Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007724
UniProt IDQ05086
Primary gene name(s)UBE3A
Synonym gene name(s)E6AP, EPVE6AP, HPVE6A
Protein nameUbiquitin-protein ligase E3A
Protein functionE3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the RAD23A and RAD23B, MCM7, which is involved in DNA replication, annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component ARNTL/BMAL1, leading to its proteasomal degradation, PubMed:24728990. {ECO:0000269|PubMed:10373495, ECO:0000269|PubMed:19204938, ECO:0000269|PubMed:19233847, ECO:0000269|PubMed:19325566, ECO:0000269|PubMed:19591933, ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:24728990}.
Subcellular locationNucleus {ECO:0000250|UniProtKB:O08759}. Cytoplasm {ECO:0000250|UniProtKB:O08759}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q05086
Gene Ontology
(Biological Process)
Complete annatation
androgen receptor signaling pathway [GO:0030521];
brain development [GO:0007420];
ovarian follicle development [GO:0001541];
positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068];
positive regulation of protein ubiquitination [GO:0031398];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
prostate gland growth [GO:0060736];
protein autoubiquitination [GO:0051865];
protein K48-linked ubiquitination [GO:0070936];
proteolysis [GO:0006508];
regulation of circadian rhythm [GO:0042752];
regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:2000058];
sperm entry [GO:0035037];
ubiquitin-dependent protein catabolic process [GO:0006511];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
metal ion binding [GO:0046872];
transcription coactivator activity [GO:0003713];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleus [GO:0005634];
proteasome complex [GO:0000502]
Protein-protein interaction113185
Phylogenetic treeQ05086
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. CD31.019921806360590.002018518576761270.00666734867169536
AZA vs. DISU-0.02565916315205750.919308965436670.994664322781536
AZA vs. IL70.1181840700860310.5391352683071360.999311006273513
AZA vs. SAHA-0.02246161626246930.9266547435226620.982828593138412
DISU vs. CD3-1.05797307111150.003884776817396410.0131563976062533
DISU vs. IL70.135079459576040.5921369283543020.873687402852218
DISU vs. SAHA0.003599576639701370.9901503522128160.999274089415579
DMSO vs. AZA-0.1568462801786760.3503194546801541
DMSO vs. CD3-1.185513101221510.0002501126869396410.00101479871498672
DMSO vs. DISU-0.1323337269176580.5882332329653390.934701463289767
DMSO vs. IL70.2819434053310770.1176092511467510.608219369138001
DMSO vs. SAHA0.1260066511979420.5931791649776610.861900137233109
HIV vs. Mock in Activation0.02970482902421980.9619369125499820.999983755607037
HIV vs. Mock in Latency0.05349939070333860.7460406588367190.999834320637052
IL7 vs. CD3-0.8930743215140850.005743756053323780.0188410765892049
SAHA vs. CD3-1.068117008229660.002751240450717950.00852234195114481
SAHA vs. IL7-0.1447739944990030.5522390313587070.764833807304406
(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 -0.108292 0.500407
(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
0.978 1.017 1.004 1.03 1.027
(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
1C4Z X-ray 2.6Å A/B/C=518-875.
1D5F X-ray 2.8Å A/B/C=518-875.
1EQX NMR - A=401-418.
2KR1 NMR - A=24-87.
4GIZ X-ray 2.5Å A/B=403-414.

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)
hsa05203 Viral carcinogenesis - Homo sapiens (human)