{"gene":"PF3D7_1406800","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2009,"finding":"GAPM3 (PF3D7_1406800) localizes to the inner membrane complex (IMC) of Plasmodium falciparum, where it forms highly SDS-resistant oligomeric complexes. GAPM3 co-purifies with cytoskeletal alveolin proteins and to some degree with the actin-myosin motor, suggesting a role in tethering the motor to the cytoskeleton.","method":"Immunofluorescence localization, SDS-PAGE oligomeric complex analysis, co-purification/co-immunoprecipitation with alveolins and actin-myosin motor components","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization with functional consequence proposed, co-purification with two distinct protein classes, single lab but multiple orthogonal methods","pmids":["19561073"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"GAPM3 (PF3D7_1406800) co-localizes with two related six-transmembrane proteins on the inner membrane complex of P. falciparum merozoites and assembles into a heteromeric complex with them, as demonstrated by immunoprecipitation with specific antibodies.","method":"Immunofluorescence colocalization, immunoprecipitation with specific antibodies","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal immunoprecipitation demonstrating heteromeric complex, single lab, two orthogonal methods","pmids":["19465059"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"GAPM3 (PF3D7_1406800) is palmitoylated in asexual-stage Plasmodium falciparum, as identified by complementary palmitoyl protein purification approaches (ABE and MLCC) coupled with quantitative mass spectrometry.","method":"Acyl-biotin exchange (ABE) and metabolic labeling with click chemistry (MLCC) coupled with quantitative mass spectrometry","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — two orthogonal biochemical palmitoylation detection methods, single lab, identifies PTM directly on the protein","pmids":["22901544"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"GAPM3 (PF3D7_1406800) co-purifies with the MyoA-GFP glideosome complex in P. falciparum schizonts, as identified by immunoprecipitation of GFP-tagged MyoA followed by LC-MS/MS, confirming its association with the glideosome motor complex.","method":"GFP-tagged co-immunoprecipitation followed by LC-MS/MS","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP with mass spectrometry identification, single lab, confirms association with glideosome complex","pmids":["28893907"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2017,"finding":"GAPM3 (PF3D7_1406800) was detected as a PhIL1-interacting protein in P. falciparum stage IV gametocytes by immunoprecipitation of PhIL1-GFP followed by LC-MS/MS, though it did not reach the applied significance threshold in that study.","method":"GFP-Trap immunoprecipitation followed by LC-MS/MS","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — detected in pull-down but did not reach significance threshold, single method, single lab","pmids":["28985225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2024,"finding":"In Plasmodium berghei, depletion of PbIMC1g (a PHIL1-complex interacting protein) caused substantially altered localization patterns and reduced expression levels (37.5–84.6%) of GAPM3, indicating that GAPM3 localization and stability depend on an intact PHIL1 complex in the IMC.","method":"Conditional knockdown of PbIMC1g with subsequent IFA and immunoblotting to assess GAPM3 localization and expression","journal":"mBio","confidence":"Low","confidence_rationale":"Tier 3 / Weak — indirect evidence from a different gene's knockdown affecting GAPM3 localization/expression, single lab, single method per readout","pmids":["39576115"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"GAPM3 (PF3D7_1406800) is a six-pass transmembrane protein of the Plasmodium falciparum inner membrane complex (IMC) that forms highly SDS-resistant oligomeric complexes, is palmitoylated, co-purifies with both cytoskeletal alveolin proteins and the actin-myosin glideosome motor (including via MyoA immunoprecipitation), assembles into a heteromeric complex with two related GAPM family members on merozoites, and requires an intact PHIL1/IMC1g-containing complex for its proper IMC localization—consistent with a structural role anchoring or bridging the glideosome motor to the subpellicular cytoskeleton."},"narrative":{"mechanistic_narrative":"GAPM3 (PF3D7_1406800) is a polytopic membrane protein of the Plasmodium falciparum inner membrane complex (IMC) that functions as a structural component linking the glideosome motor to the subpellicular cytoskeleton [PMID:19561073]. At the IMC it forms highly SDS-resistant oligomeric assemblies and co-purifies with both cytoskeletal alveolin proteins and the actin-myosin motor, consistent with a tethering role [PMID:19561073], and this motor association is corroborated by its recovery in MyoA-GFP glideosome pulldowns from schizonts [PMID:28893907]. On merozoites, GAPM3 co-localizes and assembles into a heteromeric complex with two related six-transmembrane GAPM-family proteins [PMID:19465059]. GAPM3 is palmitoylated in asexual stages, a modification consistent with its membrane residence [PMID:22901544]. Its proper IMC localization and stability depend on an intact PHIL1-complex environment: GAPM3 was detected among PhIL1-GFP interactors in gametocytes [PMID:28985225], and in P. berghei depletion of the PHIL1-complex protein IMC1g mislocalized and destabilized GAPM3 [PMID:39576115]. Beyond this structural/anchoring role, no catalytic activity or direct loss-of-function phenotype for GAPM3 itself has