Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0011970
UniProt IDP61077
Primary gene name(s)UBE2D3
Synonym gene name(s)UBC5C, UBCH5C
Protein nameUbiquitin-conjugating enzyme E2 D3
Protein functionAccepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11 E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance, DDT pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body, PML-NB formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:11743028, ECO:0000269|PubMed:12646252, ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:15496420, ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:18284575, ECO:0000269|PubMed:18508924, ECO:0000269|PubMed:18515077, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:21532592}.
Subcellular locationCell membrane {ECO:0000269|PubMed:18508924};
Peripheral membrane protein {ECO:0000269|PubMed:18508924}. Endosome membrane {ECO:0000269|PubMed:18508924};
Peripheral membrane protein {ECO:0000269|PubMed:18508924}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P61077
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
BMP signaling pathway [GO:0030509];
cellular protein modification process [GO:0006464];
DNA repair [GO:0006281];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
positive regulation of protein targeting to mitochondrion [GO:1903955];
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 monoubiquitination [GO:0006513];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061418];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
ubiquitin conjugating enzyme activity [GO:0061631];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
endosome membrane [GO:0010008];
extracellular exosome [GO:0070062];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886]
Protein-protein interaction113171
Phylogenetic treeP61077
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. CD30.9334892223792960.004618596733849120.0135853805567084
AZA vs. DISU0.1204547374232460.6331287520262860.960057478314726
AZA vs. IL70.1644293687586050.3908189734073050.999311006273513
AZA vs. SAHA-0.04292855024848790.8599351252681990.967362841663644
DISU vs. CD3-0.825496469930440.02347473068284520.0587218868757399
DISU vs. IL70.03491191984835180.8894910766493620.980137895954287
DISU vs. SAHA-0.1621072987679530.5772731756887630.863360527022461
DMSO vs. AZA-0.06332379496841530.7041858835589241
DMSO vs. CD3-1.007073277674660.001779018997980940.00562926301293486
DMSO vs. DISU-0.185342664765050.4465151831293250.887026602921028
DMSO vs. IL70.2348850835224380.1900584378346530.701025358715273
DMSO vs. SAHA0.01343027669792850.9544464354196730.989345099718124
HIV vs. Mock in Activation-0.1543868107423950.8037895816294570.999983755607037
HIV vs. Mock in Latency0.1193437765943560.4675394765589430.999834320637052
IL7 vs. CD3-0.7611729864268820.01828106558311770.0486752343286227
SAHA vs. CD3-1.000973244283020.004928409648076390.014101221453676
SAHA vs. IL7-0.2107470898732060.3857924599495260.635247228553283
(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 -0.104923 0.514087
(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
1X23 X-ray 1.8Å A/B/C/D=1-147.
2FUH NMR - A=2-147.
3L1Z X-ray 3.1Å A=1-147.
3RPG X-ray 2.6Å A=2-147.
3UGB X-ray 2.3Å A=1-147.
4BVU X-ray 2.7Å B=1-147.
4R8P X-ray 3.2Å L/N=2-147.
4S3O X-ray 2.0Å A/D=2-147.
5IFR X-ray 2.2Å A=2-147.

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)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)