{"gene":"PSMC2","run_date":"2026-04-28T19:45:45","timeline":{"discoveries":[{"year":1993,"finding":"PSMC2 (subunit 7 of the human 26S protease) was identified by peptide sequencing as identical to MSS1, a previously described modulator of HIV Tat-mediated transactivation, establishing it as an integral ATPase component of the 26S proteasome regulatory complex.","method":"N-terminal and internal peptide sequencing by CNBr cleavage and direct Edman degradation of purified 26S protease subunit 7 from human erythrocytes","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 1 — direct protein sequencing of purified native complex subunit with >12% sequence coverage confirming identity","pmids":["8500623"],"is_preprint":false},{"year":1996,"finding":"PSMC2 (MSS1/S7) functions as one of six ATPases in the 19S regulatory complex (RC) of the 26S proteasome, which is responsible for recognizing and unfolding ubiquitinated protein substrates for degradation by the 20S core particle.","method":"Biochemical reconstitution, subunit composition analysis, and functional assays of purified 26S proteasome","journal":"Annual review of biochemistry","confidence":"High","confidence_rationale":"Tier 1 — established in landmark review consolidating extensive biochemical reconstitution data; foundational mechanistic framework","pmids":["8811196"],"is_preprint":false},{"year":2000,"finding":"PSMC2 (S7) forms a specific heterodimeric pair with the ATPase S4 within the 19S regulatory complex; additionally, non-ATPase subunits S2 and S5b each form ternary complexes with the S4-S7 pair, assembling into a tetramer. The C-terminal two-thirds of PSMC2 mediates binding to S2, while its N-terminal region mediates binding to S5b.","method":"In vitro co-translation in reticulocyte lysate, co-immunoprecipitation, sedimentation analysis, and chimeric ATPase domain-mapping experiments","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP and domain-mapping with chimeric proteins; multiple orthogonal methods in a single study","pmids":["10625621"],"is_preprint":false},{"year":2000,"finding":"PSMC2 (MSS1) exists in cellular complexes lighter than the 26S proteasome and associates with multiple basal transcription factors for RNA polymerase II, including TBP, TFIIB, TFIIH, and TFIIF, suggesting a role in transcriptional regulation distinct from its proteasomal function.","method":"Glycerol gradient sedimentation, immunoblotting, and co-immunoprecipitation of endogenous complexes from rat tissues and mammalian cells","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 — co-IP without reciprocal pull-down; single lab, single method for the transcription factor associations","pmids":["11118327"],"is_preprint":false},{"year":2009,"finding":"PSMC2 is required for efficient recognition and translocation of ubiquitinated substrates into the 20S proteasome core; together with the other five ATPases in the 19S particle, it forms a ring complex that drives substrate unfolding and ATP-dependent threading into the catalytic chamber.","method":"Comprehensive biochemical and genetic analysis reviewed, including ATPase mutant studies and substrate processing assays","journal":"Annual review of biochemistry","confidence":"High","confidence_rationale":"Tier 1 — mechanistic conclusions from reconstituted in vitro systems and mutagenesis studies across multiple labs","pmids":["19489727"],"is_preprint":false},{"year":2012,"finding":"PSMC2 knockdown in microglia inhibits IκBα degradation, suppresses NF-κB activation, and reduces LPS-induced production of pro-inflammatory mediators (iNOS, nitric oxide, COX-2, prostaglandin E2), establishing a role for PSMC2 in controlling neuroinflammatory signaling via the ubiquitin-proteasome system.","method":"RNA interference knockdown in microglial cells, Western blot for IκBα/NF-κB, ELISA and colorimetric assays for inflammatory mediators","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 — clean RNAi knockdown with defined mechanistic readouts (IκBα stabilization, NF-κB suppression); single lab","pmids":["22629310"],"is_preprint":false},{"year":2013,"finding":"N-terminal Pro residue of yeast Rpt1 (the PSMC2 ortholog) undergoes mono- or di-methylation after removal of the initiator Met; deletion of the adjacent Pro-Lys (PK) sequence at positions 3–4 abolishes N-methylation, decreases cell growth, and increases stress sensitivity, implicating this modification in proteasome function.","method":"Mass spectrometry analysis of purified yeast Rpt1, site-directed mutagenesis, and growth/stress phenotype assays in yeast","journal":"Proteomics","confidence":"Medium","confidence_rationale":"Tier 1-2 — MS identification of modification plus functional mutagenesis; single organism (yeast ortholog)","pmids":["24038880"],"is_preprint":false},{"year":2017,"finding":"PSMC2 knockdown in osteosarcoma cells suppresses cell proliferation, enhances apoptosis, induces G2/M and S phase arrest, and inhibits migration and invasion in vitro and tumorigenicity in vivo; gene microarray after knockdown identifies ITGA6, FN1, CCND1, CCNE2, and TGFβR2 as downstream targets whose expression is regulated by PSMC2.","method":"RNA interference, MTT/colony assays, flow cytometry, transwell invasion assay, nude mouse xenografts, gene microarray, and Western blot validation","journal":"Oncotarget","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with multiple cellular phenotype readouts and microarray-identified downstream genes; single lab","pmids":["27888613"],"is_preprint":false},{"year":2021,"finding":"PSMC2 promotes breast cancer progression by directly interacting with plasminogen activator urokinase (PLAU); PSMC2 knockdown suppresses proliferation, apoptosis resistance, and migration in vitro and in vivo, and the PSMC2/PLAU axis was identified as the mechanistic basis by gene microarray and Ingenuity Pathway Analysis.","method":"Immunohistochemistry, shRNA knockdown, co-immunoprecipitation (direct interaction with PLAU), gene microarray with IPA, xenograft mouse models","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2-3 — co-IP establishes direct PSMC2-PLAU interaction; functional phenotypes confirmed in vivo; single lab","pmids":["34244472"],"is_preprint":false},{"year":2021,"finding":"PSMC2 promotes ovarian cancer development through regulation of CCND1; knockdown of PSMC2 decreases CCND1 expression, and overexpression of CCND1 reverses PSMC2 knockdown-induced suppression of proliferation and motility, demonstrating a mutual regulatory relationship between PSMC2 and CCND1.","method":"shRNA knockdown, gene microarray, overexpression rescue experiments, colony formation, motility assays, and xenograft models","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2-3 — epistasis by rescue experiment placing CCND1 downstream of PSMC2; single lab","pmids":["34294689"],"is_preprint":false},{"year":2021,"finding":"PSMC2 directly interacts with ITGA6 in hepatocellular carcinoma cells; PSMC2 knockdown phenocopies ITGA6 knockdown (impaired proliferation, colony formation, migration, enhanced apoptosis), and combined knockdown of both is additive, establishing a PSMC2/ITGA6 functional axis.","method":"Co-immunoprecipitation demonstrating direct interaction, gene microarray, shRNA knockdown, functional cell assays, and in vivo xenograft experiments","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2-3 — co-IP plus phenotypic epistasis; single lab","pmids":["34413286"],"is_preprint":false},{"year":2021,"finding":"PSMC2 knockdown in prostate cancer cells inhibits proliferation and migration while promoting apoptosis and cell cycle arrest; mechanistically, the regulatory effect is mediated through the Akt/Cyclin D1/CDK6 signaling pathway.","method":"qPCR, Western blot, shRNA knockdown, Celigo cell counting, colony formation, wound healing, Transwell assays, flow cytometry, and xenograft models","journal":"Cancer cell international","confidence":"Medium","confidence_rationale":"Tier 2 — pathway placement via Western blot of downstream effectors combined with loss-of-function; single lab","pmids":["33902600"],"is_preprint":false},{"year":2022,"finding":"PSMC2 promotes gastric cancer progression via induction of RPS15A and downstream mTOR pathway activation; PSMC2 and RPS15A competitively bind hsa-let-7c-3p (a miRNA), thereby elevating RPS15A levels. RPS15A overexpression rescues the growth inhibition caused by PSMC2 knockdown, and mTOR inhibitor Torin1 reverses RPS15A-promoted proliferation.","method":"GeneChip microarray, IPA, dual-luciferase reporter assays for miRNA binding, RPS15A overexpression rescue, Torin1 pharmacological inhibition, in vivo xenograft","journal":"Oncogenesis","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (luciferase, rescue, pharmacological) placing PSMC2 upstream of RPS15A/mTOR via let-7c-3p competition; single lab","pmids":["35256584"],"is_preprint":false},{"year":2022,"finding":"PSMC2 knockdown in oral squamous cell carcinoma promotes apoptosis through upregulation of pro-apoptotic proteins and downregulation of p100, p-Akt, and CDK6, while upregulating MAPK9, indicating that PSMC2 suppresses apoptosis via the PI3K/Akt pathway.","method":"Lentiviral shRNA knockdown, human apoptosis antibody array, Western blot, flow cytometry, MTT, colony formation, Transwell assays, xenograft model","journal":"Cell cycle","confidence":"Medium","confidence_rationale":"Tier 2-3 — apoptosis antibody array identifies pathway components; confirmed by Western blot; single lab","pmids":["34979867"],"is_preprint":false},{"year":2022,"finding":"PSMC2 knockdown in glioma cells inhibits proliferation and promotes apoptosis; gene-set enrichment analysis of PSMC2 co-expression genes indicates PSMC2 affects the apoptosis pathway, with changes in apoptosis-related proteins confirmed after knockdown.","method":"siRNA knockdown, CCK-8 proliferation assay, flow cytometry, Western blot, GSEA of co-expression networks","journal":"World journal of surgical oncology","confidence":"Low","confidence_rationale":"Tier 3 — functional phenotype with pathway inference from GSEA; limited mechanistic depth; single lab","pmids":["35287689"],"is_preprint":false},{"year":2021,"finding":"PSMC2 knockdown in skin cutaneous melanoma cells elevates pro-apoptotic proteins DR6, IGFBP-4, p21, and p53 while inhibiting anti-apoptotic TRAILR-3 and suppressing Wnt signaling pathway proteins, revealing that PSMC2 promotes melanoma progression through Wnt pathway regulation.","method":"Protein-chip technology, GSEA, flow cytometry, in vitro proliferation/migration/DNA damage assays, and in vivo xenograft; MG132 pharmacological mimicry and PSMC2 overexpression confirmation","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2 — protein array identification of downstream effectors confirmed by pharmacological mimicry (MG132) and overexpression; single lab","pmids":["34716318"],"is_preprint":false},{"year":2019,"finding":"PSMC2 knockdown in pancreatic cancer cells inhibits cell proliferation and enhances apoptosis (including caspase-3/7 activation), supporting a role for PSMC2 in sustaining cancer cell survival.","method":"shRNA knockdown, MTT assay, Celigo assay, Annexin V FACS, Caspase-3/7 array","journal":"Journal of Cancer","confidence":"Low","confidence_rationale":"Tier 3 — loss-of-function phenotype without specific pathway placement; single lab, limited mechanistic follow-up","pmids":["31598166"],"is_preprint":false}],"current_model":"PSMC2 (MSS1/26S protease subunit 7) is an ATPase subunit of the 19S regulatory complex of the 26S proteasome that forms a specific heterodimer with ATPase S4 and assembles into larger subcomplexes with S2 and S5b; it drives ATP-dependent unfolding and translocation of ubiquitinated substrates into the 20S catalytic core, contributes to NF-κB-mediated neuroinflammation by promoting IκBα degradation, and in multiple cancer contexts regulates proliferation, apoptosis, and migration through downstream effectors including PLAU, CCND1, ITGA6, RPS15A/mTOR, and the PI3K/Akt and Wnt signaling pathways; additionally, PSMC2 associates with basal RNA polymerase II transcription factors (TBP, TFIIB, TFIIH, TFIIF) in a proteasome-independent complex, suggesting a broader role in transcriptional regulation."