Affinage

RPS23

Small ribosomal subunit protein uS12 · UniProt P62266

Length
143 aa
Mass
15.8 kDa
Annotated
2026-06-10
34 papers in source corpus 7 papers cited in narrative 7 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPS23 (uS12) is a conserved component of the 40S small ribosomal subunit whose universally conserved PNSA loop and Pro-62 residue couple ribosome function to translational fidelity and oxygen sensing (PMID:24550447, PMID:33368752). Its conserved Pro-62 is post-translationally hydroxylated by the prolyl hydroxylase OGFOD1 in humans, which retains high affinity for and forms a stable complex with the hydroxylated substrate; loss of OGFOD1 activity triggers stress granule formation, translational arrest, and growth impairment (PMID:24550447). In fission yeast the orthologous Ofd1 dihydroxylates Rps23 Pro-62 in a complex with the nuclear import adaptor Nro1, which both imports unassembled Rps23 into the nucleus for 40S assembly and, under low oxygen, stabilizes the Ofd1-Rps23-Nro1 complex to sequester Ofd1 away from the Sre1 transcription factor, thereby licensing hypoxic gene expression (PMID:29083304). The conserved PNSA loop of uS12 contributes directly to translation initiation, elongation, and ribosome recycling, as revealed by bacterial mutations that confer cold sensitivity and ribosome biogenesis defects and that genetically interact with IF3, EF-G, ribosome recycling factor, and peptidyl-tRNA hydrolase (PMID:33368752, PMID:34889476). uS12 also functionally interacts with 16S rRNA modification, since loss of RsmG-mediated m7G527 methylation modulates streptomycin resistance and dependence phenotypes of uS12 mutants (PMID:40377667).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 1994 Medium

    Establishing the primary structure of mammalian ribosomal protein S23 defined the protein product, its post-translational N-terminal processing, and confirmed sequence identity between rat and human, anchoring all subsequent functional work.

    Evidence cDNA sequencing and Southern blot in rat

    PMID:8037726

    Open questions at the time
    • No functional or mechanistic role assigned at this stage
    • Gene copy number resolution (6-13 copies) leaves true expressed locus uncertain
  2. 2014 High

    Identifying OGFOD1 as a prolyl hydroxylase acting on RPS23 Pro-62 revealed that this ribosomal protein is a target of regulated post-translational hydroxylation linked to translational control, since loss of the modifying enzyme caused stress granule induction and translational arrest.

    Evidence In vitro hydroxylation assay, mass spectrometry, Co-IP, siRNA knockdown with wild-type vs catalytically inactive rescue in human cells

    PMID:24550447

    Open questions at the time
    • Direct effect of Pro-62 hydroxylation on ribosome function or fidelity not resolved
    • Whether the stress phenotype is caused by loss of hydroxylation per se or sequestration is unclear
  3. 2017 High

    Reconstituting the Ofd1-Rps23-Nro1 complex in fission yeast showed how Rps23 hydroxylation status and abundance act as an oxygen-sensing node that controls availability of Ofd1 to the hypoxic transcription factor Sre1, connecting ribosome assembly to hypoxic gene expression.

    Evidence In vitro pulldown binding assays, dihydroxylation assay, genetic epistasis, nuclear import and oxygen-dependent complex stabilization assays

    PMID:29083304

    Open questions at the time
    • Whether the human OGFOD1 system shares the Nro1/Sre1-equivalent oxygen-sensing circuit is not established here
    • Stoichiometry and structure of the ternary complex not resolved
  4. 2021 Medium

    Mutational analysis of the conserved PNSA loop of uS12 in bacteria assigned this element direct roles across translation initiation, elongation, and ribosome recycling, going beyond a purely structural ribosomal role.

    Evidence Bacterial rpsL mutagenesis, cold-sensitive growth, ribosome biogenesis assays, and genetic interaction with RRF and Pth (and IF3/EF-G in companion suppressor study)

    PMID:33368752 PMID:34889476

    Open questions at the time
    • Molecular mechanism by which the PNSA loop affects recycling not biochemically reconstituted
    • Relevance of bacterial uS12 loop functions to mammalian RPS23 not tested
  5. 2025 Medium

    Combinatorial genetics with the 16S rRNA methyltransferase RsmG demonstrated a functional interaction between uS12 and rRNA modification, showing that m7G527 status tunes streptomycin resistance and dependence phenotypes of uS12 mutants.

