Affinage

RNF5

E3 ubiquitin-protein ligase RNF5 · UniProt Q99942

Length
180 aa
Mass
19.9 kDa
Annotated
2026-06-10
46 papers in source corpus 30 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RNF5 is an ER- and mitochondria-anchored RING-finger E3 ubiquitin ligase whose membrane-bound activity governs innate antiviral immunity, ER-associated degradation (ERAD), autophagy, cell motility, and cellular metabolism (PMID:18270596, PMID:19285439, PMID:23093945). In antiviral signaling, RNF5 acts as a negative regulator: upon viral infection it associates with the adaptors MITA/STING and VISA/MAVS at the mitochondria and catalyzes K48-linked ubiquitination and proteasomal degradation—targeting MITA at Lys150 and VISA at Lys362/Lys461—to dampen IRF3 activation and type I interferon production (PMID:19285439, PMID:20483786). It also terminates this pathway downstream by degrading activated IRF3, with the recruitment factor JMJD6 directing RNF5 to its target (PMID:33684176). At the ER membrane, RNF5/RMA1 initiates ubiquitination of misfolded substrates such as CFTRΔF508 upstream of gp78, working with the DNAJB12/Hsc70 chaperone system (PMID:18216283, PMID:21148293), yet it can also restrain ERAD by non-degradative ubiquitination of JAMP, which limits proteasome recruitment to the ER and thereby stabilizes client GPCRs (PMID:19269966, PMID:23798571). RNF5 sets basal autophagy levels by ubiquitinating a membrane pool of the cysteine protease ATG4B to control LC3 processing (PMID:23093945), and it shapes cell adhesion and motility through K63-linked ubiquitination of paxillin that displaces it from focal adhesions (PMID:12861019). Through degradation of diverse substrates—the glutamine transporters SLC1A5/SLC38A2, PHGDH, PTEN, ACSL4, and the histone-binding protein RBBP4—RNF5 controls tumor metabolism, ferroptosis, and epigenetic programs in cancer (PMID:25759021, PMID:32783943, PMID:30456390, PMID:41203033, PMID:34518534). RNF5 maintains tissue homeostasis in vivo, regulating intestinal inflammation via S100A8 degradation (PMID:30232010) and muscle physiology and ER stress responses (PMID:18270596). Numerous viral pathogens exploit or counter RNF5: viral proteins recruit it to degrade STING or MAVS to evade immunity (PMID:31270229, PMID:35584187), while RNF5 directly ubiquitinates SARS-CoV-2 structural proteins (PMID:35100873, PMID:36737599).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 Low

    Before any function was known, the question was simply what kind of protein RNF5 encodes; cloning established it as a ubiquitously expressed RING-finger protein, foreshadowing an E3 ligase role.

    Evidence cDNA cloning, FISH/radiation hybrid mapping, Northern blot in human tissues

    PMID:9533025

    Open questions at the time
    • No enzymatic or substrate evidence at this stage
    • RING domain function not demonstrated
  2. 2003 High

    The first substrate question—does RNF5 ubiquitinate a defined target with functional consequence—was answered by showing it mediates K63-linked ubiquitination of paxillin, linking RNF5 to focal-adhesion dynamics and cell motility.

    Evidence Yeast two-hybrid, Co-IP, in vivo ubiquitination with dominant-negative Ubc13, motility assays

    PMID:12861019

    Open questions at the time
    • Physiological trigger for paxillin ubiquitination not defined
    • Did not establish ER/mitochondrial localization role
  3. 2004 Medium

    Whether RNF5's ligase activity has a developmental/structural role was addressed in C. elegans, where RNF-5 regulates UNC-95 and muscle attachment assembly, later refined to temporal control during molting.

    Evidence C. elegans genetics, RNAi, GFP localization, RING-deletion and heat-shock overexpression mutants

    PMID:15210732 PMID:20385102

    Open questions at the time
    • Mammalian orthologous muscle substrate not identified
    • Direct ubiquitination of UNC-95 in vitro not fully reconstituted
  4. 2008 High

    The defining ER quality-control role was established by placing RMA1/RNF5 upstream of gp78 in CFTRΔF508 ERAD and by in vivo mouse models linking RNF5 to ER stress and muscle physiology.