},"narrative":{"teleology":[{"year":1993,"claim":"Identification of PSMC2 as an integral 26S proteasome ATPase resolved the identity of subunit 7 and linked it to the previously cloned HIV Tat modulator MSS1, establishing its dual nomenclature and placing it within the proteasome.","evidence":"N-terminal and internal peptide sequencing of purified 26S protease subunit 7 from human erythrocytes","pmids":["8500623"],"confidence":"High","gaps":["Specific enzymatic contribution of PSMC2 versus other ATPase subunits was not defined","Stoichiometry and arrangement within the ATPase ring was unknown"]},{"year":1996,"claim":"Biochemical reconstitution of the 19S regulatory complex established that PSMC2 functions as one of six ATPases responsible for substrate recognition and unfolding, providing the mechanistic framework for its role in proteasomal degradation.","evidence":"Subunit composition analysis and functional assays of purified 26S proteasome","pmids":["8811196"],"confidence":"High","gaps":["Direct contacts between PSMC2 and neighboring ATPases were not mapped","Individual ATPase cycle contribution of PSMC2 was undefined"]},{"year":2000,"claim":"Mapping of PSMC2's assembly interactions revealed it forms a specific heterodimer with ATPase S4 and ternary complexes with S2 and S5b through distinct domains, establishing how the 19S base is built from defined subassemblies.","evidence":"Co-translation, co-immunoprecipitation, sedimentation analysis, and chimeric domain-mapping in reticulocyte lysate","pmids":["10625621"],"confidence":"High","gaps":["Structural basis of the S4–S7 heterodimer was not resolved at atomic level","Whether the tetramer intermediate is obligate for in vivo assembly was not tested"]},{"year":2000,"claim":"Detection of PSMC2 in sub-26S complexes with basal Pol II transcription factors (TBP, TFIIB, TFIIH, TFIIF) suggested a proteasome-independent transcriptional role, opening a second functional axis for the protein.","evidence":"Glycerol gradient sedimentation and co-immunoprecipitation from rat tissues and mammalian cells","pmids":["11118327"],"confidence":"Medium","gaps":["No reciprocal pull-down or reconstitution of PSMC2–transcription factor complexes was performed","Functional consequences on transcription were not directly measured","Whether this association requires ATPase activity is unknown"]},{"year":2009,"claim":"Comprehensive mechanistic analysis confirmed that the six-ATPase ring including PSMC2 provides the driving force for substrate unfolding and ATP-dependent threading into the 20S catalytic chamber, establishing the consensus model of 19S function.","evidence":"Review consolidating ATPase mutant studies and substrate processing assays across multiple labs","pmids":["19489727"],"confidence":"High","gaps":["Individual contributions of PSMC2 versus other ring ATPases to the sequential hydrolysis cycle remained unresolved","No high-resolution structure of the human PSMC2-containing ring existed at this time"]},{"year":2012,"claim":"PSMC2 knockdown in microglia stabilized IκBα and blocked NF-κB activation, directly linking PSMC2's proteasomal function to neuroinflammatory signaling and demonstrating a specific biological output of 26S-dependent degradation.","evidence":"siRNA knockdown in microglial cells with Western blot for IκBα/NF-κB and ELISA for inflammatory mediators","pmids":["22629310"],"confidence":"Medium","gaps":["Whether the effect is specific to PSMC2 or generalizable to any 19S ATPase knockdown was not addressed","In vivo neuroinflammation models were not tested"]},{"year":2013,"claim":"N-terminal methylation of the yeast PSMC2 ortholog Rpt1 was identified and shown to affect growth and stress tolerance, revealing a post-translational modification layer that tunes proteasome function.","evidence":"Mass spectrometry of purified yeast Rpt1, site-directed mutagenesis, and growth/stress assays","pmids":["24038880"],"confidence":"Medium","gaps":["Whether human PSMC2 undergoes equivalent N-terminal methylation was not examined","Mechanistic link between methylation and proteasome activity or assembly is unclear"]},{"year":2017,"claim":"Loss-of-function studies in osteosarcoma identified PSMC2 as a driver of proliferation, survival, and migration, with microarray revealing ITGA6, CCND1, CCNE2, and TGFβR2 as downstream transcriptional targets — the first cancer-type delineation of PSMC2-dependent gene programs.","evidence":"shRNA knockdown, MTT/colony assays, flow cytometry, Transwell invasion, xenograft models, and gene microarray with Western blot validation","pmids":["27888613"],"confidence":"Medium","gaps":["Whether downstream gene changes reflect direct proteasomal substrate stabilization or indirect signaling was not distinguished","No proteasome activity assay was performed alongside phenotypic readouts"]},{"year":2019,"claim":"Extension of PSMC2 cancer phenotyping to pancreatic cancer showed conserved pro-survival and anti-apoptotic roles, but without specific pathway placement, leaving the downstream mechanism in this tissue unresolved.","evidence":"shRNA knockdown, MTT, Celigo, Annexin V FACS, caspase-3/7 assay in pancreatic cancer cells","pmids":["31598166"],"confidence":"Low","gaps":["No downstream pathway or target identification was attempted","Single lab with limited mechanistic depth","No rescue or epistasis experiments"]},{"year":2021,"claim":"A wave of cancer-type studies collectively defined PSMC2's pro-tumorigenic mechanisms through distinct downstream axes: PLAU in breast cancer, CCND1 in ovarian cancer, ITGA6 in hepatocellular carcinoma, Akt/Cyclin D1/CDK6 in prostate cancer, and Wnt pathway suppression in melanoma — demonstrating context-dependent effector selection.","evidence":"Co-immunoprecipitation (PLAU, ITGA6), rescue/epistasis experiments (CCND1 overexpression), Western blot pathway analysis, protein arrays, MG132 pharmacological mimicry, and in vivo xenograft models across five cancer types","pmids":["34244472","34294689","34413286","33902600","34716318"],"confidence":"Medium","gaps":["Whether PLAU and ITGA6 are direct proteasomal substrates of PSMC2-containing proteasomes or indirect effectors is unknown","No study compared PSMC2 knockdown to general proteasome inhibition to parse PSMC2-specific effects","All studies from single labs without independent replication"]},{"year":2022,"claim":"PSMC2 was shown to regulate RPS15A/mTOR signaling in gastric cancer by competing for hsa-let-7c-3p binding, revealing a non-canonical ceRNA mechanism independent of proteasome catalytic function, alongside additional cancer phenotyping in OSCC and glioma.","evidence":"Dual-luciferase reporter assays for miRNA binding, RPS15A rescue, Torin1 pharmacological inhibition, xenografts, apoptosis antibody array, GSEA","pmids":["35256584","34979867","35287689"],"confidence":"Medium","gaps":["The ceRNA mechanism for PSMC2 transcript is unprecedented and requires independent validation","Whether PSMC2 mRNA levels are sufficient to meaningfully sequester let-7c-3p in physiological settings is unaddressed","Glioma data lack mechanistic depth beyond GSEA inference"]},{"year":null,"claim":"Key unresolved questions include whether PSMC2's transcriptional associations with Pol II factors are functionally consequential, whether its pro-tumorigenic effects are truly distinct from general proteasome inhibition, and what the structural basis of PSMC2-specific substrate processing is in the human 26S proteasome.","evidence":"","pmids":[],"confidence":"High","gaps":["No functional transcription assay has been performed with PSMC2 manipulation","No comparison of PSMC2-specific knockdown versus other 19S ATPase knockdowns in any cancer model","High-resolution cryo-EM of human PSMC2 in the context of substrate engagement has not been reported in this timeline"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[1,4]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[5,12]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[1,2,4]},{"term_id":"GO:0005654","term_label":"nucleoplasm","supporting_discovery_ids":[3]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1,2,4,5]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,11,12,13,15]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[5]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[7,11,13,15]}],"complexes":["26S proteasome","19S regulatory particle"],"partners":["PSMC6","PSMD1","PSMD5","PLAU","ITGA6","TBP","GTF2B","GTF2H1"],"other_free_text":[]},"mechanistic_narrative":"PSMC2 is one of six AAA-ATPase subunits of the 19S regulatory particle of the 26S proteasome, where it drives ATP-dependent unfolding and translocation of ubiquitinated substrates into the 20S catalytic core for degradation [PMID:8500623, PMID:8811196, PMID:19489727]. Within the 19S base, PSMC2 forms a specific heterodimer with ATPase S4 (PSMC6) and assembles into larger subcomplexes with non-ATPase subunits S2 and S5b through distinct N-terminal and C-terminal interaction domains [PMID:10625621]. Through its role in proteasome-dependent protein turnover, PSMC2 controls IκBα degradation and NF-κB activation in microglia [PMID:22629310] and regulates proliferation, apoptosis, and migration in multiple cancer types via downstream effectors including CCND1, PLAU, ITGA6, and the PI3K/Akt and mTOR pathways [PMID:34244472, PMID:34294689, PMID:34413286, PMID:35256584]. PSMC2 also exists in lighter-than-26S complexes that associate with basal RNA polymerase II transcription factors TBP, TFIIB, TFIIH, and TFIIF, indicating a proteasome-independent role in transcriptional regulation [PMID:11118327]."},"prefetch_data":{"uniprot":{"accession":"P35998","full_name":"26S proteasome regulatory subunit 7","aliases":["26S proteasome AAA-ATPase subunit RPT1","Proteasome 26S subunit ATPase 2"],"length_aa":433,"mass_kda":48.6,"function":"Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC2 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P35998/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/PSMC2","classification":"Common Essential","n_dependent_lines":1201,"n_total_lines":1208,"dependency_fraction":0.9942052980132451},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000161057","cell_line_id":"CID000116","localizations":[{"compartment":"nucleoplasm","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"PSMA1","stoichiometry":10.0},{"gene":"PSMA5","stoichiometry":10.0},{"gene":"PSMA6","stoichiometry":10.0},{"gene":"PSMB1","stoichiometry":10.0},{"gene":"PSMB2","stoichiometry":10.0},{"gene":"PSMB3","stoichiometry":10.0},{"gene":"PSMB4","stoichiometry":10.0},{"gene":"PSMB7","stoichiometry":10.0},{"gene":"PSMD12","stoichiometry":10.0},{"gene":"PSMD11","stoichiometry":10.0}],"url":"https://opencell.sf.czbiohub.org/target/CID000116","total_profiled":1310},"omim":[{"mim_id":"618784","title":"PITH DOMAIN-CONTAINING PROTEIN 1; PITHD1","url":"https://www.omim.org/entry/618784"},{"mim_id":"602707","title":"PROTEASOME 26S SUBUNIT, ATPase, 4; PSMC4","url":"https://www.omim.org/entry/602707"},{"mim_id":"602706","title":"PROTEASOME 26S SUBUNIT, ATPase, 1; PSMC1","url":"https://www.omim.org/entry/602706"},{"mim_id":"154365","title":"PROTEASOME 26S SUBUNIT, ATPase, 2; PSMC2","url":"https://www.omim.org/entry/154365"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Cytoplasmic bodies","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/PSMC2"},"hgnc":{"alias_symbol":["MSS1","S7","Nbla10058","RPT1"],"prev_symbol":[]},"alphafold":{"accession":"P35998","domains":[{"cath_id":"2.40.50.140","chopping":"88-152","consensus_level":"high","plddt":81.2665,"start":88,"end":152},{"cath_id":"3.40.50.300","chopping":"161-341","consensus_level":"high","plddt":82.1422,"start":161,"end":341},{"cath_id":"1.10.8.60","chopping":"347-421","consensus_level":"high","plddt":89.7993,"start":347,"end":421}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P35998","model_url":"https://alphafold.ebi.ac.uk/files/AF-P35998-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P35998-F1-predicted_aligned_error_v6.png","plddt_mean":80.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PSMC2","jax_strain_url":"https://www.jax.org/strain/search?query=PSMC2"},"sequence":{"accession":"P35998","fasta_url":"https://rest.uniprot.org/uniprotkb/P35998.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P35998/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P35998"}},"corpus_meta":[{"pmid":"17310983","id":"PMC_17310983","title":"Ribosomal protein S7 as a novel modulator of p53-MDM2 interaction: binding to MDM2, stabilization of p53 protein, and activation of p53 function.","date":"2007","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/17310983","citation_count":220,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19683495","id":"PMC_19683495","title":"Ribosomal protein S7 is both a regulator and a substrate of MDM2.","date":"2009","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/19683495","citation_count":180,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7989752","id":"PMC_7989752","title":"CD43 (S7) expression identifies peripheral B cell subsets.","date":"1994","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/7989752","citation_count":112,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2461734","id":"PMC_2461734","title":"Assembly of the 30S subunit from Escherichia coli ribosomes occurs via two assembly domains which are initiated by S4 and S7.","date":"1988","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2461734","citation_count":108,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9634092","id":"PMC_9634092","title":"Detection and assignment of proteins encoded by rice black streaked dwarf fijivirus S7, S8, S9 and S10.","date":"1998","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/9634092","citation_count":102,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"814400","id":"PMC_814400","title":"Specific cross-linking of proteins S7 and L4 to ribosomal RNA, by UV irradiation of Escherichia coli ribosomal subunits.","date":"1975","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/814400","citation_count":102,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8500623","id":"PMC_8500623","title":"Peptide sequencing identifies MSS1, a modulator of HIV Tat-mediated transactivation, as subunit 7 of the 26 S protease.","date":"1993","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/8500623","citation_count":90,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6338481","id":"PMC_6338481","title":"The localization of multiple sites on 16S RNA which are cross-linked to proteins S7 and S8 in Escherichia coli 30S ribosomal subunits by treatment with 2-iminothiolane.","date":"1983","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/6338481","citation_count":74,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"947902","id":"PMC_947902","title":"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.","date":"1976","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/947902","citation_count":72,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8392589","id":"PMC_8392589","title":"MSS1, a nuclear-encoded mitochondrial GTPase involved in the expression of COX1 subunit of cytochrome c oxidase.","date":"1993","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8392589","citation_count":69,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3373531","id":"PMC_3373531","title":"Probing the assembly of the 3' major domain of 16 S ribosomal RNA. Quaternary interactions involving ribosomal proteins S7, S9 and S19.","date":"1988","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/3373531","citation_count":67,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15628850","id":"PMC_15628850","title":"Structural locations and functional roles of new subsites S5, S6, and S7 in memapsin 2 (beta-secretase).","date":"2005","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15628850","citation_count":66,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"25556185","id":"PMC_25556185","title":"Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia.","date":"2015","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25556185","citation_count":65,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1100389","id":"PMC_1100389","title":"Nucleotide sequences of Escherichia coli 16-S RNA associated with ribosomal proteins S7, S9, S10, S14 and S19.","date":"1975","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1100389","citation_count":64,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9331418","id":"PMC_9331418","title":"The structure of ribosomal protein S7 at 1.9 A resolution reveals a beta-hairpin motif that binds double-stranded nucleic acids.","date":"1997","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/9331418","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6324129","id":"PMC_6324129","title":"The genes for the ribosomal proteins S12 and S7 are clustered with the gene for the EF-Tu protein on the chloroplast genome of Euglena gracilis.","date":"1984","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/6324129","citation_count":62,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24244431","id":"PMC_24244431","title":"Small ribosomal protein subunit S7 suppresses ovarian tumorigenesis through regulation of the PI3K/AKT and MAPK pathways.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24244431","citation_count":61,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21983128","id":"PMC_21983128","title":"Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway.","date":"2011","source":"Carcinogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/21983128","citation_count":61,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1105567","id":"PMC_1105567","title":"Neutron scattering measurements of separation and shape of proteins in 30S ribosomal subunit of Escherichia coli: S2-S5, S5-S8, S3-S7.","date":"1975","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/1105567","citation_count":59,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9331423","id":"PMC_9331423","title":"Ribosomal protein S7: a new RNA-binding motif with structural similarities to a DNA architectural factor.","date":"1997","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/9331423","citation_count":57,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2437528","id":"PMC_2437528","title":"RNA-protein cross-linking in Escherichia coli 30S ribosomal subunits; determination of sites on 16S RNA that are cross-linked to proteins S3, S4, S7, S9, S10, S11, S17, S18 and S21 by treatment with bis-(2-chloroethyl)-methylamine.","date":"1987","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2437528","citation_count":54,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10625621","id":"PMC_10625621","title":"Mapping subunit contacts in the regulatory complex of the 26 S proteasome. S2 and S5b form a tetramer with ATPase subunits S4 and S7.","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10625621","citation_count":53,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"776616","id":"PMC_776616","title":"Studies on the environment of protein S7 within the 30-S subunit Escherichia coli ribosomes.","date":"1976","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/776616","citation_count":53,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2437527","id":"PMC_2437527","title":"RNA-protein cross-linking in Escherichia coli 30S ribosomal subunits; determination of sites on 16S RNA that are cross-linked to proteins S3, S4, S5, S7, S8, S9, S11, S13, S19 and S21 by treatment with methyl p-azidophenyl acetimidate.","date":"1987","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2437527","citation_count":53,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8630533","id":"PMC_8630533","title":"Primary structure of ribosomal proteins S3 and S7 from Manduca sexta.","date":"1996","source":"Insect molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8630533","citation_count":52,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"18203625","id":"PMC_18203625","title":"Molecular phylogenetics of the family Cyprinidae (Actinopterygii: Cypriniformes) as evidenced by sequence variation in the first intron of S7 ribosomal protein-coding gene: further evidence from a nuclear gene of the systematic chaos in the family.","date":"2007","source":"Molecular phylogenetics and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/18203625","citation_count":52,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10867193","id":"PMC_10867193","title":"Phylogenetic relationships of bluetongue viruses based on gene S7.","date":"2000","source":"Virus research","url":"https://pubmed.ncbi.nlm.nih.gov/10867193","citation_count":49,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7016341","id":"PMC_7016341","title":"Identification of ribosomal protein S7 as a repressor of translation within the str operon of E. coli.","date":"1981","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/7016341","citation_count":46,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7507167","id":"PMC_7507167","title":"Post-transcriptional regulation of the str operon in Escherichia coli. Ribosomal protein S7 inhibits coupled translation of S7 but not its independent translation.","date":"1994","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/7507167","citation_count":45,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2499762","id":"PMC_2499762","title":"Genes for the ribosomal proteins S12 and S7 and elongation factors EF-G and EF-Tu of the cyanobacterium, Anacystis nidulans: structural homology between 16S rRNA and S7 mRNA.","date":"1989","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/2499762","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2338940","id":"PMC_2338940","title":"Genes for the plastid elongation factor Tu and ribosomal protein S7 and six tRNA genes on the 73 kb DNA from Astasia longa that resembles the chloroplast DNA of Euglena.","date":"1990","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/2338940","citation_count":43,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21550419","id":"PMC_21550419","title":"Knockdown of ribosomal protein S7 causes developmental abnormalities via p53 dependent and independent pathways in zebrafish.","date":"2011","source":"The international journal of biochemistry & cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21550419","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28455333","id":"PMC_28455333","title":"A Novel Quorum-Quenching N-Acylhomoserine Lactone Acylase from Acidovorax sp. Strain MR-S7 Mediates Antibiotic Resistance.","date":"2017","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28455333","citation_count":40,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7681943","id":"PMC_7681943","title":"Interaction of Escherichia coli ribosomal protein S7 with 16S rRNA.","date":"1993","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/7681943","citation_count":39,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12937172","id":"PMC_12937172","title":"A functional interaction between ribosomal proteins S7 and S11 within the bacterial ribosome.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12937172","citation_count":38,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6989601","id":"PMC_6989601","title":"Effect of ultraviolet irradiation on 30-S ribosomal subunits. Identification of the RNA region crosslinked to protein S7.","date":"1980","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/6989601","citation_count":37,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8289236","id":"PMC_8289236","title":"Post-transcriptional regulation of the str operon in Escherichia coli. Structural and mutational analysis of the target site for translational repressor S7.","date":"1994","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/8289236","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17006740","id":"PMC_17006740","title":"Fusion of carbohydrate binding modules from Thermotoga neapolitana with a family 10 xylanase from Bacillus halodurans S7.","date":"2006","source":"Extremophiles : life under extreme conditions","url":"https://pubmed.ncbi.nlm.nih.gov/17006740","citation_count":34,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"32667627","id":"PMC_32667627","title":"Circular RNA S-7 promotes ovarian cancer EMT via sponging miR-641 to up-regulate ZEB1 and MDM2.","date":"2020","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/32667627","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10948989","id":"PMC_10948989","title":"Phylogenetic analysis of the S7 gene does not segregate Chinese strains of bluetongue virus into a single topotype.","date":"2000","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/10948989","citation_count":33,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2513185","id":"PMC_2513185","title":"Sequence analysis of the peptide-elongation factor EF-2 gene, downstream from those of ribosomal proteins H-S12 and H-S7, from the archaebacterial extreme halophile, Halobacterium halobium.","date":"1989","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2513185","citation_count":32,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"27888613","id":"PMC_27888613","title":"PSMC2 is up-regulated in osteosarcoma and regulates osteosarcoma cell proliferation, apoptosis and migration.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/27888613","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8437584","id":"PMC_8437584","title":"Characterization of the S7 ribosomal protein gene in wheat mitochondria.","date":"1993","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/8437584","citation_count":31,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10581179","id":"PMC_10581179","title":"Identification of a mammalian mitochondrial homolog of ribosomal protein S7.","date":"1999","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/10581179","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9731210","id":"PMC_9731210","title":"Nuclear import and nucleolar accumulation of the human ribosomal protein S7 depends on both a minimal nuclear localization sequence and an adjacent basic region.","date":"1998","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/9731210","citation_count":30,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33184379","id":"PMC_33184379","title":"Ribosomal protein S7 ubiquitination during ER stress in yeast is associated with selective mRNA translation and stress outcome.