Affinage

RPL23A

Large ribosomal subunit protein uL23 · UniProt P62750

Round 2 corrected
Length
156 aa
Mass
17.7 kDa
Annotated
2026-04-28
70 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL23A (uL23) is a conserved component of the 60S large ribosomal subunit positioned at the polypeptide tunnel exit, where it serves as a critical docking platform for factors that act on nascent chains — including mTORC2, which cotranslationally phosphorylates Akt at Thr450 to prevent its ubiquitination, and the signal recognition particle (SRP), whose C-terminal helix contacts the uL23 intra-tunnel loop to scan translating ribosomes before signal-sequence exposure (PMID:21045808, PMID:28134917). RPL23A is imported into the nucleus via a basic domain recognized by multiple importin β-like receptors (importin β, transportin, RanBP5, RanBP7), representing an archetype of a nuclear import signal that predates receptor diversification (PMID:9687515). Outside the ribosome, RPL23A participates in p53 regulation: it sequesters RPL11 from MDM2, and its depletion frees RPL11 to inhibit MDM2 and stabilize p53, promoting apoptosis; RPL23A itself is targeted for K48-linked ubiquitination and proteasomal degradation by the HERC3 HECT E3 ligase, coupling RPL23A turnover to c-Myc/p21 cell-cycle control (PMID:34782045, PMID:35637966). IFN-β treatment suppresses RPL23A expression in tumor cells, and antisense inhibition of RPL23A reduces proliferation, consistent with its role in sustaining translational capacity and cell growth (PMID:9053844).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1993 Medium

    Identification of RPL23A as a conserved 60S ribosomal protein established the gene's fundamental role in translation and revealed extensive gene copy number in the rat genome, setting the stage for functional studies.

    Evidence cDNA cloning, Southern blot, and cross-species sequence comparison in rat

    PMID:8428950

    Open questions at the time
    • No functional data beyond sequence homology
    • Pseudogene versus active-copy status of the 18–20 gene copies unresolved
  2. 1997 Medium

    Genomic characterization of human RPL23A mapped it to 17q11, revealed a TATA-box promoter unusual for mammalian ribosomal protein genes, and IFN-β-mediated downregulation with antisense-phenotype studies demonstrated that RPL23A expression is required for cell proliferation.

    Evidence Genomic cloning, FISH mapping, Northern blot in IFN-β-treated tumor lines, antisense colony formation assay

    PMID:9053844 PMID:9417910

    Open questions at the time
    • Mechanism of IFN-β-induced downregulation unknown
    • Antisense approach did not distinguish ribosomal from extra-ribosomal functions
  3. 1998 High

    Demonstrating that RPL23A is imported into the nucleus by four distinct importin β-family receptors via a basic domain revealed both its nuclear import pathway and a potentially ancestral import signal.

    Evidence In vitro nuclear import assays with recombinant import receptors and domain mapping

    PMID:9687515

    Open questions at the time
    • Relative contribution of each receptor in vivo unknown
    • Whether the basic domain import signal is used for other ribosomal proteins not determined
  4. 2007 High

    Cross-species complementation showed Drosophila L23a can substitute for yeast L25 in ribosome biogenesis, confirming conserved function but also revealing that the insect-specific N-terminal extension impairs late rRNA processing.

    Evidence Yeast chromosomal L25 disruption with fly L23a plasmid rescue, pulse-chase rRNA analysis

    PMID:17584789

    Open questions at the time
    • Whether the N-terminal extension has a positive function in Drosophila ribosomes not tested
    • No structural data on how fly L23a integrates into yeast ribosome
  5. 2010 High

    Discovery that mTORC2 docks at the ribosomal tunnel exit via RPL23A and cotranslationally phosphorylates nascent Akt revealed a major extra-ribosomal signaling function for RPL23A beyond translation.

    Evidence Reciprocal Co-IP (mTORC2–RPL23A), polysome fractionation, cotranslational phosphorylation assay

    PMID:21045808

    Open questions at the time
    • Whether RPL23A directly contacts mTORC2 subunits or acts via ribosome context unresolved
    • Generality of cotranslational phosphorylation for substrates other than Akt not established
  6. 2013 High

    High-resolution cryo-EM structures of human and Drosophila 80S ribosomes confirmed RPL23A's position at the tunnel exit and revealed metazoan-specific structural elaborations surrounding it.

