| 2009 |
RNF5 interacts with MITA/STING in a viral-infection-dependent manner and targets MITA at Lys150 for K48-linked ubiquitination and proteasomal degradation at the mitochondria, thereby negatively regulating virus-triggered IRF3 activation and type I IFN production. |
Co-immunoprecipitation, ubiquitination assay, knockdown/overexpression with reporter assays, subcellular fractionation/localization |
Immunity |
High |
19285439
|
| 2010 |
RNF5 interacts with VISA/MAVS at mitochondria in a viral-infection-dependent manner via the C-terminal transmembrane domain of VISA, and targets VISA at K362 and K461 for K48-linked ubiquitination and degradation, downregulating type I IFN induction. |
Co-immunoprecipitation, domain mapping, site-specific mutagenesis (K362, K461), ubiquitination assay, knockdown/overexpression |
Journal of immunology |
High |
20483786
|
| 2008 |
RNF5/RMA1 functions as an E3 ubiquitin ligase upstream of gp78 in ERAD of CFTRΔf508; RMA1 initiates ubiquitination of CFTRΔf508 and gp78 then acts as an E4-like factor to extend polyubiquitin chains, with both requiring the gp78 CUE domain for substrate recognition. |
siRNA knockdown, in vitro ubiquitination assay, domain deletion/swap analysis, Co-immunoprecipitation |
Molecular biology of the cell |
High |
18216283
|
| 2003 |
RNF5 associates with the amino-terminal domain of paxillin and mediates its K63-linked polyubiquitination (dependent on intact RING and C-terminal domains and Ubc13), altering paxillin localization from focal adhesions to the cytoplasm and inhibiting cell motility. |
Yeast two-hybrid, Co-immunoprecipitation, in vivo ubiquitination assay, dominant-negative Ubc13, fluorescence microscopy, motility assays |
Molecular and cellular biology |
High |
12861019
|
| 2012 |
RNF5 associates with and ubiquitinates a membrane-associated pool of the cysteine protease ATG4B, controlling its stability and thereby limiting LC3 processing, phagophore/autophagosome formation, and basal autophagy levels; loss of RNF5 increases autophagy and enhances bacterial clearance. |
Co-immunoprecipitation, ubiquitination assay, RNF5 mutant (ligase-active but ATG4B-binding deficient), LC3 puncta quantification, RNF5-/- MEFs and mice, C. elegans RNAi, bacterial infection model |
PLoS genetics |
High |
23093945
|
| 2010 |
RNF5 associates with JAMP (JNK-associated membrane protein) at the ER membrane and mediates Ubc13-dependent non-canonical (non-degradative) ubiquitination of JAMP, which inhibits JAMP's interaction with Rpt5 and p97, thereby reducing proteasome recruitment to the ER and limiting ERAD efficiency of misfolded proteins such as CFTRΔf508. |
Co-immunoprecipitation, ubiquitination assay, dominant-negative Ubc13, accumulation assays for misfolded CFTR and TCRα |
The Journal of biological chemistry |
High |
19269966
|
| 2010 |
DNAJB12/JB12 cooperates with cytosolic Hsc70 and the E3 ligase RMA1/RNF5 to target nascent CFTR and CFTRΔf508 for ERAD; elevated JB12 increases Hsc70 association with ER forms of CFTR and the RMA1 E3 complex, while depletion of JB12 increases CFTR folding efficiency up to threefold. |
Overexpression and siRNA knockdown, Co-immunoprecipitation, CFTR folding/trafficking assays |
Molecular biology of the cell |
Medium |
21148293
|
| 2004 |
In C. elegans, RNF-5 regulates the LIM domain protein UNC-95, which is required for muscle attachment structure assembly; RNF-5 co-localizes with UNC-95 in dense bodies and controls its expression and localization. Loss of RNF-5 RING domain causes structural defects in muscle adhesion sites. |
C. elegans genetics, RNAi, GFP fusion localization, RING domain deletion mutant analysis |
The Journal of cell biology |
Medium |
15210732
|
| 2015 |
RNF5 associates with, ubiquitinates, and promotes proteasomal degradation of the glutamine carrier proteins SLC1A5 and SLC38A2 following paclitaxel-induced ER stress in breast cancer cells, thereby decreasing glutamine uptake, TCA cycle components, and mTOR signaling while increasing autophagy and cell death. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, metabolic profiling, in vivo tumor models (Rnf5-/- MMTV-PyMT mice) |
Cancer cell |
High |
25759021
|
| 2018 |
RNF5 ubiquitinates S100A8 in intestinal epithelial cells leading to its proteasomal degradation; loss of RNF5 results in enhanced S100A8 secretion, mucosal CD4+ T cell induction, and Th1 pro-inflammatory responses, with RNF5 maintaining intestinal homeostasis. |
Co-immunoprecipitation, ubiquitination assay, Rnf5-/- mice, DSS colitis model, S100A8-neutralizing antibody rescue, immunofluorescence |
Cell reports |