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33184379","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1766869","id":"PMC_1766869","title":"A paradigm for local conformational control of function in the ribosome: binding of ribosomal protein S19 to Escherichia coli 16S rRNA in the presence of S7 is required for methylation of m2G966 and blocks methylation of m5C967 by their respective methyltransferases.","date":"1991","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/1766869","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"15525707","id":"PMC_15525707","title":"Assembly of the 30S ribosomal subunit: positioning ribosomal protein S13 in the S7 assembly branch.","date":"2004","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/15525707","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2822717","id":"PMC_2822717","title":"Nucleotide sequence, promoter analysis, and linkage mapping of the unusually organized operon encoding ribosomal proteins S7 and S12 in maize chloroplast.","date":"1987","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2822717","citation_count":29,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7029472","id":"PMC_7029472","title":"Apparent association constants for E. coli ribosomal proteins S4, S7, S8, S15, S17 and S20 binding to 16S RNA.","date":"1981","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/7029472","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8774896","id":"PMC_8774896","title":"A functional role for some Fugu introns larger than the typical short ones: the example of the gene coding for ribosomal protein S7 and snoRNA U17.","date":"1996","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/8774896","citation_count":28,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34244472","id":"PMC_34244472","title":"Overexpression of PSMC2 promotes the tumorigenesis and development of human breast cancer via regulating plasminogen activator urokinase (PLAU).","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34244472","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1637863","id":"PMC_1637863","title":"Photochemical cross-linking of the anticodon loop of yeast tRNA(Phe) to 30S-subunit protein S7 at the ribosomal A and P sites.","date":"1992","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/1637863","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"21331890","id":"PMC_21331890","title":"Molecular characterization of segments S7 to S10 of a southern rice black-streaked dwarf virus isolate from maize in northern China.","date":"2011","source":"Virologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/21331890","citation_count":27,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35256584","id":"PMC_35256584","title":"PSMC2 promotes the progression of gastric cancer via induction of RPS15A/mTOR pathway.","date":"2022","source":"Oncogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/35256584","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11118327","id":"PMC_11118327","title":"Tissue and cell distribution of a mammalian proteasomal ATPase, MSS1, and its complex formation with the basal transcription factors.","date":"2000","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/11118327","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2478339","id":"PMC_2478339","title":"Analysis of lymphoid population in scid mice; detection of a potential B lymphocyte progenitor population present at normal levels in scid mice by three color flow cytometry with B220 and S7.","date":"1989","source":"Current topics in microbiology and immunology","url":"https://pubmed.ncbi.nlm.nih.gov/2478339","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"20224169","id":"PMC_20224169","title":"Indirect ELISA and indirect immunofluorescent antibody assay for detecting the antibody against murine norovirus S7 in mice.","date":"2010","source":"Experimental animals","url":"https://pubmed.ncbi.nlm.nih.gov/20224169","citation_count":26,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30222246","id":"PMC_30222246","title":"The structure of INI1/hSNF5 RPT1 and its interactions with the c-MYC:MAX heterodimer provide insights into the interplay between MYC and the SWI/SNF chromatin remodeling complex.","date":"2018","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/30222246","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1737755","id":"PMC_1737755","title":"The yeast ribosomal protein S7 and its genes.","date":"1992","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1737755","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2685749","id":"PMC_2685749","title":"Ribosomal proteins S7 and L1 are located close to the decoding site of E. coli ribosome--affinity labeling studies with modified tRNAs carrying photoreactive probes attached adjacent to the 3'-end of the anticodon.","date":"1989","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2685749","citation_count":25,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"10772857","id":"PMC_10772857","title":"Tagging ribosomal protein S7 allows rapid identification of mutants defective in assembly and function of 30 S subunits.","date":"2000","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10772857","citation_count":24,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9582096","id":"PMC_9582096","title":"Matching the crystallographic structure of ribosomal protein S7 to a three-dimensional model of the 16S ribosomal RNA.","date":"1998","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/9582096","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6394951","id":"PMC_6394951","title":"Comparative electron microscopic study on the location of ribosomal proteins S3 and S7 on the surface of the E. coli 30S subunit using monoclonal and conventional antibody.","date":"1984","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/6394951","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7525976","id":"PMC_7525976","title":"Mutational and structural analysis of the RNA binding site for Escherichia coli ribosomal protein S7.","date":"1994","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/7525976","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"16757802","id":"PMC_16757802","title":"Cloning, sequence analysis, and expression of a gene encoding an endoxylanase from Bacillus halodurans S7.","date":"2006","source":"Molecular biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/16757802","citation_count":23,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31598166","id":"PMC_31598166","title":"PSMC2 is Up-regulated in Pancreatic Cancer and Promotes Cancer Cell Proliferation and Inhibits Apoptosis.","date":"2019","source":"Journal of Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/31598166","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"23563151","id":"PMC_23563151","title":"Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation.","date":"2013","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/23563151","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11160889","id":"PMC_11160889","title":"Ribosomal protein S7 from Escherichia coli uses the same determinants to bind 16S ribosomal RNA and its messenger RNA.","date":"2001","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/11160889","citation_count":22,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34294689","id":"PMC_34294689","title":"PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration.","date":"2021","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/34294689","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6196023","id":"PMC_6196023","title":"Electron microscopic investigations on the location of rat liver ribosomal proteins S3a, S5, S6, S7 and S9 by means of antibody labeling.","date":"1983","source":"Biomedica biochimica acta","url":"https://pubmed.ncbi.nlm.nih.gov/6196023","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"17426918","id":"PMC_17426918","title":"Molecular analysis of the genome segments S1, S4, S6, S7 and S12 of a Rice gall dwarf virus isolate from Thailand; completion of the genomic sequence.","date":"2007","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/17426918","citation_count":21,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11158540","id":"PMC_11158540","title":"Chloroplast ribosomal protein S7 of Chlamydomonas binds to chloroplast mRNA leader sequences and may be involved in translation initiation.","date":"2001","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/11158540","citation_count":20,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33980829","id":"PMC_33980829","title":"INI1/SMARCB1 Rpt1 domain mimics TAR RNA in binding to integrase to facilitate HIV-1 replication.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33980829","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9672632","id":"PMC_9672632","title":"Rice ragged stunt oryzavirus genome segments S7 and S10 encode non-structural proteins of M(r) 68,025 (Pns7) and M(r) 32,364 (Pns10).","date":"1997","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/9672632","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"9268371","id":"PMC_9268371","title":"Specific interactions of the autoantigen L7 with multi-zinc finger protein ZNF7 and ribosomal protein S7.","date":"1997","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9268371","citation_count":19,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34413286","id":"PMC_34413286","title":"PSMC2/ITGA6 axis plays critical role in the development and progression of hepatocellular carcinoma.","date":"2021","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/34413286","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2423965","id":"PMC_2423965","title":"Multiple crosslinks of proteins S7, S9, S13 to domains 3 and 4 of 16S RNA in the 30S particle.","date":"1986","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2423965","citation_count":18,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"30688636","id":"PMC_30688636","title":"Identification of a novel membrane-associated protein from the S7 segment of grass carp reovirus.","date":"2019","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/30688636","citation_count":17,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"11121577","id":"PMC_11121577","title":"Proteins S7, S10, S16 and S19 of the human 40S ribosomal subunit are most resistant to dissociation by salt.","date":"2000","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/11121577","citation_count":17,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"24038880","id":"PMC_24038880","title":"N-Terminal methylation of proteasome subunit Rpt1 in yeast.","date":"2013","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/24038880","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"12902042","id":"PMC_12902042","title":"The S7 gene and VP7 protein are highly conserved among temporally and geographically distinct American isolates of epizootic hemorrhagic disease virus.","date":"2003","source":"Virus research","url":"https://pubmed.ncbi.nlm.nih.gov/12902042","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"3279390","id":"PMC_3279390","title":"Protein binding sites on Escherichia coli 16S ribosomal RNA; RNA regions that are protected by proteins S7, S9 and S19, and by proteins S8, S15 and S17.","date":"1988","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/3279390","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2438658","id":"PMC_2438658","title":"Protein binding sites on Escherichia coli 16S RNA; RNA regions that are protected by proteins S7, S14 and S19 in the presence or absence of protein S9.","date":"1987","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2438658","citation_count":16,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35287689","id":"PMC_35287689","title":"PSMC2 is overexpressed in glioma and promotes proliferation and anti-apoptosis of glioma cells.","date":"2022","source":"World journal of surgical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35287689","citation_count":15,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33555546","id":"PMC_33555546","title":"Cellular Trafficking of Glutathione Transferase M2-2 Between U373MG and SHSY-S7 Cells is Mediated by Exosomes.","date":"2021","source":"Neurotoxicity research","url":"https://pubmed.ncbi.nlm.nih.gov/33555546","citation_count":14,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7890730","id":"PMC_7890730","title":"The phosphorylated ribosomal protein S7 in Tetrahymena is homologous with mammalian S4 and the phosphorylated residues are located in the C-terminal region. Structural characterization of proteins separated by two-dimensional polyacrylamide gel electrophoresis.","date":"1995","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7890730","citation_count":14,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"385062","id":"PMC_385062","title":"The primary structure of ribosomal protein S7 from E. coli strains K and B.","date":"1979","source":"Biochimie","url":"https://pubmed.ncbi.nlm.nih.gov/385062","citation_count":14,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"6990204","id":"PMC_6990204","title":"Analysis of rpsD mutations in Escherichia coli. IV. Accumulation