    Evidence Cryo-EM atomic model building of human and Drosophila 80S ribosomes

    PMID:23636399 PMID:25901680

    Open questions at the time
    • Structures are of resting or stalled ribosomes; conformation during active mTORC2 or SRP docking not captured
  7. 2017 High

    Showing that bacterial SRP's signal-sequence-binding domain penetrates the ribosomal tunnel to contact the uL23 intra-tunnel loop established that RPL23A enables SRP to sense translation status before signal-sequence emergence, resolving how SRP scans ribosomes efficiently.

    Evidence In vivo crosslinking, genetic epistasis, SRP–ribosome binding assays in bacteria

    PMID:28134917

    Open questions at the time
    • Whether eukaryotic SRP uses the same intra-tunnel contact with RPL23A not demonstrated
    • Structural basis of the SRP–uL23 contact at atomic resolution lacking
  8. 2021 Medium

    Two studies revealed extra-ribosomal roles for RPL23A in p53 regulation: RPL23A sequesters RPL11 from MDM2, and a native RPL23A-derived peptide inhibits RPL26-governed p53 translation, connecting RPL23A levels to apoptotic signaling.

    Evidence Co-IP of RPL23A–RPL11 interaction with siRNA KD and p53 readouts in irradiated spermatogonia; peptidomics with Co-IP of PDRL23A–RPL26 and in vivo myocardial I/R model

    PMID:34782045 PMID:34808368

    Open questions at the time
    • Whether the RPL23A peptide is generated physiologically at functional concentrations requires confirmation
    • Stoichiometry of free (extra-ribosomal) RPL23A relative to ribosome-bound pool not quantified
    • RPL23A–RPL11 interaction validated in one cell system only
  9. 2022 High

    Identification of HERC3 as the E3 ubiquitin ligase that K48-ubiquitinates RPL23A for proteasomal degradation linked RPL23A turnover to c-Myc/p21-dependent cell-cycle control in colorectal cancer, establishing a regulated degradation axis.

    Evidence Co-IP, mass spectrometry, GST pull-down, in vivo ubiquitylation assay, cycloheximide chase, gain/loss-of-function rescue in CRC cells

    PMID:35637966

    Open questions at the time
    • Whether HERC3 ubiquitinates ribosome-bound or free RPL23A not resolved
    • Upstream signals that activate HERC3 toward RPL23A unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the ribosomal versus extra-ribosomal pools of RPL23A are partitioned and regulated, and whether the mTORC2-docking, SRP-scanning, MDM2-p53, and HERC3-mediated degradation functions are coordinated or mutually exclusive.
  • No quantitative measurement of free vs. ribosome-incorporated RPL23A
  • Structural basis of mTORC2 or eukaryotic SRP docking on RPL23A at atomic resolution absent
  • Whether HERC3-mediated RPL23A degradation feeds back on ribosome biogenesis not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005840 ribosome 5 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2 R-HSA-5357801 Programmed Cell Death 1
Partners
HERC3KPNB1RANBP5RICTORRPL11RPL26TNPO1
Complex memberships
60S large ribosomal subunit80S ribosome

