Affinage

Showing RPS3 — US3 is a alias.

RPS3

Small ribosomal subunit protein uS3 · UniProt P23396

Length
243 aa
Mass
26.7 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPS3 (uS3) is a multifunctional protein of the 40S small ribosomal subunit that contributes both to canonical translation and to a set of moonlighting roles in DNA repair, ribosome quality control, and NF-κB signaling (PMID:28223523, PMID:21399639, PMID:30893611). Within the ribosome it occupies the mRNA entry channel, where conserved residues Arg116/Arg117 stabilize mRNA contacts and tune translation initiation: their substitution reduces bulk initiation, alters near-cognate UUG start codon selection, and shifts discrimination against poorly contexted AUG codons (PMID:28223523). It also contacts mRNA at the A site of the 48S complex as the major TISU-element binding protein, an interaction coordinated with eIF1A and handed off to RPS10e upon 80S formation (PMID:28584194, PMID:30420357). Through these entry-channel contacts RPS3 maintains translational fidelity, preventing +1 frameshifting at inhibitory codon pairs together with Mbf1 and Asc1/RACK1 (PMID:30465652) and participating in No-Go Decay endonucleolytic cleavage (PMID:30475795). RPS3 is a target of ribosome quality control: sequential ubiquitination at lysine 212 — monoubiquitination followed by Hel2/Rsp5-mediated K63-linked polyubiquitination, balanced by the Ubp3/USP10 (mammalian RNF123/USP10) deubiquitinase axis — triggers dissociation of nonfunctional 80S ribosomes during 18S nonfunctional rRNA decay (PMID:30893611, PMID:29147007, PMID:28956756). Biogenesis of RPS3 depends on the ankyrin-repeat chaperone Yar1, which binds nascent Rps3, prevents its aggregation, and accompanies it to the nucleus, with import proceeding via the importin α/β pathway recognizing an N-terminal NLS adjacent to the Yar1-binding site (PMID:22570489, PMID:24021814, PMID:27819319). Outside the ribosome, RPS3 acts as a base-damage endonuclease cleaving AP sites, thymine glycols, and UV lesions (PMID:15707971), a role mobilized by PKCδ-dependent phosphorylation that relocalizes it from the ribosome to repair nuclear and (under ROS, via HSP90/HSP70/TOM70) mitochondrial DNA (PMID:19059439, PMID:23911537). As a 'specifier' subunit of NF-κB, RPS3 directs p65 to specific proinflammatory target genes; its nuclear translocation requires IKKβ-mediated phosphorylation at Ser209, a step targeted by bacterial effectors NleH1 and NleC (PMID:21399639, PMID:25756944, PMID:24145029). RPS3 abundance and signaling output are further controlled by ubiquitin-dependent degradation through UBE2J1-TRIM25 (at K214) and RNF138, modulating NF-κB activity and apoptosis (PMID:36567344, PMID:29371697).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 2004 Medium

    Established that RPS3 carries an apoptotic function genetically separable from its ribosomal and DNA-repair roles, first framing RPS3 as a multifunctional protein.

    Evidence GFP-fusion imaging, overexpression with caspase activity assays, and domain deletion mapping in lymphocytic cells

    PMID:14988002

    Open questions at the time
    • Mechanism linking nuclear-membrane relocalization to caspase-8/3 activation not defined
    • Physiological trigger for the apoptotic function not identified
  2. 2005 Medium

    Demonstrated that RPS3 has intrinsic broad-specificity DNA endonuclease activity, providing the biochemical basis for its non-ribosomal DNA-repair role.

    Evidence In vitro endonuclease assays on defined AP, thymine glycol, and UV-damaged DNA substrates

    PMID:15707971

    Open questions at the time
    • No catalytic residue identified by mutagenesis
    • No structural model of the active site
    • In vivo contribution to repair not established here
  3. 2008 Medium

    Showed that PKCδ phosphorylation switches RPS3 from a ribosomal to a DNA-repair function by mobilizing it to the nucleus and enhancing endonuclease activity.

    Evidence Kinase assay, subcellular fractionation, siRNA knockdown with phospho-dead mutant rescue against genotoxic stress

    PMID:19059439

    Open questions at the time
    • Phosphosite not mapped
    • Quantitative partition between ribosomal and nuclear pools not defined
  4. 2013 Medium

    Extended the repair role to mitochondria, showing ROS-driven mitochondrial accumulation of RPS3 regulated by an HSP90/HSP70-TOM70 import axis.

    Evidence Co-IP, fractionation, geldanamycin inhibition, and mtDNA damage assays

    PMID:23911537

    Open questions at the time
    • Direct mtDNA endonuclease activity in organello not shown
    • Relationship to nuclear repair pool unclear
  5. 2011 High

    Identified IKKβ phosphorylation of RPS3 at Ser209 as the gate for its nuclear translocation and function as an NF-κB specifier subunit directing gene-specific transcription.

    Evidence Phospho-specific mutagenesis, kinase assays, nuclear fractionation, gnotobiotic piglet infection with NleH1, reporter assays

    PMID:21399639

    Open questions at the time
    • How RPS3 confers promoter specificity to NF-κB not mechanistically resolved
    • Generality across stimuli beyond infection not defined
  6. 2004 Medium

    Defined the chaperone Yar1 as a dedicated escort for Rps3 in 40S biogenesis, placing it in the ribosome assembly pathway alongside Ltv1.