of minor forms of protein S7(K) in ribosomes of rpsD mutant strains due to translational read-through.","date":"1980","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/6990204","citation_count":14,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34979867","id":"PMC_34979867","title":"PSMC2 knockdown inhibits the progression of oral squamous cell carcinoma by promoting apoptosis via PI3K/Akt pathway.","date":"2022","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/34979867","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"33902600","id":"PMC_33902600","title":"Silencing of PSMC2 inhibits development and metastasis of prostate cancer through regulating proliferation, apoptosis and migration.","date":"2021","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/33902600","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"1368664","id":"PMC_1368664","title":"The nucleotide sequences of Bacillus stearothermophilus ribosomal protein S12 and S7 genes: comparison with the str operon of Escherichia coli.","date":"1991","source":"Agricultural and biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/1368664","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"19909821","id":"PMC_19909821","title":"Phylogenetic relationships of North American phoxinins (Actinopterygii: Cypriniformes: Leuciscidae) as inferred from S7 nuclear DNA sequences.","date":"2009","source":"Molecular phylogenetics and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/19909821","citation_count":13,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"28510697","id":"PMC_28510697","title":"BCCIPβ modulates the ribosomal and extraribosomal function of S7 through a direct interaction.","date":"2017","source":"Journal of molecular cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/28510697","citation_count":12,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"2226813","id":"PMC_2226813","title":"The primary structure of rat ribosomal protein S7.","date":"1990","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/2226813","citation_count":12,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"31932644","id":"PMC_31932644","title":"A novel biphenyl compound IMB-S7 ameliorates hepatic fibrosis in BDL rats by suppressing Sp1-mediated integrin αv expression.","date":"2020","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/31932644","citation_count":12,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"22629310","id":"PMC_22629310","title":"Inhibition of 26S protease regulatory subunit 7 (MSS1) suppresses neuroinflammation.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22629310","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"35371040","id":"PMC_35371040","title":"BmCPV-Derived Circular DNA vcDNA-S7 Mediated by Bombyx mori Reverse Transcriptase (RT) Regulates BmCPV Infection.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35371040","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"34716318","id":"PMC_34716318","title":"PSMC2 knockdown suppressed tumor progression of skin cutaneous melanoma.","date":"2021","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/34716318","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"7700227","id":"PMC_7700227","title":"Inactivation of the UAS1 of STA1 by glucose and STA10 and identification of two loci, SNS1 and MSS1, involved in STA10-dependent repression in Saccharomyces cerevisiae.","date":"1995","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/7700227","citation_count":11,"is_preprint":false,"source_track":"pubmed_title"},{"pmid":"8811196","id":"PMC_8811196","title":"Structure and functions of the 20S and 26S proteasomes.","date":"1996","source":"Annual review of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8811196","citation_count":2108,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16189514","id":"PMC_16189514","title":"Towards a proteome-scale map of the human protein-protein interaction network.","date":"2005","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/16189514","citation_count":2090,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12167863","id":"PMC_12167863","title":"Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein.","date":"2002","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12167863","citation_count":1924,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22658674","id":"PMC_22658674","title":"Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22658674","citation_count":1718,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"16169070","id":"PMC_16169070","title":"A human protein-protein interaction network: a resource for annotating the proteome.","date":"2005","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/16169070","citation_count":1704,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12477932","id":"PMC_12477932","title":"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.","date":"2002","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12477932","citation_count":1479,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19489727","id":"PMC_19489727","title":"Recognition and processing of ubiquitin-protein conjugates by the proteasome.","date":"2009","source":"Annual review of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19489727","citation_count":1398,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"20562859","id":"PMC_20562859","title":"Network organization of the human autophagy system.","date":"2010","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/20562859","citation_count":1286,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"19615732","id":"PMC_19615732","title":"Defining the human deubiquitinating enzyme interaction landscape.","date":"2009","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/19615732","citation_count":1282,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12808466","id":"PMC_12808466","title":"Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts.","date":"2003","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12808466","citation_count":1236,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12809610","id":"PMC_12809610","title":"DNA deamination mediates innate immunity to retroviral infection.","date":"2003","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/12809610","citation_count":1150,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26186194","id":"PMC_26186194","title":"The BioPlex Network: A Systematic Exploration of the Human Interactome.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26186194","citation_count":1118,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"28514442","id":"PMC_28514442","title":"Architecture of the human interactome defines protein communities and disease networks.","date":"2017","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/28514442","citation_count":1085,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26496610","id":"PMC_26496610","title":"A human interactome in three quantitative dimensions organized by stoichiometries and abundances.","date":"2015","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/26496610","citation_count":1015,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14564014","id":"PMC_14564014","title":"Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex.","date":"2003","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/14564014","citation_count":1006,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"25416956","id":"PMC_25416956","title":"A proteome-scale map of the human interactome network.","date":"2014","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/25416956","citation_count":977,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12808465","id":"PMC_12808465","title":"The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA.","date":"2003","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/12808465","citation_count":912,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"23503661","id":"PMC_23503661","title":"Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.","date":"2013","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/23503661","citation_count":870,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32296183","id":"PMC_32296183","title":"A reference map of the human binary protein interactome.","date":"2020","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/32296183","citation_count":849,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14743216","id":"PMC_14743216","title":"A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.","date":"2004","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/14743216","citation_count":841,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"29507755","id":"PMC_29507755","title":"VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation.","date":"2018","source":"Cell discovery","url":"https://pubmed.ncbi.nlm.nih.gov/29507755","citation_count":829,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14528300","id":"PMC_14528300","title":"The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif.","date":"2003","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/14528300","citation_count":798,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12859895","id":"PMC_12859895","title":"Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif.","date":"2003","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/12859895","citation_count":763,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"17353931","id":"PMC_17353931","title":"Large-scale mapping of human protein-protein interactions by mass spectrometry.","date":"2007","source":"Molecular systems biology","url":"https://pubmed.ncbi.nlm.nih.gov/17353931","citation_count":733,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"33961781","id":"PMC_33961781","title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.","date":"2021","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33961781","citation_count":705,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"22939629","id":"PMC_22939629","title":"A census of human soluble protein complexes.","date":"2012","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/22939629","citation_count":689,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14528301","id":"PMC_14528301","title":"HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation.","date":"2003","source":"Nature medicine","url":"https://pubmed.ncbi.nlm.nih.gov/14528301","citation_count":679,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"26472760","id":"PMC_26472760","title":"Gene essentiality and synthetic lethality in haploid human cells.","date":"2015","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/26472760","citation_count":657,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"21873635","id":"PMC_21873635","title":"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium.","date":"2011","source":"Briefings in bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/21873635","citation_count":656,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"14527406","id":"PMC_14527406","title":"HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability.","date":"2003","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/14527406","citation_count":607,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":44202,"output_tokens":2946,"usd":0.088398},"stage2":{"model":"claude-opus-4-6","input_tokens":6332,"output_tokens":2451,"usd":0.139403},"total_usd":0.527229,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":55464,"output_tokens":4508,"usd":0.117006},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":7803,"output_tokens":3304,"usd":0.182422}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"PSMC2 (MSS1/subunit 7) was identified as an integral component of the human 26S protease (proteasome), confirmed by direct peptide sequencing showing 22 N-terminal amino acids and internal CNBr peptides from subunit 7 are identical to the MSS1 sequence, with matching molecular weight (~49 kDa).\",\n      \"method\": \"Peptide sequence analysis of purified 26S proteasome subunit 7 from human erythrocytes\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct protein sequencing establishing identity of PSMC2 as 26S proteasome subunit\",\n      \"pmids\": [\"8500623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"PSMC2 (S7) forms specific subunit contacts within the 19S regulatory complex of the 26S proteasome: S2 and S5b form a tetramer with ATPase subunits S4 and S7 (PSMC2). S2 binds the C-terminal two-thirds of S7, while S5b binds S7's N-terminal region. PSMC2 pairs specifically with S4 (but not S6-S8 or S6'-S10b dimers).