been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Establishing where GAPM3 acts and what it binds was the first question; localizing it to the IMC and showing co-purification with alveolins and the motor defined it as a candidate structural bridge between the glideosome and the cytoskeleton.","evidence":"Immunofluorescence, SDS-resistant oligomer analysis, and co-purification with alveolins and actin-myosin motor components in P. falciparum","pmids":["19561073"],"confidence":"Medium","gaps":["Co-purification does not establish direct binding partners","No loss-of-function test of the proposed tethering role","Stoichiometry and architecture of the oligomers undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Whether GAPM3 acts alone or within a family assembly was addressed by showing it forms a heteromeric complex with two related six-transmembrane proteins on merozoites.","evidence":"Immunofluorescence colocalization and immunoprecipitation with specific antibodies in P. falciparum merozoites","pmids":["19465059"],"confidence":"Medium","gaps":["Identities/roles of the two partner proteins not detailed here","Functional consequence of the heteromeric assembly untested","Complex composition in other life stages unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"How a multipass membrane protein is anchored/regulated was partly answered by identifying GAPM3 as a palmitoylated protein in asexual stages.","evidence":"Acyl-biotin exchange and metabolic click labeling with quantitative mass spectrometry in P. falciparum","pmids":["22901544"],"confidence":"Medium","gaps":["Palmitoylation sites not mapped","Functional role of the modification untested","Responsible palmitoyltransferase unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"The earlier partial co-purification with the motor was strengthened by recovering GAPM3 in a MyoA-GFP glideosome pulldown, confirming association with the motor complex.","evidence":"GFP-tagged MyoA co-immunoprecipitation followed by LC-MS/MS in P. falciparum 3D7 schizonts","pmids":["28893907"],"confidence":"Medium","gaps":["Does not establish direct GAPM3-MyoA contact","No demonstration that GAPM3 is required for motor assembly or function"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2017,"claim":"Linkage of GAPM3 to the PHIL1 structural network was first hinted by its detection among PhIL1 interactors in gametocytes.","evidence":"PhIL1-GFP GFP-Trap immunoprecipitation followed by LC-MS/MS in P. falciparum 3D7 stage IV gametocytes","pmids":["28985225"],"confidence":"Low","gaps":["Did not reach the study's significance threshold","Single pulldown without reciprocal validation","Direct vs indirect association unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2024,"claim":"Whether GAPM3 IMC localization depends on the PHIL1 network was addressed by showing that depleting the PHIL1-complex protein IMC1g mislocalizes and destabilizes GAPM3.","evidence":"Conditional knockdown of PbIMC1g with IFA and immunoblotting readouts in P. berghei","pmids":["39576115"],"confidence":"Low","gaps":["Indirect evidence from a different gene's knockdown","Shown in P. berghei, not P. falciparum","Does not distinguish direct dependency from general IMC disruption"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The intrinsic function of GAPM3 itself—whether it is required for glideosome assembly, motility, or invasion—remains unresolved because no direct loss-of-function study of GAPM3 has been reported.","evidence":"No timeline discovery directly perturbs GAPM3 and measures a phenotype","pmids":[],"confidence":"Low","gaps":["No GAPM3 knockout/knockdown phenotype","No structural model of the oligomer or its motor/cytoskeleton contacts","Molecular activity beyond structural anchoring undefined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GAPM heteromeric complex with two related six-transmembrane GAPM-family proteins [#1]","MyoA-GFP glideosome/actin-myosin motor co-purifying complex [#0, #3]","PHIL1/IMC1g-associated IMC complex [#4, #5]"],"partners":["CYTOSKELETAL ALVEOLIN PROTEINS [#0]","ACTIN-MYOSIN (MYOA) GLIDEOSOME MOTOR [#0, #3]","TWO RELATED GAPM-FAMILY SIX-TRANSMEMBRANE PROTEINS [#1]","PHIL1 [#4]","IMC1G (P. BERGHEI) [#5]"],"other_free_text":["Forms highly SDS-resistant oligomeric complexes [#0]","Palmitoylated in asexual stages [#2]","IMC localization and protein stability depend on an intact PHIL1 complex (shown via IMC1g depletion in P. berghei) [#5]","No direct GAPM3 loss-of-function phenotype reported in the available corpus"]}},"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":"42267842","id":"","title":"The inner membrane complex protein, IMC55, is dispensable for intraerythrocytic development of Plasmodium falciparum.","date":"2026","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/42267842","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39576115","id":"","title":"An inner membrane complex protein IMC1g in Plasmodium berghei is involved in asexual stage schizogony and parasite transmission.","date":"2024","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/39576115","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37867646","id":"","title":"Identification of Novel, Potent, and Selective Compounds against Malaria Using Glideosomal-Associated Protein 50 as a Drug Target.","date":"2023","source":"ACS omega","url":"https://pubmed.ncbi.nlm.nih.gov/37867646","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41390482","id":"","title":"An ER-resident lipid scramblase is crucial for biogenesis and function of apicomplexan parasite secretory organelles.