Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002475
UniProt IDQ8WZ73
Primary gene name(s)RFFL
Synonym gene name(s)RNF189, RNF34L
Protein nameE3 ubiquitin-protein ligase rififylin
Protein functionE3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling. {ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:22609986}.
Subcellular locationCytoplasm, cytosol. Cell membrane;
Peripheral membrane protein. Recycling endosome membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250}. Note=The FYVE-type zinc finger may mediate phosphatidylinositol phosphate-binding and control subcellular localization.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8WZ73
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis [GO:2001271];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of signal transduction by p53 class mediator [GO:1901797];
negative regulation of tumor necrosis factor-mediated signaling pathway [GO:0010804];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein K48-linked ubiquitination [GO:0070936];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of fibroblast migration [GO:0010762];
regulation of TOR signaling [GO:0032006];
ubiquitin-dependent protein catabolic process [GO:0006511]
Gene Ontology
(Molecular Function)
Complete annatation
ligase activity [GO:0016874];
p53 binding [GO:0002039];
protease binding [GO:0002020];
protein kinase binding [GO:0019901];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin protein ligase binding [GO:0031625];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome membrane [GO:0010008];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886];
recycling endosome membrane [GO:0055038]
Protein-protein interaction125593
Phylogenetic treeQ8WZ73
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. CD3-1.184958397304720.0003666671734459110.001513217270574
AZA vs. DISU0.2788263058830540.2706839152012070.844979868064549
AZA vs. IL7-0.2800385192364160.1463133464672990.91433709423781
AZA vs. SAHA-0.03289423479631110.8927766583950850.976874050805
DISU vs. CD31.450980046333468.72495956766306e-050.00050371520690522
DISU vs. IL7-0.5679672289858960.02459975522712590.199806740328083
DISU vs. SAHA-0.3101764820909920.2873594314403880.669883061289726
DMSO vs. AZA-0.0441671354525790.792517413652391
DMSO vs. CD31.128598642062840.0004989895754816680.00186117305140662
DMSO vs. DISU-0.3251134858265160.1830533675606270.697822984298268
DMSO vs. IL7-0.2284781586549230.2050087609068940.715726510113809
DMSO vs. SAHA0.00478134225932750.9838242510214350.995914397274463
HIV vs. Mock in Activation0.1651434021639480.7911046708320620.999983755607037
HIV vs. Mock in Latency0.05018571387582940.7616847858126490.999834320637052
IL7 vs. CD30.9123281621647930.004905946664557460.0164987358489234
SAHA vs. CD31.127119804924360.001653807355543550.00550538476873012
SAHA vs. IL70.243351887959090.3182463778602220.566916320002953
(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 -0.202668 0.175918
(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
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
1Y02 X-ray 1.8Å A=26-145.

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