{"gene":"PSMG1","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":1998,"finding":"PSMG1 (c21-LRP) was identified as a novel gene on human chromosome 21 encoding a 288-amino acid leucine-rich protein of 32.8 kDa with two predicted transmembrane helices, expressed highly in testis and the Jurkat T cell line.","method":"cDNA sequencing, Northern blot, RT-PCR, computational protein analysis","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction and expression analysis only; no functional assay","pmids":["9784380"],"is_preprint":false},{"year":2000,"finding":"DSCR2/PSMG1 mRNA levels correlate with cellular proliferation: expression was detected in all proliferating human tumor cell lines tested, and DSCR2 mRNA levels correlated with cell growth in T98G and Jurkat cells in response to treatments, suggesting a role in cell proliferation.","method":"Northern blot, expression analysis across human cell lines and mouse developmental stages","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, expression correlation only, no direct functional perturbation experiment","pmids":["10872820"],"is_preprint":false},{"year":2004,"finding":"DSCR2/PSMG1 localizes to the endoplasmic reticulum (ER) of mammalian cells as a soluble protein on the cytoplasmic face, and is not an integral membrane protein; truncated forms lacking predicted transmembrane helices remained associated with the ER.","method":"Immunocytochemistry, fluorescence assays, membrane fractionation in transfected cells","journal":"European journal of histochemistry : EJH","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunocytochemistry and membrane fractionation, two orthogonal methods, single lab","pmids":["15590417"],"is_preprint":false},{"year":2005,"finding":"DSCR2/PSMG1 is synthesized as a 43 kDa precursor from which the N-terminus is cleaved to yield a 41 kDa polypeptide; the protein undergoes additional co- or post-translational modifications (not N-glycosylation) increasing its apparent molecular weight from the predicted 32.8 kDa by ~10 kDa; it localizes to a cytoplasmic compartment as a soluble form.","method":"Transient transfection in COS-1 and HEK293 cells, in vitro mutagenesis of N-glycosylation site, intracellular localization studies, membrane fractionation assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis and fractionation in two cell lines, single lab with multiple orthogonal methods","pmids":["15670775"],"is_preprint":false},{"year":2008,"finding":"DSCR2/PSMG1 physically interacts with PPARβ (a nuclear receptor) and inhibits its ligand-induced transcriptional activity; PPARβ also decreases the solubility of DSCR2, increasing levels of insoluble DSCR2.","method":"Yeast two-hybrid screening of human fetal brain cDNA library, co-immunoprecipitation in HEK293 cells, transcriptional reporter assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal validation by Y2H and Co-IP plus functional transcriptional assay, single lab","pmids":["18793612"],"is_preprint":false},{"year":2020,"finding":"miR-484 directly targets PSMG1 (confirmed by luciferase assay and immunoblotting), and PSMG1 knockdown rescues the reduction in cancer cell mobility caused by miR-484 inhibition, placing PSMG1 as a downstream effector in a miR-484-PSMG1 axis regulating prostate cancer cell migration.","method":"Luciferase reporter assay, immunoblotting, siRNA knockdown, cell migration assay in prostate cancer cell lines","journal":"Bioscience reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct target validation by luciferase and immunoblot plus functional rescue, single lab, two orthogonal methods","pmids":["32338277"],"is_preprint":false},{"year":2025,"finding":"PSMG2 forms a heterodimer with PSMG1 and promotes assembly of the 20S proteasome; knockdown of PSMG2 (the heterodimeric partner) caused accumulation of polyubiquitinated proteins, increased ER stress, and activated apoptosis and autophagy as compensatory mechanisms in head and neck cancer cell lines.","method":"shRNA knockdown, in vitro and in vivo proliferation assays, immunoblotting for polyubiquitinated proteins and ER stress markers, autophagy/apoptosis assays","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional KD with defined molecular phenotype in vitro and in vivo, single lab; PSMG1 role inferred as the heterodimeric partner of PSMG2","pmids":["40303289"],"is_preprint":false}],"current_model":"PSMG1 (DSCR2/c21-LRP) is a proteasome assembly chaperone that forms a heterodimer with PSMG2 to promote 20S proteasome assembly; it localizes to the cytoplasmic face of the endoplasmic reticulum as a soluble protein, undergoes N-terminal cleavage and uncharacterized post-translational modifications, physically interacts with and inhibits the transcriptional activity of PPARβ, and acts downstream of miR-484 to regulate cancer cell migration."