    Evidence Reciprocal co-IP, genetic suppression by RPS3 overexpression, polysome profiling in yeast

    PMID:15611164

    Open questions at the time
    • Order of Yar1 vs Ltv1 action only inferred genetically
    • Structural basis of binding not addressed here
  7. 2012 High

    Showed Yar1 directly binds Rps3, protects it from aggregation, and accompanies it from cytoplasm to nucleus, defining it as a specific Rps3 chaperone.

    Evidence Co-IP, in vitro aggregation assays, yeast deletion/suppression genetics, pre-rRNA and 40S export assays

    PMID:22570489

    Open questions at the time
    • Hand-off from Yar1 to nuclear assembly factors not yet defined
  8. 2013 High

    Provided the structural basis for Yar1-mediated protection of Rps3 and stepwise partner exchange during assembly.

    Evidence X-ray crystallography of the yeast Rps3–Yar1 complex at 2.8 Å

    PMID:24021814

    Open questions at the time
    • Structure of import-competent intermediates absent
    • No human RPS3 structure in this context
  9. 2016 High

    Resolved the import logic, showing the importin α/β pathway recognizes an Rps3 NLS adjacent to the Yar1 site, with Kap60 displacing Yar1 yet a trimeric complex being possible.

    Evidence In vitro reconstitution, pull-downs, affinity purification, and NLS mutagenesis

    PMID:27819319

    Open questions at the time
    • In vivo sequence of Yar1 release versus import not directly timed
    • Dimerization functional significance unclear
  10. 2017 High

    Pinpointed Rps3 entry-channel residues Arg116/Arg117 as direct mRNA contacts that govern start codon selection accuracy and PIC stabilization.

    Evidence In vitro 48S PIC reconstitution, UUG-selection genetics, and conserved-residue mutagenesis

    PMID:28223523

    Open questions at the time
    • Contribution to scanning dynamics in vivo not fully quantified
  11. 2017 Medium

    Identified RPS3 as the major TISU-element A-site contact protein, coordinated with eIF1A and exchanged for RPS10e upon 80S assembly.

    Evidence Site-specific UV cross-linking of complexes on TISU mRNA and mutagenesis

    PMID:28584194

    Open questions at the time
    • Structural basis of the RPS3→RPS10e switch unresolved
  12. 2019 Medium

    Showed that eIF1A's interaction with RPS3 (and RPS10) sets the ribosome's open/closed conformational state, with cancer eIF1A mutations weakening this contact to favor scanning of long 5' UTRs.

    Evidence Co-IP, ribosome profiling, eIF1A mutation/knockdown, reporter assays

    PMID:30420357

    Open questions at the time
    • Direct conformational measurement of RPS3 contact not performed
  13. 2018 Medium

    Demonstrated that entry-tunnel Rps3 residues mediate the endonucleolytic cleavage step of No-Go Decay, separable from ribosome ubiquitination.

    Evidence Structure-guided mutagenesis, NGD reporter, cleavage-product Northern blot, sensitivity assays in yeast

    PMID:30475795

    Open questions at the time
    • Whether Rps3 itself catalyzes cleavage or recruits a nuclease unresolved
  14. 2018 Medium

    Established that Rps3 maintains reading frame at inhibitory codon pairs, acting with Mbf1 and Asc1/RACK1 to suppress +1 frameshifting.

    Evidence Yeast genetics, frameshifting reporters, double-mutant epistasis

    PMID:30465652

    Open questions at the time
    • Molecular basis of frame maintenance at the entry site not structurally defined
  15. 2017 Medium

    Connected Rps3 ubiquitination to quality control, defining a Hel2/RNF123 (ubiquitination) versus Ubp3/USP10 (deubiquitination) balance coupled to RQC and autophagy.

    Evidence Co-IP, yeast genetics, ubiquitination assays, autophagosome localization across yeast and mammalian cells

    PMID:29147007

    Open questions at the time
    • Functional outcome of the autophagy link not fully defined
  16. 2017 Medium

    Placed Rps3 within the 18S nonfunctional rRNA decay machinery via its modified C-terminal tail, alongside Asc1/RACK1 in genetically separable NRD pathways.

    Evidence Yeast genetics, Northern blot of mutant 18S rRNA, double-mutant epistasis

    PMID:28956756

    Open questions at the time
    • Identity of the C-terminal modification not determined here
  17. 2019 High

    Defined the molecular trigger of 18S NRD: sequential ubiquitination of Rps3 at K212 drives ATPase-dependent dissociation of nonfunctional ribosomes.

    Evidence Yeast genetics, sucrose gradient fractionation, K212 site mapping, E3-ligase and Slh1 ATPase mutants

    PMID:30893611

    Open questions at the time
    • Structural basis of how K212 ubiquitin signals subunit splitting unresolved
  18. 2019 Medium

    Revealed a non-ribosomal RNA-binding role: RPS3 stabilizes SIRT1 mRNA via 3' UTR AUUUA motifs to promote hepatocellular carcinoma.

    Evidence RNA-seq, RIP, binding-site mapping, gain/loss-of-function assays

    PMID:30517713

    Open questions at the time
    • Breadth of RPS3-stabilized mRNA targets not defined
    • Link to ribosomal pool unclear
  19. 2015 Medium

    Showed bacterial NleC indirectly disrupts RPS3's NF-κB specifier function by cleaving p65 to a fragment that blocks the p65–RPS3 interaction.

