{"gene":"PF3D7_1355100","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2010,"finding":"PfMCM6 (PF3D7_1355100) was identified as a physical interactor of the malarial CDK Pfmrk via a bacterial two-hybrid screen of a P. falciparum cDNA library, and was shown to be a substrate of Pfmrk-mediated phosphorylation; PfMAT1 was demonstrated to confer substrate specificity to the Pfmrk kinase complex for this phosphorylation.","method":"Bacterial two-hybrid screen (protein interaction identification) and in vitro/cell-based phosphorylation assay (substrate validation)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — bacterial two-hybrid identification plus phosphorylation substrate assay, but single lab and limited orthogonal validation of PfMCM6 specifically","pmids":["20332005"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, MCM6 (PF3D7_1355100) physically interacts with the cyclin-dependent kinase Pfmrk and serves as a phosphorylation substrate of the Pfmrk–PfMAT1 kinase complex (with PfMAT1 conferring substrate specificity), suggesting MCM6 participates in nuclear DNA replication machinery regulated by this CDK; beyond its membership in this kinase–substrate relationship, no further mechanistic details about MCM6's own catalytic or structural role have been established in the available literature."},"narrative":{"mechanistic_narrative":"In P. falciparum, MCM6 (PF3D7_1355100) is a physical interactor and phosphorylation substrate of the malarial cyclin-dependent kinase Pfmrk, linking it to CDK-regulated nuclear processes; substrate specificity for this phosphorylation is conferred by PfMAT1 within the Pfmrk kinase complex [PMID:20332005]. Beyond this kinase–substrate relationship [PMID:20332005], no further mechanistic detail about MCM6's own catalytic activity, structural role, or DNA replication licensing function has been characterized in the available corpus.","teleology":[{"year":2010,"claim":"It was unknown which parasite proteins are targeted by the malarial CDK Pfmrk; identifying MCM6 as both a physical partner and a phosphorylation substrate established a direct link between this kinase and MCM6, and showed PfMAT1 confers specificity for MCM6 phosphorylation.","evidence":"Bacterial two-hybrid screen of a P. falciparum cDNA library plus in vitro/cell-based phosphorylation assay","pmids":["20332005"],"confidence":"Medium","gaps":["The phosphorylation site(s) on MCM6 and the functional consequence of phosphorylation were not defined","MCM6's own catalytic or structural role in DNA replication was not demonstrated","Interaction rests on a single lab with limited orthogonal validation of MCM6 specifically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether MCM6 functions in P. falciparum DNA replication licensing, its assembly into an MCM complex, and the physiological role of its Pfmrk-mediated phosphorylation remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No demonstration of MCM6 helicase or replication-licensing activity in this organism","No structural model or complex composition established for MCM6","Functional impact of Pfmrk/PfMAT1-mediated phosphorylation on MCM6 not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFMRK (MALARIAL CYCLIN-DEPENDENT KINASE)","PFMAT1"],"other_free_text":["PF3D7_1355100 (MCM6) is a phosphorylation substrate of the Pfmrk kinase complex, with PfMAT1 conferring substrate specificity [#0].","No mechanistic evidence in the corpus establishes MCM6's own catalytic, structural, or DNA replication licensing function beyond its interaction with and phosphorylation by Pfmrk."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"3088783","id":"PMC_3088783","title":"Rapid repeated DNA replication during microgametogenesis and DNA synthesis in young zygotes of Plasmodium berghei.","date":"1986","source":"Transactions of the Royal Society of Tropical Medicine and Hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/3088783","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2440713","id":"PMC_2440713","title":"Plasmodium species: flow cytometry and microfluorometry assessments of DNA content and synthesis.","date":"1987","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2440713","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"3283664","id":"PMC_3283664","title":"DNA synthesis in gametocytes of Plasmodium falciparum.","date":"1988","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/3283664","citation_count":47,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20332005","id":"PMC_20332005","title":"The malarial CDK Pfmrk and its effector PfMAT1 phosphorylate DNA replication proteins and co-localize in the