Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007738
UniProt IDO95071
Primary gene name(s)UBR5
Synonym gene name(s)EDD, EDD1, HYD, KIAA0896
Protein nameE3 ubiquitin-protein ligase UBR5
Protein functionE3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation, By similarity. Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein, TopBP1 in the DNA damage response. Plays an essential role in extraembryonic development. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. {ECO:0000250, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692}.
Subcellular locationNucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O95071
Gene Ontology
(Biological Process)
Complete annatation
cell proliferation [GO:0008283];
cellular response to DNA damage stimulus [GO:0006974];
DNA repair [GO:0006281];
negative regulation of double-strand break repair [GO:2000780];
negative regulation of histone H2A K63-linked ubiquitination [GO:1901315];
positive regulation of canonical Wnt signaling pathway [GO:0090263];
positive regulation of catenin import into nucleus [GO:0035413];
positive regulation of gene expression [GO:0010628];
positive regulation of protein import into nucleus, translocation [GO:0033160];
progesterone receptor signaling pathway [GO:0050847];
protein polyubiquitination [GO:0000209];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
RNA binding [GO:0003723];
ubiquitin-protein transferase activity [GO:0004842];
ubiquitin-ubiquitin ligase activity [GO:0034450];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction119501
Phylogenetic treeO95071
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is also observed
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. CD30.07498224793858610.818606920059710.876655073123486
AZA vs. DISU0.1759222620644890.4873591327556830.931429104131977
AZA vs. IL70.01956229990122190.9187748554208760.999311006273513
AZA vs. SAHA0.3765136194209740.1228259121580.445546604181731
DISU vs. CD30.08795287231456170.8089172521820340.869358238941394
DISU vs. IL7-0.1653714636777710.5120667320954350.83301939459622
DISU vs. SAHA0.2020643159182720.4905143604443390.818755335724514
DMSO vs. AZA0.05454883244054740.7440671712791791
DMSO vs. CD3-0.03134057157278480.9218122408144330.946067003771554
DMSO vs. DISU-0.1230687498939410.6142918276560730.93954565955977
DMSO vs. IL7-0.02782929425746160.8767165530628650.972990683025815
DMSO vs. SAHA0.3149700056174390.1815502803990960.514312833814809
HIV vs. Mock in Activation0.2331013836691540.7097213294324050.999983755607037
HIV vs. Mock in Latency0.1337395557245150.4162380822502440.999834320637052
IL7 vs. CD3-0.04797272643322790.8811228428130340.924441778970163
SAHA vs. CD30.276717883985980.4330599435873390.546761699033672
SAHA vs. IL70.3533468163228890.1469073183083460.361843286957517
(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 0.14415 0.426289
(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
1.022 1.034 0.973 0.909 0.946
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
-1.76 <0.0001 -0.3 0.0758 0.07 0.7486 Cell growth and proliferation at 4 hpi
(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
1I2T X-ray 1.0Å A=2393-2453.
2QHO X-ray 1.8Å B/D/F/H=180-230.
3PT3 X-ray 1.9Å A/B=2687-2799.

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

HIV Partner Interaction Type PubMed
Vpr interacts with 23612978
Vpr complexes with 17360488
HIV-1 virus replication enhanced by expression of human gene 18976975

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)