    Evidence Co-IP, cleavage assays, C. rodentium mouse infection, NF-κB reporters

    PMID:25756944

    Open questions at the time
    • Stoichiometric basis of amplification not quantified
  20. 2013 Medium

    Defined how NleH1 inhibits RPS3 nuclear translocation by acting through CRKL–IKKβ rather than directly phosphorylating RPS3 or IKKβ.

    Evidence Large-scale kinase substrate screen, co-IP, siRNA rescue, fractionation, mutagenesis

    PMID:24145029

    Open questions at the time
    • How CRKL phosphorylation feeds into IKKβ activity not fully resolved
  21. 2015 Low

    Suggested an MIF–RPS3 complex sequesters RPS3, with ionizing radiation triggering dissociation to activate NF-κB.

    Evidence Co-IP, xenograft model, NF-κB reporters

    PMID:25900216

    Open questions at the time
    • Single co-IP without reciprocal validation of the dissociation mechanism
    • How dissociation mechanistically activates NF-κB unresolved
  22. 2019 Low

    Suggested LCN2 enhances NF-κB by binding RPS3 and strengthening RPS3–p65 interaction in oral cancer cells.

    Evidence Co-IP, LCN2 overexpression/knockdown, NF-κB activity assay

    PMID:31819048

    Open questions at the time
    • Single co-IP with limited mechanistic detail on how binding enhances p65 association
  23. 2018 Medium

    Identified RNF138 as an E3 ligase that degrades nuclear rpS3 to confer radioresistance, with rpS3 otherwise driving DDIT3-dependent apoptosis.

    Evidence Co-IP, interactome analysis, RNF138 knockout, xenograft model in GBM

    PMID:29371697

    Open questions at the time
    • Ubiquitination site on rpS3 not mapped here
    • Mechanism of rpS3–DDIT3 apoptosis not detailed
  24. 2020 Medium

    Placed Rps3 in a LXN–HECTD1 complex regulating IκBα turnover and thereby NF-κB inflammatory output.

    Evidence Proteomics, co-IP, IκBα ubiquitination assay, LXN-knockout colitis mouse model

    PMID:32555320

    Open questions at the time
    • Direct role of Rps3 versus HECTD1 in IκBα ubiquitination not separated
  25. 2021 Medium

    Showed circPLCE1-411 promotes RPS3 degradation by displacing it from HSP90α, dampening NF-κB nuclear translocation in colorectal cancer.

    Evidence Co-IP, LC-MS identification, gain/loss-of-function, xenograft model

    PMID:34412652

    Open questions at the time
    • E3 ligase mediating the degradation not identified here
  26. 2022 Medium

    Defined UBE2J1-TRIM25 as an E2-E3 pair that polyubiquitinates RPS3 at K214 for degradation, restraining NF-κB signaling in colorectal cancer.