},"narrative":{"mechanistic_narrative":"PSMG1 (DSCR2/c21-LRP), a chromosome 21–encoded leucine-rich protein, functions as a proteasome assembly chaperone that forms a heterodimer with PSMG2 to promote assembly of the 20S proteasome [PMID:40303289]. Rather than behaving as the integral membrane protein predicted from its sequence, PSMG1 localizes as a soluble protein to the cytoplasmic face of the endoplasmic reticulum [PMID:15590417], and is synthesized as a precursor whose N-terminus is cleaved and which undergoes additional non-glycosylation post-translational modifications [PMID:15670775]. Loss of its heterodimeric partner PSMG2 causes accumulation of polyubiquitinated proteins, ER stress, and compensatory apoptosis and autophagy, linking the PSMG1–PSMG2 module to maintenance of cellular proteostasis [PMID:40303289]. Beyond this assembly role, PSMG1 physically interacts with the nuclear receptor PPARβ and inhibits its ligand-induced transcriptional activity [PMID:18793612], and it acts as a downstream effector of miR-484 to regulate prostate cancer cell migration [PMID:32338277]. Its early association with proliferating tumor cells [PMID:10872820] is consistent with this proteostatic and pro-migratory role, but the structural basis of the heterodimer and the mechanism connecting these activities have not been characterized in the available corpus.","teleology":[{"year":1998,"claim":"Establishing the gene's existence and basic features was the first step: a novel chromosome 21 gene encoding a leucine-rich protein was identified before any function was known.","evidence":"cDNA sequencing, Northern blot and computational protein analysis identifying a 288-aa leucine-rich protein with two predicted transmembrane helices","pmids":["9784380"],"confidence":"Low","gaps":["Computational prediction only with no functional assay","Predicted transmembrane topology not experimentally validated","No protein partners or pathway identified"]},{"year":2000,"claim":"The first functional hint linked expression to proliferation, raising the question of whether the gene participates in cell growth control.","evidence":"Northern blot expression correlation across proliferating tumor cell lines and growth-modulated T98G/Jurkat cells","pmids":["10872820"],"confidence":"Low","gaps":["Correlation only, no direct perturbation","Does not establish causal role in proliferation","Mechanism unknown"]},{"year":2005,"claim":"Resolving the protein's true topology and processing answered whether the predicted transmembrane protein is actually membrane-integral: it is a soluble, ER-associated protein that is N-terminally cleaved and post-translationally modified.","evidence":"Immunocytochemistry, membrane fractionation, and N-glycosylation site mutagenesis in COS-1/HEK293 cells","pmids":["15590417","15670775"],"confidence":"Medium","gaps":["Identity of the post-translational modifications adding ~10 kDa not determined","Functional consequence of N-terminal cleavage unknown","ER-targeting mechanism for a soluble protein unresolved"]},{"year":2008,"claim":"Identification of a PPARβ interaction provided the first direct partner and a candidate transcriptional-regulatory function distinct from proteostasis.","evidence":"Yeast two-hybrid screen, co-immunoprecipitation in HEK293 cells, and transcriptional reporter assay","pmids":["18793612"],"confidence":"Medium","gaps":["Structural basis and stoichiometry of the interaction unknown","Physiological context where PSMG1 regulates PPARβ unestablished","Relationship between PPARβ binding and proteasome assembly role unclear"]},{"year":2020,"claim":"Placing PSMG1 downstream of miR-484 connected its expression to a defined functional output, cancer cell migration.","evidence":"Luciferase reporter assay, immunoblotting, siRNA knockdown and migration assay in prostate cancer cell lines","pmids":["32338277"],"confidence":"Medium","gaps":["Molecular mechanism by which PSMG1 promotes migration not defined","Whether the proteasome-assembly function mediates migration untested","Single-lab, single-cancer-type evidence"]},{"year":2025,"claim":"Defining PSMG1 as the PSMG2 heterodimer partner that promotes 20S proteasome assembly established its core molecular role in proteostasis.","evidence":"shRNA knockdown of PSMG2 with proliferation assays, polyubiquitin/ER-stress immunoblotting and autophagy/apoptosis readouts in head and neck cancer cells in vitro and in vivo","pmids":["40303289"],"confidence":"Medium","gaps":["PSMG1's contribution inferred from its partner rather than directly perturbed","No structural model of the PSMG1-PSMG2 heterodimer in this work","Direct demonstration of PSMG1 in 20S assembly intermediates not shown"]},{"year":null,"claim":"How PSMG1's distinct activities — 20S proteasome assembly chaperoning, ER association, PPARβ inhibition, and miR-484-dependent migration control — mechanistically interrelate remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the PSMG1-PSMG2 assembly chaperone","Identity of post-translational modifications unknown","Whether transcriptional and proteostatic roles are independent functions is undetermined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[6]}],"localization":[{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2,3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2,3]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[6]}],"complexes":["PSMG1-PSMG2 proteasome assembly chaperone heterodimer"],"partners":["PSMG2","PPARB"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95456","full_name":"Proteasome assembly chaperone 1","aliases":["Chromosome 21 leucine-rich protein","C21-LRP","Down syndrome critical region protein 2","Proteasome chaperone homolog 1","Pba1"],"length_aa":288,"mass_kda":32.9,"function":"Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization","subcellular_location":"Cytoplasm; Endoplasmic reticulum","url":"https://www.uniprot.org/uniprotkb/O95456/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PSMG1","classification":"Not Classified","n_dependent_lines":686,"n_total_lines":1208,"dependency_fraction":0.5678807947019867},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000183527","cell_line_id":"CID000110","localizations":[{"compartment":"cytoplasmic","grade":3},{"compartment":"nucleoplasm","grade":3}],"interactors":[{"gene":"PSMG4","stoichiometry":10.0},{"gene":"PSMG2","stoichiometry":10.0},{"gene":"POMP","stoichiometry":10.0},{"gene":"CSNK2A2","stoichiometry":0.2},{"gene":"PSMA1","stoichiometry":0.2},{"gene":"PSMA3","stoichiometry":0.2},{"gene":"PSMA4","stoichiometry":0.2},{"gene":"PSMA5","stoichiometry":0.2},{"gene":"PSMA6","stoichiometry":0.2},{"gene":"PSMB1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000110","total_profiled":1310},"omim":[{"mim_id":"619183","title":"PROTEASOME-ASSOCIATED AUTOINFLAMMATORY SYNDROME 4; PRAAS4","url":"https://www.omim.org/entry/619183"},{"mim_id":"617528","title":"PROTEASOME ASSEMBLY CHAPERONE 3; PSMG3","url":"https://www.omim.org/entry/617528"},{"mim_id":"613386","title":"PROTEASOME MATURATION PROTEIN; POMP","url":"https://www.omim.org/entry/613386"},{"mim_id":"612567","title":"INFLAMMATORY BOWEL DISEASE 25, AUTOSOMAL RECESSIVE; IBD25","url":"https://www.omim.org/entry/612567"},{"mim_id":"609702","title":"PROTEASOME ASSEMBLY CHAPERONE 2; PSMG2","url":"https://www.omim.org/entry/609702"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoplasm","reliability":"Enhanced"},{"location":"Golgi apparatus","reliability":"Enhanced"},{"location":"Cytosol","reliability":"Enhanced"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":37.6}],"url":"https://www.proteinatlas.org/search/PSMG1"},"hgnc":{"alias_symbol":["c21-LRP","LRPC21","PAC1"],"prev_symbol":["DSCR2"]},"alphafold":{"accession":"O95456","domains":[{"cath_id":"3.40.50.10900","chopping":"53-102_116-283","consensus_level":"medium","plddt":88.1453,"start":53,"end":283}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95456","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95456-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95456-F1-predicted_aligned_error_v6.png","plddt_mean":81.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PSMG1","jax_strain_url":"https://www.jax.org/strain/search?query=PSMG1"},"sequence":{"accession":"O95456","fasta_url":"https://rest.uniprot.org/uniprotkb/O95456.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95456/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95456"}},"corpus_meta":[{"pmid":"21830272","id":"PMC_21830272","title":"Distinct 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\"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"PSMG1 (c21-LRP) was identified as a novel gene on human chromosome 21 encoding a 288-amino acid leucine-rich protein of 32.8 kDa with two predicted transmembrane helices, expressed highly in testis and the Jurkat T cell line.\",\n      \"method\": \"cDNA sequencing, Northern blot, RT-PCR, computational protein analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction and expression analysis only; no functional assay\",\n      \"pmids\": [\"9784380\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"DSCR2/PSMG1 mRNA levels correlate with cellular proliferation: expression was detected in all proliferating human tumor cell lines tested, and DSCR2 mRNA levels correlated with cell growth in T98G and Jurkat cells in response to treatments, suggesting a role in cell proliferation.