\",\n      \"method\": \"In vitro co-translation, co-sedimentation, immunoprecipitation, and chimeric ATPase domain-mapping experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal biochemical methods (co-translation, sedimentation, IP, chimeric proteins) in single study\",\n      \"pmids\": [\"10625621\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"MSS1 (PSMC2) is ubiquitously distributed in mammalian tissues and cells, but its ratio relative to the 20S proteasome core varies greatly among tissues (concentrated in thymus). Glycerol gradient sedimentation revealed MSS1 exists in protein complexes lighter than the full proteasome. MSS1 was found to associate with multiple basal transcription factors for RNA polymerase II, including TBP, TFIIB, TFIIH, and TFIIF, suggesting a role in transcriptional regulation distinct from proteolysis.\",\n      \"method\": \"Glycerol gradient sedimentation, co-immunoprecipitation with transcription factors, Western blot across rat tissues\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — co-IP with transcription factors in single study; localization data from fractionation\",\n      \"pmids\": [\"11118327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Knockdown of PSMC2 (MSS1) in microglia by RNAi significantly reduced IκBα degradation, inhibited NF-κB activation, and suppressed LPS-induced production of pro-inflammatory mediators (iNOS, nitric oxide, COX-2, PGE2), placing PSMC2 in the ubiquitin-26S proteasome pathway controlling NF-κB-mediated neuroinflammation.\",\n      \"method\": \"RNA interference knockdown in microglia with downstream signaling readouts (Western blot, nitric oxide assay, COX-2/PGE2 measurement)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype and pathway placement (NF-κB/IκBα axis), single lab\",\n      \"pmids\": [\"22629310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PSMC2 knockdown in osteosarcoma cells suppressed cell proliferation, enhanced apoptosis, caused G2/M and/or S phase arrest, decreased colony formation, inhibited migration and invasion, and reduced tumorigenicity in nude mice. Gene microarray following PSMC2 knockdown identified downstream genes including ITGA6, FN1, CCND1, CCNE2, and TGFβR2, confirmed by Western blot.\",\n      \"method\": \"shRNA knockdown, MTT assay, flow cytometry, transwell assay, xenograft mouse model, gene microarray, Western blot\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined phenotypic readouts and downstream gene identification, single lab\",\n      \"pmids\": [\"27888613\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 promotes breast cancer progression by interacting with plasminogen activator urokinase (PLAU); PSMC2 knockdown suppressed proliferation, apoptosis resistance, and migration in vitro and in vivo. Gene microarray and IPA identified PLAU as a downstream effector of PSMC2.\",\n      \"method\": \"Loss-of-function (shRNA), gene microarray with IPA analysis, in vitro and xenograft in vivo experiments, interaction validated by co-IP\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — loss-of-function with downstream target identification and interaction shown, single lab\",\n      \"pmids\": [\"34244472\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 promotes ovarian cancer development via CCND1; knockdown of PSMC2 decreased colony formation, cell motility, and proliferation while increasing apoptosis in vitro and in vivo. Gene microarray identified CCND1 as a downstream target of PSMC2, with mutual regulation demonstrated—CCND1 knockdown enhanced and CCND1 overexpression reversed effects of PSMC2 knockdown.\",\n      \"method\": \"shRNA knockdown, gene microarray, CCND1 overexpression rescue experiments, xenograft mouse model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with rescue by downstream target overexpression, single lab\",\n      \"pmids\": [\"34294689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PSMC2 promotes gastric cancer progression via induction of RPS15A and mTOR pathway; PSMC2 knockdown inhibited RPS15A expression and mTOR pathway activity, which was reversed by RPS15A overexpression. PSMC2 and RPS15A were shown to competitively bind hsa-let-7c-3p by dual-luciferase reporter assay.\",\n      \"method\": \"shRNA knockdown, gene microarray, IPA, RPS15A overexpression rescue, mTOR inhibitor (Torin1) experiment, dual-luciferase reporter assay\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods with rescue experiments placing PSMC2 upstream of RPS15A/mTOR, single lab\",\n      \"pmids\": [\"35256584\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 directly interacts with ITGA6 in hepatocellular carcinoma cells; PSMC2 knockdown impaired proliferation, colony formation, migration, and promoted apoptosis. ITGA6 was identified as a downstream target, with mutual regulation demonstrated between PSMC2 and ITGA6.\",\n      \"method\": \"shRNA knockdown, gene microarray, IPA, co-IP demonstrating direct interaction, ITGA6 knockdown comparison experiments, xenograft mouse model\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — loss-of-function, direct interaction shown by co-IP, downstream target validated, single lab\",\n      \"pmids\": [\"34413286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 knockdown in prostate cancer cells inhibited proliferation, colony formation, and migration while promoting apoptosis and cell cycle arrest; the mechanism involves the Akt/Cyclin D1/CDK6 signaling pathway.\",\n      \"method\": \"shRNA knockdown, Celigo cell counting, colony formation assay, wound-healing/Transwell assay, flow cytometry, xenograft mouse model, pathway protein analysis\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotype and pathway placement (Akt/Cyclin D1/CDK6), single lab\",\n      \"pmids\": [\"33902600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PSMC2 knockdown in glioma cells inhibited proliferation and promoted apoptosis; gene-set enrichment analysis of PSMC2 co-expression genes indicated regulation of the apoptosis pathway, confirmed by changes in apoptosis-related proteins upon PSMC2 knockdown.\",\n      \"method\": \"siRNA knockdown, CCK-8 assay, GSEA, flow cytometry, Western blot for apoptosis proteins\",\n      \"journal\": \"World journal of surgical oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, KD with phenotype but limited mechanistic pathway validation beyond apoptosis protein changes\",\n      \"pmids\": [\"35287689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PSMC2 knockdown in oral squamous cell carcinoma suppressed proliferation and migration while promoting apoptosis via the PI3K/Akt pathway; knockdown downregulated p100, p-Akt, CDK6 and upregulated MAPK9; human apoptosis antibody array identified downstream pro-apoptotic proteins.\",\n      \"method\": \"Lentivirus-mediated shRNA knockdown, MTT assay, colony formation, flow cytometry, transwell/scratch assay, apoptosis antibody array, xenograft mouse model\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple cellular readouts, pathway proteins measured, in vivo validation, single lab\",\n      \"pmids\": [\"34979867\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PSMC2 (also known as MSS1 or 26S proteasome subunit 7) is an ATPase subunit of the 19S regulatory complex of the 26S proteasome, where it forms specific subunit contacts (including a tetramer with S2, S4, and S5b) and associates with basal transcription factors; it promotes IκBα degradation and NF-κB-mediated inflammation, and its overexpression in multiple cancers drives proliferation, survival, and invasion through downstream effectors including CCND1, ITGA6, PLAU, and the mTOR/Akt/Cyclin D1 signaling axes.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper and extract discoveries only from KEEP papers.\n\n**Classification:**\n\nFrom the retrieved corpus (100 papers):\n- Papers about PSMC2 (26S proteasome subunit ATPase 2/MSS1): PMID 8500623, 10625621, 11118327, 22629310, 27888613, 34244472, 35256584, 34294689, 34413286, 33902600, 35287689, 34979867, 33980829 (EXCLUDE - about INI1/SMARCB1), 24038880 (yeast Rpt1/PSMC2 ortholog - KEEP)\n\n- All other papers: About ribosomal protein S7 (RPS7/bacterial S7), viral S7 segments, CD43/S7 antibody, zebrafish RPS7, etc. → EXCLUDE (alias collision)\n\nFrom the gene2pubmed-curated papers:\n- PMID 8811196 (26S proteasome structure/function review) — KEEP\n- PMID 19489727 (proteasome recognition review) — KEEP\n- PMID 24038880 (Rpt1 N-methylation in yeast) — KEEP\n- All APOBEC3G, interactome network, autophagy, PARKIN papers — these are large-scale datasets that detected PSMC2 as an interactor but describe no mechanism specific to PSMC2 → treat as low-level evidence only if useful\n- Interactome papers (PMID 16189514, 16169070, 26186194, 28514442, 26496610, 25416956, 32296183, 17353931, 22939629, 33961781) — KEEP for interaction data\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"PSMC2 (subunit 7 of the human 26S protease) was identified by peptide sequencing as identical to MSS1, a previously described modulator of HIV Tat-mediated transactivation, establishing it as an integral ATPase component of the 26S proteasome regulatory complex.\",\n      \"method\": \"N-terminal and internal peptide sequencing by CNBr cleavage and direct Edman degradation of purified 26S protease subunit 7 from human erythrocytes\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — direct protein sequencing of purified native complex subunit with >12% sequence coverage confirming identity\",\n      \"pmids\": [\"8500623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"PSMC2 (MSS1/S7) functions as one of six ATPases in the 19S regulatory complex (RC) of the 26S proteasome, which is responsible for recognizing and unfolding ubiquitinated protein substrates for degradation by the 20S core particle.\",\n      \"method\": \"Biochemical reconstitution, subunit composition analysis, and functional assays of purified 26S proteasome\",\n      \"journal\": \"Annual review of biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — established in landmark review consolidating extensive biochemical reconstitution data; foundational mechanistic framework\",\n      \"pmids\": [\"8811196\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"PSMC2 (S7) forms a specific heterodimeric pair with the ATPase S4 within the 19S regulatory complex; additionally, non-ATPase subunits S2 and S5b each form ternary complexes with the S4-S7 pair, assembling into a tetramer. The C-terminal two-thirds of PSMC2 mediates binding to S2, while its N-terminal region mediates binding to S5b.\",\n      \"method\": \"In vitro co-translation in reticulocyte lysate, co-immunoprecipitation, sedimentation analysis, and chimeric ATPase domain-mapping experiments\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP and domain-mapping with chimeric proteins; multiple orthogonal methods in a single study\",\n      \"pmids\": [\"10625621\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"PSMC2 (MSS1) exists in cellular complexes lighter than the 26S proteasome and associates with multiple basal transcription factors for RNA polymerase II, including TBP, TFIIB, TFIIH, and TFIIF, suggesting a role in transcriptional regulation distinct from its proteasomal function.\",\n      \"method\": \"Glycerol gradient sedimentation, immunoblotting, and co-immunoprecipitation of endogenous complexes from rat tissues and mammalian cells\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — co-IP without reciprocal pull-down; single lab, single method for the transcription factor associations\",\n      \"pmids\": [\"11118327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"PSMC2 is required for efficient recognition and translocation of ubiquitinated substrates into the 20S proteasome core; together with the other five ATPases in the 19S particle, it forms a ring complex that drives substrate unfolding and ATP-dependent threading into the catalytic chamber.\",\n      \"method\": \"Comprehensive biochemical and genetic analysis reviewed, including ATPase mutant studies and substrate processing assays\",\n      \"journal\": \"Annual review of biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — mechanistic conclusions from reconstituted in vitro systems and mutagenesis studies across multiple labs\",\n      \"pmids\": [\"19489727\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PSMC2 knockdown in microglia inhibits IκBα degradation, suppresses NF-κB activation, and reduces LPS-induced production of pro-inflammatory mediators (iNOS, nitric oxide, COX-2, prostaglandin E2), establishing a role for PSMC2 in controlling neuroinflammatory signaling via the ubiquitin-proteasome system.\",\n      \"method\": \"RNA interference knockdown in microglial cells, Western blot for IκBα/NF-κB, ELISA and colorimetric assays for inflammatory mediators\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean RNAi knockdown with defined mechanistic readouts (IκBα stabilization, NF-κB suppression); single lab\",\n      \"pmids\": [\"22629310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"N-terminal Pro residue of yeast Rpt1 (the PSMC2 ortholog) undergoes mono- or di-methylation after removal of the initiator Met; deletion of the adjacent Pro-Lys (PK) sequence at positions 3–4 abolishes N-methylation, decreases cell growth, and increases stress sensitivity, implicating this modification in proteasome function.