    Evidence Co-IP, ubiquitination assay, K214 mutagenesis, NF-κB pathway readouts

    PMID:36567344

    Open questions at the time
    • Relationship between K214 (degradation) and K212/K214 RQC ubiquitination not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPS3's distinct functional pools — ribosomal, DNA-repair endonuclease, NF-κB specifier, and mRNA stabilizer — are quantitatively partitioned and coordinately regulated within a cell remains unresolved.
  • No unified model integrating phosphorylation, ubiquitination, and partner-binding switches
  • Catalytic residues of the DNA endonuclease activity not defined
  • Structural basis of the NF-κB specifier role missing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0005198 structural molecule activity 2 GO:0045182 translation regulator activity 2 GO:0140097 catalytic activity, acting on DNA 2 GO:0140110 transcription regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005840 ribosome 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-73894 DNA Repair 2
Partners
EIF1AXHECTD1HSP90AA1IKBKBRELARNF138TRIM25YAR1
Complex memberships
40S ribosomal small subunitNF-κB (p65-RPS3 specifier complex)RPS3-Yar1 chaperone complexUBE2J1-TRIM25 E2-E3 complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 RPS3 induces apoptosis as a third function independent of its DNA repair and ribosomal roles. GFP-rpS3 relocalizes to the nuclear membrane during rpS3-induced apoptosis in lymphocytic cells, and transient expression activates caspase-8/caspase-3 and sensitizes cells to cytokine-induced apoptosis. Deletion analysis showed DNA repair and apoptosis functions use independent domains. GFP fusion live imaging, transient overexpression, caspase activity assays, deletion analysis FEBS letters Medium 14988002
2011 IKKβ phosphorylates RPS3 at Ser209, which is required for nuclear translocation of RPS3 and its function as a subunit of NF-κB that directs specific gene transcription. E. coli O157:H7 virulence protein NleH1 specifically inhibits this IKKβ-mediated Ser209 phosphorylation, blocking RPS3 nuclear translocation and NF-κB target gene expression. Phospho-specific mutagenesis, kinase assays, nuclear fractionation, NleH1 bacterial infection model (gnotobiotic piglet), reporter assays Nature immunology High 21399639
2008 PKCδ phosphorylates RPS3, causing its mobilization from the ribosome to the nucleus for DNA repair. Phosphorylated rpS3 is found only in the non-ribosomal fraction, and its endonuclease activity is increased upon phosphorylation. Knockdown of rpS3 increases sensitivity to genotoxic stress, which is rescued by wild-type but not phosphorylation-defective rpS3. Kinase assay, subcellular fractionation, siRNA knockdown, endonuclease activity assay, rescue experiment with phospho-dead mutant Biochimica et biophysica acta Medium 19059439
2013 When ROS levels increase, rpS3 accumulates in mitochondria to repair damaged mitochondrial DNA. Nuclear import into mitochondria is regulated by interaction with HSP90 and HSP70 via TOM70. Geldanamycin (HSP90 inhibitor) decreases rpS3–HSP90 interaction and stimulates mitochondrial accumulation of rpS3, which reduces cellular ROS and rescues mtDNA damage. Co-immunoprecipitation, subcellular fractionation, pharmacological inhibition (geldanamycin), mtDNA damage assay Biochimica et biophysica acta Medium 23911537
2005 Mammalian rpS3 functions as a broad-specificity base-damage endonuclease, cleaving DNA containing AP sites, thymine glycols, pyrimidine dimers, and other UV-damaged lesions. It lacks glycosylase activity but has endonuclease activity on multiple DNA lesions. Its activity is inhibited by MgCl2 on AP DNA but not on UV-irradiated DNA. In vitro endonuclease assay on defined DNA substrates, supercoiled vs. relaxed DNA substrates, MgCl2 inhibition experiments Biochemical and biophysical research communications Medium 15707971
2012 The ankyrin repeat protein Yar1 (yeast) directly interacts with ribosomal protein Rps3, accompanies newly synthesized Rps3 from cytoplasm to nucleus where it assembles into pre-ribosomal subunits, and protects Rps3 from aggregation in vitro and increases its solubility in vivo. Yar1 acts as a specific chaperone for Rps3. Co-immunoprecipitation, in vitro aggregation assay, yeast genetics (deletion strains, suppression by RPS3 overexpression), 20S pre-rRNA accumulation and 40S export assays The Journal of biological chemistry High 22570489
2013 Crystal structure of yeast rpS3 in complex with its chaperone Yar1 resolved at 2.8 Å. The structure explains how Yar1 protects rpS3 from aggregation while facilitating nuclear import, and suggests a stepwise exchange of molecular partners during ribosome assembly. X-ray crystallography at 2.8 Å resolution Journal of molecular biology High 24021814
2016 Newly synthesized Rps3 forms a dimer associated with one Yar1 chaperone molecule. Nuclear import of Rps3 proceeds via the classical importin α/β (Kap60/Kap95) pathway, which recognizes an N-terminal NLS in Rps3 directly adjacent to the Yar1-binding site. Kap60 binding to the Rps3 NLS displaces Yar1 in vitro, yet a trimeric Rps3/Yar1/Kap60 complex can be reconstituted in vitro and is detected in vivo. In vitro reconstitution of protein complexes, pull-down assays, affinity purifications, NLS mapping by mutagenesis Scientific reports High 27819319
2004 Yar1 (yeast) physically interacts with Rps3 and with Ltv1 (a pre-40S particle component). Genetic and biochemical evidence shows Yar1 and Ltv1 function in 40S subunit production. Overexpression of RPS3 suppresses stress sensitivity and ribosome biogenesis defects of Δyar1 but not Δltv1 mutants, placing Yar1 upstream of/at Rps3 in the assembly pathway. Co-immunoprecipitation, yeast genetic epistasis (suppression by RPS3 overexpression), polysome profiling Genetics Medium 15611164
2017 Rps3/uS3 resides in the mRNA entry channel of the 40S subunit and contacts mRNA via conserved residues Arg116 and Arg117. Substitutions at these residues reduce bulk translation initiation, diminish near-cognate UUG start codon selection, and increase discrimination against AUG in poor Kozak context. In vitro reconstitution showed these residues stabilize TC binding to 48S PICs with UUG codons (closed PIN state), and Arg116/117 are crucial for PIC-mRNA contacts at the entry channel. In vitro reconstitution of 48S PICs, yeast genetics (UUG selection assays), mutagenesis of conserved residues, translation initiation assays Proceedings of the National Academy of Sciences of the United States of America High 28223523
