{"gene":"RPS8","run_date":"2026-06-10T07:46:27","timeline":{"discoveries":[{"year":2011,"finding":"RPS8 (ribosomal protein S8) physically associates with CDK11p46 (a 46 kDa isoform of the PITSLRE kinase family), as identified by His pull-down and mass spectrometry and confirmed in vitro and in vivo. RPS8 is not a substrate of CDK11p46. Together, RPS8 and CDK11p46 synergistically suppress translation in both cap-dependent and IRES-dependent manners, and sensitize cells to Fas ligand-induced apoptosis.","method":"His pull-down, mass spectrometry, co-immunoprecipitation (in vitro and in vivo), translation reporter assays, cell apoptosis assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal binding confirmed in vitro and in vivo with two orthogonal methods (pull-down + Co-IP) and functional translation/apoptosis assays, single lab","pmids":["21371428"],"is_preprint":false},{"year":2024,"finding":"Fish RPS8 (40S ribosomal protein S8) acts as a host antiviral factor against Snakehead vesiculovirus (SHVV): overexpression of RPS8 inhibited SHVV replication, while knockdown of RPS8 promoted it. The SHVV leader RNA (30-nt ncRNA) physically interacts with RPS8 and counteracts its antiviral effect, thereby promoting viral replication.","method":"RNA-protein binding assay, overexpression and knockdown experiments, viral replication assays","journal":"Fish & shellfish immunology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single set of OE/KD experiments in a fish system with limited mechanistic detail on the molecular mechanism","pmids":["38432538"],"is_preprint":false}],"current_model":"Human/mammalian RPS8 is a component of the 40S ribosomal small subunit that physically interacts with CDK11p46 to synergistically suppress both cap-dependent and IRES-dependent translation and sensitize cells to apoptosis; additionally, RPS8 functions as an antiviral factor whose activity can be antagonized by viral non-coding leader RNA."},"narrative":{"mechanistic_narrative":"RPS8 is a component of the 40S small ribosomal subunit that contributes to translational control and stress responses. It physically associates with CDK11p46, a kinase of the PITSLRE family, without serving as its substrate, and the two proteins synergistically suppress both cap-dependent and IRES-dependent translation while sensitizing cells to Fas ligand-induced apoptosis [PMID:21371428]. Beyond this translational/apoptotic axis, no further mechanistic detail of RPS8 in mammalian systems has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"Established that RPS8 is not merely a structural ribosomal protein but a partner that, with CDK11p46, actively represses translation and promotes apoptosis, linking a ribosomal protein to translational shutdown and cell death.","evidence":"His pull-down and mass spectrometry with reciprocal Co-IP (in vitro and in vivo), translation reporter assays, and Fas ligand apoptosis assays in human cells","pmids":["21371428"],"confidence":"Medium","gaps":["Molecular mechanism by which the RPS8–CDK11p46 pair suppresses translation is not defined","Whether the interaction occurs on assembled ribosomes or as free protein is unresolved","No structural model of the RPS8–CDK11p46 interface"]},{"year":2024,"claim":"Extended RPS8 function to innate antiviral defense by showing it restricts viral replication and is targeted by a viral non-coding leader RNA, indicating ribosomal proteins can serve as direct antiviral effectors antagonized by viral RNA.","evidence":"RNA-protein binding assay plus overexpression/knockdown and viral replication assays in a fish (Snakehead vesiculovirus) system","pmids":["38432538"],"confidence":"Low","gaps":["Single lab, single OE/KD dataset in a fish model with limited mechanistic detail","Molecular basis of how leader RNA binding neutralizes RPS8 antiviral activity is unknown","Conservation of this antiviral role in mammals is untested"]},{"year":null,"claim":"Whether the translational-suppression/apoptotic role and the antiviral role of RPS8 share a common molecular mechanism, and how either relates to its core function in the 40S subunit, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying mechanism linking translation control, apoptosis, and antiviral activity","No structural or biochemical characterization of RPS8 within the ribosome in these contexts"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0]}],"pathway":[],"complexes":["40S ribosomal subunit"],"partners":["CDK11B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P62241","full_name":"Small ribosomal subunit protein eS8","aliases":["40S ribosomal protein S8"],"length_aa":208,"mass_kda":24.2,"function":"Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797)","subcellular_location":"Cytoplasm; Membrane; Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/P62241/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPS8","classification":"Common Essential","n_dependent_lines":1208,"n_total_lines":1208,"dependency_fraction":1.