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Rat RPL23A encodes a 156-amino-acid, 17,684 Da protein of the 60S ribosomal large subunit. Hybridization of the L23a cDNA to nuclear DNA digests indicated 18–20 gene copies. RPL23A is homologous to yeast L25, archaebacterial L23, and E. coli L23, establishing it as a conserved member of the L23 ribosomal protein family. cDNA cloning, sequence analysis, Southern blot hybridization The Journal of biological chemistry Medium 8428950
1997 The human RPL23A gene spans ~4.0 kb with 5 exons and 4 introns, encodes a 156-amino-acid protein absolutely conserved with rat RPL23A, and maps to cytogenetic band 17q11 by FISH. The 5′ flanking region contains a canonical TATA box and CAAT box, the first identified in a mammalian ribosomal protein gene. Genomic cloning, sequencing, fluorescence in situ hybridization (FISH) Genomics Medium 9417910
1997 RPL23A (mda-20) mRNA is down-regulated by interferon-beta (IFN-β) treatment in multiple human tumor cell lines. Ectopic expression of antisense RPL23A in HeLa cells reduces colony formation, demonstrating a direct antiproliferative consequence of inhibiting RPL23A expression. Growth suppression alone (serum starvation) was insufficient to reduce RPL23A levels, implicating IFN-β-specific biochemical changes. Subtraction hybridization, Northern blot, antisense expression/colony formation assay Oncogene Medium 9053844
1998 RPL23A is imported into the nucleus via at least four importin β-like receptors (importin β, transportin, RanBP5, RanBP7) that bind directly to a very basic region of RPL23A, bypassing the classical importin α/β pathway. This basic domain was proposed as an archetypal nuclear import signal that predates divergence of import receptors. In vitro nuclear import assays, direct binding studies with recombinant import receptors, domain mapping The EMBO journal High 9687515
1999 Drosophila RPL23A (PBP-3) physically interacts with the auto-modification domain of Poly(ADP-ribose) polymerase (PARP), identified by Far-Western screening. Drosophila L23a contains a unique histone H1-like N-terminal extension rich in Ala, Lys, and Pro, suggesting dual functions in ribosome organization and DNA binding. Far-Western screening of cDNA library, sequence analysis Gene Low 9931508
2000 Human RPL23A interacts with vaccinia virus protein E3L in a yeast two-hybrid assay using a HeLa cDNA library. Yeast two-hybrid screen Virus genes Low 11129635
2007 Drosophila L23a can functionally substitute for yeast L25 in ribosome biogenesis: a yeast strain with the chromosomal L25 gene disrupted survives when expressing FLAG-tagged fly L23a. The fly protein supports growth but with a reduced rate; pulse-chase experiments show delayed rRNA processing, notably conversion of 27S precursor to mature 25S rRNA, revealing that the unique N-terminal extension of insect L23a is tolerated within the ribosome but impairs late rRNA maturation kinetics. Yeast complementation (chromosomal gene disruption + plasmid rescue), pulse-chase rRNA processing analysis Nucleic acids research High 17584789
2010 mTORC2 stably interacts with RPL23A at the large ribosomal subunit tunnel exit and co-localizes with actively translating ribosomes. During translation of Akt, mTORC2 mediates cotranslational phosphorylation of Akt at the turn motif site (Thr450), preventing cotranslational ubiquitination of the nascent chain. Co-immunoprecipitation (mTORC2 with rpL23a), polysome fractionation, cotranslational phosphorylation assay, ribosome tunnel exit localization The EMBO journal High 21045808
2013 Human and Drosophila 80S ribosome cryo-EM structures place RPL23A (uL23) at the large subunit tunnel exit, revealing co-evolution of metazoan-specific rRNA expansions with ribosomal proteins including RPL23A and showing two additional structural layers unique to metazoan ribosomes. Cryo-electron microscopy, atomic model building Nature High 23636399
2015 Near-atomic cryo-EM structure of the human 80S ribosome (average 3.6 Å, reaching 2.9 Å in stable regions) provides detailed structural context for RPL23A as a component of the 60S subunit, revealing its positioning and interactions within the ribosomal architecture. Single-particle cryo-electron microscopy, atomic model building Nature High 25901680
2017 Bacterial SRP's C-terminal helix of its signal-sequence-binding domain penetrates into the ribosomal tunnel and contacts the intra-tunnel loop of ribosomal protein uL23 (RPL23A ortholog). This contact allows SRP to sense the translational status of the ribosome before the signal sequence is exposed at the surface, enabling early scanning of translating ribosomes. In vivo crosslinking, genetic epistasis, biochemical SRP-ribosome binding assays Nature microbiology High 28134917
2021 A native peptide derived from RPL23A (PDRL23A), identified by intracellular peptidomics under hypoxic conditions, interacts with ribosomal protein RPL26, thereby hampering RPL26-governed p53 mRNA translation. This reduces p53 protein levels and p53-mediated apoptosis under hypoxia. PDRL23A pretreatment in vivo inhibited I/R-induced cardiomyocyte death and improved cardiac function. Intracellular peptidomics, Co-IP (PDRL23A–RPL26 interaction), polysome/translation assays, in vitro hypoxia model, in vivo myocardial I/R mouse model Pharmacological research Medium 34808368
2021 Ionizing radiation (IR) decreases RPL23A expression in mouse spermatogonia in vivo and in GC-1 cells in vitro. Knockdown of RPL23A weakens the RPL23A–RPL11 protein interaction, freeing RPL11 to inhibit MDM2, which in turn stabilizes p53, leading to spermatogonia apoptosis via the RPL23A–RPL11–MDM2–p53 pathway. X-ray irradiation, siRNA knockdown, immunoprecipitation (RPL23A–RPL11 interaction), immunofluorescence, flow cytometry, immunoblotting Biomedical and environmental sciences Medium 34782045
2022 HERC3 E3 ubiquitin ligase directly interacts with RPL23A (identified by Co-IP and mass spectrometry), and ubiquitinates RPL23A via K48-linked polyubiquitination through its HECT domain, targeting RPL23A for proteasomal degradation. RPL23A independently regulates colorectal cancer cell cycle progression and proliferation. Through RPL23A, HERC3 modulates the ubiquitination of p21 and expression of c-Myc and p21. Co-immunoprecipitation, mass spectrometry, GST pull-down, in vivo ubiquitylation assay, cycloheximide chase, gain/loss-of-function assays, rescue experiments International journal of biological sciences High 35637966

