Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002509
UniProt IDQ9NTX7
Primary gene name(s)RNF146
Synonym gene name(s)unknown
Protein nameE3 ubiquitin-protein ligase RNF146
Protein functionE3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated, PARsylated proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins, TNKS and TNKS2, which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate, NMDA receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation, By similarity. Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine, MNNG and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair. {ECO:0000250, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21602803, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151, ECO:0000269|PubMed:22267412}.
Subcellular locationCytoplasm, cytosol. Nucleus. Note=Translocates to the nucleus after DNA damage, such as laser-induced DNA breaks, and concentrates at DNA breaks. This translocation requires PARP1 activation and PAR-binding.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NTX7
Gene Ontology
(Biological Process)
Complete annatation
positive regulation of canonical Wnt signaling pathway [GO:0090263];
protein autoubiquitination [GO:0051865];
protein K48-linked ubiquitination [GO:0070936];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
poly-ADP-D-ribose binding [GO:0072572];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nucleus [GO:0005634]
Protein-protein interaction123598
Phylogenetic treeQ9NTX7
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. CD30.06546424029146810.8420130355561740.894007695334816
AZA vs. DISU0.2311719764029050.3649038287135940.896211275303082
AZA vs. IL7-0.04742032822078460.8073210263652590.999311006273513
AZA vs. SAHA0.1830101950818140.4564375920060550.796612279946656
DISU vs. CD30.1525697377468880.6744383085091090.770162881816408
DISU vs. IL7-0.2873333981316270.2584632395605140.643915606738515
DISU vs. SAHA-0.04663569686638350.8742188526309180.967008806477817
DMSO vs. AZA-0.02233781582045660.895541414663171
DMSO vs. CD3-0.09840163860511810.759117536154850.826726355972877
DMSO vs. DISU-0.2551734803709780.3004268974977570.807887568985919
DMSO vs. IL7-0.0180391378871730.9210196800425630.98354773913261
DMSO vs. SAHA0.1981476899841890.4037111236413140.746770759645673
HIV vs. Mock in Activation-0.09914995452883790.8735618168476790.999983755607037
HIV vs. Mock in Latency0.02375637842385730.8866631807185630.999834320637052
IL7 vs. CD3-0.1047483743138280.7451547963648940.829542223408708
SAHA vs. CD30.09255903673894970.794380623833880.853656163721961
SAHA vs. IL70.2270938798116640.3543681601135130.604338233459791
(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) TRUE
(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 -0.0708435 0.714966
(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
0.915 1.951 2.058 2.123 2.025
(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
2D8T NMR - A=27-84.
3V3L X-ray 1.6Å A/B=100-184.

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
not found