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CAPRIN1","stoichiometry":10.0},{"gene":"EIF2S3","stoichiometry":10.0},{"gene":"EIF3B","stoichiometry":10.0},{"gene":"EIF3G","stoichiometry":10.0},{"gene":"EMC8","stoichiometry":10.0},{"gene":"ENY2","stoichiometry":10.0},{"gene":"FTH1","stoichiometry":10.0},{"gene":"RACK1","stoichiometry":10.0},{"gene":"RBM8A","stoichiometry":10.0},{"gene":"RPL10A","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/search/RPS8","total_profiled":1310},"omim":[{"mim_id":"600357","title":"RIBOSOMAL PROTEIN S8; RPS8","url":"https://www.omim.org/entry/600357"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Endoplasmic reticulum","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPS8"},"hgnc":{"alias_symbol":["S8","eS8"],"prev_symbol":[]},"alphafold":{"accession":"P62241","domains":[{"cath_id":"3.10.290.70","chopping":"34-203","consensus_level":"medium","plddt":93.5915,"start":34,"end":203}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P62241","model_url":"https://alphafold.ebi.ac.uk/files/AF-P62241-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P62241-F1-predicted_aligned_error_v6.png","plddt_mean":93.0},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPS8","jax_strain_url":"https://www.jax.org/strain/search?query=RPS8"},"sequence":{"accession":"P62241","fasta_url":"https://rest.uniprot.org/uniprotkb/P62241.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P62241/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P62241"}},"corpus_meta":[{"pmid":"15958793","id":"PMC_15958793","title":"Soybean phytophthora resistance gene Rps8 maps closely to the Rps3 region.","date":"2005","source":"The Journal of heredity","url":"https://pubmed.ncbi.nlm.nih.gov/15958793","citation_count":36,"is_preprint":false},{"pmid":"24244571","id":"PMC_24244571","title":"RPS8--a new informative DNA marker for phylogeny of Babesia and Theileria parasites in China.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24244571","citation_count":20,"is_preprint":false},{"pmid":"21371428","id":"PMC_21371428","title":"CDK11p46 and RPS8 associate with each other and suppress translation in a synergistic manner.","date":"2011","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/21371428","citation_count":17,"is_preprint":false},{"pmid":"35150190","id":"PMC_35150190","title":"RXLR effector gene Avr3a from Phytophthora sojae is recognized by Rps8 in soybean.","date":"2022","source":"Molecular plant pathology","url":"https://pubmed.ncbi.nlm.nih.gov/35150190","citation_count":10,"is_preprint":false},{"pmid":"23747103","id":"PMC_23747103","title":"Discrimination between ovine Babesia and Theileria species in China based on the ribosomal protein S8 (RPS8) gene.","date":"2013","source":"Veterinary parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/23747103","citation_count":7,"is_preprint":false},{"pmid":"26382041","id":"PMC_26382041","title":"A PCR-RFLP Assay targeting RPS8 gene for the discrimination between bovine Babesia and Theileria species in China.","date":"2015","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/26382041","citation_count":7,"is_preprint":false},{"pmid":"38432538","id":"PMC_38432538","title":"Snakehead vesiculovirus (SHVV) leader RNA interacts with host antiviral factors RPS8 and L13a and promotes virus replication.","date":"2024","source":"Fish & shellfish immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38432538","citation_count":1,"is_preprint":false},{"pmid":"41629013","id":"PMC_41629013","title":"Microbial degradation of thifensulfuron-methyl by Klebsiella grimontii ES8 and its degradative enzyme kg-RutF: Mechanistic insights and bioremediation potential.","date":"2026","source":"Pesticide biochemistry and physiology","url":"https://pubmed.ncbi.nlm.nih.gov/41629013","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5895,"output_tokens":647,"usd":0.013695,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6992,"output_tokens":1248,"usd":0.03308,"stage2_stop_reason":"end_turn"},"total_usd":0.046775,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"RPS8 (ribosomal protein S8) physically associates with CDK11p46 (a 46 kDa isoform of the PITSLRE kinase family), as identified by His pull-down and mass spectrometry and confirmed in vitro and in vivo. RPS8 is not a substrate of CDK11p46. Together, RPS8 and CDK11p46 synergistically suppress translation in both cap-dependent and IRES-dependent manners, and sensitize cells to Fas ligand-induced apoptosis.