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2013 Structures of the human and Drosophila 80S ribosome. Nature 481 23636399
2020 SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses. Cell 449 33080218
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
1998 Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells. The EMBO journal 431 9687515
2010 Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery. Journal of proteome research 422 20020773
2013 The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry 413 23463506
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 The molecular mechanics of eukaryotic translation. Annual review of biochemistry 396 15189156
2015 Structure of the human 80S ribosome. Nature 380 25901680
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2003 Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 276 14567916
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2010 mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide. The EMBO journal 269 21045808
2010 Genotypic characterization of UL23 thymidine kinase and UL30 DNA polymerase of clinical isolates of herpes simplex virus: natural polymorphism and mutations associated with resistance to antivirals. Antimicrobial agents and chemotherapy 110 20733037
2001 Enhanced expression of S8, L12, L23a, L27 and L30 ribosomal protein mRNAs in human hepatocellular carcinoma. Anticancer research 69 11724303
2017 Expression Profiling of Ribosomal Protein Gene Family in Dehydration Stress Responses and Characterization of Transgenic Rice Plants Overexpressing RPL23A for Water-Use Efficiency and Tolerance to Drought and Salt Stresses. Frontiers in chemistry 57 29184886
2018 Human cytomegalovirus UL23 inhibits transcription of interferon-γ stimulated genes and blocks antiviral interferon-γ responses by interacting with human N-myc interactor protein. PLoS pathogens 43 29377960
1997 Suppression of human ribosomal protein L23A expression during cell growth inhibition by interferon-beta. Oncogene 39 9053844
2017 The signal recognition particle contacts uL23 and scans substrate translation inside the ribosomal tunnel. Nature microbiology 38 28134917
2002 The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components. The Journal of general virology 37 12029146
1999 Poly(ADP-ribose) polymerase interacts with novel Drosophila ribosomal proteins, L22 and l23a, with unique histone-like amino-terminal extensions. Gene 33 9931508
1993 The primary structure of rat ribosomal protein L23a. The application of homology search to the identification of genes for mammalian and yeast ribosomal proteins and a correlation of rat and yeast ribosomal proteins. The Journal of biological chemistry 32 8428950
2005 The two ribosomal protein L23A genes are differentially transcribed in Arabidopsis thaliana. Genome 28 16121241
2019 Construction of a US7/US8/UL23/US3-deleted recombinant pseudorabies virus and evaluation of its pathogenicity in dogs. Veterinary microbiology 24 31902487
2021 Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2. Journal of bioenergetics and biomembranes 23 34036483
2013 Over-expression of 60s ribosomal L23a is associated with cellular proliferation in SAG resistant clinical isolates of Leishmania donovani. PLoS neglected tropical diseases 22 24340105
2008 Transcript profiling demonstrates absence of dosage compensation in Arabidopsis following loss of a single RPL23a paralog. Planta 21 18566829
2011 Biochemical analysis of infected cell polypeptide (ICP)0, ICP4, UL7 and UL23 incorporated into extracellular herpes simplex virus type 1 virions. The Journal of general virology 20 22158881
2007 Cloning and characterization of a ribosomal protein L23a from Haemaphysalis qinghaiensis eggs by immuno screening of a cDNA expression library. Experimental & applied acarology 18 17406794