High |
30232010
|
| 2019 |
NDV V protein recruits E3 ubiquitin ligase RNF5 to polyubiquitinate and degrade MAVS at Lys362 and Lys461 via the ubiquitin-proteasome pathway, thereby inhibiting IFN-β production during NDV infection. |
Co-immunoprecipitation, ubiquitination assay, site-specific mutagenesis (K362, K461), overexpression/knockdown with IFN-β reporter |
Journal of virology |
Medium |
31270229
|
| 2022 |
PRV tegument protein UL13 interacts with the CDN domain of STING and recruits RNF5 to promote K27-/K29-linked ubiquitination and degradation of STING, suppressing STING-mediated antiviral signaling and type I IFN production. |
Co-immunoprecipitation, ubiquitination assay (linkage-specific), domain mapping, RNF5 knockdown, infection model with UL13-deficient PRV |
PLoS pathogens |
Medium |
35584187
|
| 2022 |
RNF5 mediates K15 ubiquitination of the SARS-CoV-2 M (membrane) protein, enhancing M-E complex formation and promoting M trafficking from Golgi to autophagosomes for virion release; the deubiquitinase POH1 negatively regulates this process. |
RNAi screen, Co-immunoprecipitation, ubiquitination assay (site-specific K15), confocal microscopy, virion release assay |
mBio |
Medium |
35100873
|
| 2023 |
RNF5 interacts with and catalyzes ubiquitination of the SARS-CoV-2 envelope (E) protein at K63, leading to its degradation by the ubiquitin-proteasome system and inhibiting SARS-CoV-2 replication. |
Co-immunoprecipitation, ubiquitination assay (site-specific K63 of E), viral replication assays, mouse infection model with pharmacological RNF5 activator |
Signal transduction and targeted therapy |
Medium |
36737599
|
| 2021 |
RNF5 induces K29-linked ubiquitin chains on the histone-binding protein RBBP4, promoting its recruitment to and epigenetic regulation of genes involved in AML maintenance, with RNF5 inhibition sensitizing AML cells to HDAC inhibitors. |
Co-immunoprecipitation, linkage-specific ubiquitination assay (K29), chromatin assays, AML cell lines, patient-derived xenograft models, Rnf5 KD in MLL-AF9 leukemogenesis mouse model |
Nature communications |
High |
34518534
|
| 2020 |
RNF5 interacts with and ubiquitinates PHGDH, targeting it for degradation; acetylation of PHGDH at K58 (by Tip60, reversed by SIRT2) disrupts RNF5-PHGDH interaction, stabilizing PHGDH and promoting breast cancer cell proliferation. |
Co-immunoprecipitation, ubiquitination assay, site-specific mutagenesis (K58), acetyltransferase/deacetylase identification (Tip60/SIRT2), cell proliferation assays |
Cell reports |
Medium |
32783943
|
| 2018 |
RNF5 is identified as the E3 ubiquitin ligase responsible for PTEN ubiquitination and proteasomal degradation in Smo-null pancreatic fibroblasts; GSK3β phosphorylation marks PTEN for this RNF5-mediated ubiquitination, and RNF5 knockdown rescues PTEN levels. |
Unbiased proteomic screen, Co-immunoprecipitation, ubiquitination assay, RNF5 siRNA knockdown, GSK3β inhibitor rescue |
Life science alliance |
Medium |
30456390
|
| 2013 |
RNF5 interacts with β2-adrenergic receptor (β2AR) and prostaglandin D2 receptor (DP) at the ER but does not ubiquitinate them directly; instead, RNF5 ubiquitinates JAMP to prevent proteasome recruitment to the ER, thereby stabilizing these GPCRs from JAMP-mediated proteasomal degradation. |
Gel-free proteomics, Co-immunoprecipitation, confocal colocalization, siRNA knockdown, overexpression with receptor level quantification |
Molecular endocrinology |
Medium |
23798571
|
| 2008 |
Transgenic overexpression of RNF5 in mouse muscle causes early-onset muscle wasting, degeneration, and altered ER chaperone activity, while RNF5 KO mice show delayed muscle regeneration and delayed ER stress markers after cardiotoxin injury, establishing RNF5 as a regulator of muscle physiology and ER stress in vivo. |
Transgenic and KO mouse models, histopathology, ER stress marker analysis, cardiotoxin injury model |
PloS one |
Medium |
18270596
|
| 2009 |
RNF5 is anchored to the ER membrane and its E3 ligase activity is required for its function in ERAD; RNF5 is expressed and localized at the ER where it participates in recognition and processing of misfolded proteins including CFTRΔf508. |
Subcellular fractionation, localization studies, functional ERAD assay with misfolded CFTR substrates in transgenic/KO mice |
PloS one |
Medium |
18270596
|
| 2010 |
In C. elegans, RNF-5 E3 ligase levels increase specifically during molting, where it ubiquitinates the dense body protein UNC-95, leading to decreased UNC-95 concentration at dense bodies; persistent high RNF-5 expression causes failure of ecdysis, establishing RNF-5 as a temporal regulator of muscle attachment dynamics during molting. |