\",\n      \"method\": \"His pull-down, mass spectrometry, co-immunoprecipitation (in vitro and in vivo), translation reporter assays, cell apoptosis assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal binding confirmed in vitro and in vivo with two orthogonal methods (pull-down + Co-IP) and functional translation/apoptosis assays, single lab\",\n      \"pmids\": [\"21371428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Fish RPS8 (40S ribosomal protein S8) acts as a host antiviral factor against Snakehead vesiculovirus (SHVV): overexpression of RPS8 inhibited SHVV replication, while knockdown of RPS8 promoted it. The SHVV leader RNA (30-nt ncRNA) physically interacts with RPS8 and counteracts its antiviral effect, thereby promoting viral replication.\",\n      \"method\": \"RNA-protein binding assay, overexpression and knockdown experiments, viral replication assays\",\n      \"journal\": \"Fish & shellfish immunology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single set of OE/KD experiments in a fish system with limited mechanistic detail on the molecular mechanism\",\n      \"pmids\": [\"38432538\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Human/mammalian RPS8 is a component of the 40S ribosomal small subunit that physically interacts with CDK11p46 to synergistically suppress both cap-dependent and IRES-dependent translation and sensitize cells to apoptosis; additionally, RPS8 functions as an antiviral factor whose activity can be antagonized by viral non-coding leader RNA.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPS8 is a component of the 40S small ribosomal subunit that contributes to translational control and stress responses. It physically associates with CDK11p46, a kinase of the PITSLRE family, without serving as its substrate, and the two proteins synergistically suppress both cap-dependent and IRES-dependent translation while sensitizing cells to Fas ligand-induced apoptosis [#0]. Beyond this translational/apoptotic axis, no further mechanistic detail of RPS8 in mammalian systems has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established that RPS8 is not merely a structural ribosomal protein but a partner that, with CDK11p46, actively represses translation and promotes apoptosis, linking a ribosomal protein to translational shutdown and cell death.\",\n      \"evidence\": \"His pull-down and mass spectrometry with reciprocal Co-IP (in vitro and in vivo), translation reporter assays, and Fas ligand apoptosis assays in human cells\",\n      \"pmids\": [\n        \"21371428\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism by which the RPS8\\u2013CDK11p46 pair suppresses translation is not defined\",\n        \"Whether the interaction occurs on assembled ribosomes or as free protein is unresolved\",\n        \"No structural model of the RPS8\\u2013CDK11p46 interface\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended RPS8 function to innate antiviral defense by showing it restricts viral replication and is targeted by a viral non-coding leader RNA, indicating ribosomal proteins can serve as direct antiviral effectors antagonized by viral RNA.\",\n      \"evidence\": \"RNA-protein binding assay plus overexpression/knockdown and viral replication assays in a fish (Snakehead vesiculovirus) system\",\n      \"pmids\": [\n        \"38432538\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, single OE/KD dataset in a fish model with limited mechanistic detail\",\n        \"Molecular basis of how leader RNA binding neutralizes RPS8 antiviral activity is unknown\",\n        \"Conservation of this antiviral role in mammals is untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the translational-suppression/apoptotic role and the antiviral role of RPS8 share a common molecular mechanism, and how either relates to its core function in the 40S subunit, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unifying mechanism linking translation control, apoptosis, and antiviral activity\",\n        \"No structural or biochemical characterization of RPS8 within the ribosome in these contexts\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0003723\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      },\n      {\n        \"term_id\": \"GO:0005198\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005840\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [],\n    \"complexes\": [\n      \"40S ribosomal subunit\"\n    ],\n    \"partners\": [\n      \"CDK11B\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":1,"faith_total":1,"faith_pct":100.0}}