    Evidence Bacterial genetics, MIC determination, rsmG/uS12 double-mutant analysis

    PMID:40377667

    Open questions at the time
    • Mechanistic basis of the uS12-rRNA modification crosstalk not defined
    • Restricted to antibiotic-resistance phenotypes

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether the bacterial uS12 PNSA-loop functions in fidelity and recycling, and the fission yeast oxygen-sensing circuit, are mechanistically conserved in the human RPS23-OGFOD1 system remains unresolved.
  • No structural model of human RPS23 hydroxylation within the assembled 40S
  • No demonstration that human Pro-62 hydroxylation alters translational fidelity
  • Human equivalents of Nro1/Sre1 oxygen-sensing not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005840 ribosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-8953897 Cellular responses to stimuli 1
Partners
NRO1OFD1OGFOD1
Complex memberships
40S ribosomal subunitOfd1-Rps23-Nro1 complex

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 OGFOD1 is a prolyl hydroxylase that catalyzes the post-translational hydroxylation of Pro-62 in human RPS23 (small ribosomal protein S23). Unusually, OGFOD1 retains high affinity for and forms a stable complex with the hydroxylated RPS23 substrate. Knockdown or inactivation of OGFOD1 caused stress granule induction, translational arrest, and growth impairment, complemented by wild-type but not catalytically inactive OGFOD1. In vitro hydroxylation assay, mass spectrometry, Co-IP/stable complex characterization, siRNA knockdown with phenotypic rescue by wild-type vs. inactive OGFOD1 Proceedings of the National Academy of Sciences of the United States of America High 24550447
2017 In fission yeast, Nro1 (nuclear import adaptor) binds unassembled uS12/Rps23, and Ofd1 (prolyl-3,4-dihydroxylase) dihydroxylates Rps23 Pro-62 in complex with Nro1. Concurrently, Nro1 imports Rps23 into the nucleus for assembly into 40S ribosomes. Low oxygen inhibits Ofd1 hydroxylase activity and stabilizes the Ofd1-Rps23-Nro1 complex, sequestering Ofd1 from its substrate Sre1 transcription factor, thereby freeing Sre1 to activate hypoxic gene expression. In vitro studies demonstrated direct binding of Ofd1 to Rps23, Nro1, and Sre1 through a consensus binding sequence. Rps23 expression level modulates Sre1 activity by changing the substrate pool available to Ofd1. In vitro binding assays (pulldown), dihydroxylation assay, genetic epistasis, nuclear import experiments, oxygen-dependent complex stabilization assays eLife High 29083304
2021 A mutation in the universally conserved PNSA loop of uS12 (L48K in E. coli) causes a cold-sensitive phenotype and ribosome biogenesis defect. The L48K mutation impairs translation initiation and elongation steps. Genetic interactions with ribosome recycling factor (RRF) and peptidyl-tRNA hydrolase (Pth) reveal a novel role for the PNSA loop of uS12 in ribosome recycling. Bacterial genetics (rpsL gene mutagenesis), cold-sensitive growth phenotype, ribosome biogenesis assays, genetic interaction analysis with RRF and Pth Molecular microbiology Medium 33368752
2021 In E. coli, mutations in uS12 (V32L or H76L) suppress growth defects caused by an unconventional initiator tRNA. H76L enhances fidelity of initiator tRNA selection, while V32L compensates for deficient fidelity through ribosome recycling factor (RRF)-dependent mechanisms. Genetic networks between uS12, IF3, initiator tRNA, EF-G, RRF, and Pth collectively govern translation fidelity. Suppressor genetics (spontaneous suppressor isolation), growth phenotype analysis, genetic epistasis with IF3, RRF, EF-G, and Pth Molecular microbiology Medium 34889476
2025 RsmG methylation of G527 in 16S rRNA functionally interacts with uS12: loss of m7G527 methylation (rsmG inactivation) alters streptomycin resistance phenotypes of specific uS12 mutants and, combined with uS12 R85H, generates very high streptomycin resistance. rsmG null mutations combined with specific uS12 alterations can also generate streptomycin dependence or pseudo-dependence. Bacterial genetics, MIC determination, combinatorial rsmG/uS12 double mutant analysis Archives of microbiology Medium 40377667
1994 The primary structure of rat ribosomal protein S23 was determined: it has 142 amino acids (N-terminal methionine is removed post-translationally), molecular weight 15,666 Da. The rat sequence is identical to human RPS23. The gene exists in 6–13 copies in the rat genome and the mRNA is ~650 nucleotides. cDNA sequencing, Southern blot hybridization Biochemical and biophysical research communications Medium 8037726
2010 Amphioxus RPS23 (BjRPS23) acts as a pattern recognition receptor capable of binding LPS, LTA, and PGN, and as an antimicrobial effector killing Gram-negative and Gram-positive bacteria. The core antimicrobial region was mapped to residues 67–84. BjRPS23 functions by membranolytic mechanisms including interaction with bacterial membranes via LPS/LTA/PGN, membrane depolarization, and stimulation of intracellular ROS production in bacteria. Recombinant protein production, direct bacterial killing assays, pattern recognition binding assays, truncation/deletion mapping, membrane depolarization assays, ROS measurement Developmental and comparative immunology Medium 32423862

