Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0010636
UniProt IDO00308
Primary gene name(s)WWP2
Synonym gene name(s)unknown
Protein nameNEDD4-like E3 ubiquitin-protein ligase WWP2
Protein functionE3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells, ESCs the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation. {ECO:0000269|PubMed:19274063, ECO:0000269|PubMed:19651900}.
Subcellular locationNucleus {ECO:0000269|PubMed:19274063, ECO:0000269|PubMed:20858735}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O00308
Gene Ontology
(Biological Process)
Complete annatation
cellular protein modification process [GO:0006464];
negative regulation of gene expression [GO:0010629];
negative regulation of protein transport [GO:0051224];
negative regulation of sequence-specific DNA binding transcription factor activity [GO:0043433];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of transporter activity [GO:0032410];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein autoubiquitination [GO:0051865];
protein K63-linked ubiquitination [GO:0070534];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of ion transmembrane transport [GO:0034765];
regulation of membrane potential [GO:0042391];
regulation of potassium ion transmembrane transporter activity [GO:1901016];
viral entry into host cell [GO:0046718]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
RNA polymerase II transcription factor binding [GO:0001085];
transcriptional activator activity, RNA polymerase II transcription factor binding [GO:0001190];
transcription factor binding [GO:0008134];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
extracellular exosome [GO:0070062];
membrane [GO:0016020];
nucleus [GO:0005634];
ubiquitin ligase complex [GO:0000151]
Protein-protein interaction116244
Phylogenetic treeO00308
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. CD3-0.2526707159489330.4406226015846930.561944817319723
AZA vs. DISU0.3379265578813960.1833619002344390.769779115514854
AZA vs. IL70.005302369765690130.9780634274467780.999311006273513
AZA vs. SAHA-0.299095355696370.2223444134317460.591185155897186
DISU vs. CD30.5774755815337630.1126091444639890.204621385600951
DISU vs. IL7-0.3423012914232410.1768087972389760.544847223707598
DISU vs. SAHA-0.634104744636880.03175926384963620.213907417334137
DMSO vs. AZA0.08415923908005420.6168784770108311
DMSO vs. CD30.3245554035291230.310785643304060.422523753846734
DMSO vs. DISU-0.2559255490708550.2966643113644390.806755049278686
DMSO vs. IL7-0.07135048756956170.6922765506193290.936954851917814
DMSO vs. SAHA-0.388167938411070.1009753040304170.375581462692133
HIV vs. Mock in Activation0.2424710682136450.6969251548358790.999983755607037
HIV vs. Mock in Latency0.09655245926739350.5600867560805670.999834320637052
IL7 vs. CD30.2633698947423990.4129636219115210.55021662450918
SAHA vs. CD3-0.06963032151060630.8441784166572380.889758619319106
SAHA vs. IL7-0.3067697973411770.2091385854808950.444084383369349
(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 -0.0995853 0.557486
(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
4Y07 X-ray 2.5Å A=492-865.

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
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
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