    Evidence siRNA epistasis, in vitro ubiquitination, domain swaps, transgenic/KO mice with cardiotoxin injury

    PMID:18216283 PMID:18270596

    Open questions at the time
    • Endogenous substrate spectrum during ERAD incomplete
    • Mechanism coupling RNF5 to retrotranslocation machinery unresolved
  5. 2009 High

    The question of how RNF5 controls antiviral immunity was answered by demonstrating infection-dependent association with and K48-linked degradation of MITA/STING at Lys150, defining RNF5 as a negative regulator of type I IFN.

    Evidence Reciprocal Co-IP, K150 site-specific mutagenesis, subcellular fractionation, reporter assays

    PMID:19285439

    Open questions at the time
    • Signal that activates RNF5 during infection not defined
    • Selectivity between STING and other adaptors unclear
  6. 2010 High

    RNF5's antiviral target range was extended to the mitochondrial adaptor VISA/MAVS (K362/K461) and its ERAD activity was shown to be bidirectional, with non-degradative ubiquitination of JAMP limiting proteasome recruitment to the ER.

    Evidence Domain mapping, K362/K461 mutagenesis, Ubc13 dominant-negative, misfolded-substrate accumulation assays

    PMID:19269966 PMID:20483786 PMID:21148293

    Open questions at the time
    • How RNF5 switches between degradative and non-degradative chains is unknown
    • Relative contribution of MAVS vs STING degradation in vivo not quantified
  7. 2012 High

    The link between RNF5 and autophagy was established by showing it ubiquitinates a membrane pool of ATG4B to limit LC3 processing and basal autophagy, with loss enhancing bacterial clearance.

    Evidence Co-IP, ubiquitination assay, binding-deficient RNF5 mutant, RNF5-/- MEFs/mice, C. elegans RNAi, infection model

    PMID:23093945

    Open questions at the time
    • Ubiquitination linkage type on ATG4B not specified
    • Regulation of the membrane-restricted ATG4B pool unclear
  8. 2015 High

    The metabolic role of RNF5 was defined by showing ER-stress-driven degradation of glutamine transporters SLC1A5/SLC38A2, connecting RNF5 to tumor glutamine uptake, mTOR signaling, and therapy response.

    Evidence Co-IP, ubiquitination, transporter knockdown epistasis, metabolic profiling, Rnf5-/- MMTV-PyMT mice

    PMID:25759021

    Open questions at the time
    • Upstream sensor coupling paclitaxel-induced ER stress to RNF5 activation unknown
    • Whether this extends beyond breast cancer not addressed
  9. 2018 High

    RNF5's roles in tissue homeostasis and additional cancer pathways were expanded through S100A8 degradation controlling intestinal inflammation and PTEN degradation in pancreatic fibroblasts, plus a small-molecule inhibitor validating ATG4B/paxillin as engageable targets.

    Evidence Rnf5-/- mice, DSS colitis with antibody rescue; proteomic screen and GSK3β-inhibitor rescue; virtual-screen inhibitor with CFTR rescue in primary CF cells

    PMID:29754957 PMID:30232010 PMID:30456390

    Open questions at the time
    • PTEN finding relies on a single-lab Smo-null context
    • Inhibitor specificity across the full substrate set not mapped
  10. 2021 Medium

    Recruitment-factor logic and epigenetic substrates emerged, with JMJD6 directing RNF5 to degrade activated IRF3 and RNF5 placing K29 chains on RBBP4 to sustain AML-related gene programs.

    Evidence Proteomic screens, Co-IP, K48- and K29-linkage-specific ubiquitination, JMJD6 KO mice, AML PDX and MLL-AF9 models

    PMID:33684176 PMID:34518534

    Open questions at the time
    • Structural basis for adaptor-directed substrate selection unknown
    • How K29 chains on RBBP4 alter chromatin recruitment mechanistically unresolved
  11. 2022 Medium

    Viral exploitation of RNF5 was demonstrated as pathogens recruit it to degrade immune adaptors (NDV V → MAVS; PRV UL13 → STING), while RNF5 conversely restrains STING-driven cardiac inflammation.

    Evidence Co-IP, linkage- and site-specific ubiquitination, domain mapping, infection and cardiac hypertrophy mouse models

    PMID:31270229 PMID:35584187 PMID:36270989

    Open questions at the time
    • Single-lab findings for individual viral hijack mechanisms
    • Linkage types reported (K27/K29 on STING) differ from canonical K48 and need integration
  12. 2023 Medium

    RNF5 was shown to directly ubiquitinate viral structural proteins and additional receptor substrates, including SARS-CoV-2 M and E proteins and Eph receptors, broadening its impact on viral life cycles and cancer signaling.