\",\n      \"method\": \"Mass spectrometry analysis of purified yeast Rpt1, site-directed mutagenesis, and growth/stress phenotype assays in yeast\",\n      \"journal\": \"Proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 — MS identification of modification plus functional mutagenesis; single organism (yeast ortholog)\",\n      \"pmids\": [\"24038880\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PSMC2 knockdown in osteosarcoma cells suppresses cell proliferation, enhances apoptosis, induces G2/M and S phase arrest, and inhibits migration and invasion in vitro and tumorigenicity in vivo; gene microarray after knockdown identifies ITGA6, FN1, CCND1, CCNE2, and TGFβR2 as downstream targets whose expression is regulated by PSMC2.\",\n      \"method\": \"RNA interference, MTT/colony assays, flow cytometry, transwell invasion assay, nude mouse xenografts, gene microarray, and Western blot validation\",\n      \"journal\": \"Oncotarget\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with multiple cellular phenotype readouts and microarray-identified downstream genes; single lab\",\n      \"pmids\": [\"27888613\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 promotes breast cancer progression by directly interacting with plasminogen activator urokinase (PLAU); PSMC2 knockdown suppresses proliferation, apoptosis resistance, and migration in vitro and in vivo, and the PSMC2/PLAU axis was identified as the mechanistic basis by gene microarray and Ingenuity Pathway Analysis.\",\n      \"method\": \"Immunohistochemistry, shRNA knockdown, co-immunoprecipitation (direct interaction with PLAU), gene microarray with IPA, xenograft mouse models\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — co-IP establishes direct PSMC2-PLAU interaction; functional phenotypes confirmed in vivo; single lab\",\n      \"pmids\": [\"34244472\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 promotes ovarian cancer development through regulation of CCND1; knockdown of PSMC2 decreases CCND1 expression, and overexpression of CCND1 reverses PSMC2 knockdown-induced suppression of proliferation and motility, demonstrating a mutual regulatory relationship between PSMC2 and CCND1.\",\n      \"method\": \"shRNA knockdown, gene microarray, overexpression rescue experiments, colony formation, motility assays, and xenograft models\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — epistasis by rescue experiment placing CCND1 downstream of PSMC2; single lab\",\n      \"pmids\": [\"34294689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 directly interacts with ITGA6 in hepatocellular carcinoma cells; PSMC2 knockdown phenocopies ITGA6 knockdown (impaired proliferation, colony formation, migration, enhanced apoptosis), and combined knockdown of both is additive, establishing a PSMC2/ITGA6 functional axis.\",\n      \"method\": \"Co-immunoprecipitation demonstrating direct interaction, gene microarray, shRNA knockdown, functional cell assays, and in vivo xenograft experiments\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — co-IP plus phenotypic epistasis; single lab\",\n      \"pmids\": [\"34413286\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 knockdown in prostate cancer cells inhibits proliferation and migration while promoting apoptosis and cell cycle arrest; mechanistically, the regulatory effect is mediated through the Akt/Cyclin D1/CDK6 signaling pathway.\",\n      \"method\": \"qPCR, Western blot, shRNA knockdown, Celigo cell counting, colony formation, wound healing, Transwell assays, flow cytometry, and xenograft models\",\n      \"journal\": \"Cancer cell international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — pathway placement via Western blot of downstream effectors combined with loss-of-function; single lab\",\n      \"pmids\": [\"33902600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PSMC2 promotes gastric cancer progression via induction of RPS15A and downstream mTOR pathway activation; PSMC2 and RPS15A competitively bind hsa-let-7c-3p (a miRNA), thereby elevating RPS15A levels. RPS15A overexpression rescues the growth inhibition caused by PSMC2 knockdown, and mTOR inhibitor Torin1 reverses RPS15A-promoted proliferation.\",\n      \"method\": \"GeneChip microarray, IPA, dual-luciferase reporter assays for miRNA binding, RPS15A overexpression rescue, Torin1 pharmacological inhibition, in vivo xenograft\",\n      \"journal\": \"Oncogenesis\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (luciferase, rescue, pharmacological) placing PSMC2 upstream of RPS15A/mTOR via let-7c-3p competition; single lab\",\n      \"pmids\": [\"35256584\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PSMC2 knockdown in oral squamous cell carcinoma promotes apoptosis through upregulation of pro-apoptotic proteins and downregulation of p100, p-Akt, and CDK6, while upregulating MAPK9, indicating that PSMC2 suppresses apoptosis via the PI3K/Akt pathway.\",\n      \"method\": \"Lentiviral shRNA knockdown, human apoptosis antibody array, Western blot, flow cytometry, MTT, colony formation, Transwell assays, xenograft model\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — apoptosis antibody array identifies pathway components; confirmed by Western blot; single lab\",\n      \"pmids\": [\"34979867\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PSMC2 knockdown in glioma cells inhibits proliferation and promotes apoptosis; gene-set enrichment analysis of PSMC2 co-expression genes indicates PSMC2 affects the apoptosis pathway, with changes in apoptosis-related proteins confirmed after knockdown.\",\n      \"method\": \"siRNA knockdown, CCK-8 proliferation assay, flow cytometry, Western blot, GSEA of co-expression networks\",\n      \"journal\": \"World journal of surgical oncology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — functional phenotype with pathway inference from GSEA; limited mechanistic depth; single lab\",\n      \"pmids\": [\"35287689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PSMC2 knockdown in skin cutaneous melanoma cells elevates pro-apoptotic proteins DR6, IGFBP-4, p21, and p53 while inhibiting anti-apoptotic TRAILR-3 and suppressing Wnt signaling pathway proteins, revealing that PSMC2 promotes melanoma progression through Wnt pathway regulation.\",\n      \"method\": \"Protein-chip technology, GSEA, flow cytometry, in vitro proliferation/migration/DNA damage assays, and in vivo xenograft; MG132 pharmacological mimicry and PSMC2 overexpression confirmation\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — protein array identification of downstream effectors confirmed by pharmacological mimicry (MG132) and overexpression; single lab\",\n      \"pmids\": [\"34716318\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PSMC2 knockdown in pancreatic cancer cells inhibits cell proliferation and enhances apoptosis (including caspase-3/7 activation), supporting a role for PSMC2 in sustaining cancer cell survival.\",\n      \"method\": \"shRNA knockdown, MTT assay, Celigo assay, Annexin V FACS, Caspase-3/7 array\",\n      \"journal\": \"Journal of Cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — loss-of-function phenotype without specific pathway placement; single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"31598166\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PSMC2 (MSS1/26S protease subunit 7) is an ATPase subunit of the 19S regulatory complex of the 26S proteasome that forms a specific heterodimer with ATPase S4 and assembles into larger subcomplexes with S2 and S5b; it drives ATP-dependent unfolding and translocation of ubiquitinated substrates into the 20S catalytic core, contributes to NF-κB-mediated neuroinflammation by promoting IκBα degradation, and in multiple cancer contexts regulates proliferation, apoptosis, and migration through downstream effectors including PLAU, CCND1, ITGA6, RPS15A/mTOR, and the PI3K/Akt and Wnt signaling pathways; additionally, PSMC2 associates with basal RNA polymerase II transcription factors (TBP, TFIIB, TFIIH, TFIIF) in a proteasome-independent complex, suggesting a broader role in transcriptional regulation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PSMC2 is an AAA-ATPase subunit of the 19S regulatory particle of the 26S proteasome that participates in proteasomal substrate recognition and unfolding, with broad roles in protein homeostasis, NF-κB signaling, and cell cycle control. Within the 19S complex, PSMC2 (subunit S7) pairs specifically with S4 and forms a tetramer with S2, S4, and S5b through distinct N-terminal and C-terminal interaction domains [PMID:10625621], and it also associates with RNA polymerase II basal transcription factors (TBP, TFIIB, TFIIH, TFIIF) in complexes lighter than the intact proteasome [PMID:11118327]. PSMC2 is required for IκBα degradation and NF-κB activation in microglia, linking proteasome function to neuroinflammatory signaling [PMID:22629310]. Knockdown studies across multiple cancer types consistently show that PSMC2 sustains proliferation, survival, and migration through downstream effectors including CCND1, ITGA6, PLAU, and the Akt/mTOR signaling axes [PMID:27888613, PMID:34294689, PMID:33902600, PMID:35256584].\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Establishing molecular identity: direct peptide sequencing proved that the previously cloned MSS1 cDNA encodes subunit 7 of the human 26S proteasome, anchoring PSMC2 as a core proteasomal ATPase.\",\n      \"evidence\": \"N-terminal and internal CNBr peptide sequencing of purified 26S proteasome subunit 7 from human erythrocytes\",\n      \"pmids\": [\"8500623\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Position and contacts of S7 within the 19S ring were unknown\",\n        \"No functional data distinguishing PSMC2 from other ATPase subunits\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Defining the subunit interaction map: biochemical reconstitution showed PSMC2 pairs specifically with S4 (not other ATPase dimers) and nucleates a tetramer with S2 and S5b via distinct N- and C-terminal domains, establishing the modular assembly logic of the 19S ATPase ring.\",\n      \"evidence\": \"In vitro co-translation, co-sedimentation, immunoprecipitation, and chimeric domain-mapping experiments\",\n      \"pmids\": [\"10625621\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the S7–S4 specificity not resolved at atomic level\",\n        \"Whether the S2–S4–S7–S5b tetramer is an obligate assembly intermediate in vivo was untested\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Expanding function beyond proteolysis: PSMC2 was found in sub-proteasomal complexes that co-immunoprecipitate with basal transcription factors TBP, TFIIB, TFIIH, and TFIIF, suggesting a proteasome-independent role in RNA polymerase II transcription.\",\n      \"evidence\": \"Glycerol gradient sedimentation and co-immunoprecipitation with transcription factors from rat tissues\",\n      \"pmids\": [\"11118327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of the PSMC2–transcription factor interaction not demonstrated\",\n        \"No reciprocal pull-down or reconstitution to confirm direct binding\",\n        \"Whether this association occurs in a proteasome-free context in vivo was unresolved\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linking PSMC2 to a specific signaling pathway: RNAi knockdown in microglia showed PSMC2 is required for IκBα degradation and NF-κB activation, placing proteasomal PSMC2 function upstream of neuroinflammatory mediator production.\",\n      \"evidence\": \"siRNA knockdown in microglia with Western blot for IκBα/NF-κB, nitric oxide, COX-2, and PGE2 readouts\",\n      \"pmids\": [\"22629310\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether PSMC2 has a specific non-redundant role versus general proteasome impairment was not distinguished\",\n        \"No assessment in primary neurons or in vivo neuroinflammation models\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"First cancer-functional study: PSMC2 knockdown in osteosarcoma suppressed proliferation, migration, and tumorigenicity and identified downstream targets (CCND1, ITGA6, FN1, CCNE2, TGFβR2), establishing PSMC2 as a pro-tumorigenic factor.\",\n      \"evidence\": \"shRNA knockdown with in vitro assays, xenograft mouse model, gene microarray, and Western blot validation\",\n      \"pmids\": [\"27888613\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether effects are direct or secondary to global proteasome dysfunction not resolved\",\n        \"Mechanism linking PSMC2 to each downstream gene not established\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identification of specific downstream effectors and interaction partners across cancers: independent studies showed PSMC2 physically interacts with PLAU (breast cancer) and ITGA6 (hepatocellular carcinoma) and regulates CCND1 (ovarian cancer) and Akt/Cyclin D1/CDK6 (prostate cancer), converging on cell cycle and migration pathways.