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41390482","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35775739","id":"","title":"Inner membrane complex proteomics reveals a palmitoylation regulation critical for intraerythrocytic development of malaria parasite.","date":"2022","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/35775739","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34324609","id":"","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":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31673027","id":"","title":"Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites.","date":"2019","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/31673027","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27128092","id":"","title":"Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics.","date":"2016","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/27128092","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28893907","id":"","title":"Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28893907","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28985225","id":"","title":"Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development.","date":"2017","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/28985225","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22901544","id":"","title":"Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis.","date":"2012","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/22901544","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24612102","id":"","title":"The inner membrane complex through development of Toxoplasma gondii and Plasmodium.","date":"2014","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/24612102","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"26175406","id":"","title":"Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites.","date":"2015","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/26175406","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GAPM3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16887,"output_tokens":1664,"usd":0.03781,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6715,"output_tokens":2866,"usd":0.052612,"stage2_stop_reason":"end_turn"},"total_usd":0.090422,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"GAPM3 (PF3D7_1406800) localizes to the inner membrane complex (IMC) of Plasmodium falciparum, where it forms highly SDS-resistant oligomeric complexes. GAPM3 co-purifies with cytoskeletal alveolin proteins and to some degree with the actin-myosin motor, suggesting a role in tethering the motor to the cytoskeleton.\",\n      \"method\": \"Immunofluorescence localization, SDS-PAGE oligomeric complex analysis, co-purification/co-immunoprecipitation with alveolins and actin-myosin motor components\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization with functional consequence proposed, co-purification with two distinct protein classes, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"19561073\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"GAPM3 (PF3D7_1406800) co-localizes with two related six-transmembrane proteins on the inner membrane complex of P. falciparum merozoites and assembles into a heteromeric complex with them, as demonstrated by immunoprecipitation with specific antibodies.\",\n      \"method\": \"Immunofluorescence colocalization, immunoprecipitation with specific antibodies\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal immunoprecipitation demonstrating heteromeric complex, single lab, two orthogonal methods\",\n      \"pmids\": [\"19465059\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"GAPM3 (PF3D7_1406800) is palmitoylated in asexual-stage Plasmodium falciparum, as identified by complementary palmitoyl protein purification approaches (ABE and MLCC) coupled with quantitative mass spectrometry.\",\n      \"method\": \"Acyl-biotin exchange (ABE) and metabolic labeling with click chemistry (MLCC) coupled with quantitative mass spectrometry\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — two orthogonal biochemical palmitoylation detection methods, single lab, identifies PTM directly on the protein\",\n      \"pmids\": [\"22901544\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"GAPM3 (PF3D7_1406800) co-purifies with the MyoA-GFP glideosome complex in P. falciparum schizonts, as identified by immunoprecipitation of GFP-tagged MyoA followed by LC-MS/MS, confirming its association with the glideosome motor complex.\",\n      \"method\": \"GFP-tagged co-immunoprecipitation followed by LC-MS/MS\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP with mass spectrometry identification, single lab, confirms association with glideosome complex\",\n      \"pmids\": [\"28893907\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"GAPM3 (PF3D7_1406800) was detected as a PhIL1-interacting protein in P. falciparum stage IV gametocytes by immunoprecipitation of PhIL1-GFP followed by LC-MS/MS, though it did not reach the applied significance threshold in that study.\",\n      \"method\": \"GFP-Trap immunoprecipitation followed by LC-MS/MS\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — detected in pull-down but did not reach significance threshold, single method, single lab\",\n      \"pmids\": [\"28985225\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In Plasmodium berghei, depletion of PbIMC1g (a PHIL1-complex interacting protein) caused substantially altered localization patterns and reduced expression levels (37.5–84.6%) of GAPM3, indicating that GAPM3 localization and stability depend on an intact PHIL1 complex in the IMC.