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Showing RPS7ES7 is a alias.

RPS7

Small ribosomal subunit protein eS7 · UniProt P62081

Length
194 aa
Mass
22.1 kDa
Annotated
2026-06-10
28 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPS7/eS7 is a structural protein of the small (40S) ribosomal subunit that supports translation initiation and, beyond the ribosome, acts as an RNA-binding regulator and a node in the p53-coupled ribosomal stress response (PMID:39127721, PMID:38326908, PMID:35871033). On the ribosome, its conserved N-terminal region is required for efficient 40S function and for recruitment of initiation factors eIF3 and eIF2 (PMID:19969550), and its ubiquitination state on the free 40S subunit is dynamically controlled: the E3 ligases CNOT4 and RNF10 together with RACK1 act upstream of the deubiquitinase OTUD6, which removes ubiquitin from RPS7 specifically on free 40S subunits to modulate the recyclable 40S pool and thereby set global translation levels (PMID:39127721). As an extra-ribosomal RNA-binding protein, RPS7 binds AUUUA motifs in the LOXL2 3'-UTR to stabilize LOXL2 mRNA, stabilizing ITGB1 and activating FAK/SRC signaling to drive hepatocellular carcinoma adhesion, migration, and metastasis (PMID:38326908). RPS7 expression is embedded in oncogenic transcriptional circuits, being activated by c-Myc through an E-box (downstream of PIM1) and by SMYD2 promoter binding, while it suppresses HIF-1α-driven glycolysis in colorectal cancer (PMID:26735579, PMID:33935284, PMID:30247545). Loss of RPS7 activates a ribosomal stress signal upstream of p53, a relationship demonstrated genetically in mouse and exploited pharmacologically: the covalent molecular glue DPB modifies MKRN2 Cys335 to create a neo-interface that drives MKRN2-mediated ubiquitination and degradation of RPS7, selectively killing p53-deficient tumor cells through nucleolar stress and apoptosis (PMID:41991154, PMID:23382688). A heterozygous RPS7 p.V134F variant impairs translational activity and activates ribosomal stress, linking RPS7 to Diamond-Blackfan anemia (PMID:35871033).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2009 Medium

    Established that the RPS7-family N-terminus is functionally required for 40S subunit activity, answering whether this protein contributes to the mechanics of translation initiation rather than being merely structural ballast.

    Evidence Yeast complementation with truncated rpS5 variants and biochemical assays of 40S function and initiation factor recruitment

    PMID:19969550

    Open questions at the time
    • Performed on yeast ortholog, not directly human RPS7
    • Does not define which initiation factor contacts are direct
  2. 2013 Medium

    Placed Rps7 upstream of p53 in the ribosomal stress pathway in a whole organism, showing its loss triggers a p53-dependent developmental phenotype.

    Evidence Two mouse Rps7 mutant alleles with Trp53 double-mutant epistasis and morphological phenotyping

    PMID:23382688

    Open questions at the time
    • CNS defects were p53-independent, indicating an unexplained second mechanism
    • Molecular trigger linking Rps7 loss to p53 not resolved
  3. 2014 Medium

    Identified physical translation-machinery partners of RPS7 and linked its abundance to translation and proliferation.

    Evidence Co-IP/MALDI-TOF MS, colocalization, and FRET in bovine mammary epithelial cells with overexpression studies

    PMID:25281768

    Open questions at the time
    • Non-human cell model
    • Functional consequence of the 14-3-3γ and eIF1AX interactions not dissected
  4. 2015 Medium

    Showed RPS7 transcription is repressed via chromatin-level control, defining how a viral oncoprotein silences RPS7 through SIRT7-mediated H3K18 deacetylation.

    Evidence ChIP, HBx ectopic expression, SIRT7 depletion, HBx transgenic mice, and deubiquitinase inhibition

    PMID:26442981

    Open questions at the time
    • Single lab
    • Downstream consequence of RPS7 repression for translation not quantified
  5. 2016 Medium

    Defined an extra-ribosomal tumor-suppressive function by placing RPS7 upstream of HIF-1α in glycolytic control.