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1979 Sequence of the 16 S-23 s spacer region in two ribosomal RNA operons of Escherichia coli. The Journal of biological chemistry 109 372188
2014 OGFOD1 catalyzes prolyl hydroxylation of RPS23 and is involved in translation control and stress granule formation. Proceedings of the National Academy of Sciences of the United States of America 99 24550447
1976 The isolation of eukaryotic ribosomal proteins. The purification and characterization of the 40 S ribosomal subunit proteins S2, S3, S4, S5, S6, S7, S8, S9, S13, S23/S24, S27, and S28. The Journal of biological chemistry 72 947902
1987 Three mutants of herpes simplex virus type 2: one lacking the genes US10, US11 and US12 and two in which Rs has been extended by 6 kb to 0.91 map units with loss of Us sequences between 0.94 and the Us/TRs junction. The Journal of general virology 50 3027237
2006 Members of the HCMV US12 family of predicted heptaspanning membrane proteins have unique intracellular distributions, including association with the cytoplasmic virion assembly complex. Virology 39 17188320
2010 Characterization of in vitro generated metabolites of the selective androgen receptor modulators S-22 and S-23 and in vivo comparison to post-administration canine urine specimens. Drug testing and analysis 37 20967890
1996 p53 transactivation domain mutant Q22, S23 is impaired for repression of promoters and mediation of apoptosis. Oncogene 29 8668332
2006 Primate cytomegalovirus US12 gene family: a distinct and diverse clade of seven-transmembrane proteins. Virology 26 16904149
2006 Herpes simplex virus genes Us3, Us5, and Us12 differentially regulate cytotoxic T lymphocyte-induced cytotoxicity. Viral immunology 26 16987059
2020 Identification and functional characterization of ribosomal protein S23 as a new member of antimicrobial protein. Developmental and comparative immunology 25 32423862
2000 Subtyping of uncultured bartonellae using sequence comparison of 16 S/23 S rRNA intergenic spacer regions amplified directly from infected blood. Molecular and cellular probes 25 10799268
2019 Identification of S23 causing both interspecific hybrid male sterility and environment-conditioned male sterility in rice. Rice (New York, N.Y.) 19 30820693
2010 The Rps23rg gene family originated through retroposition of the ribosomal protein s23 mRNA and encodes proteins that decrease Alzheimer's beta-amyloid level and tau phosphorylation. Human molecular genetics 18 20650958
2006 Infection-dependent nuclear localization of US17, a member of the US12 family of human cytomegalovirus-encoded seven-transmembrane proteins. Journal of virology 15 16414996
2017 Morphology, topology and dimensions of the heart and arteries of genetically normal and mutant mouse embryos at stages S21-S23. Journal of anatomy 14 28776665
2020 Metabolic studies of selective androgen receptor modulators RAD140 and S-23 in horses. Drug testing and analysis 13 32853476
2015 Dysregulated COL3A1 and RPL8, RPS16, and RPS23 in Disc Degeneration Revealed by Bioinformatics Methods. Spine 13 25893343
2013 Overexpression, purification, molecular characterization and pharmacological evaluation for anticancer activity of ribosomal protein S23 from the giant panda (Ailuropoda melanoleuca). Molecular medicine reports 13 23591681
2021 A mutation in the ribosomal protein uS12 reveals novel functions of its universally conserved PNSA loop. Molecular microbiology 10 33368752
2009 Thiosulfate oxidation by Comamonas sp. S23 isolated from a sulfur spring. Current microbiology 9 19189181
2020 Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses. Virology journal 8 32650799
2017 Prolyl dihydroxylation of unassembled uS12/Rps23 regulates fungal hypoxic adaptation. eLife 8 29083304
1994 The primary structure of rat ribosomal protein S23. Biochemical and biophysical research communications 8 8037726
2021 Systematic evolution of initiation factor 3 and the ribosomal protein uS12 optimizes Escherichia coli growth with an unconventional initiator tRNA. Molecular microbiology 7 34889476
2023 HCMV-encoded viral protein US12 promotes autophagy by inducing autophagy flux. Biochemical and biophysical research communications 5 36898229
2023 Draft Genome Sequence of Enterobacter cloacae S23 a Plant Growth-promoting Passenger Endophytic Bacterium Isolated from Groundnut Nodule Possesses Stress Tolerance Traits. Current genomics 5 37920731
2022 In vitro characterization of S-23 metabolites produced by human liver microsomes, and subsequent application to urine after a controlled oral administration. Journal of pharmaceutical and biomedical analysis 5 35182830
2022 Molecular characterization and expression of RPS23 and HPSE and their association with hematologic parameters in sheep. Gene 4 35718240
2005 Ribosomal protein genes S23 and L35 from amphioxus Branchiostoma belcheri tsingtauense: identification and copy number. Acta biochimica et biophysica Sinica 3 16077906
2016 A cluster of 3' coterminal transcripts from US12-US17 locus of human cytomegalovirus. Virus genes 2 26931512
2025 Investigations Into the Urinary Metabolite Elimination Profile of the Selective Androgen Receptor Modulator S-23 in Studies Mimicking Contaminated Product Ingestion for Doping Control Purposes. Biomedical chromatography : BMC 1 40277337
2024 Detection of the selective androgen receptor modulator S-23 and its metabolites in equine urine and plasma following oral administration. Drug testing and analysis 1 38982651
2023 Discovery of a Novel Intron in US10/US11/US12 of HSV-1 Strain 17. Viruses 1 38005822
2025 RsmG methylation of 16S rRNA affects the function of ribosomal protein uS12. Archives of microbiology 0 40377667

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