    Evidence RNAi screen, site-specific ubiquitination (K15 on M, K63 on E), Co-IP, virion-release assays, EphA2/A3/A4 ubiquitination, xenograft models

    PMID:35100873 PMID:36656913 PMID:36737599 PMID:37816703

    Open questions at the time
    • Opposite effects on different SARS-CoV-2 proteins (pro- vs anti-viral) not reconciled
    • Single-lab evidence for each receptor substrate
  13. 2025 Medium

    Recent work extended RNF5 substrates to lipid-metabolism and ferroptosis regulators (IGF2BP1, ACSL4) and probed ERAD-network redundancy, indicating RNF5 operates within a partially compensable degradation system.

    Evidence IP-MS, K63/K48 ubiquitination assays, AAV9 RNF5 overexpression, ferroptosis assays, HiBiT ERAD assay with multiple E3 knockouts (preprint)

    PMID:39734009 PMID:41203033 PMID:bio_10.1101_2025.05.07.652780

    Open questions at the time
    • ERAD compensation finding is an unreviewed preprint
    • How RNF5 substrate selection is partitioned among redundant ER ligases unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying question remains: what determines RNF5's choice of ubiquitin chain linkage (K48, K63, K29, K27) and substrate across its many contexts, and how is its activity switched on by infection, ER stress, or adaptor recruitment.
  • No structural model linking RING activity to linkage specificity
  • Activation/regulation of RNF5 itself largely uncharacterized
  • Ligase-independent activities (e.g. caspase-3-dependent HBV Core degradation) not mechanistically resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 11 GO:0016740 transferase activity 6 GO:0016874 ligase activity 3
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005739 mitochondrion 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
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

