{"gene":"PF3D7_0423500","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2009,"finding":"GAPM2 (PF3D7_0423500) is a six-pass transmembrane protein that localizes to the inner membrane complex (IMC) of P. falciparum, where it forms highly SDS-resistant oligomeric complexes and co-purifies with cytoskeletal alveolin proteins and, to some degree, with the actin-myosin motor, supporting an IMC-anchoring role.","method":"Subcellular fractionation, SDS-PAGE/Western blot (SDS-resistant complex analysis), co-purification experiments with cytoskeletal and motor components","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — direct localization and co-purification with multiple partners shown in single lab, but no reconstitution or mutagenesis; functional role inferred from biochemical associations rather than loss-of-function","pmids":["19561073"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"GAPM2 (PF3D7_0423500), together with two related six-pass transmembrane proteins, localizes to the inner membrane complex of P. falciparum merozoites and assembles into a heteromeric complex, as demonstrated by immunoprecipitation with specific antibodies.","method":"Immunofluorescence colocalization, immunoprecipitation with specific antibodies, baculovirus/insect-cell expression, reconstitution into artificial liposomes","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — reciprocal immunoprecipitation establishes heteromeric complex assembly and IMC localization; single lab but multiple orthogonal methods (IF + Co-IP + liposome reconstitution)","pmids":["19465059"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"GAPM2 (PF3D7_0423500) is part of a PhIL1-associated protein complex that co-exists with the glideosome motor complex in the IMC; conditional depletion of GAPM2 abolishes merozoite reorientation/gliding and blocks invasion of host RBCs, while initial attachment to RBCs remains unaffected.","method":"Experimental genetics (conditional knockdown/knockout), invasion assays, gliding/reorientation assays, immunofluorescence","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotypes (failed reorientation, failed invasion, intact initial attachment) and complex membership established; single lab but multiple orthogonal functional readouts","pmids":["34324609"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"GAPM2 (PF3D7_0423500) is a six-pass transmembrane protein that resides in the inner membrane complex of P. falciparum merozoites as part of SDS-resistant oligomeric and heteromeric complexes (including a PhIL1-associated complex), where it co-purifies with cytoskeletal alveolin proteins and the actin-myosin motor; loss of GAPM2 specifically abrogates merozoite reorientation and gliding after initial RBC attachment, thereby blocking host cell invasion."},"narrative":{"mechanistic_narrative":"GAPM2 (PF3D7_0423500) is a six-pass transmembrane protein of the Plasmodium falciparum inner membrane complex (IMC) that functions as an anchoring component linking the IMC membrane to the underlying cytoskeleton and motor machinery [PMID:19561073]. It forms highly SDS-resistant oligomeric complexes and co-purifies with cytoskeletal alveolin proteins and, in part, with the actin-myosin motor, and it assembles into a heteromeric complex together with related six-pass transmembrane proteins in merozoites [PMID:19561073, PMID:19465059]. GAPM2 additionally belongs to a PhIL1-associated complex that co-exists with the glideosome motor in the IMC [PMID:34324609]. Functionally, conditional depletion of GAPM2 abolishes merozoite reorientation and gliding after the parasite has attached to the red blood cell, thereby blocking host cell invasion while leaving initial RBC attachment intact [PMID:34324609]. Beyond this IMC-anchoring and invasion role, no further mechanistic detail on GAPM2 has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Establishing where GAPM2 resides and what it associates with was the first step in assigning it a structural role: it was shown to be an IMC-localized six-pass transmembrane protein forming SDS-resistant complexes with cytoskeletal alveolins and the actin-myosin motor, implicating it in anchoring the IMC to the subpellicular cytoskeleton.","evidence":"Subcellular fractionation, SDS-resistant complex analysis by SDS-PAGE/Western, and co-purification with cytoskeletal and motor components in P. falciparum","pmids":["19561073"],"confidence":"Medium","gaps":["Anchoring role inferred from co-purification, not from loss-of-function or reconstitution","Direct binding partners within the SDS-resistant complex not resolved","Stoichiometry and architecture of the oligomeric complex unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"To test whether GAPM2 acts alone or within a defined assembly, it was shown to co-assemble with two related six-pass transmembrane proteins into a heteromeric IMC complex in merozoites, defining it as a member of an oligomeric membrane platform rather than an isolated protein.","evidence":"Immunofluorescence colocalization, reciprocal immunoprecipitation, baculovirus/insect-cell expression, and liposome reconstitution in P. falciparum","pmids":["19465059"],"confidence":"Medium","gaps":["Identity of GAPM2-specific contributions versus its paralogous partners not separated","Functional consequence of heteromeric assembly not tested","Whether complex assembly requires the reconstituted membrane environment in vivo unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"The functional requirement for