{"gene":"PRR16","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2014,"finding":"PRR16 (Largen) overexpression increases mammalian cell size in a screen-identified, mTOR-independent manner; in vitro evidence showed Largen preferentially stimulates translation of specific mRNA subsets, including those encoding mitochondrial proteins, leading to increased mitochondrial mass and greater ATP production; conditional transgenic mouse overexpression confirmed increased cell size in vivo.","method":"Genetic screen for cell-size-controlling genes; in vitro translation assay; mitochondrial mass/ATP measurements in Largen-overexpressing cells; conditional transgenic mouse model","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (in vitro translation assay, mitochondrial functional assay, in vivo transgenic model) in a single rigorous study establishing a defined cellular mechanism","pmids":["24656129"],"is_preprint":false},{"year":2022,"finding":"PRR16/Largen binds directly to ABI2 (Abl interactor 2); this interaction interferes with ABI2's inhibition of ABL1 kinase, increasing ABL1 Y412 phosphorylation, which in turn promotes epithelial-mesenchymal transition (EMT), migration, and invasion in breast cancer cells.","method":"Binding partner screen (Co-IP/pulldown); ABI2 gene silencing; ABI2 overexpression; ABL1 phosphorylation (Y412) immunoblotting; migration and invasion assays in MCF7 cells","journal":"Biomolecules & therapeutics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction validated with silencing experiments and phosphorylation readout, single lab, two orthogonal functional methods","pmids":["35719027"],"is_preprint":false},{"year":2008,"finding":"PRR16/DSC54 (stem cell protein DSC54) is overexpressed in human fetal placental venous endothelial cells (HPVEC) compared to arterial endothelial cells, and HPVEC exhibit enhanced differentiation potential into adipocytes and osteoblasts, associating PRR16 expression with a juvenile venous/progenitor phenotype.","method":"Gene expression profiling of isolated HPAEC vs HPVEC; functional adipogenic/osteogenic differentiation assays","journal":"Differentiation; research in biological diversity","confidence":"Low","confidence_rationale":"Tier 3 / Weak — gene expression correlation with differentiation phenotype, no direct manipulation of PRR16, single lab","pmids":["18673379"],"is_preprint":false}],"current_model":"PRR16 (Largen) is a cell size regulator that preferentially stimulates translation of mitochondrial mRNAs to increase mitochondrial mass and ATP production, thereby enlarging mammalian cells independently of mTOR/Hippo signaling; additionally, PRR16 binds ABI2 and disrupts its inhibition of ABL1 kinase, activating ABL1 and promoting epithelial-mesenchymal transition."},"narrative":{"mechanistic_narrative":"PRR16 (Largen) is a regulator of mammalian cell size that acts post-transcriptionally by preferentially stimulating translation of specific mRNA subsets, including those encoding mitochondrial proteins, thereby increasing mitochondrial mass and ATP production to drive cell enlargement independently of mTOR signaling [PMID:24656129]. This growth-promoting activity was confirmed in vivo, where conditional transgenic overexpression increased cell size [PMID:24656129]. In a distinct activity, PRR16 binds directly to ABI2 and interferes with ABI2-mediated inhibition of ABL1 kinase, increasing ABL1 Y412 phosphorylation and promoting epithelial-mesenchymal transition, migration, and invasion in breast cancer cells [PMID:35719027]. Beyond these translational and ABL1-axis roles, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Established that PRR16 controls cell size through a defined molecular route — preferential translation of mitochondrial mRNAs — rather than through canonical mTOR growth signaling.","evidence":"Genetic screen for cell-size genes, in vitro translation assays, mitochondrial mass/ATP measurements, and a conditional transgenic mouse model","pmids":["24656129"],"confidence":"High","gaps":["Molecular mechanism by which PRR16 selects specific mRNAs for translation is not defined","No structural or biochemical characterization of how PRR16 engages the translation machinery","Direct binding partners mediating the translational selectivity are unidentified"]},{"year":2022,"claim":"Identified a separate, growth-independent function whereby PRR16 activates ABL1 kinase by sequestering its inhibitor ABI2, linking PRR16 to EMT and invasion in cancer.","evidence":"Binding partner screen (Co-IP/pulldown), ABI2 silencing and overexpression, ABL1 Y412 phosphoblotting, and migration/invasion assays in MCF7 cells","pmids":["35719027"],"confidence":"Medium","gaps":["Single-lab finding; mapping of the PRR16–ABI2 interaction interface not determined","Relationship between the cell-size/translation role and the ABL1 axis is unresolved","In vivo relevance of the ABL1 activation to tumor progression not tested"]},{"year":2008,"claim":"Correlated PRR16 expression with a venous/progenitor endothelial phenotype, the earliest observation linking the gene to cell state.","evidence":"Gene expression profiling of arterial vs venous fetal placental endothelial cells with adipogenic/osteogenic differentiation assays","pmids":["18673379"],"confidence":"Low","gaps":["Correlative only — no direct manipulation of PRR16 to establish causality","No mechanistic link to the translational or ABL1 functions","Single lab, no functional follow-up"]},{"year":null,"claim":"How PRR16's translational selectivity, ABL1 activation, and endothelial-state association mechanistically interconnect remains unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying molecular mechanism linking the two characterized activities","No structural data on PRR16 or its functional domains","Direct RNA or protein binding determinants undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[0]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1]}],"localization":[],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":[],"partners":["ABI2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q569H4","full_name":"Protein Largen","aliases":["Mesenchymal stem cell protein DSC54","Proline-rich protein 16"],"length_aa":304,"mass_kda":32.8,"function":"Regulator of cell size that promotes cell size increase independently of mTOR and Hippo signaling pathways. Acts by stimulating the translation of specific mRNAs, including those encoding proteins affecting mitochondrial functions. Increases mitochondrial mass and respiration","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q569H4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PRR16","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PRR16","total_profiled":1310},"omim":[{"mim_id":"615931","title":"PROLINE-RICH PROTEIN 16; PRR16","url":"https://www.omim.org/entry/615931"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Midbody","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"tongue","ntpm":28.3}],"url":"https://www.proteinatlas.org/search/PRR16"},"hgnc":{"alias_symbol":["DSC54"],"prev_symbol":[]},"alphafold":{"accession":"Q569H4","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q569H4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q569H4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q569H4-F1-predicted_aligned_error_v6.png","plddt_mean":63.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PRR16","jax_strain_url":"https://www.jax.org/strain/search?query=PRR16"},"sequence":{"accession":"Q569H4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q569H4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q569H4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q569H4"}},"corpus_meta":[{"pmid":"24243566","id":"PMC_24243566","title":"Maternal preconception body mass index and offspring cord blood DNA methylation: exploration of early life origins of disease.","date":"2013","source":"Environmental and molecular mutagenesis","url":"https://pubmed.ncbi.nlm.nih.gov/24243566","citation_count":101,"is_preprint":false},{"pmid":"18673379","id":"PMC_18673379","title":"Human fetal placental endothelial cells have a mature arterial and a juvenile venous phenotype with adipogenic and osteogenic differentiation potential.","date":"2008","source":"Differentiation; research in biological diversity","url":"https://pubmed.ncbi.nlm.nih.gov/18673379","citation_count":95,"is_preprint":false},{"pmid":"32311840","id":"PMC_32311840","title":"Identification of cancer stem cell characteristics in liver hepatocellular carcinoma by WGCNA analysis of transcriptome stemness index.","date":"2020","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32311840","citation_count":81,"is_preprint":false},{"pmid":"37945807","id":"PMC_37945807","title":"Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.","date":"2023","source":"Nature human behaviour","url":"https://pubmed.ncbi.nlm.nih.gov/37945807","citation_count":39,"is_preprint":false},{"pmid":"24656129","id":"PMC_24656129","title":"Largen: a molecular regulator of mammalian cell size control.","date":"2014","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/24656129","citation_count":27,"is_preprint":false},{"pmid":"31397435","id":"PMC_31397435","title":"[Novel Genes Associated with the Development of Carotid Paragangliomas].","date":"2019","source":"Molekuliarnaia biologiia","url":"https://pubmed.ncbi.nlm.nih.gov/31397435","citation_count":15,"is_preprint":false},{"pmid":"35719027","id":"PMC_35719027","title":"PRR16/Largen Induces Epithelial-Mesenchymal Transition through the Interaction with ABI2 Leading to the Activation of ABL1 Kinase.","date":"2022","source":"Biomolecules & therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/35719027","citation_count":10,"is_preprint":false},{"pmid":"38091677","id":"PMC_38091677","title":"Epigenetic transgenerational effects of PM2.5 collected from southern Taiwan on sperm functions and DNA methylation in mouse offspring.","date":"2023","source":"Ecotoxicology and environmental safety","url":"https://pubmed.ncbi.nlm.nih.gov/38091677","citation_count":8,"is_preprint":false},{"pmid":"35608337","id":"PMC_35608337","title":"Genetic and genomic analysis of oxygen consumption in mice.","date":"2022","source":"Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie","url":"https://pubmed.ncbi.nlm.nih.gov/35608337","citation_count":3,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6857,"output_tokens":859,"usd":0.016728,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7346,"output_tokens":1478,"usd":0.03684,"stage2_stop_reason":"end_turn"},"total_usd":0.053568,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"PRR16 (Largen) overexpression increases mammalian cell size in a screen-identified, mTOR-independent manner; in vitro evidence showed Largen preferentially stimulates translation of specific mRNA subsets, including those encoding mitochondrial proteins, leading to increased mitochondrial mass and greater ATP production; conditional transgenic mouse overexpression confirmed increased cell size in vivo.