    Evidence RPS7 overexpression/knockdown with HIF-1α rescue, xenografts, and tissue microarray in CRC

    PMID:26735579

    Open questions at the time
    • Mechanism by which RPS7 suppresses HIF-1α not identified
    • Single lab
  6. 2019 Medium

    Integrated RPS7 into the PIM1–c-Myc oncogenic axis, showing its transcription is c-Myc/E-box-driven and that it mediates PIM1-dependent translation and growth.

    Evidence 40S fractionation, E-box reporter, RPS7 knockdown/overexpression rescue, and xenografts in prostate cancer cells

    PMID:30247545

    Open questions at the time
    • Direct vs indirect contribution of RPS7 to PIM1 phenotype not fully separated
    • Single lab
  7. 2019 Low

    Linked RPS7 to a migratory phenotype through EMT marker regulation in prostate cancer.

    Evidence RPS7 siRNA knockdown with EMT marker Western blots and migration/proliferation assays

    PMID:30737160

    Open questions at the time
    • Single knockdown approach with no direct mechanistic target beyond marker changes
    • No rescue or in vivo confirmation
  8. 2021 Medium

    Added a second transcriptional activator, showing SMYD2 binds the RPS7 promoter and acts through RPS7 to drive lung adenocarcinoma aggressiveness.

    Evidence ChIP-qPCR, RNA-seq, SMYD2 knockdown/AZ505 inhibition with RPS7 rescue, and in vivo tumor assays

    PMID:33935284

    Open questions at the time
    • Rescue only partial, indicating SMYD2 acts through additional targets
    • Single lab
  9. 2022 Medium

    Provided a defined disease-causing variant, establishing that RPS7 p.V134F impairs translation and triggers ribosomal stress in Diamond-Blackfan anemia.

    Evidence Cellular model of the p.V134F variant with translational activity and ribosomal stress assays

    PMID:35871033

    Open questions at the time
    • Single variant in a cellular model
    • Structural basis of the functional impairment not resolved
  10. 2024 High

    Resolved the regulatory logic of RPS7 ubiquitination, identifying OTUD6 as the deubiquitinase acting on free-40S RPS7 with CNOT4/RNF10/RACK1 upstream, and tying this cycle to global translation control.

    Evidence Reciprocal Co-IP, monoubiquitinated-protein enrichment from catalytically inactive OTUD6 Drosophila, in vivo genetic epistasis, and translation assays

    PMID:39127721

    Open questions at the time
    • Functional output of the RPS7 ubiquitin mark on 40S recycling at structural level not defined
    • Whether disease/cancer-associated RPS7 alterations alter this cycle untested
  11. 2024 High

    Defined RPS7 as a sequence-specific RNA-binding protein with a metastatic effector pathway, showing it stabilizes LOXL2 mRNA via 3'-UTR AUUUA motifs to activate ITGB1/FAK/SRC signaling.

    Evidence RIP, RNA pull-down, RNA-seq, luciferase reporter, RNA decay, and CRISPR knockout in HCC

    PMID:38326908

    Open questions at the time
    • Whether ribosomal and mRNA-stabilizing pools of RPS7 are distinct not established
    • Generality of AUUUA-motif binding beyond LOXL2 unknown
  12. 2024 Medium

    Provided structural and evolutionary context, showing the archaeal ancestor NusA2 (homolog of eS7) uses a zinc finger and KH-like domains to bind single-stranded RNA.

    Evidence X-ray crystallography, RNA-binding assays, mutagenesis, and phylogenetic analysis of archaeal NusA2

    PMID:39504966

    Open questions at the time
    • Applies to archaeal NusA2, an evolutionary inference for human eS7
    • RNA-binding domain mapping not confirmed in human RPS7
  13. 2025 Medium

    Dissected dosage buffering of RPS7 production, showing paralog cross-regulation through 3'-UTR stability and Fhl1p-dependent transcription in yeast.

    Evidence Yeast gene deletion, 3'-UTR mutagenesis, mRNA stability and promoter assays, and Fhl1p epistasis

    PMID:40445952

    Open questions at the time
    • Yeast paralog system; human RPS7 has a single locus
    • Relevance to mammalian RPS7 dosage control not demonstrated
  14. 2026 High

    Demonstrated RPS7 as a druggable synthetic-lethal target, showing a covalent molecular glue redirects MKRN2 to ubiquitinate and degrade RPS7, killing p53-deficient cells through nucleolar stress.