GAPM2 was resolved by conditional depletion, which showed that GAPM2 is part of a PhIL1-associated complex coexisting with the glideosome and is specifically required for merozoite reorientation and gliding after attachment, thereby defining its stage in the invasion sequence.","evidence":"Conditional knockdown/knockout with invasion, gliding, and reorientation assays plus immunofluorescence in P. falciparum","pmids":["34324609"],"confidence":"High","gaps":["Molecular mechanism coupling GAPM2 to motor-driven reorientation not defined","Whether GAPM2 loss disrupts overall IMC/cytoskeleton integrity or acts more selectively unclear","Direct interaction between GAPM2 and PhIL1 versus indirect complex membership not distinguished"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How GAPM2 mechanically transmits force from the actin-myosin motor to the IMC membrane to drive reorientation and gliding, and which direct partners mediate this coupling, remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of GAPM2 or its complexes","Direct binding partners and force-transmission mechanism undefined","Role, if any, in other life-cycle stages beyond merozoite invasion untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["SDS-resistant IMC oligomeric complex with cytoskeletal alveolin proteins and actin-myosin motor [#0]","Heteromeric complex with two related six-pass transmembrane proteins [#1]","PhIL1-associated complex coexisting with the glideosome motor [#2]"],"partners":["CYTOSKELETAL ALVEOLIN PROTEINS [#0]","ACTIN-MYOSIN MOTOR COMPONENTS [#0]","TWO RELATED SIX-PASS TRANSMEMBRANE PROTEINS [#1]","PHIL1-ASSOCIATED COMPLEX MEMBERS [#2]"],"other_free_text":["Six-pass transmembrane topology [#0]","Conditional depletion blocks merozoite reorientation/gliding and RBC invasion while leaving initial attachment intact [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19561073","id":"PMC_19561073","title":"A novel family of Apicomplexan glideosome-associated proteins with an inner membrane-anchoring role.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19561073","citation_count":103,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19465059","id":"PMC_19465059","title":"A complex of three related membrane proteins is conserved on malarial merozoites.","date":"2009","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/19465059","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34324609","id":"PMC_34324609","title":"Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes.","date":"2021","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/34324609","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfGAPM2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4144,"output_tokens":981,"usd":0.013574,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5761,"output_tokens":2161,"usd":0.041415,"stage2_stop_reason":"end_turn"},"total_usd":0.054989,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"GAPM2 (PF3D7_0423500) is a six-pass transmembrane protein that localizes to the inner membrane complex (IMC) of P. falciparum, where it forms highly SDS-resistant oligomeric complexes and co-purifies with cytoskeletal alveolin proteins and, to some degree, with the actin-myosin motor, supporting an IMC-anchoring role.\",\n      \"method\": \"Subcellular fractionation, SDS-PAGE/Western blot (SDS-resistant complex analysis), co-purification experiments with cytoskeletal and motor components\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — direct localization and co-purification with multiple partners shown in single lab, but no reconstitution or mutagenesis; functional role inferred from biochemical associations rather than loss-of-function\",\n      \"pmids\": [\"19561073\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"GAPM2 (PF3D7_0423500), together with two related six-pass transmembrane proteins, localizes to the inner membrane complex of P. falciparum merozoites and assembles into a heteromeric complex, as demonstrated by immunoprecipitation with specific antibodies.\",\n      \"method\": \"Immunofluorescence colocalization, immunoprecipitation with specific antibodies, baculovirus/insect-cell expression, reconstitution into artificial liposomes\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — reciprocal immunoprecipitation establishes heteromeric complex assembly and IMC localization; single lab but multiple orthogonal methods (IF + Co-IP + liposome reconstitution)\",\n      \"pmids\": [\"19465059\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GAPM2 (PF3D7_0423500) is part of a PhIL1-associated protein complex that co-exists with the glideosome motor complex in the IMC; conditional depletion of GAPM2 abolishes merozoite reorientation/gliding and blocks invasion of host RBCs, while initial attachment to RBCs remains unaffected.