{"gene":"PRR19","run_date":"2026-06-10T06:43:36","timeline":{"discoveries":[{"year":2020,"finding":"PRR19 physically interacts with cyclin-like CNTD1 and the two proteins co-localize at crossover sites during meiosis; they are interdependent for their accumulation at these sites, forming a functional partnership required for meiotic crossing over.","method":"Co-immunoprecipitation (physical interaction), co-localization by immunofluorescence, loss-of-function mouse mutants showing interdependent accumulation","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal interaction (Co-IP) plus co-localization and genetic interdependence in a single study, single lab","pmids":["32555348"],"is_preprint":false},{"year":2020,"finding":"PRR19 is required for timely repair of programmed meiotic DNA double-strand breaks and for the formation of crossover-specific recombination complexes, as established by loss-of-function mouse mutants.","method":"Genetic knockout/loss-of-function in mouse with cytological readouts of DSB repair kinetics and crossover-specific recombination complex formation","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype, single lab, multiple cytological readouts","pmids":["32555348"],"is_preprint":false},{"year":2020,"finding":"CNTD1, the binding partner of PRR19, interacts with cyclin-dependent kinase CDK2, which also accumulates at crossover-specific recombination complexes, suggesting the PRR19-CNTD1 complex promotes crossover differentiation via CDK2 regulation.","method":"Co-immunoprecipitation of CNTD1 with CDK2; immunolocalization of CDK2 at crossover sites","journal":"Nature Communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — CDK2 interaction is with CNTD1 (not PRR19 directly), single lab, single Co-IP method, mechanistic link to PRR19 is inferential","pmids":["32555348"],"is_preprint":false}],"current_model":"PRR19 functions as a partner of cyclin-like CNTD1, co-localizing at meiotic crossover sites and depending on CNTD1 for its accumulation; together they promote timely repair of programmed DNA double-strand breaks and formation of crossover-specific recombination complexes, potentially by regulating CDK2 activity to drive crossover differentiation in mouse meiosis."},"narrative":{"mechanistic_narrative":"PRR19 is a meiosis-specific factor that promotes crossover formation during the repair of programmed DNA double-strand breaks [PMID:32555348]. It functions in a partnership with the cyclin-like protein CNTD1: the two proteins physically interact, co-localize at crossover sites, and depend on each other for their accumulation at these sites [PMID:32555348]. Loss of PRR19 in mouse delays the repair of programmed meiotic DSBs and impairs formation of crossover-specific recombination complexes [PMID:32555348]. Beyond this PRR19–CNTD1 partnership and its role in meiotic crossing over, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Established that PRR19 acts not in isolation but as a dedicated partner of the cyclin-like CNTD1, defining a physical and functional unit at meiotic crossover sites.","evidence":"Co-immunoprecipitation, co-localization immunofluorescence, and interdependent accumulation in loss-of-function mouse mutants","pmids":["32555348"],"confidence":"Medium","gaps":["Direct interaction interface and binding stoichiometry not defined","Whether the interaction is direct or bridged by other meiotic proteins not resolved","No structural model of the PRR19-CNTD1 complex"]},{"year":2020,"claim":"Defined the cellular consequence of PRR19 loss, showing it is required for timely DSB repair and for assembly of crossover-specific recombination complexes.","evidence":"Mouse genetic knockout with cytological readouts of DSB repair kinetics and crossover marker formation","pmids":["32555348"],"confidence":"Medium","gaps":["Molecular activity of PRR19 itself remains undefined","How PRR19 mechanistically drives crossover-specific complex assembly is unknown","No biochemical substrate or enzymatic function identified"]},{"year":2020,"claim":"Linked the PRR19-CNTD1 partnership to CDK2, proposing crossover differentiation is driven through CDK2 regulation.","evidence":"Co-immunoprecipitation of CNTD1 with CDK2 and CDK2 immunolocalization at crossover sites","pmids":["32555348"],"confidence":"Low","gaps":["CDK2 interaction is with CNTD1, not PRR19 directly; PRR19's role in CDK2 regulation is inferential","Single Co-IP without reciprocal or reconstitution validation","Whether CDK2 activity is altered by the PRR19-CNTD1 complex not demonstrated"]},{"year":null,"claim":"The intrinsic molecular activity of PRR19 and the mechanism by which it and CNTD1 control crossover-specific recombination remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No enzymatic or biochemical activity attributed to PRR19","Mechanism of recruitment to crossover sites uncharacterized","Human PRR19 function not directly addressed in the corpus"]}],"mechanism_profile":{"molecular_activity":[],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[1]}],"complexes":[],"partners":["CNTD1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A6NJB7","full_name":"Proline-rich protein 19","aliases":[],"length_aa":356,"mass_kda":38.7,"function":"Promotes meiotic crossing over formation through its interaction with CNTD1 by participating in the crossover differentiation step of crossover-specific recombination intermediates","subcellular_location":"Nucleus; Chromosome","url":"https://www.uniprot.org/uniprotkb/A6NJB7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PRR19","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/PRR19","total_profiled":1310},"omim":[{"mim_id":"621177","title":"PROLINE-RICH PROTEIN 19; PRR19","url":"https://www.omim.org/entry/621177"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Nucleoli rim","reliability":"Approved"},{"location":"Mitotic chromosome","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"},{"location":"Mitochondria","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"testis","ntpm":20.4}],"url":"https://www.proteinatlas.org/search/PRR19"},"hgnc":{"alias_symbol":["MGC70924"],"prev_symbol":[]},"alphafold":{"accession":"A6NJB7","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NJB7","model_url":"https://alphafold.ebi.ac.uk/files/AF-A6NJB7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A6NJB7-F1-predicted_aligned_error_v6.png","plddt_mean":52.