Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002521
UniProt IDP78317
Primary gene name(s)RNF4
Synonym gene name(s)SNURF
Protein nameE3 ubiquitin-protein ligase RNF4
Protein functionE3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:19307308, ECO:0000269|PubMed:20026589, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20943951}.
Subcellular locationCytoplasm. Nucleus. Nucleus, PML body. Nucleus, nucleoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P78317
Gene Ontology
(Biological Process)
Complete annatation
androgen receptor signaling pathway [GO:0030521];
negative regulation of protein sumoylation [GO:0033234];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein autoubiquitination [GO:0051865];
protein K11-linked ubiquitination [GO:0070979];
protein K48-linked ubiquitination [GO:0070936];
protein K63-linked ubiquitination [GO:0070534];
protein K6-linked ubiquitination [GO:0085020];
protein ubiquitination [GO:0016567];
regulation of kinetochore assembly [GO:0090234];
regulation of spindle assembly [GO:0090169];
response to arsenic-containing substance [GO:0046685];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
androgen receptor binding [GO:0050681];
DNA binding [GO:0003677];
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
nucleosome binding [GO:0031491];
SUMO polymer binding [GO:0032184];
transcription coactivator activity [GO:0003713];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PML body [GO:0016605];
SUMO-targeted ubiquitin ligase complex [GO:0033768]
Protein-protein interaction111974
Phylogenetic treeP78317
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. CD30.4987967731060190.1286505760444840.215341065472572
AZA vs. DISU0.06524167726391890.7963056457819950.981946742545343
AZA vs. IL70.03853858094992130.8410495400564470.999311006273513
AZA vs. SAHA-0.007709402608642450.974769136486830.99371873405989
DISU vs. CD3-0.4458627429404590.2190722562807610.341569630862246
DISU vs. IL7-0.0359362260356650.8864407703805570.979411801047119
DISU vs. SAHA-0.07120453242462760.8068089411125570.949717707951327
DMSO vs. AZA0.00791904395158490.9622914108658481
DMSO vs. CD3-0.5037063260037540.115805697098270.192095664697803
DMSO vs. DISU-0.05959108709775480.8068514690109440.978074663187325
DMSO vs. IL70.03810913651957730.8320495060388260.963051812112721
DMSO vs. SAHA-0.02144509907671450.9274866081918560.982957785137714
HIV vs. Mock in Activation-0.03890422920775730.9501017485872250.999983755607037
HIV vs. Mock in Latency0.00252396802938980.987795156254680.999834320637052
IL7 vs. CD3-0.4530910756257910.1588809080673010.271238363993895
SAHA vs. CD3-0.5306610844658810.1344057986862760.220762439913044
SAHA vs. IL7-0.04920073187915360.839805343828540.931578905943881
(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) FALSE
(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 -0.313581 0.0216872
(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
2EA6 NMR - A=122-183.
2XEU X-ray 1.5Å A=130-190.
4PPE X-ray 2.0Å A/B=120-190.

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
not found