\",\n      \"method\": \"Northern blot, expression analysis across human cell lines and mouse developmental stages\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, expression correlation only, no direct functional perturbation experiment\",\n      \"pmids\": [\"10872820\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"DSCR2/PSMG1 localizes to the endoplasmic reticulum (ER) of mammalian cells as a soluble protein on the cytoplasmic face, and is not an integral membrane protein; truncated forms lacking predicted transmembrane helices remained associated with the ER.\",\n      \"method\": \"Immunocytochemistry, fluorescence assays, membrane fractionation in transfected cells\",\n      \"journal\": \"European journal of histochemistry : EJH\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunocytochemistry and membrane fractionation, two orthogonal methods, single lab\",\n      \"pmids\": [\"15590417\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"DSCR2/PSMG1 is synthesized as a 43 kDa precursor from which the N-terminus is cleaved to yield a 41 kDa polypeptide; the protein undergoes additional co- or post-translational modifications (not N-glycosylation) increasing its apparent molecular weight from the predicted 32.8 kDa by ~10 kDa; it localizes to a cytoplasmic compartment as a soluble form.\",\n      \"method\": \"Transient transfection in COS-1 and HEK293 cells, in vitro mutagenesis of N-glycosylation site, intracellular localization studies, membrane fractionation assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis and fractionation in two cell lines, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"15670775\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"DSCR2/PSMG1 physically interacts with PPARβ (a nuclear receptor) and inhibits its ligand-induced transcriptional activity; PPARβ also decreases the solubility of DSCR2, increasing levels of insoluble DSCR2.\",\n      \"method\": \"Yeast two-hybrid screening of human fetal brain cDNA library, co-immunoprecipitation in HEK293 cells, transcriptional reporter assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal validation by Y2H and Co-IP plus functional transcriptional assay, single lab\",\n      \"pmids\": [\"18793612\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"miR-484 directly targets PSMG1 (confirmed by luciferase assay and immunoblotting), and PSMG1 knockdown rescues the reduction in cancer cell mobility caused by miR-484 inhibition, placing PSMG1 as a downstream effector in a miR-484-PSMG1 axis regulating prostate cancer cell migration.\",\n      \"method\": \"Luciferase reporter assay, immunoblotting, siRNA knockdown, cell migration assay in prostate cancer cell lines\",\n      \"journal\": \"Bioscience reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct target validation by luciferase and immunoblot plus functional rescue, single lab, two orthogonal methods\",\n      \"pmids\": [\"32338277\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PSMG2 forms a heterodimer with PSMG1 and promotes assembly of the 20S proteasome; knockdown of PSMG2 (the heterodimeric partner) caused accumulation of polyubiquitinated proteins, increased ER stress, and activated apoptosis and autophagy as compensatory mechanisms in head and neck cancer cell lines.\",\n      \"method\": \"shRNA knockdown, in vitro and in vivo proliferation assays, immunoblotting for polyubiquitinated proteins and ER stress markers, autophagy/apoptosis assays\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional KD with defined molecular phenotype in vitro and in vivo, single lab; PSMG1 role inferred as the heterodimeric partner of PSMG2\",\n      \"pmids\": [\"40303289\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PSMG1 (DSCR2/c21-LRP) is a proteasome assembly chaperone that forms a heterodimer with PSMG2 to promote 20S proteasome assembly; it localizes to the cytoplasmic face of the endoplasmic reticulum as a soluble protein, undergoes N-terminal cleavage and uncharacterized post-translational modifications, physically interacts with and inhibits the transcriptional activity of PPARβ, and acts downstream of miR-484 to regulate cancer cell migration.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PSMG1 (DSCR2/c21-LRP), a chromosome 21–encoded leucine-rich protein, functions as a proteasome assembly chaperone that forms a heterodimer with PSMG2 to promote assembly of the 20S proteasome [#6]. Rather than behaving as the integral membrane protein predicted from its sequence, PSMG1 localizes as a soluble protein to the cytoplasmic face of the endoplasmic reticulum [#2], and is synthesized as a precursor whose N-terminus is cleaved and which undergoes additional non-glycosylation post-translational modifications [#3]. Loss of its heterodimeric partner PSMG2 causes accumulation of polyubiquitinated proteins, ER stress, and compensatory apoptosis and autophagy, linking the PSMG1–PSMG2 module to maintenance of cellular proteostasis [#6]. Beyond this assembly role, PSMG1 physically interacts with the nuclear receptor PPARβ and inhibits its ligand-induced transcriptional activity [#4], and it acts as a downstream effector of miR-484 to regulate prostate cancer cell migration [#5]. Its early association with proliferating tumor cells [#1] is consistent with this proteostatic and pro-migratory role, but the structural basis of the heterodimer and the mechanism connecting these activities have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Establishing the gene's existence and basic features was the first step: a novel chromosome 21 gene encoding a leucine-rich protein was identified before any function was known.