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PRR19","jax_strain_url":"https://www.jax.org/strain/search?query=PRR19"},"sequence":{"accession":"A6NJB7","fasta_url":"https://rest.uniprot.org/uniprotkb/A6NJB7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A6NJB7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A6NJB7"}},"corpus_meta":[{"pmid":"32555348","id":"PMC_32555348","title":"Proline-rich protein PRR19 functions with cyclin-like CNTD1 to promote meiotic crossing over in mouse.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32555348","citation_count":28,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2694,"output_tokens":731,"usd":0.009524,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7118,"output_tokens":1346,"usd":0.03462,"stage2_stop_reason":"end_turn"},"total_usd":0.044144,"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\": 2020,\n      \"finding\": \"PRR19 physically interacts with cyclin-like CNTD1 and the two proteins co-localize at crossover sites during meiosis; they are interdependent for their accumulation at these sites, forming a functional partnership required for meiotic crossing over.\",\n      \"method\": \"Co-immunoprecipitation (physical interaction), co-localization by immunofluorescence, loss-of-function mouse mutants showing interdependent accumulation\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal interaction (Co-IP) plus co-localization and genetic interdependence in a single study, single lab\",\n      \"pmids\": [\"32555348\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PRR19 is required for timely repair of programmed meiotic DNA double-strand breaks and for the formation of crossover-specific recombination complexes, as established by loss-of-function mouse mutants.\",\n      \"method\": \"Genetic knockout/loss-of-function in mouse with cytological readouts of DSB repair kinetics and crossover-specific recombination complex formation\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype, single lab, multiple cytological readouts\",\n      \"pmids\": [\"32555348\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CNTD1, the binding partner of PRR19, interacts with cyclin-dependent kinase CDK2, which also accumulates at crossover-specific recombination complexes, suggesting the PRR19-CNTD1 complex promotes crossover differentiation via CDK2 regulation.\",\n      \"method\": \"Co-immunoprecipitation of CNTD1 with CDK2; immunolocalization of CDK2 at crossover sites\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — CDK2 interaction is with CNTD1 (not PRR19 directly), single lab, single Co-IP method, mechanistic link to PRR19 is inferential\",\n      \"pmids\": [\"32555348\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"PRR19 functions as a partner of cyclin-like CNTD1, co-localizing at meiotic crossover sites and depending on CNTD1 for its accumulation; together they promote timely repair of programmed DNA double-strand breaks and formation of crossover-specific recombination complexes, potentially by regulating CDK2 activity to drive crossover differentiation in mouse meiosis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PRR19 is a meiosis-specific factor that promotes crossover formation during the repair of programmed DNA double-strand breaks [#1]. It functions in a partnership with the cyclin-like protein CNTD1: the two proteins physically interact, co-localize at crossover sites, and depend on each other for their accumulation at these sites [#0]. Loss of PRR19 in mouse delays the repair of programmed meiotic DSBs and impairs formation of crossover-specific recombination complexes [#1]. Beyond this PRR19–CNTD1 partnership and its role in meiotic crossing over, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Established that PRR19 acts not in isolation but as a dedicated partner of the cyclin-like CNTD1, defining a physical and functional unit at meiotic crossover sites.\",\n      \"evidence\": \"Co-immunoprecipitation, co-localization immunofluorescence, and interdependent accumulation in loss-of-function mouse mutants\",\n      \"pmids\": [\"32555348\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct interaction interface and binding stoichiometry not defined\",\n        \"Whether the interaction is direct or bridged by other meiotic proteins not resolved\",\n        \"No structural model of the PRR19-CNTD1 complex\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined the cellular consequence of PRR19 loss, showing it is required for timely DSB repair and for assembly of crossover-specific recombination complexes.\",\n      \"evidence\": \"Mouse genetic knockout with cytological readouts of DSB repair kinetics and crossover marker formation\",\n      \"pmids\": [\"32555348\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular activity of PRR19 itself remains undefined\",\n        \"How PRR19 mechanistically drives crossover-specific complex assembly is unknown\",\n        \"No biochemical substrate or enzymatic function identified\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linked the PRR19-CNTD1 partnership to CDK2, proposing crossover differentiation is driven through CDK2 regulation.\",\n      \"evidence\": \"Co-immunoprecipitation of CNTD1 with CDK2 and CDK2 immunolocalization at crossover sites\",\n      \"pmids\": [\"32555348\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"CDK2 interaction is with CNTD1, not PRR19 directly; PRR19's role in CDK2 regulation is inferential\",\n        \"Single Co-IP without reciprocal or reconstitution validation\",\n        \"Whether CDK2 activity is altered by the PRR19-CNTD1 complex not demonstrated\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic molecular activity of PRR19 and the mechanism by which it and CNTD1 control crossover-specific recombination remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No enzymatic or biochemical activity attributed to PRR19\",\n        \"Mechanism of recruitment to crossover sites uncharacterized\",\n        \"Human PRR19 function not directly addressed in the corpus\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CNTD1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":3,"faith_total":3,"faith_pct":100.0}}