nucleus.","date":"2010","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/20332005","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfMCM6"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41316302","id":"PMC_41316302","title":"Unusual replication dynamics during Plasmodium falciparum schizogony.","date":"2025","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/41316302","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["DNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4507,"output_tokens":450,"usd":0.010136,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4985,"output_tokens":1119,"usd":0.02645,"stage2_stop_reason":"end_turn"},"total_usd":0.036586,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"PfMCM6 (PF3D7_1355100) was identified as a physical interactor of the malarial CDK Pfmrk via a bacterial two-hybrid screen of a P. falciparum cDNA library, and was shown to be a substrate of Pfmrk-mediated phosphorylation; PfMAT1 was demonstrated to confer substrate specificity to the Pfmrk kinase complex for this phosphorylation.\",\n      \"method\": \"Bacterial two-hybrid screen (protein interaction identification) and in vitro/cell-based phosphorylation assay (substrate validation)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — bacterial two-hybrid identification plus phosphorylation substrate assay, but single lab and limited orthogonal validation of PfMCM6 specifically\",\n      \"pmids\": [\"20332005\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, MCM6 (PF3D7_1355100) physically interacts with the cyclin-dependent kinase Pfmrk and serves as a phosphorylation substrate of the Pfmrk–PfMAT1 kinase complex (with PfMAT1 conferring substrate specificity), suggesting MCM6 participates in nuclear DNA replication machinery regulated by this CDK; beyond its membership in this kinase–substrate relationship, no further mechanistic details about MCM6's own catalytic or structural role have been established in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In P. falciparum, MCM6 (PF3D7_1355100) is a physical interactor and phosphorylation substrate of the malarial cyclin-dependent kinase Pfmrk, linking it to CDK-regulated nuclear processes; substrate specificity for this phosphorylation is conferred by PfMAT1 within the Pfmrk kinase complex [#0]. Beyond this kinase–substrate relationship [#0], no further mechanistic detail about MCM6's own catalytic activity, structural role, or DNA replication licensing function has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"It was unknown which parasite proteins are targeted by the malarial CDK Pfmrk; identifying MCM6 as both a physical partner and a phosphorylation substrate established a direct link between this kinase and MCM6, and showed PfMAT1 confers specificity for MCM6 phosphorylation.\",\n      \"evidence\": \"Bacterial two-hybrid screen of a P. falciparum cDNA library plus in vitro/cell-based phosphorylation assay\",\n      \"pmids\": [\"20332005\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The phosphorylation site(s) on MCM6 and the functional consequence of phosphorylation were not defined\",\n        \"MCM6's own catalytic or structural role in DNA replication was not demonstrated\",\n        \"Interaction rests on a single lab with limited orthogonal validation of MCM6 specifically\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether MCM6 functions in P. falciparum DNA replication licensing, its assembly into an MCM complex, and the physiological role of its Pfmrk-mediated phosphorylation remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No demonstration of MCM6 helicase or replication-licensing activity in this organism\",\n        \"No structural model or complex composition established for MCM6\",\n        \"Functional impact of Pfmrk/PfMAT1-mediated phosphorylation on MCM6 not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"Pfmrk (malarial cyclin-dependent kinase)\", \"PfMAT1\"],\n    \"other_free_text\": [\n      \"PF3D7_1355100 (MCM6) is a phosphorylation substrate of the Pfmrk kinase complex, with PfMAT1 conferring substrate specificity [#0].\",\n      \"No mechanistic evidence in the corpus establishes MCM6's own catalytic, structural, or DNA replication licensing function beyond its interaction with and phosphorylation by Pfmrk.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1355100","name":null,"product":"DNA replication licensing factor MCM6","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1131600","name":null,"product":"DNA replication licensing factor MCM6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1116800","name":null,"product":"DNA replication licensing factor MCM6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MCM6","evaluation":null}