C. elegans genetics, heat-shock promoter overexpression, ubiquitination assay for UNC-95, fluorescence microscopy of dense body dynamics |
Biochemical and biophysical research communications |
Medium |
20385102
|
| 2021 |
JMJD6 recruits RNF5 to promote K48-linked ubiquitination and degradation of activated IRF3, negatively regulating type I IFN production in response to cytosolic viral RNA; genetic deletion of JMJD6 enhances IFN-I production in an RNF5-dependent manner. |
Unbiased proteomic screen, Co-immunoprecipitation, ubiquitination assay (K48-linked), JMJD6 KO mice via piggyBac transposon, viral infection assays |
PLoS pathogens |
Medium |
33684176
|
| 2022 |
RNF5 promotes K48-linked polyubiquitination and proteasomal degradation of STING, attenuating STING-mediated cardiac inflammation and pathological cardiac hypertrophy; protein-protein interaction between RNF5 and STING was confirmed. |
Co-immunoprecipitation, K48-specific ubiquitination assay, gain- and loss-of-function in cardiac hypertrophy mouse model |
Cell death & disease |
Medium |
36270989
|
| 2023 |
RNF5 interacts with EphA2 (Ephrin receptor A2) and induces its ubiquitination and proteasomal degradation, decreasing EphA2 cell surface levels, altering phosphorylation balance at S897/Y772, and reducing ERK phosphorylation while increasing p53 in HER2-negative breast cancer cells. |
Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, phosphorylation analysis, xenograft tumor models |
Cell death & disease |
Medium |
37816703
|
| 2023 |
RNF5 interacts with EphA3 and EphA4 and induces their ubiquitination and degradation; RNF5 inhibition increases EphA3/EphA4 levels, reduces ERK and Akt activation, and suppresses KSHV lytic replication in PEL cells. |
Co-immunoprecipitation, ubiquitination assay, pharmacological RNF5 inhibition, PEL xenograft tumor model, viral gene expression analysis |
PLoS pathogens |
Medium |
36656913
|
| 2024 |
RNF5 promotes K63-type ubiquitination of IGF2BP1, enhancing CPT1A mRNA stabilization through m6A modification and increasing fatty acid oxidation in steatotic HCC; PPARγ activates RNF5 expression specifically in HCC cells, placing RNF5 in a PPARγ-RNF5-IGF2BP1-CPT1A axis. |
Protein interaction analysis, Co-immunoprecipitation, ubiquitination assay (K63-specific), lipidomics, transcriptomics, in vitro and in vivo HCC models |
Cancer letters |
Medium |
39734009
|
| 2018 |
Pharmacological inhibition of RNF5 with a small molecule (inh-02), identified by computational docking and virtual screening, modulates known RNF5 targets ATG4B and paxillin and promotes significant F508del-CFTR rescue in CF patient-derived bronchial epithelial cells. |
Computational docking/virtual screening, in vitro RNF5 inhibition assay, cell-based CFTR rescue assay in primary CF cells, target engagement via ATG4B/paxillin modulation |
Cell chemical biology |
Medium |
29754957
|
| 2025 |
RNF5 interacts with ACSL4 via its transmembrane region and mediates ACSL4 ubiquitination and degradation, thereby attenuating ferroptosis in cardiomyocytes and conferring cardioprotection against myocardial ischemia/reperfusion injury. |
Co-immunoprecipitation, IP-MS, ubiquitination assay, AAV9-mediated RNF5 overexpression in mice, ferroptosis and ROS assays |
Biochemical pharmacology |
Medium |
41203033
|
| 2025 |
In the absence of RNF5/RNF185 function, AMFR (a Hrd1 ortholog involved in ERAD-M branch) can partially compensate to facilitate degradation of mutant CFTR, revealing a bypass mechanism in the ERAD network; SYVN1 (another Hrd1 ortholog) did not show the same compensatory effect. |
Multiple E3 ligase knockouts/knockdowns combined with HiBiT-based ERAD assay, functional complementation analysis |
bioRxivpreprint |
Medium |
bio_10.1101_2025.05.07.652780
|
| 2041 |
RNF5 inhibits HBV replication by promoting degradation of HBV Core protein through a Caspase-3-dependent (non-ubiquitin-proteasome) pathway; this antiviral function does not rely on RNF5's E3 ubiquitin ligase activity. |
Co-immunoprecipitation, caspase-3 inhibitor rescue, E3 ligase activity mutant, viral replication assays |
Frontiers in microbiology |
Low |
40236486
|
| 1997 |
RNF5 encodes a RING-finger protein containing a zinc-chelating domain expressed ubiquitously in human tissues; it was mapped to chromosome 6p21.31 proximal to the MHC region, and shares homology with a C. elegans protein. |
cDNA cloning, FISH mapping, radiation hybrid mapping, Northern blot expression survey |
Cytogenetics and cell genetics |
Low |
9533025
|