];
regulation of transcription, DNA-templated [GO:0006355];
regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061418]
Gene Ontology
(Molecular Function)
Complete annatation
enzyme binding [GO:0019899];
transcription factor binding [GO:0008134];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
membrane [GO:0016020];
mitochondrion [GO:0005739];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
VCB complex [GO:0030891]
Protein-protein interaction113269
Phylogenetic treeP40337
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. CD3-0.6924624234972930.03518371605231550.0742597631060775
AZA vs. DISU-0.04109514169465460.8708330335586310.991631204917382
AZA vs. IL7-0.09659410926856930.6153329415587410.999311006273513
AZA vs. SAHA0.03224459337492880.8950121840854880.976874050805
DISU vs. CD30.6394296537850740.07860815039601410.154208649019979
DISU vs. IL7-0.06471401219708240.7971289566570740.955044588749828
DISU vs. SAHA0.07407281520958990.7995373350919130.947611448346196
DMSO vs. AZA-0.1225164678138510.4646844060681781
DMSO vs. CD30.560068010552210.08062544815467090.143233770807797
DMSO vs. DISU-0.08278155631955980.7342135955407710.967463501141537
DMSO vs. IL70.03287737149938510.8549213959049560.968145026881951
DMSO vs. SAHA0.1472062153279250.5331895049353250.830053079712082
HIV vs. Mock in Activation-0.07243059709341420.9073173842923090.999983755607037
HIV vs. Mock in Latency0.06377124803765090.6989474244811830.999834320637052
IL7 vs. CD30.6038017129851410.06104233338321230.129153718568944
SAHA vs. CD30.6993676583117750.04887888632883010.097087757608471
SAHA vs. IL70.1245272424792450.6101542429555460.803384394115367
(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) unknown
(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 -0.0728833 0.670816
(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
unknown unknown unknown unknown unknown
(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
1LM8 X-ray 1.8Å V=54-213.
1LQB X-ray 2.0Å C=54-213.
1VCB X-ray 2.7Å C/F/I/L=54-213.
3ZRC X-ray 2.9Å C/F/I/L=54-213.
3ZRF X-ray 2.8Å C/F/I/L=54-213.
3ZTC X-ray 2.6Å C/F/I/L=54-213.
3ZTD X-ray 2.7Å C/F/I/L=54-213.
3ZUN X-ray 2.5Å C/F/I/L=54-213.
4AJY X-ray 1.7Å V=54-213.
4AWJ X-ray 2.5Å C/F/I/L=54-213.
4B95 X-ray 2.8Å C/F/I/L=54-213.
4B9K X-ray 2.0Å C/F/I/L=54-213.
4BKS X-ray 2.2Å C/F/I/L=54-213.
4BKT X-ray 2.3Å C/F/I/L=54-213.
4W9C X-ray 2.2Å C/F/I/L=54-213.
4W9D X-ray 2.2Å C/F/I/L=54-213.
4W9E X-ray 2.6Å C/F/I/L=54-213.
4W9F X-ray 2.1Å C/F/I/L=54-213.
4W9G X-ray 2.7Å C/F/I/L=54-213.
4W9H X-ray 2.1Å C/F/I/L=54-213.
4W9I X-ray 2.4Å C/F/I/L=54-213.
4W9J X-ray 2.2Å C/F/I/L=54-213.
4W9K X-ray 2.1Å C/F/I/L=54-213.
4W9L X-ray 2.2Å C/F/I/L=54-213.
4WQO X-ray 3.2Å A=1-213.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)