\",\n      \"method\": \"Genetic screen for cell-size-controlling genes; in vitro translation assay; mitochondrial mass/ATP measurements in Largen-overexpressing cells; conditional transgenic mouse model\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (in vitro translation assay, mitochondrial functional assay, in vivo transgenic model) in a single rigorous study establishing a defined cellular mechanism\",\n      \"pmids\": [\"24656129\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PRR16/Largen binds directly to ABI2 (Abl interactor 2); this interaction interferes with ABI2's inhibition of ABL1 kinase, increasing ABL1 Y412 phosphorylation, which in turn promotes epithelial-mesenchymal transition (EMT), migration, and invasion in breast cancer cells.\",\n      \"method\": \"Binding partner screen (Co-IP/pulldown); ABI2 gene silencing; ABI2 overexpression; ABL1 phosphorylation (Y412) immunoblotting; migration and invasion assays in MCF7 cells\",\n      \"journal\": \"Biomolecules & therapeutics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction validated with silencing experiments and phosphorylation readout, single lab, two orthogonal functional methods\",\n      \"pmids\": [\"35719027\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PRR16/DSC54 (stem cell protein DSC54) is overexpressed in human fetal placental venous endothelial cells (HPVEC) compared to arterial endothelial cells, and HPVEC exhibit enhanced differentiation potential into adipocytes and osteoblasts, associating PRR16 expression with a juvenile venous/progenitor phenotype.\",\n      \"method\": \"Gene expression profiling of isolated HPAEC vs HPVEC; functional adipogenic/osteogenic differentiation assays\",\n      \"journal\": \"Differentiation; research in biological diversity\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — gene expression correlation with differentiation phenotype, no direct manipulation of PRR16, single lab\",\n      \"pmids\": [\"18673379\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PRR16 (Largen) is a cell size regulator that preferentially stimulates translation of mitochondrial mRNAs to increase mitochondrial mass and ATP production, thereby enlarging mammalian cells independently of mTOR/Hippo signaling; additionally, PRR16 binds ABI2 and disrupts its inhibition of ABL1 kinase, activating ABL1 and promoting epithelial-mesenchymal transition.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PRR16 (Largen) is a regulator of mammalian cell size that acts post-transcriptionally by preferentially stimulating translation of specific mRNA subsets, including those encoding mitochondrial proteins, thereby increasing mitochondrial mass and ATP production to drive cell enlargement independently of mTOR signaling [#0]. This growth-promoting activity was confirmed in vivo, where conditional transgenic overexpression increased cell size [#0]. In a distinct activity, PRR16 binds directly to ABI2 and interferes with ABI2-mediated inhibition of ABL1 kinase, increasing ABL1 Y412 phosphorylation and promoting epithelial-mesenchymal transition, migration, and invasion in breast cancer cells [#1]. Beyond these translational and ABL1-axis roles, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Established that PRR16 controls cell size through a defined molecular route — preferential translation of mitochondrial mRNAs — rather than through canonical mTOR growth signaling.\",\n      \"evidence\": \"Genetic screen for cell-size genes, in vitro translation assays, mitochondrial mass/ATP measurements, and a conditional transgenic mouse model\",\n      \"pmids\": [\"24656129\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism by which PRR16 selects specific mRNAs for translation is not defined\",\n        \"No structural or biochemical characterization of how PRR16 engages the translation machinery\",\n        \"Direct binding partners mediating the translational selectivity are unidentified\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified a separate, growth-independent function whereby PRR16 activates ABL1 kinase by sequestering its inhibitor ABI2, linking PRR16 to EMT and invasion in cancer.\",\n      \"evidence\": \"Binding partner screen (Co-IP/pulldown), ABI2 silencing and overexpression, ABL1 Y412 phosphoblotting, and migration/invasion assays in MCF7 cells\",\n      \"pmids\": [\"35719027\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab finding; mapping of the PRR16–ABI2 interaction interface not determined\",\n        \"Relationship between the cell-size/translation role and the ABL1 axis is unresolved\",\n        \"In vivo relevance of the ABL1 activation to tumor progression not tested\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Correlated PRR16 expression with a venous/progenitor endothelial phenotype, the earliest observation linking the gene to cell state.\",\n      \"evidence\": \"Gene expression profiling of arterial vs venous fetal placental endothelial cells with adipogenic/osteogenic differentiation assays\",\n      \"pmids\": [\"18673379\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Correlative only — no direct manipulation of PRR16 to establish causality\",\n        \"No mechanistic link to the translational or ABL1 functions\",\n        \"Single lab, no functional follow-up\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PRR16's translational selectivity, ABL1 activation, and endothelial-state association mechanistically interconnect remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unifying molecular mechanism linking the two characterized activities\",\n        \"No structural data on PRR16 or its functional domains\",\n        \"Direct RNA or protein binding determinants undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ABI2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}