\",\n      \"evidence\": \"shRNA knockdown, gene microarrays, co-immunoprecipitation for PLAU and ITGA6, CCND1 overexpression rescue, and xenograft models across four cancer types\",\n      \"pmids\": [\"34244472\", \"34413286\", \"34294689\", \"33902600\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus proteasome-mediated effects on each partner remain ambiguous\",\n        \"No structural or stoichiometric data for the PSMC2–PLAU or PSMC2–ITGA6 interactions\",\n        \"Cross-cancer comparison of downstream targets not performed in isogenic backgrounds\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extension to additional signaling axes: PSMC2 was placed upstream of RPS15A/mTOR in gastric cancer (via competitive ceRNA binding of hsa-let-7c-3p) and upstream of PI3K/Akt in oral squamous cell carcinoma, broadening the effector network.\",\n      \"evidence\": \"shRNA knockdown, RPS15A overexpression rescue, mTOR inhibitor (Torin1) experiments, dual-luciferase reporter assay, apoptosis antibody array, xenograft models\",\n      \"pmids\": [\"35256584\", \"34979867\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The ceRNA mechanism (PSMC2 mRNA sponging let-7c-3p) requires independent validation\",\n        \"Relative contribution of proteasomal versus non-proteasomal PSMC2 functions to cancer phenotypes is unresolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether PSMC2's pro-tumorigenic and transcription-related functions are mechanistically separable from its core proteasomal ATPase activity, and no structure of PSMC2-specific interaction interfaces with non-proteasomal partners exists.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No separation-of-function mutants distinguishing proteasomal from non-proteasomal roles\",\n        \"No high-resolution structure of PSMC2 complexed with transcription factors or cancer-associated partners\",\n        \"Physiological relevance in non-cancer primary tissues beyond neuroinflammation is unexplored\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 9, 11]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [4, 6, 9]}\n    ],\n    \"complexes\": [\n      \"26S proteasome 19S regulatory particle\",\n      \"S2-S4-S5b-S7 ATPase tetramer\"\n    ],\n    \"partners\": [\n      \"PSMC6\",\n      \"PSMD1\",\n      \"PSMD2\",\n      \"PLAU\",\n      \"ITGA6\",\n      \"CCND1\",\n      \"RPS15A\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"PSMC2 is one of six AAA-ATPase subunits of the 19S regulatory particle of the 26S proteasome, where it drives ATP-dependent unfolding and translocation of ubiquitinated substrates into the 20S catalytic core for degradation [PMID:8500623, PMID:8811196, PMID:19489727]. Within the 19S base, PSMC2 forms a specific heterodimer with ATPase S4 (PSMC6) and assembles into larger subcomplexes with non-ATPase subunits S2 and S5b through distinct N-terminal and C-terminal interaction domains [PMID:10625621]. Through its role in proteasome-dependent protein turnover, PSMC2 controls IκBα degradation and NF-κB activation in microglia [PMID:22629310] and regulates proliferation, apoptosis, and migration in multiple cancer types via downstream effectors including CCND1, PLAU, ITGA6, and the PI3K/Akt and mTOR pathways [PMID:34244472, PMID:34294689, PMID:34413286, PMID:35256584]. PSMC2 also exists in lighter-than-26S complexes that associate with basal RNA polymerase II transcription factors TBP, TFIIB, TFIIH, and TFIIF, indicating a proteasome-independent role in transcriptional regulation [PMID:11118327].\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Identification of PSMC2 as an integral 26S proteasome ATPase resolved the identity of subunit 7 and linked it to the previously cloned HIV Tat modulator MSS1, establishing its dual nomenclature and placing it within the proteasome.\",\n      \"evidence\": \"N-terminal and internal peptide sequencing of purified 26S protease subunit 7 from human erythrocytes\",\n      \"pmids\": [\"8500623\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Specific enzymatic contribution of PSMC2 versus other ATPase subunits was not defined\",\n        \"Stoichiometry and arrangement within the ATPase ring was unknown\"\n      ]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Biochemical reconstitution of the 19S regulatory complex established that PSMC2 functions as one of six ATPases responsible for substrate recognition and unfolding, providing the mechanistic framework for its role in proteasomal degradation.\",\n      \"evidence\": \"Subunit composition analysis and functional assays of purified 26S proteasome\",\n      \"pmids\": [\"8811196\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct contacts between PSMC2 and neighboring ATPases were not mapped\",\n        \"Individual ATPase cycle contribution of PSMC2 was undefined\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Mapping of PSMC2's assembly interactions revealed it forms a specific heterodimer with ATPase S4 and ternary complexes with S2 and S5b through distinct domains, establishing how the 19S base is built from defined subassemblies.\",\n      \"evidence\": \"Co-translation, co-immunoprecipitation, sedimentation analysis, and chimeric domain-mapping in reticulocyte lysate\",\n      \"pmids\": [\"10625621\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the S4–S7 heterodimer was not resolved at atomic level\",\n        \"Whether the tetramer intermediate is obligate for in vivo assembly was not tested\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Detection of PSMC2 in sub-26S complexes with basal Pol II transcription factors (TBP, TFIIB, TFIIH, TFIIF) suggested a proteasome-independent transcriptional role, opening a second functional axis for the protein.\",\n      \"evidence\": \"Glycerol gradient sedimentation and co-immunoprecipitation from rat tissues and mammalian cells\",\n      \"pmids\": [\"11118327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal pull-down or reconstitution of PSMC2–transcription factor complexes was performed\",\n        \"Functional consequences on transcription were not directly measured\",\n        \"Whether this association requires ATPase activity is unknown\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Comprehensive mechanistic analysis confirmed that the six-ATPase ring including PSMC2 provides the driving force for substrate unfolding and ATP-dependent threading into the 20S catalytic chamber, establishing the consensus model of 19S function.\",\n      \"evidence\": \"Review consolidating ATPase mutant studies and substrate processing assays across multiple labs\",\n      \"pmids\": [\"19489727\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Individual contributions of PSMC2 versus other ring ATPases to the sequential hydrolysis cycle remained unresolved\",\n        \"No high-resolution structure of the human PSMC2-containing ring existed at this time\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"PSMC2 knockdown in microglia stabilized IκBα and blocked NF-κB activation, directly linking PSMC2's proteasomal function to neuroinflammatory signaling and demonstrating a specific biological output of 26S-dependent degradation.\",\n      \"evidence\": \"siRNA knockdown in microglial cells with Western blot for IκBα/NF-κB and ELISA for inflammatory mediators\",\n      \"pmids\": [\"22629310\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the effect is specific to PSMC2 or generalizable to any 19S ATPase knockdown was not addressed\",\n        \"In vivo neuroinflammation models were not tested\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"N-terminal methylation of the yeast PSMC2 ortholog Rpt1 was identified and shown to affect growth and stress tolerance, revealing a post-translational modification layer that tunes proteasome function.\",\n      \"evidence\": \"Mass spectrometry of purified yeast Rpt1, site-directed mutagenesis, and growth/stress assays\",\n      \"pmids\": [\"24038880\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether human PSMC2 undergoes equivalent N-terminal methylation was not examined\",\n        \"Mechanistic link between methylation and proteasome activity or assembly is unclear\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Loss-of-function studies in osteosarcoma identified PSMC2 as a driver of proliferation, survival, and migration, with microarray revealing ITGA6, CCND1, CCNE2, and TGFβR2 as downstream transcriptional targets — the first cancer-type delineation of PSMC2-dependent gene programs.\",\n      \"evidence\": \"shRNA knockdown, MTT/colony assays, flow cytometry, Transwell invasion, xenograft models, and gene microarray with Western blot validation\",\n      \"pmids\": [\"27888613\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether downstream gene changes reflect direct proteasomal substrate stabilization or indirect signaling was not distinguished\",\n        \"No proteasome activity assay was performed alongside phenotypic readouts\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extension of PSMC2 cancer phenotyping to pancreatic cancer showed conserved pro-survival and anti-apoptotic roles, but without specific pathway placement, leaving the downstream mechanism in this tissue unresolved.\",\n      \"evidence\": \"shRNA knockdown, MTT, Celigo, Annexin V FACS, caspase-3/7 assay in pancreatic cancer cells\",\n      \"pmids\": [\"31598166\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No downstream pathway or target identification was attempted\",\n        \"Single lab with limited mechanistic depth\",\n        \"No rescue or epistasis experiments\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"A wave of cancer-type studies collectively defined PSMC2's pro-tumorigenic mechanisms through distinct downstream axes: PLAU in breast cancer, CCND1 in ovarian cancer, ITGA6 in hepatocellular carcinoma, Akt/Cyclin D1/CDK6 in prostate cancer, and Wnt pathway suppression in melanoma — demonstrating context-dependent effector selection.\",\n      \"evidence\": \"Co-immunoprecipitation (PLAU, ITGA6), rescue/epistasis experiments (CCND1 overexpression), Western blot pathway analysis, protein arrays, MG132 pharmacological mimicry, and in vivo xenograft models across five cancer types\",\n      \"pmids\": [\"34244472\", \"34294689\", \"34413286\", \"33902600\", \"34716318\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether PLAU and ITGA6 are direct proteasomal substrates of PSMC2-containing proteasomes or indirect effectors is unknown\",\n        \"No study compared PSMC2 knockdown to general proteasome inhibition to parse PSMC2-specific effects\",\n        \"All studies from single labs without independent replication\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"PSMC2 was shown to regulate RPS15A/mTOR signaling in gastric cancer by competing for hsa-let-7c-3p binding, revealing a non-canonical ceRNA mechanism independent of proteasome catalytic function, alongside additional cancer phenotyping in OSCC and glioma.\",\n      \"evidence\": \"Dual-luciferase reporter assays for miRNA binding, RPS15A rescue, Torin1 pharmacological inhibition, xenografts, apoptosis antibody array, GSEA\",\n      \"pmids\": [\"35256584\", \"34979867\", \"35287689\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The ceRNA mechanism for PSMC2 transcript is unprecedented and requires independent validation\",\n        \"Whether PSMC2 mRNA levels are sufficient to meaningfully sequester let-7c-3p in physiological settings is unaddressed\",\n        \"Glioma data lack mechanistic depth beyond GSEA inference\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include whether PSMC2's transcriptional associations with Pol II factors are functionally consequential, whether its pro-tumorigenic effects are truly distinct from general proteasome inhibition, and what the structural basis of PSMC2-specific substrate processing is in the human 26S proteasome.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No functional transcription assay has been performed with PSMC2 manipulation\",\n        \"No comparison of PSMC2-specific knockdown versus other 19S ATPase knockdowns in any cancer model\",\n        \"High-resolution cryo-EM of human PSMC2 in the context of substrate engagement has not been reported in this timeline\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [5, 12]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1, 2, 4]},\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1, 2, 4, 5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 11, 12, 13, 15]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [7, 11, 13, 15]}\n    ],\n    \"complexes\": [\n      \"26S proteasome\",\n      \"19S regulatory particle\"\n    ],\n    \"partners\": [\n      \"PSMC6\",\n      \"PSMD1\",\n      \"PSMD5\",\n      \"PLAU\",\n      \"ITGA6\",\n      \"TBP\",\n      \"GTF2B\",\n      \"GTF2H1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}