\",\n      \"method\": \"Experimental genetics (conditional knockdown/knockout), invasion assays, gliding/reorientation assays, immunofluorescence\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotypes (failed reorientation, failed invasion, intact initial attachment) and complex membership established; single lab but multiple orthogonal functional readouts\",\n      \"pmids\": [\"34324609\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"GAPM2 (PF3D7_0423500) is a six-pass transmembrane protein that resides in the inner membrane complex of P. falciparum merozoites as part of SDS-resistant oligomeric and heteromeric complexes (including a PhIL1-associated complex), where it co-purifies with cytoskeletal alveolin proteins and the actin-myosin motor; loss of GAPM2 specifically abrogates merozoite reorientation and gliding after initial RBC attachment, thereby blocking host cell invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GAPM2 (PF3D7_0423500) is a six-pass transmembrane protein of the Plasmodium falciparum inner membrane complex (IMC) that functions as an anchoring component linking the IMC membrane to the underlying cytoskeleton and motor machinery [#0]. It forms highly SDS-resistant oligomeric complexes and co-purifies with cytoskeletal alveolin proteins and, in part, with the actin-myosin motor, and it assembles into a heteromeric complex together with related six-pass transmembrane proteins in merozoites [#0, #1]. GAPM2 additionally belongs to a PhIL1-associated complex that co-exists with the glideosome motor in the IMC [#2]. Functionally, conditional depletion of GAPM2 abolishes merozoite reorientation and gliding after the parasite has attached to the red blood cell, thereby blocking host cell invasion while leaving initial RBC attachment intact [#2]. Beyond this IMC-anchoring and invasion role, no further mechanistic detail on GAPM2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing where GAPM2 resides and what it associates with was the first step in assigning it a structural role: it was shown to be an IMC-localized six-pass transmembrane protein forming SDS-resistant complexes with cytoskeletal alveolins and the actin-myosin motor, implicating it in anchoring the IMC to the subpellicular cytoskeleton.\",\n      \"evidence\": \"Subcellular fractionation, SDS-resistant complex analysis by SDS-PAGE/Western, and co-purification with cytoskeletal and motor components in P. falciparum\",\n      \"pmids\": [\"19561073\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Anchoring role inferred from co-purification, not from loss-of-function or reconstitution\",\n        \"Direct binding partners within the SDS-resistant complex not resolved\",\n        \"Stoichiometry and architecture of the oligomeric complex unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"To test whether GAPM2 acts alone or within a defined assembly, it was shown to co-assemble with two related six-pass transmembrane proteins into a heteromeric IMC complex in merozoites, defining it as a member of an oligomeric membrane platform rather than an isolated protein.\",\n      \"evidence\": \"Immunofluorescence colocalization, reciprocal immunoprecipitation, baculovirus/insect-cell expression, and liposome reconstitution in P. falciparum\",\n      \"pmids\": [\"19465059\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Identity of GAPM2-specific contributions versus its paralogous partners not separated\",\n        \"Functional consequence of heteromeric assembly not tested\",\n        \"Whether complex assembly requires the reconstituted membrane environment in vivo unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The functional requirement for GAPM2 was resolved by conditional depletion, which showed that GAPM2 is part of a PhIL1-associated complex coexisting with the glideosome and is specifically required for merozoite reorientation and gliding after attachment, thereby defining its stage in the invasion sequence.\",\n      \"evidence\": \"Conditional knockdown/knockout with invasion, gliding, and reorientation assays plus immunofluorescence in P. falciparum\",\n      \"pmids\": [\"34324609\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism coupling GAPM2 to motor-driven reorientation not defined\",\n        \"Whether GAPM2 loss disrupts overall IMC/cytoskeleton integrity or acts more selectively unclear\",\n        \"Direct interaction between GAPM2 and PhIL1 versus indirect complex membership not distinguished\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GAPM2 mechanically transmits force from the actin-myosin motor to the IMC membrane to drive reorientation and gliding, and which direct partners mediate this coupling, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of GAPM2 or its complexes\",\n        \"Direct binding partners and force-transmission mechanism undefined\",\n        \"Role, if any, in other life-cycle stages beyond merozoite invasion untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"SDS-resistant IMC oligomeric complex with cytoskeletal alveolin proteins and actin-myosin motor [#0]\",\n      \"Heteromeric complex with two related six-pass transmembrane proteins [#1]\",\n      \"PhIL1-associated complex coexisting with the glideosome motor [#2]\"\n    ],\n    \"partners\": [\n      \"Cytoskeletal alveolin proteins [#0]\",\n      \"Actin-myosin motor components [#0]\",\n      \"Two related six-pass transmembrane proteins [#1]\",\n      \"PhIL1-associated complex members [#2]\"\n    ],\n    \"other_free_text\": [\n      \"Six-pass transmembrane topology [#0]\",\n      \"Conditional depletion blocks merozoite reorientation/gliding and RBC invasion while leaving initial attachment intact [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0423500","name":null,"product":"glideosome associated protein with multiple membrane spans 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0523900","name":null,"product":"glideosome associated protein with multiple membrane spans 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0515400","name":null,"product":"glideosome associated protein with multiple membrane spans 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GAPM2","evaluation":null}