\",\n      \"evidence\": \"cDNA sequencing, Northern blot and computational protein analysis identifying a 288-aa leucine-rich protein with two predicted transmembrane helices\",\n      \"pmids\": [\"9784380\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational prediction only with no functional assay\", \"Predicted transmembrane topology not experimentally validated\", \"No protein partners or pathway identified\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"The first functional hint linked expression to proliferation, raising the question of whether the gene participates in cell growth control.\",\n      \"evidence\": \"Northern blot expression correlation across proliferating tumor cell lines and growth-modulated T98G/Jurkat cells\",\n      \"pmids\": [\"10872820\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Correlation only, no direct perturbation\", \"Does not establish causal role in proliferation\", \"Mechanism unknown\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Resolving the protein's true topology and processing answered whether the predicted transmembrane protein is actually membrane-integral: it is a soluble, ER-associated protein that is N-terminally cleaved and post-translationally modified.\",\n      \"evidence\": \"Immunocytochemistry, membrane fractionation, and N-glycosylation site mutagenesis in COS-1/HEK293 cells\",\n      \"pmids\": [\"15590417\", \"15670775\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the post-translational modifications adding ~10 kDa not determined\", \"Functional consequence of N-terminal cleavage unknown\", \"ER-targeting mechanism for a soluble protein unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Identification of a PPARβ interaction provided the first direct partner and a candidate transcriptional-regulatory function distinct from proteostasis.\",\n      \"evidence\": \"Yeast two-hybrid screen, co-immunoprecipitation in HEK293 cells, and transcriptional reporter assay\",\n      \"pmids\": [\"18793612\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis and stoichiometry of the interaction unknown\", \"Physiological context where PSMG1 regulates PPARβ unestablished\", \"Relationship between PPARβ binding and proteasome assembly role unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing PSMG1 downstream of miR-484 connected its expression to a defined functional output, cancer cell migration.\",\n      \"evidence\": \"Luciferase reporter assay, immunoblotting, siRNA knockdown and migration assay in prostate cancer cell lines\",\n      \"pmids\": [\"32338277\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism by which PSMG1 promotes migration not defined\", \"Whether the proteasome-assembly function mediates migration untested\", \"Single-lab, single-cancer-type evidence\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Defining PSMG1 as the PSMG2 heterodimer partner that promotes 20S proteasome assembly established its core molecular role in proteostasis.\",\n      \"evidence\": \"shRNA knockdown of PSMG2 with proliferation assays, polyubiquitin/ER-stress immunoblotting and autophagy/apoptosis readouts in head and neck cancer cells in vitro and in vivo\",\n      \"pmids\": [\"40303289\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PSMG1's contribution inferred from its partner rather than directly perturbed\", \"No structural model of the PSMG1-PSMG2 heterodimer in this work\", \"Direct demonstration of PSMG1 in 20S assembly intermediates not shown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PSMG1's distinct activities — 20S proteasome assembly chaperoning, ER association, PPARβ inhibition, and miR-484-dependent migration control — mechanistically interrelate remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of the PSMG1-PSMG2 assembly chaperone\", \"Identity of post-translational modifications unknown\", \"Whether transcriptional and proteostatic roles are independent functions is undetermined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\"PSMG1-PSMG2 proteasome assembly chaperone heterodimer\"],\n    \"partners\": [\"PSMG2\", \"PPARB\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}