    Evidence QTRP, CoIP-MS neo-interface mapping, Cys335 mutagenesis, KO/rescue, and orthotopic NSCLC mouse model

    PMID:41991154

    Open questions at the time
    • Whether physiological MKRN2 regulates RPS7 absent the glue is unknown
    • Selectivity determinants beyond p53 status not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the ribosomal pool and the extra-ribosomal RNA-binding/transcriptional pool of RPS7 are partitioned, and how its ubiquitination cycle mechanistically couples to p53-dependent stress signaling, remains unresolved.
  • No structure of human RPS7 bound to target mRNA
  • Direct biochemical link between RPS7 ubiquitin status and p53 activation not established
  • Whether free-40S RPS7 ubiquitination governs the cancer/DBA phenotypes untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 2
Localization
GO:0005840 ribosome 3
Complex memberships
40S ribosomal subunit

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 The deubiquitinase OTUD6 deubiquitinates RPS7/eS7 specifically on the free 40S ribosome (not on 43S/48S initiation complexes or translating ribosomes), with the E3 ligases CNOT4 and RNF10 and the 40S protein RACK1 functioning upstream of OTUD6. OTUD6 protein abundance bidirectionally regulates global protein translation levels, suggesting OTUD6 promotes translation initiation by modulating the pool of free 40S ribosomes available for recycling. Coimmunoprecipitation, enrichment of monoubiquitinated proteins from catalytically inactive OTUD6 Drosophila, genetic epistasis in vivo, global protein translation assays Nature communications High 39127721
2024 RPS7 functions as an RNA-binding protein that stabilizes LOXL2 mRNA by binding to AUUUA motifs in the 3155–3375 region of the LOXL2 3'-UTR, increasing LOXL2 mRNA abundance and protein expression, which in turn maintains ITGB1 protein stability and activates ITGB1-mediated FAK/SRC signaling to promote HCC cell adhesion, migration, invasion, and lung metastasis. RNA immunoprecipitation (RIP), RNA pull-down, RNA sequencing, dual luciferase reporter assay, nascent RNA capture assay, RNA decay assay, CRISPR-Cas9 knockout, gain- and loss-of-function analyses Journal of experimental & clinical cancer research : CR High 38326908
2015 The viral oncoprotein HBx stabilizes SIRT7 deacetylase by preventing its ubiquitin-mediated proteasomal degradation; HBx-accumulated SIRT7 is recruited to the RPS7 promoter, promotes H3K18 deacetylation at that locus, and thereby represses RPS7 transcription. Inhibition of cellular deubiquitinase activity restored RPS7 transcription. Chromatin immunoprecipitation, ectopic expression of HBx, SIRT7 depletion, HBx transgenic mice, deubiquitinase inhibition assay, clonogenicity assay Scientific reports Medium 26442981
2016 RPS7 inhibits colorectal cancer glycolysis by suppressing HIF-1α expression and downstream glycolytic proteins GLUT4 and LDHB; ectopic HIF-1α overexpression abrogates the growth-inhibitory effects of RPS7 overexpression, placing RPS7 upstream of HIF-1α in this pathway. RPS7 overexpression and knockdown in CRC cells, HIF-1α rescue experiments, in vivo xenograft assays, tissue microarray, Western blotting Oncotarget Medium 26735579
2021 The protein methyltransferase SMYD2 activates RPS7 transcription by binding to the RPS7 promoter; SMYD2-driven increases in proliferation, migration, and invasion of lung adenocarcinoma cells are partially reversed by RPS7 knockdown, placing RPS7 downstream of SMYD2 in this oncogenic pathway. Chromatin immunoprecipitation-quantitative PCR, RNA-seq, SMYD2 knockdown and AZ505 inhibitor treatment, RPS7 rescue experiments, in vivo tumor growth assays Cell death & disease Medium 33935284
2019 Kinase PIM1 is a component of the small 40S ribosomal subunit and regulates RPS7 protein levels; PIM1 enhances c-Myc protein stability, and c-Myc drives RPS7 transcription via a functional E-box motif upstream of the RPS7 transcription start site. RPS7 knockdown reduces prostate cancer cell growth in vitro and in vivo, and RPS7 overexpression rescues the condensed cellular body and decreased protein translation caused by PIM1 inhibition. Ribosomal subunit fractionation (PIM1 in 40S), E-box reporter assay, RPS7 knockdown and overexpression in PC3 cells, in vivo xenograft, Western blotting Carcinogenesis Medium 30247545