2017 RPS3 is the major TISU-element binding protein at the A site of the 48S ribosomal complex. Upon 80S complex formation, RPS3 interaction weakens and binding switches to RPS10e. TISU-directed translation initiation is particularly dependent on eIF1A, which interacts with both RPS3 and RPS10e. Site-specific UV cross-linking of ribosomal complexes assembled on TISU mRNA, comprehensive mutagenesis Molecular and cellular biology Medium 28584194
2018 Rps3/uS3 acts with Mbf1 and Asc1/RACK1 to prevent +1 frameshifting at inhibitory CGA-CGA codon pairs in yeast. Mutations in RPS3 near the mRNA entry site allow frameshifting. Mbf1 and Rps3 cooperate to maintain reading frame of stalled ribosomes. Frameshifting involves competition between codons entering the A site when the P-site CGA codon destabilizes elongation. Yeast genetic analysis, frameshifting reporter assays, double mutant analysis (epistasis) eLife Medium 30465652
2019 Sequential ubiquitination of uS3/Rps3 at lysine 212 is required for 18S non-functional rRNA decay (NRD). Mag2-mediated monoubiquitination followed by Hel2- and Rsp5-mediated K63-linked polyubiquitination triggers dissociation of the non-functional 80S ribosome into subunits, which requires the ATPase activity of Slh1 (Rqt2), as well as Asc1 and Dom34. Yeast genetics, sucrose gradient fractionation, ubiquitination site mapping (K212), E3 ligase deletion mutants, ATPase mutant analysis Cell reports High 30893611
2017 The balance of Rps3 mono-ubiquitination is controlled by reciprocal action of Hel2 E3 ligase (ubiquitination) and Ubp3 deubiquitinase (deubiquitination) in yeast, and their mammalian counterparts RNF123 and USP10 in mammalian cells. Rps3 mono-ubiquitination is coupled to ribosome quality control and autophagy. Co-immunoprecipitation, yeast genetic analysis, ubiquitination assays, autophagosome localization Experimental & molecular medicine Medium 29147007
2017 Asc1/RACK1 and Rps3 are factors in 18S nonfunctional rRNA decay (NRD) in yeast. A small region of the Rps3 C-terminal tail subject to post-translational modification is crucial for 18S NRD. Complete stabilization of mutant 18S rRNA occurs in dom34Δ;asc1Δ double mutants, indicating two genetically separable NRD pathways. Yeast genetic analysis, Northern blot for mutant 18S rRNA levels, epistasis in double mutants RNA Medium 28956756
2018 Residues of Rps3 at the mRNA entry tunnel of the ribosomal small subunit are important for No-Go Decay (NGD). Mutations in these entry-channel contact residues significantly reduce accumulation of NGD cleavage products, render cells sensitive to NGD-triggering agents, and are distinct from effects on ribosome ubiquitination, suggesting Rps3 plays a role in the endonucleolytic cleavage step of NGD independent of upstream RQC events. Yeast genetics with site-directed mutagenesis of mRNA-contact residues, NGD reporter assay, cleavage product Northern blot, sensitivity assays PLoS genetics Medium 30475795
2019 RPS3 functions as an RNA-binding protein that stabilizes SIRT1 mRNA post-transcriptionally by binding to AUUUA motifs in the 3' UTR (positions 3448-3530) of SIRT1 mRNA, thereby promoting HCC tumorigenesis. RNA-seq, RIP (RNA immunoprecipitation), gain/loss-of-function assays, 3' UTR binding site mapping Nucleic acids research Medium 30517713
2015 NleC metalloprotease of A/E pathogens cleaves p65, generating a p65(1-38) fragment that interferes with the interaction between p65 and RPS3, disrupting RPS3's role as a 'specifier' subunit of NF-κB for proinflammatory gene transcription. This amplifies the effect of cleaving a small percentage of p65. Co-immunoprecipitation, cleavage assays, mouse infection model (C. rodentium), NF-κB reporter assays PLoS pathogens Medium 25756944
2013 E. coli NleH1 virulence effector prevents nuclear translocation of RPS3 to inhibit NF-κB by binding to CRKL, which interacts with IKKβ. NleH1 kinase activity is required to phosphorylate CRKL, and CRKL knockdown prevents NleH1 from inhibiting RPS3 nuclear translocation. Neither RPS3 nor IKKβ is a direct NleH1 kinase substrate. Large-scale kinase substrate screen (~9,000 proteins), co-immunoprecipitation, siRNA knockdown, nuclear fractionation, mutagenesis The Journal of biological chemistry Medium 24145029
2018 RNF138 E3 ubiquitin ligase ubiquitinates nuclear rpS3 in irradiated GBM cells, leading to ubiquitin-dependent degradation of rpS3 and consequent radioresistance. In ΔRNF138 cells, nuclear rpS3 accumulates and interacts with DDIT3, leading to DDIT3-induced apoptosis. Co-immunoprecipitation, interactome analysis, RNF138 knockout, in vivo xenograft model Experimental & molecular medicine Medium 29371697
2022 The E2-E3 ubiquitin complex UBE2J1-TRIM25 physically interacts with RPS3 and targets it for poly-ubiquitination and degradation at the K214 residue, leading to reduced RPS3 levels, restraint of NF-κB nuclear translocation, and inactivation of NF-κB signaling in colorectal cancer cells. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K214), overexpression/knockdown with NF-κB pathway readout Oncogene Medium 36567344
2021 circPLCE1-encoded protein circPLCE1-411 promotes ubiquitin-dependent degradation of RPS3 by binding to the HSP90α/RPS3 complex and facilitating dissociation of RPS3 from HSP90α, thereby reducing NF-κB nuclear translocation in colorectal cancer cells. Co-immunoprecipitation, LC-MS protein identification, gain/loss of function assays, in vivo xenograft model Molecular cancer Medium 34412652
2020 Latexin (LXN) forms a functional complex with HECTD1 (E3 ubiquitin ligase) and Rps3. LXN deficiency enhances the HECTD1–Rps3 interaction, promoting ubiquitination and degradation of IκBα (a HECTD1 substrate), thereby enhancing NF-κB inflammatory responses. Ectopic LXN expression leads to IκBα accumulation. Proteomics, co-immunoprecipitation, IκBα ubiquitination assay, LXN knockout mouse model (DSS-colitis) Scientific reports Medium 32555320
2015 RPS3 physically interacts with MIF (macrophage migration inhibitory factor) under unirradiated conditions. Ionizing radiation induces dissociation of the MIF-rpS3 complex, activating NF-κB and its target genes. MIF-rpS3 dissociation also modulates epithelial-mesenchymal transition marker expression and pro-inflammatory cytokine secretion. Co-immunoprecipitation, xenograft tumor model, NF-κB reporter assays Journal of cellular biochemistry Low 25900216
2019 LCN2 promotes NF-κB activation by binding to RPS3 and enhancing the interaction between RPS3 and p65 in oral squamous cell carcinoma cells. Co-immunoprecipitation, LCN2 overexpression/knockdown, NF-κB activity assay Cell death & disease Low 31819048
2019 Cancer-associated eIF1A N-terminal tail mutations diminish eIF1A interaction with RPS3 and RPS10, retaining the ribosome in an open state that facilitates scanning of long 5' UTR-containing cell cycle genes. Co-immunoprecipitation, ribosome profiling, eIF1A knockdown/mutation, reporter assays Molecular and cellular biology Medium 30420357

