Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002478
UniProt IDQ8NHY2
Primary gene name(s)RFWD2
Synonym gene name(s)COP1, RNF200
Protein nameE3 ubiquitin-protein ligase RFWD2
Protein functionE3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53, TP53 ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation. {ECO:0000269|PubMed:12466024, ECO:0000269|PubMed:12615916, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15103385, ECO:0000269|PubMed:19805145, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:21625211}.
Subcellular locationNucleus speckle. Cytoplasm. Note=In the nucleus, it forms nuclear speckles.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8NHY2
Gene Ontology
(Biological Process)
Complete annatation
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
response to ionizing radiation [GO:0010212]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
focal adhesion [GO:0005925];
Golgi membrane [GO:0000139];
nuclear speck [GO:0016607];
nucleoplasm [GO:0005654]
Protein-protein interaction122136
Phylogenetic treeQ8NHY2
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. CD30.5210437460695960.1145124037014610.196306977773933
AZA vs. DISU0.1016495206283270.6887252936031920.968313969505284
AZA vs. IL7-0.006073733462136210.9749612661760540.999311006273513
AZA vs. SAHA-0.02030482385461910.9339192061322390.98546908573948
DISU vs. CD3-0.4321216479045570.2349991683915760.359705266484019
DISU vs. IL7-0.116602709270350.6443753226813940.895862180767171
DISU vs. SAHA-0.1208526248189510.6791367851421370.904055046347007
DMSO vs. AZA-0.1470417032823550.3849122898406131
DMSO vs. CD3-0.6783691820186460.03566613162070610.0723747673580196
DMSO vs. DISU-0.2503266930621910.3067687583336730.812005271058955
DMSO vs. IL70.1480947788745220.4137001351941240.849431971949253
DMSO vs. SAHA0.1193307553806880.6141985919256790.872893091789338
HIV vs. Mock in Activation-0.1695408830669350.7856005247596030.999983755607037
HIV vs. Mock in Latency0.02647542231423690.873582684017180.999834320637052
IL7 vs. CD3-0.5186186570306420.1088919745307080.202433242735738
SAHA vs. CD3-0.5665947134795720.1123998805089940.191527159573783
SAHA vs. IL7-0.01797298669371790.9413816307295670.977433992396851
(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 -0.140193 0.421679
(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
0.811 1.415 0.905 0.858 1.167
(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
5HQG X-ray 2.0Å A=376-731.
5IGQ X-ray 3.9Å A/B/C/D/E/F=386-731.

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
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)