2019 RPS7 knockdown in prostate cancer cells upregulates the epithelial marker E-cadherin and downregulates mesenchymal markers N-cadherin and Snail, indicating that RPS7 promotes cell migration by activating the epithelial-to-mesenchymal transition (EMT) pathway. RPS7 siRNA knockdown, Western blotting for EMT markers, transwell migration assay, MTT proliferation assay Urologic oncology Low 30737160
2014 RPS7 physically interacts with 14-3-3γ and eIF1AX in bovine mammary epithelial cells, as established by co-immunoprecipitation/mass spectrometry, colocalization, and FRET analysis; overexpression of RPS7 promotes protein translation and cell proliferation. Co-immunoprecipitation, MALDI-TOF/TOF peptide mass fingerprinting, colocalization microscopy, FRET, overexpression studies Archives of biochemistry and biophysics Medium 25281768
2009 The N-terminal region of eukaryotic rpS5 (the yeast/human ortholog of bacterial rpS7, corresponding to RPS7 family) is required for efficient translation initiation; N-terminal truncations of yeast rpS5 impair 40S subunit function and reduce recruitment of initiation factors eIF3 and eIF2 to the ribosome. Yeast complementation with truncated rpS5 variants, biochemical analysis of 40S subunit function, measurement of initiation factor recruitment Nucleic acids research Medium 19969550
2026 The covalent molecular glue DPB recruits RPS7 to the E3 ubiquitin ligase MKRN2 (via covalent modification of MKRN2 Cys335), creating a neo-interface that leads to ubiquitination and proteasomal degradation of RPS7, triggering nucleolar stress and apoptosis selectively in p53-deficient NSCLC cells. Quantitative thiol-reactivity proteomics (QTRP), co-immunoprecipitation-mass spectrometry, site-directed mutagenesis, genetic knockout/rescue, biophysical assays, in vivo orthotopic mouse model British journal of pharmacology High 41991154
2013 Rps7 loss-of-function in mouse results in decreased body size, skeletal abnormalities, white spotting, eye malformations, and CNS developmental defects; these phenotypes (excluding CNS defects) are ameliorated by Trp53 deficiency, placing Rps7 upstream of p53 in the shared ribosomal stress pathway. Mouse genetic models (Rps7(Mtu) and Rps7(Zma) mutations), Trp53 double-mutant epistasis, morphological and neuroanatomical phenotyping PLoS genetics Medium 23382688
2022 A heterozygous missense mutation RPS7 p.V134F causes ribosomal stress activation and impairs protein translational activity in a cellular model, establishing a mechanistic link between this specific RPS7 variant and translational deficiency in Diamond-Blackfan anemia. Cellular model of RPS7 p.V134F variant, protein translational activity assays, ribosomal stress activation assays, erythrocyte metabolism analysis Blood cells, molecules & diseases Medium 35871033
2024 Archaeal NusA2 is the evolutionary ancestor of eukaryotic ribosomal protein eS7 (RPS7); crystal structures of NusA2 reveal an N-terminal zinc finger followed by two KH-like domains that bind single-stranded RNA, and mutations in the zinc finger compromise structural integrity, supporting the structural homology between NusA2 and eS7. X-ray crystallography (3.1 Å and 1.68 Å), RNA-binding assays, mutagenesis, molecular dynamics simulations, structure-guided phylogenetic analysis Structure (London, England : 1993) Medium 39504966
2025 In S. cerevisiae, the two RPS7 paralogs (RPS7A and RPS7B) are differentially regulated: deletion of RPS7A upregulates RPS7B mRNA but not vice versa; 3'-UTR sequences critically control the stability of both paralog mRNAs; Fhl1p is required for RPS7B but not RPS7A transcription; and Rps7Ap abundance regulates the activity of both promoters, establishing a buffering system for Rps7p production. Yeast gene deletion, 3'-UTR mutagenesis, mRNA stability assays, promoter activity assays, Fhl1p deletion epistasis PloS one Medium 40445952