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proceedings of the National Academy of Sciences of the United States of America 319 8876135
2016 Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study. The Lancet. Global health 151 26833239
2007 US3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin A/C in infected cells. Journal of virology 146 17428859
2004 Herpes simplex virus protein kinase US3 activates and functionally overlaps protein kinase A to block apoptosis. Proceedings of the National Academy of Sciences of the United States of America 134 15192152
2004 RpS3, a DNA repair endonuclease and ribosomal protein, is involved in apoptosis. FEBS letters 129 14988002
2013 Herpes simplex virus 1 serine/threonine kinase US3 hyperphosphorylates IRF3 and inhibits beta interferon production. Journal of virology 125 24049179
2011 IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7. Nature immunology 124 21399639
1987 Identification of the herpes simplex virus protein kinase as the product of viral gene US3. The Journal of general virology 122 2822848
2005 Identification of proteins phosphorylated directly by the Us3 protein kinase encoded by herpes simplex virus 1. Journal of virology 104 15994828
1995 The US3-encoded protein kinase from pseudorabies virus affects egress of virions from the nucleus. The Journal of general virology 104 9049392
2004 The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology 102 14980482
2006 Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31. Journal of virology 101 16415024
2005 The protein encoded by the US3 orthologue of Marek's disease virus is required for efficient de-envelopment of perinuclear virions and involved in actin stress fiber breakdown. Journal of virology 101 15767401
2014 Herpes simplex virus 1 protein kinase US3 hyperphosphorylates p65/RelA and dampens NF-κB activation. Journal of virology 100 24807716
2007 Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3. Journal of virology 99 17652388
2000 Human cytomegalovirus gene products US3 and US6 down-regulate trophoblast class I MHC molecules. Journal of immunology (Baltimore, Md. : 1950) 94 10623826
2014 HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation. Proceedings of the National Academy of Sciences of the United States of America 89 24449861
2019 Vitamin D promotes the cisplatin sensitivity of oral squamous cell carcinoma by inhibiting LCN2-modulated NF-κB pathway activation through RPS3. Cell death & disease 85 31819048
2021 A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation. Molecular cancer 79 34412652
2019 Sequential Ubiquitination of Ribosomal Protein uS3 Triggers the Degradation of Non-functional 18S rRNA. Cell reports 79 30893611
2006 Composition of pseudorabies virus particles lacking tegument protein US3, UL47, or UL49 or envelope glycoprotein E. Journal of virology 76 16415010
2012 An essential pentatricopeptide repeat protein facilitates 5' maturation and translation initiation of rps3 mRNA in maize mitochondria. The Plant cell 73 22773745
2011 Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function. Journal of virology 70 21653669
2013 Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance. Biochimica et biophysica acta 67 23911537
2008 Herpes simplex virus type 1 Us3 gene deletion influences toll-like receptor responses in cultured monocytic cells. Virology journal 67 19025601
2020 β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by the Herpes Simplex Virus 1 US3 Protein. Journal of virology 63 31801859
2003 The herpes simplex virus 1 US3 protein kinase blocks caspase-dependent double cleavage and activation of the proapoptotic protein BAD. Journal of virology 63 12743316
2009 Fast evolution of the retroprocessed mitochondrial rps3 gene in Conifer II and further evidence for the phylogeny of gymnosperms. Molecular phylogenetics and evolution 62 19761858
2008 PKCdelta-dependent functional switch of rpS3 between translation and DNA repair. Biochimica et biophysica acta 61 19059439
2003 Pseudorabies virus US3 protein kinase mediates actin stress fiber breakdown. Journal of virology 61 12885923
2000 Expression of herpes simplex virus type 2 US3 affects the Cdc42/Rac pathway and attenuates c-Jun N-terminal kinase activation. Genes to cells : devoted to molecular & cellular mechanisms 59 11168588
2012 Yar1 protects the ribosomal protein Rps3 from aggregation. The Journal of biological chemistry 58 22570489
2003 The Us3 protein kinase of herpes simplex virus 1 blocks apoptosis and induces phosporylation of the Bcl-2 family member Bad. Experimental cell research 57 14597423
1991 RNA editing makes mistakes in plant mitochondria: editing loses sense in transcripts of a rps19 pseudogene and in creating stop codons in coxI and rps3 mRNAs of Oenothera. Nucleic acids research 57 1762921
2015 Metalloprotease NleC suppresses host NF-κB/inflammatory responses by cleaving p65 and interfering with the p65/RPS3 interaction. PLoS pathogens 56 25756944
2011 US3 protein kinase of HSV-1 cycles between the cytoplasm and nucleus and interacts with programmed cell death protein 4 (PDCD4) to block apoptosis. Proceedings of the National Academy of Sciences of the United States of America 55 21844356
