Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002460
UniProt IDP62877
Primary gene name(s)RBX1
Synonym gene name(s)RNF75, ROC1
Protein nameE3 ubiquitin-protein ligase RBX1
Protein functionE3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase, CRLs complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair. CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets, PubMed:27565346. The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme, like CDC34, to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. {ECO:0000269|PubMed:10579999, ECO:0000269|PubMed:11027288, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19679664, ECO:0000269|PubMed:27565346}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:11027288}. Nucleus {ECO:0000269|PubMed:11027288}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P62877
Gene Ontology
(Biological Process)
Complete annatation
DNA damage response, detection of DNA damage [GO:0042769];
global genome nucleotide-excision repair [GO:0070911];
MAPK cascade [GO:0000165];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
nucleotide-excision repair, DNA damage recognition [GO:0000715];
nucleotide-excision repair, DNA duplex unwinding [GO:0000717];
nucleotide-excision repair, DNA incision [GO:0033683];
nucleotide-excision repair, DNA incision, 3'-to lesion [GO:0006295];
nucleotide-excision repair, DNA incision, 5'-to lesion [GO:0006296];
nucleotide-excision repair, preincision complex assembly [GO:0006294];
nucleotide-excision repair, preincision complex stabilization [GO:0006293];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein monoubiquitination [GO:0006513];
protein neddylation [GO:0045116];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of transcription from RNA polymerase II promoter in response to hypoxia [GO:0061418];
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process [GO:0031146];
transcription-coupled nucleotide-excision repair [GO:0006283];
viral process [GO:0016032];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
cullin family protein binding [GO:0097602];
ligase activity [GO:0016874];
NEDD8 transferase activity [GO:0019788];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842];
ubiquitin-ubiquitin ligase activity [GO:0034450];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
Cul2-RING ubiquitin ligase complex [GO:0031462];
Cul3-RING ubiquitin ligase complex [GO:0031463];
Cul4A-RING E3 ubiquitin ligase complex [GO:0031464];
Cul4B-RING E3 ubiquitin ligase complex [GO:0031465];
Cul5-RING ubiquitin ligase complex [GO:0031466];
Cul7-RING ubiquitin ligase complex [GO:0031467];
cullin-RING ubiquitin ligase complex [GO:0031461];
cytosol [GO:0005829];
nuclear SCF ubiquitin ligase complex [GO:0043224];
nucleoplasm [GO:0005654];
SCF ubiquitin ligase complex [GO:0019005];
VCB complex [GO:0030891]
Protein-protein interaction115301
Phylogenetic treeP62877
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. CD30.8967676311193030.006929751407020010.01910466676543
AZA vs. DISU-0.1773254458018820.4861288591654640.931429104131977
AZA vs. IL70.2046119645214690.2910843012152040.999311006273513
AZA vs. SAHA-0.7621920152999010.002168019935421370.0352163065803252
DISU vs. CD3-1.085783519783610.0034751243678750.0119954258578768
DISU vs. IL70.3720365768035540.1424650451700750.491919001767977
DISU vs. SAHA-0.5833333293729840.050253639008670.280508367962839
DMSO vs. AZA-0.0472048173090640.7807732556346031
DMSO vs. CD3-0.9529251553328820.003397524733906750.0098848253316087
DMSO vs. DISU0.1288399669461230.5994135359916430.93753627269269
DMSO vs. IL70.2585787472924760.1540912503867630.658612304956181
DMSO vs. SAHA-0.7217718865232990.002699692255909490.0359744137832113
HIV vs. Mock in Activation-0.04882561989612610.9374908777380120.999983755607037
HIV vs. Mock in Latency-0.02217328018248380.8947502548213340.999834320637052
IL7 vs. CD3-0.6854428848375810.03460695736954760.0816195694619293
SAHA vs. CD3-1.682919394408263.55906001481276e-062.5263793887531e-05
SAHA vs. IL7-0.9692821434515769.55315740156504e-050.00189479335093673
(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) FALSE
(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 0.270388 0.151032
(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
218117_at 1.57 Yes upregulated in CD4+ cells
218117_at 1.63 Yes upregulated in CD8+ cells

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
1LDJ X-ray 3.0Å B=19-108.
1LDK X-ray 3.1Å C=19-108.
1U6G X-ray 3.1Å B=1-108.
2HYE X-ray 3.1Å D=1-108.
2LGV NMR - A=12-108.
3DPL X-ray 2.6Å R=5-108.
3DQV X-ray 3.0Å R/Y=5-108.
3RTR X-ray 3.2Å B/D/F/H=5-108.
4F52 X-ray 3.0Å B/D=5-108.
4P5O X-ray 3.1Å B/D=5-108.

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

HIV Partner Interaction Type PubMed
Vif interacts with 25912140
Vif complexes with 14564014

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03420 Nucleotide excision repair - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04350 TGF-beta signaling pathway - Homo sapiens (human)
hsa04710 Circadian rhythm - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)