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Mutation of the diamond-blackfan anemia gene Rps7 in mouse results in morphological and neuroanatomical phenotypes. PLoS genetics 43 23382688
2016 RPS7 inhibits colorectal cancer growth via decreasing HIF-1α-mediated glycolysis. Oncotarget 41 26735579
2021 SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7. Cell death & disease 40 33935284
2019 Kinase PIM1 promotes prostate cancer cell growth via c-Myc-RPS7-driven ribosomal stress. Carcinogenesis 24 30247545
2009 Yeast strains with N-terminally truncated ribosomal protein S5: implications for the evolution, structure and function of the Rps5/Rps7 proteins. Nucleic acids research 24 19969550
2014 Molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in bovine mammary epithelial cells. Archives of biochemistry and biophysics 23 25281768
2024 RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling. Journal of experimental & clinical cancer research : CR 22 38326908
1995 The single-ring Thermoanaerobacter brockii chaperonin 60 (Tbr-EL7) dimerizes to Tbr-EL14.Tbr-ES7 under protein folding conditions. Biochemistry 22 7578105
2019 RPS7 promotes cell migration through targeting epithelial-mesenchymal transition in prostate cancer. Urologic oncology 20 30737160
2017 ES7, encoding a ferredoxin-dependent glutamate synthase, functions in nitrogen metabolism and impacts leaf senescence in rice. Plant science : an international journal of experimental plant biology 19 28483051
2015 Stabilization of SIRT7 deacetylase by viral oncoprotein HBx leads to inhibition of growth restrictive RPS7 gene and facilitates cellular transformation. Scientific reports 18 26442981
2022 Baicalein Inhibits the SMYD2/RPS7 Signaling Pathway to Inhibit the Occurrence and Metastasis of Lung Cancer. Journal of oncology 12 35432530
2018 Heterologous expression of three antigenic proteins from Angiostrongylus cantonensis: ES-7, Lec-5, and 14-3-3 in mammalian cells. Molecular and biochemical parasitology 8 29555232
2022 Identification of RPS7 as the Biomarker of Ferroptosis in Acute Kidney Injury. BioMed research international 7 36277893
2022 Identification of new aptamer BC-3 targeting RPS7 from rapid screening for bladder carcinoma. Genes & diseases 7 37492709
2020 Aberrant splicing due to a novel RPS7 variant causes Diamond-Blackfan Anemia associated with spontaneous remission and meningocele. International journal of hematology 6 32772263
2019 Insight into subtilisin E-S7 cleavage pattern based on crystal structure and hydrolysates peptide analysis. Biochemical and biophysical research communications 6 30914195
1981 Biochemical genetics of rat esterases: another genetically determined variant, Es-7, is linked to five other esterase loci. Biochemical genetics 6 7337688
2024 OTUD6 deubiquitination of RPS7/eS7 on the free 40 S ribosome regulates global protein translation and stress. Nature communications 4 39127721
2022 Splice-site variant in the RPS7 5'-UTR leads to a decrease in the mRNA level and development of Diamond-Blackfan anemia. Clinical genetics 4 36057918
2022 Missense mutation in RPS7 causes Diamond-Blackfan anemia via alteration of erythrocyte metabolism, protein translation and induction of ribosomal stress. Blood cells, molecules & diseases 2 35871033
2010 Impact of genomic environment on mitochondrial rps7 mRNA features in grasses. Molecular genetics and genomics : MGG 2 20652591
2020 Author Correction: Stabilization of SIRT7 deacetylase by viral oncoprotein HBx leads to inhibition of growth restrictive RPS7 gene and facilitates cellular transformation. Scientific reports 1 32601345
2012 Potential role of tRNAs in wheat and Lolium mitochondrial rps7 transcript processing. Genome 1 22891636
2026 Generation of iPSC and isogenic gene-corrected lines from a patient with RPS7 (c.277_279delGTC)-mutated Diamond-Blackfan anemia syndrome. Stem cell research 0 41529448
2026 A covalent molecular glue hijacks the E3 ligase MKRN2 to degrade the ribosomal protein RPS7 and induce synthetic lethality in p53-deficient NSCLC cells. British journal of pharmacology 0 41991154
2025 Beyond the ORF: Paralog-specific regulation of RPS7/eS7 mRNAs via 3'-UTRs and promoter sequences. PloS one 0 40445952
2024 Archaeal NusA2 is the ancestor of ribosomal protein eS7 in eukaryotes. Structure (London, England : 1993) 0 39504966

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