2004 The pseudorabies virus US3 protein is a component of primary and of mature virions. Journal of virology 55 14722286
2018 Mt-rps3 is an ancient gene which provides insight into the evolution of fungal mitochondrial genomes. Molecular phylogenetics and evolution 53 29763662
2002 U(S)3 protein kinase of herpes simplex virus 1 blocks caspase 3 activation induced by the products of U(S)1.5 and U(L)13 genes and modulates expression of transduced U(S)1.5 open reading frame in a cell type-specific manner. Journal of virology 53 11752164
2019 Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3. PLoS pathogens 52 30682178
2018 RNF138-mediated ubiquitination of rpS3 is required for resistance of glioblastoma cells to radiation-induced apoptosis. Experimental & molecular medicine 52 29371697
2009 Analysis of filamentous process induction and nuclear localization properties of the HSV-2 serine/threonine kinase Us3. Virology 52 19945726
2010 Keep it in the subfamily: the conserved alphaherpesvirus US3 protein kinase. The Journal of general virology 51 20943887
2009 Regulation of the catalytic activity of herpes simplex virus 1 protein kinase Us3 by autophosphorylation and its role in pathogenesis. Journal of virology 50 19297494
2006 Role of pseudorabies virus Us3 protein kinase during neuronal infection. Journal of virology 50 16775327
2005 Characterization of a wide range base-damage-endonuclease activity of mammalian rpS3. Biochemical and biophysical research communications 50 15707971
2004 Genetic and biochemical interactions among Yar1, Ltv1 and Rps3 define novel links between environmental stress and ribosome biogenesis in Saccharomyces cerevisiae. Genetics 50 15611164
2011 Herpes simplex virus 1 protein kinase Us3 and major tegument protein UL47 reciprocally regulate their subcellular localization in infected cells. Journal of virology 49 21734045
2017 Rps3/uS3 promotes mRNA binding at the 40S ribosome entry channel and stabilizes preinitiation complexes at start codons. Proceedings of the National Academy of Sciences of the United States of America 47 28223523
2013 Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination. Virology 47 23478027
2009 Differences in the regulatory and functional effects of the Us3 protein kinase activities of herpes simplex virus 1 and 2. Journal of virology 47 19740999
2003 The herpes simplex virus-1 Us3 protein kinase blocks CD8T cell lysis by preventing the cleavage of Bid by granzyme B. Cell death and differentiation 46 12934063
1994 Rps3 and rpl16 genes do not overlap in Oenothera mitochondria: GTG as a potential translation initiation codon in plant mitochondria? Plant molecular biology 46 8193306
2019 RNA-binding protein RPS3 contributes to hepatocarcinogenesis by post-transcriptionally up-regulating SIRT1. Nucleic acids research 45 30517713
2004 The pseudorabies virus serine/threonine kinase Us3 contains mitochondrial, nuclear and membrane localization signals. Virus genes 45 15215691
1999 Evolution of the mitochondrial rps3 intron in perennial and annual angiosperms and homology to nad5 intron 1. Molecular biology and evolution 45 10331271
2010 Transduced PEP-1-ribosomal protein S3 (rpS3) ameliorates 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. Toxicology 43 20709134
2018 Multi-protein bridging factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting. eLife 42 30465652
2017 Modulating cellular balance of Rps3 mono-ubiquitination by both Hel2 E3 ligase and Ubp3 deubiquitinase regulates protein quality control. Experimental & molecular medicine 42 29147007
2013 Herpes simplex virus 1 protein kinase Us3 phosphorylates viral dUTPase and regulates its catalytic activity in infected cells. Journal of virology 42 24173231
1993 The pathogenicity of a US3 protein kinase-deficient mutant of herpes simplex virus type 2 in mice. Archives of virology 42 8257288
2006 U(S)3 and U(S)3.5 protein kinases of herpes simplex virus 1 differ with respect to their functions in blocking apoptosis and in virion maturation and egress. Journal of virology 41 16571792
2017 Efficient and Accurate Translation Initiation Directed by TISU Involves RPS3 and RPS10e Binding and Differential Eukaryotic Initiation Factor 1A Regulation. Molecular and cellular biology 40 28584194
2007 A point mutation in the putative ATP binding site of the pseudorabies virus US3 protein kinase prevents Bad phosphorylation and cell survival following apoptosis induction. Virus research 40 17499381
2014 Herpes simplex virus protein kinases US3 and UL13 modulate VP11/12 phosphorylation, virion packaging, and phosphatidylinositol 3-kinase/Akt signaling activity. Journal of virology 39 24741093
2013 Us3 kinase encoded by herpes simplex virus 1 mediates downregulation of cell surface major histocompatibility complex class I and evasion of CD8+ T cells. PloS one 38 23951282
2022 UBE2J1 inhibits colorectal cancer progression by promoting ubiquitination and degradation of RPS3. Oncogene 37 36567344
