Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004168
UniProt IDP49427
Primary gene name(s)CDC34
Synonym gene name(s)UBCH3, UBE2R1
Protein nameUbiquitin-conjugating enzyme E2 R1
Protein functionAccepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11 E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2 E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10373550, ECO:0000269|PubMed:10871850, ECO:0000269|PubMed:11675391, ECO:0000269|PubMed:12037680, ECO:0000269|PubMed:15652359, ECO:0000269|PubMed:17461777, ECO:0000269|PubMed:17698585, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19126550, ECO:0000269|PubMed:19945379, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421}.
Subcellular locationCytoplasm. Nucleus. Note=The phosphorylation of the C-terminal tail plays an important role in mediating nuclear localization. Colocalizes with beta-tubulin on mitotic spindles in anaphase.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P49427
Gene Ontology
(Biological Process)
Complete annatation
cellular protein modification process [GO:0006464];
cellular response to interferon-beta [GO:0035458];
DNA replication initiation [GO:0006270];
G1/S transition of mitotic cell cycle [GO:0000082];
negative regulation of cAMP-mediated signaling [GO:0043951];
positive regulation of inclusion body assembly [GO:0090261];
positive regulation of neuron apoptotic process [GO:0043525];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein K48-linked ubiquitination [GO:0070936];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
response to growth factor [GO:0070848]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
ubiquitin conjugating enzyme activity [GO:0061631];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction107432
Phylogenetic treeP49427
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. CD30.4359605527096710.1859185469312560.288140291963793
AZA vs. DISU0.0166977286907380.9479686065785640.996442780563503
AZA vs. IL7-0.1917247514059910.3278887654278420.999311006273513
AZA vs. SAHA0.2625997805429170.2885367638418910.660903081317833
DISU vs. CD3-0.4305426851445440.2407340371062470.366362935420451
DISU vs. IL7-0.2184533203842670.404778818819160.765682152318219
DISU vs. SAHA0.2482728193786390.43167321778190.77941141310543
DMSO vs. AZA-0.04942069986521040.7733555303322521
DMSO vs. CD3-0.4965728866396990.1231027761596820.201997965673195
DMSO vs. DISU-0.06801075647834410.7828282292232360.972485484658656
DMSO vs. IL7-0.1347768977668470.4624578931151120.875759470793367
DMSO vs. SAHA0.3068315543946940.1995942893331750.538625360393097
HIV vs. Mock in Activation0.3934744383128070.5323463609020360.999983755607037
HIV vs. Mock in Latency-0.1428483148914680.3980111078864270.999834320637052
IL7 vs. CD3-0.6231432611780080.05498034224664950.118855634233488
SAHA vs. CD3-0.1963731341613860.5795200598851960.68043375944448
SAHA vs. IL70.4524353998727350.08429890671441690.258908255870644
(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 0.302295 0.0371618
(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
0.853 1.066 1.084 1.194 1.157
(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
2OB4 X-ray 2.4Å A=7-184.
3RZ3 X-ray 2.3Å A/B/C/D=7-184.
4MDK X-ray 2.6Å A/B/C/D=7-184.

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

HIV Partner Interaction Type PubMed
Vif cooperates with 22190037

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)