{"gene":"PF3D7_1311400","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2015,"finding":"AP1M1 (Pfμ1), the mu-1 subunit of the AP-1 adaptor protein complex in P. falciparum, localizes to the Golgi/ER compartment in trophozoites, as shown by GFP fusion live-cell imaging and co-localization with Golgi/ER markers; Brefeldin A treatment altered this localization, confirming Golgi association.","method":"GFP fusion live-cell imaging, immunofluorescence analysis, Brefeldin A pharmacological perturbation","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional perturbation (Brefeldin A), single lab, two orthogonal methods (live imaging + IFA)","pmids":["25573429"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"In schizont-stage parasites, AP1M1 (Pfμ1) co-localizes with rhoptry proteins RAP1 and Clag3.1, and immunoprecipitation revealed a physical interaction between AP1M1 and PfRAP1, suggesting AP1M1 participates in trafficking cargo to rhoptry organelles, possibly via an intermediate transmembrane cargo receptor.","method":"Immunofluorescence co-localization, immunoprecipitation","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP plus co-localization, single lab, two orthogonal methods supporting the interaction","pmids":["25573429"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"AlF4 treatment of parasites expressing AP1M1 (Pfμ1) caused a shift of the protein to a predominantly ER-associated compartment and decreased co-localization with the Golgi marker GRASP, implicating AP1M1 in active vesicular trafficking steps at the Golgi.","method":"Pharmacological perturbation with AlF4, immunofluorescence co-localization with GRASP marker","journal":"Biochimica et biophysica acta","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single perturbation method, no mutagenesis or reconstitution to confirm mechanism","pmids":["25573429"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"AP1M1 (PF3D7_1311400), the mu-1 subunit of the P. falciparum AP-1 adaptor complex, localizes to the Golgi/ER in trophozoites and co-localizes with and physically interacts with the rhoptry protein RAP1 in schizonts, placing it in a vesicular trafficking pathway responsible for routing proteins to rhoptry organelles."},"narrative":{"mechanistic_narrative":"AP1M1 (PF3D7_1311400) is the mu-1 subunit of the P. falciparum AP-1 adaptor protein complex and functions in vesicular trafficking within the parasite secretory pathway [PMID:25573429]. In trophozoites, AP1M1 localizes to the Golgi/ER compartment, a placement confirmed by Brefeldin A sensitivity [PMID:25573429]. In schizonts it co-localizes with the rhoptry proteins RAP1 and Clag3.1 and physically interacts with PfRAP1 by immunoprecipitation, positioning AP1M1 in a trafficking route that routes cargo toward rhoptry organelles, possibly via an intermediate transmembrane cargo receptor [PMID:25573429]. Beyond its Golgi/ER localization and its association with RAP1, no further mechanistic detail — including its specific cargo-recognition motifs or the composition of its trafficking pathway — has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Establishing where the AP-1 mu-1 subunit acts required determining its subcellular localization; imaging placed AP1M1 at the Golgi/ER, implicating it in the early secretory pathway.","evidence":"GFP fusion live-cell imaging and IFA co-localization with Golgi/ER markers, with Brefeldin A perturbation, in P. falciparum","pmids":["25573429"],"confidence":"Medium","gaps":["Does not define the specific vesicular step or cargo AP1M1 handles at the Golgi/ER","Localization shown for a GFP fusion, not endogenous protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To link AP1M1 to a trafficking destination, the study tested whether it associates with rhoptry cargo; co-localization and Co-IP with PfRAP1 tied AP1M1 to the routing of proteins to rhoptry organelles.","evidence":"Immunofluorescence co-localization with RAP1 and Clag3.1 plus immunoprecipitation of AP1M1 with PfRAP1 in schizont-stage P. falciparum","pmids":["25573429"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal validation; direct versus indirect interaction unresolved","The proposed intermediate transmembrane cargo receptor is inferred, not identified","No functional test (e.g. knockdown) showing AP1M1 is required for RAP1/rhoptry delivery"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To probe whether AP1M1 participates in active trafficking rather than static residence, AlF4 was used to arrest vesicle dynamics; the resulting ER shift and loss of Golgi co-localization implicated AP1M1 in active Golgi trafficking steps.","evidence":"AlF4 pharmacological perturbation with IFA co-localization against the Golgi marker GRASP in P. falciparum","pmids":["25573429"],"confidence":"Low","gaps":["Single perturbation method with no mutagenesis or reconstitution to confirm mechanism","Does not establish which trafficking step AP1M1 mediates","Indirect pharmacological readout only"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether AP1M1 is functionally required for rhoptry protein trafficking and how it recognizes its cargo remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic loss-of-function data on AP1M1 in the corpus","Cargo-recognition determinants and the full AP-1 complex assembly in this parasite are uncharacterized","The proposed intermediate cargo receptor has not been identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["AP-1 adaptor protein complex"],"partners":["PFRAP1 (RAP1)"],"other_free_text":["Co-localizes with rhoptry proteins RAP1 and Clag3.1 in schizonts [#1]","Golgi/ER localization is Brefeldin A- and AlF4-sensitive, implicating active vesicular trafficking [#0, #2]","Proposed to route cargo to rhoptry organelles, possibly via an unidentified intermediate transmembrane cargo receptor [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25573429","id":"PMC_25573429","title":"A role for adaptor protein complex 1 in protein targeting to rhoptry organelles in Plasmodium falciparum.","date":"2015","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/25573429","citation_count":22,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3412,"output_tokens":883,"usd":0.01174,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5605,"output_tokens":1953,"usd":0.038425,"stage2_stop_reason":"end_turn"},"total_usd":0.050165,"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\": 2015,\n      \"finding\": \"AP1M1 (Pfμ1), the mu-1 subunit of the AP-1 adaptor protein complex in P. falciparum, localizes to the Golgi/ER compartment in trophozoites, as shown by GFP fusion live-cell imaging and co-localization with Golgi/ER markers; Brefeldin A treatment altered this localization, confirming Golgi association.