2021 Cisplatin-Resistant Gastric Cancer Cells Promote the Chemoresistance of Cisplatin-Sensitive Cells via the Exosomal RPS3-Mediated PI3K-Akt-Cofilin-1 Signaling Axis. Frontiers in cell and developmental biology 37 33644057
2015 Dissociation of MIF-rpS3 complex and sequential NF-κB activation is involved in IR-induced metastatic conversion of NSCLC. Journal of cellular biochemistry 37 25900216
1994 Identification of a target protein of US3 protein kinase of herpes simplex virus type 2. The Journal of general virology 37 8046410
1992 Location, characterization and expression of lytic enzyme-encoding gene, lytA, of Lactococcus lactis bacteriophage phi US3. Gene 37 1355060
2009 The kinase activity of pseudorabies virus US3 is required for modulation of the actin cytoskeleton. Virology 36 19136132
2015 RPS3 regulates melanoma cell growth and apoptosis by targeting Cyto C/Ca2+/MICU1 dependent mitochondrial signaling. Oncotarget 35 26336993
2012 Suppression of extracellular signal-regulated kinase activity in herpes simplex virus 1-infected cells by the Us3 protein kinase. Journal of virology 33 22593153
2018 Us3 Protein Kinase Encoded by HSV: The Precise Function and Mechanism on Viral Life Cycle. Advances in experimental medicine and biology 32 29896662
2015 Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression. Journal of virology 32 25878107
2013 Suppression of apoptosis by pseudorabies virus Us3 protein kinase through the activation of PI3-K/Akt and NF-κB pathways. Research in veterinary science 32 23835241
2013 Crystal structure of the yeast ribosomal protein rpS3 in complex with its chaperone Yar1. Journal of molecular biology 32 24021814
2007 Herpes simplex virus Us3(-) mutant as oncolytic strategy and synergizes with phosphatidylinositol 3-kinase-Akt targeting molecular therapeutics. Clinical cancer research : an official journal of the American Association for Cancer Research 32 17908985
2021 The US3 Kinase of Herpes Simplex Virus Phosphorylates the RNA Sensor RIG-I To Suppress Innate Immunity. Journal of virology 31 34935440
2007 In transduced cells, the US3 protein kinase of herpes simplex virus 1 precludes activation and induction of apoptosis by transfected procaspase 3. Journal of virology 30 17634220
2002 Herpes simplex virus type 2 US3 blocks apoptosis induced by sorbitol treatment. Microbes and infection 30 12067830
2022 Alphaherpesvirus US3 protein-mediated inhibition of the m6A mRNA methyltransferase complex. Cell reports 29 35858564
2020 Latexin deficiency in mice up-regulates inflammation and aggravates colitis through HECTD1/Rps3/NF-κB pathway. Scientific reports 29 32555320
2018 Feline Herpesvirus 1 US3 Blocks the Type I Interferon Signal Pathway by Targeting Interferon Regulatory Factor 3 Dimerization in a Kinase-Independent Manner. Journal of virology 29 29618645
2017 ASC1 and RPS3: new actors in 18S nonfunctional rRNA decay. RNA (New York, N.Y.) 28 28956756
2016 Nuclear import of dimerized ribosomal protein Rps3 in complex with its chaperone Yar1. Scientific reports 28 27819319
2013 Phosphorylation of a herpes simplex virus 1 dUTPase by a viral protein kinase, Us3, dictates viral pathogenicity in the central nervous system but not at the periphery. Journal of virology 28 24352467
1999 Identification of the US3 gene product of BHV-1 as a protein kinase and characterization of BHV-1 mutants of the US3 gene. Virus research 27 10854163
1995 The rps3-rpl16-nad3-rps12 gene cluster in rice mitochondrial DNA is transcribed from alternative promoters. Current genetics 27 7788722
2013 Alphaherpesviral US3 kinase induces cofilin dephosphorylation to reorganize the actin cytoskeleton. Journal of virology 26 23365433
2020 Differentiating the Roles of UL16, UL21, and Us3 in the Nuclear Egress of Herpes Simplex Virus Capsids. Journal of virology 25 32321804
2009 Pseudorabies virus US3- and UL49.5-dependent and -independent downregulation of MHC I cell surface expression in different cell types. Virology 25 19819514
2021 Pseudorabies Virus US3 Protein Inhibits IFN-β Production by Interacting With IRF3 to Block Its Activation. Frontiers in microbiology 24 34745071
2019 Cancer-Associated Eukaryotic Translation Initiation Factor 1A Mutants Impair Rps3 and Rps10 Binding and Enhance Scanning of Cell Cycle Genes. Molecular and cellular biology 24 30420357
2019 Construction of a US7/US8/UL23/US3-deleted recombinant pseudorabies virus and evaluation of its pathogenicity in dogs. Veterinary microbiology 24 31902487
2018 Interactions between the mRNA and Rps3/uS3 at the entry tunnel of the ribosomal small subunit are important for no-go decay. PLoS genetics 24 30475795
2013 Escherichia coli virulence protein NleH1 interaction with the v-Crk sarcoma virus CT10 oncogene-like protein (CRKL) governs NleH1 inhibition of the ribosomal protein S3 (RPS3)/nuclear factor κB (NF-κB) pathway. The Journal of biological chemistry 24 24145029
2004 Structural and functional analysis of human cytomegalovirus US3 protein. Journal of virology 24 14671122
2006 Herpes simplex virus US3 protein kinase regulates virus-induced apoptosis in olfactory and vomeronasal chemosensory neurons in vivo. Microbes and infection 23 16815072

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