2022 HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle. International journal of biological sciences 17 35637966
2000 The vaccinia virus E3L protein interacts with SUMO-1 and ribosomal protein L23a in a yeast two hybrid assay. Virus genes 17 11129635
2001 Establishment of Arabidopsis thaliana ribosomal protein RPL23A-1 as a functional homologue of Saccharomyces cerevisiae ribosomal protein L25. Plant molecular biology 15 11575722
1997 Cloning, sequencing, gene organization, and localization of the human ribosomal protein RPL23A gene. Genomics 15 9417910
2023 Biological role and diagnostic utility of ribosomal protein L23a pseudogene 53 in cutaneous melanoma. Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology 13 37456695
2019 UL23, UL30, and UL5 characterization of HSV1 clinical strains isolated from hematology department patients. Antiviral research 13 31152759
2021 Human Cytomegalovirus UL23 Attenuates Signal Transducer and Activator of Transcription 1 Phosphorylation and Type I Interferon Response. Frontiers in microbiology 12 34305856
2007 Functional conservation between structurally diverse ribosomal proteins from Drosophila melanogaster and Saccharomyces cerevisiae: fly L23a can substitute for yeast L25 in ribosome assembly and function. Nucleic acids research 12 17584789
2019 Genetic association of DDIT3, RPL23A, SESN2 and NR4A1 genes with milk yield and composition in dairy cattle. Animal genetics 11 30815908
2012 cDNA cloning, overexpression, purification and pharmacologic evaluation for anticancer activity of ribosomal protein L23A gene (RPL23A) from the Giant Panda. International journal of molecular sciences 11 22408443
2021 Identification of a novel native peptide derived from 60S ribosomal protein L23a that translationally regulates p53 to reduce myocardial ischemia-reperfusion. Pharmacological research 10 34808368
2024 Human cytomegalovirus UL23 exploits PD-L1 inhibitory signaling pathway to evade T cell-mediated cytotoxicity. mBio 9 38829126
2023 Human Cytomegalovirus UL23 Antagonizes the Antiviral Effect of Interferon-γ by Restraining the Expression of Specific IFN-Stimulated Genes. Viruses 8 37112994
2021 Ionizing Radiation-Induced RPL23a Reduction Regulates Apoptosis via RPL11-MDM2-p53 Pathway in Mouse Spermatogonia. Biomedical and environmental sciences : BES 7 34782045
2014 Cloning and characterization of a ribosomal protein L23a gene from Small Tail Han sheep by screening of a cDNA expression library. Meta gene 7 25606432
2025 Human cytomegalovirus tegument protein UL23 promotes gastric cancer immune evasion by facilitating PD-L1 transcription. Molecular medicine (Cambridge, Mass.) 6 39934685
2023 Novel UL23 and UL30 substitutions in HSV1 and HSV2 viruses related to polymorphism or drug resistance. Antiviral research 5 37453453
2019 Preparation and identification of polyclonal antibody against human cytomegalovirus encoding protein UL23. Protein expression and purification 4 31051245
2020 Generation and Application of Mouse Monoclonal Antibody Against Human Cytomegalovirus UL23. Viral immunology 2 32181702
2019 V348I mutation in UL23 gene of human herpesvirus 1 in a case of herpetic hepatitis and haemophagocytic lymphohistiocytosis. New microbes and new infections 2 30988955
2007 Histone H1-like, lysine-rich low complexity amino acid extensions in mosquito ribosomal proteins RpL23a and RpS6 have evolved independently. Archives of insect biochemistry and physiology 2 17212354
2026 The UL23 thymidine kinase of Marek's disease virus is a target for anti-HSV drug development. Antiviral research 0 41544776
2026 Marek's disease virus hijacks host nucleotide metabolism via UL23-mediated c-Myc activation. Veterinary microbiology 0 41775051
2025 Human cytomegalovirus UL23 inhibits immune cell migration and blocks antiviral immune cell responses by reducing the expression of chemokines CCL2 and CCL5. Virulence 0 40521898