\",\n      \"method\": \"GFP fusion live-cell imaging, immunofluorescence analysis, Brefeldin A pharmacological perturbation\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional perturbation (Brefeldin A), single lab, two orthogonal methods (live imaging + IFA)\",\n      \"pmids\": [\"25573429\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In schizont-stage parasites, AP1M1 (Pfμ1) co-localizes with rhoptry proteins RAP1 and Clag3.1, and immunoprecipitation revealed a physical interaction between AP1M1 and PfRAP1, suggesting AP1M1 participates in trafficking cargo to rhoptry organelles, possibly via an intermediate transmembrane cargo receptor.\",\n      \"method\": \"Immunofluorescence co-localization, immunoprecipitation\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP plus co-localization, single lab, two orthogonal methods supporting the interaction\",\n      \"pmids\": [\"25573429\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"AlF4 treatment of parasites expressing AP1M1 (Pfμ1) caused a shift of the protein to a predominantly ER-associated compartment and decreased co-localization with the Golgi marker GRASP, implicating AP1M1 in active vesicular trafficking steps at the Golgi.\",\n      \"method\": \"Pharmacological perturbation with AlF4, immunofluorescence co-localization with GRASP marker\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single perturbation method, no mutagenesis or reconstitution to confirm mechanism\",\n      \"pmids\": [\"25573429\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"AP1M1 (PF3D7_1311400), the mu-1 subunit of the P. falciparum AP-1 adaptor complex, localizes to the Golgi/ER in trophozoites and co-localizes with and physically interacts with the rhoptry protein RAP1 in schizonts, placing it in a vesicular trafficking pathway responsible for routing proteins to rhoptry organelles.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"AP1M1 (PF3D7_1311400) is the mu-1 subunit of the P. falciparum AP-1 adaptor protein complex and functions in vesicular trafficking within the parasite secretory pathway [#0]. In trophozoites, AP1M1 localizes to the Golgi/ER compartment, a placement confirmed by Brefeldin A sensitivity [#0]. In schizonts it co-localizes with the rhoptry proteins RAP1 and Clag3.1 and physically interacts with PfRAP1 by immunoprecipitation, positioning AP1M1 in a trafficking route that routes cargo toward rhoptry organelles, possibly via an intermediate transmembrane cargo receptor [#1]. Beyond its Golgi/ER localization and its association with RAP1, no further mechanistic detail — including its specific cargo-recognition motifs or the composition of its trafficking pathway — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Establishing where the AP-1 mu-1 subunit acts required determining its subcellular localization; imaging placed AP1M1 at the Golgi/ER, implicating it in the early secretory pathway.\",\n      \"evidence\": \"GFP fusion live-cell imaging and IFA co-localization with Golgi/ER markers, with Brefeldin A perturbation, in P. falciparum\",\n      \"pmids\": [\"25573429\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Does not define the specific vesicular step or cargo AP1M1 handles at the Golgi/ER\",\n        \"Localization shown for a GFP fusion, not endogenous protein\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To link AP1M1 to a trafficking destination, the study tested whether it associates with rhoptry cargo; co-localization and Co-IP with PfRAP1 tied AP1M1 to the routing of proteins to rhoptry organelles.\",\n      \"evidence\": \"Immunofluorescence co-localization with RAP1 and Clag3.1 plus immunoprecipitation of AP1M1 with PfRAP1 in schizont-stage P. falciparum\",\n      \"pmids\": [\"25573429\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal validation; direct versus indirect interaction unresolved\",\n        \"The proposed intermediate transmembrane cargo receptor is inferred, not identified\",\n        \"No functional test (e.g. knockdown) showing AP1M1 is required for RAP1/rhoptry delivery\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To probe whether AP1M1 participates in active trafficking rather than static residence, AlF4 was used to arrest vesicle dynamics; the resulting ER shift and loss of Golgi co-localization implicated AP1M1 in active Golgi trafficking steps.\",\n      \"evidence\": \"AlF4 pharmacological perturbation with IFA co-localization against the Golgi marker GRASP in P. falciparum\",\n      \"pmids\": [\"25573429\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single perturbation method with no mutagenesis or reconstitution to confirm mechanism\",\n        \"Does not establish which trafficking step AP1M1 mediates\",\n        \"Indirect pharmacological readout only\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether AP1M1 is functionally required for rhoptry protein trafficking and how it recognizes its cargo remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No genetic loss-of-function data on AP1M1 in the corpus\",\n        \"Cargo-recognition determinants and the full AP-1 complex assembly in this parasite are uncharacterized\",\n        \"The proposed intermediate cargo receptor has not been identified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\"AP-1 adaptor protein complex\"],\n    \"partners\": [\"PfRAP1 (RAP1)\"],\n    \"other_free_text\": [\n      \"Co-localizes with rhoptry proteins RAP1 and Clag3.1 in schizonts [#1]\",\n      \"Golgi/ER localization is Brefeldin A- and AlF4-sensitive, implicating active vesicular trafficking [#0, #2]\",\n      \"Proposed to route cargo to rhoptry organelles, possibly via an unidentified intermediate transmembrane cargo receptor [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1311400","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0302500, PF3D7_1017300, PF3D7_1410400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1311400","name":null,"product":"AP-1 complex subunit mu-1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1409900","name":null,"product":"AP-1 complex subunit mu-1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1411800","name":null,"product":"AP-1 complex subunit mu-1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"AP1M1","evaluation":null}