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 407 19285439
2015 Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies. Cancer cell 196 25759021
2008 Gp78 cooperates with RMA1 in endoplasmic reticulum-associated degradation of CFTRDeltaF508. Molecular biology of the cell 193 18216283
2010 The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation. Journal of immunology (Baltimore, Md. : 1950) 157 20483786
2019 Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5-/- mice. Nature communications 137 30940817
2010 The endoplasmic reticulum-associated Hsp40 DNAJB12 and Hsc70 cooperate to facilitate RMA1 E3-dependent degradation of nascent CFTRDeltaF508. Molecular biology of the cell 109 21148293
2012 Regulation of ATG4B stability by RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection. PLoS genetics 100 23093945
2003 RNF5, a RING finger protein that regulates cell motility by targeting paxillin ubiquitination and altered localization. Molecular and cellular biology 100 12861019
2019 Newcastle Disease Virus V Protein Degrades Mitochondrial Antiviral Signaling Protein To Inhibit Host Type I Interferon Production via E3 Ubiquitin Ligase RNF5. Journal of virology 91 31270229
2022 Pseudorabies virus tegument protein UL13 recruits RNF5 to inhibit STING-mediated antiviral immunity. PLoS pathogens 74 35584187
2022 The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release. mBio 59 35100873
2020 Acetylation Stabilizes Phosphoglycerate Dehydrogenase by Disrupting the Interaction of E3 Ligase RNF5 to Promote Breast Tumorigenesis. Cell reports 59 32783943
2018 Pharmacological Inhibition of the Ubiquitin Ligase RNF5 Rescues F508del-CFTR in Cystic Fibrosis Airway Epithelia. Cell chemical biology 54 29754957
2009 Regulation of endoplasmic reticulum-associated degradation by RNF5-dependent ubiquitination of JNK-associated membrane protein (JAMP). The Journal of biological chemistry 54 19269966
2008 The ER-bound RING finger protein 5 (RNF5/RMA1) causes degenerative myopathy in transgenic mice and is deregulated in inclusion body myositis. PloS one 54 18270596
2018 Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis. Cell reports 53 30232010
2023 The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation. Signal transduction and targeted therapy 49 36737599
2007 Increased expression of the E3 ubiquitin ligase RNF5 is associated with decreased survival in breast cancer. Cancer research 48 17804730
2021 The ubiquitin ligase RNF5 determines acute myeloid leukemia growth and susceptibility to histone deacetylase inhibitors. Nature communications 45 34518534
2015 Genetic Inhibition Of The Ubiquitin Ligase Rnf5 Attenuates Phenotypes Associated To F508del Cystic Fibrosis Mutation. Scientific reports 44 26183966
2004 The LIM domain protein UNC-95 is required for the assembly of muscle attachment structures and is regulated by the RING finger protein RNF-5 in C. elegans. The Journal of cell biology 41 15210732
2018 Disruption of stromal hedgehog signaling initiates RNF5-mediated proteasomal degradation of PTEN and accelerates pancreatic tumor growth. Life science alliance 34 30456390
2013 Novel, gel-free proteomics approach identifies RNF5 and JAMP as modulators of GPCR stability. Molecular endocrinology (Baltimore, Md.) 30 23798571
2022 E3 ubiquitin ligase RNF5 attenuates pathological cardiac hypertrophy through STING. Cell death & disease 24 36270989
2021 JMJD6 negatively regulates cytosolic RNA induced antiviral signaling by recruiting RNF5 to promote activated IRF3 K48 ubiquitination. PLoS pathogens 21 33684176
1997 Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human homologue of a putative zinc-finger gene from Caenorhabditis elegans. Cytogenetics and cell genetics 19 9533025
2024 RNF5 exacerbates steatotic HCC by enhancing fatty acid oxidation via the improvement of CPT1A stability. Cancer letters 17 39734009
2017 RNF5, DAB2 and Friends: Novel Drug Targets for Cystic Fibrosis. Current pharmaceutical design 17 27719636
2010 Molting-specific downregulation of C. elegans body-wall muscle attachment sites: the role of RNF-5 E3 ligase. Biochemical and biophysical research communications 17 20385102
2023 Suppression of KSHV lytic replication and primary effusion lymphoma by selective RNF5 inhibition. PLoS pathogens 16 36656913
2022 E3 ligase RNF5 inhibits type I interferon response in herpes simplex virus keratitis through the STING/IRF3 signaling pathway. Frontiers in microbiology 16 35992663
2024 Human gastric cancer progression and stabilization of ATG2B through RNF5 binding facilitated by autophagy-associated CircDHX8. Cell death & disease 14 38866787
2020 Inactivation of the Caenorhabditis elegans RNF-5 E3 ligase promotes IRE-1-independent ER functions. Autophagy 12 32981418
2019 Ubiquitin ligase RNF5 serves an important role in the development of human glioma. Oncology letters 12 31611975
2023 Black carp RNF5 inhibits STING/IFN signaling through promoting K48-linked ubiquitination and degradation of STING. Developmental and comparative immunology 9 37100266
2022 Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors. Cancers 8 35406574
2024 RNF5: inhibiting antiviral immunity and shaping virus life cycle. Frontiers in immunology 7 38250078
2023 Downregulation of EphA2 stability by RNF5 limits its tumor-suppressive function in HER2-negative breast cancers. Cell death & disease 7 37816703
2024 Swine RNF5 positively regulates the antiviral activity of IFITM1 by mediating the degradation of ABHD16A. Journal of virology 5 39601593
2023 Negatively regulation of MAVS-mediated antiviral innate immune response by E3 ligase RNF5 in black carp. Fish & shellfish immunology 5 36740081
2025 RNF5 inhibits HBV replication by mediating caspase-3-dependent degradation of core protein. Frontiers in microbiology 1 40236486
2025 RNF5-mediated ubiquitination of ACSL4 attenuates ferroptosis and confers cardioprotection against myocardial ischemia/reperfusion injury. Biochemical pharmacology 1 41203033
2026 The E3 ligase RNF5 facilitates viral replication by suppressing innate immune responses in grouper. Fish & shellfish immunology 0 41534736
2026 Umbilical cord mesenchymal stromal cells-derived HGF inhibits STING-mediated pyroptosis to alleviate cerebral ischemia/reperfusion injury via c-Met/β-catenin/RNF5 pathway. Journal of translational medicine 0 41845461
2026 S100A8 lactylation at K23/K36 reduces RNF5-dependent degradation and promotes colorectal cancer progression. Biochemical and biophysical research communications 0 42048751
2025 Protein and gene levels of DNAJC21 and RNF5 as drug targets for immune thrombocytopenia: optimized post-GWAS insights. Hematology (Amsterdam, Netherlands) 0 41175382

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