\",\n      \"method\": \"Conditional knockdown of PbIMC1g with subsequent IFA and immunoblotting to assess GAPM3 localization and expression\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — indirect evidence from a different gene's knockdown affecting GAPM3 localization/expression, single lab, single method per readout\",\n      \"pmids\": [\"39576115\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"GAPM3 (PF3D7_1406800) is a six-pass transmembrane protein of the Plasmodium falciparum inner membrane complex (IMC) that forms highly SDS-resistant oligomeric complexes, is palmitoylated, co-purifies with both cytoskeletal alveolin proteins and the actin-myosin glideosome motor (including via MyoA immunoprecipitation), assembles into a heteromeric complex with two related GAPM family members on merozoites, and requires an intact PHIL1/IMC1g-containing complex for its proper IMC localization—consistent with a structural role anchoring or bridging the glideosome motor to the subpellicular cytoskeleton.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GAPM3 (PF3D7_1406800) is a polytopic membrane protein of the Plasmodium falciparum inner membrane complex (IMC) that functions as a structural component linking the glideosome motor to the subpellicular cytoskeleton [#0]. At the IMC it forms highly SDS-resistant oligomeric assemblies and co-purifies with both cytoskeletal alveolin proteins and the actin-myosin motor, consistent with a tethering role [#0], and this motor association is corroborated by its recovery in MyoA-GFP glideosome pulldowns from schizonts [#3]. On merozoites, GAPM3 co-localizes and assembles into a heteromeric complex with two related six-transmembrane GAPM-family proteins [#1]. GAPM3 is palmitoylated in asexual stages, a modification consistent with its membrane residence [#2]. Its proper IMC localization and stability depend on an intact PHIL1-complex environment: GAPM3 was detected among PhIL1-GFP interactors in gametocytes [#4], and in P. berghei depletion of the PHIL1-complex protein IMC1g mislocalized and destabilized GAPM3 [#5]. Beyond this structural/anchoring role, no catalytic activity or direct loss-of-function phenotype for GAPM3 itself has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Establishing where GAPM3 acts and what it binds was the first question; localizing it to the IMC and showing co-purification with alveolins and the motor defined it as a candidate structural bridge between the glideosome and the cytoskeleton.\",\n      \"evidence\": \"Immunofluorescence, SDS-resistant oligomer analysis, and co-purification with alveolins and actin-myosin motor components in P. falciparum\",\n      \"pmids\": [\"19561073\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Co-purification does not establish direct binding partners\", \"No loss-of-function test of the proposed tethering role\", \"Stoichiometry and architecture of the oligomers undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether GAPM3 acts alone or within a family assembly was addressed by showing it forms a heteromeric complex with two related six-transmembrane proteins on merozoites.\",\n      \"evidence\": \"Immunofluorescence colocalization and immunoprecipitation with specific antibodies in P. falciparum merozoites\",\n      \"pmids\": [\"19465059\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identities/roles of the two partner proteins not detailed here\", \"Functional consequence of the heteromeric assembly untested\", \"Complex composition in other life stages unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"How a multipass membrane protein is anchored/regulated was partly answered by identifying GAPM3 as a palmitoylated protein in asexual stages.\",\n      \"evidence\": \"Acyl-biotin exchange and metabolic click labeling with quantitative mass spectrometry in P. falciparum\",\n      \"pmids\": [\"22901544\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Palmitoylation sites not mapped\", \"Functional role of the modification untested\", \"Responsible palmitoyltransferase unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The earlier partial co-purification with the motor was strengthened by recovering GAPM3 in a MyoA-GFP glideosome pulldown, confirming association with the motor complex.\",\n      \"evidence\": \"GFP-tagged MyoA co-immunoprecipitation followed by LC-MS/MS in P. falciparum 3D7 schizonts\",\n      \"pmids\": [\"28893907\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not establish direct GAPM3-MyoA contact\", \"No demonstration that GAPM3 is required for motor assembly or function\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Linkage of GAPM3 to the PHIL1 structural network was first hinted by its detection among PhIL1 interactors in gametocytes.\",\n      \"evidence\": \"PhIL1-GFP GFP-Trap immunoprecipitation followed by LC-MS/MS in P. falciparum 3D7 stage IV gametocytes\",\n      \"pmids\": [\"28985225\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Did not reach the study's significance threshold\", \"Single pulldown without reciprocal validation\", \"Direct vs indirect association unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether GAPM3 IMC localization depends on the PHIL1 network was addressed by showing that depleting the PHIL1-complex protein IMC1g mislocalizes and destabilizes GAPM3.\",\n      \"evidence\": \"Conditional knockdown of PbIMC1g with IFA and immunoblotting readouts in P. berghei\",\n      \"pmids\": [\"39576115\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Indirect evidence from a different gene's knockdown\", \"Shown in P. berghei, not P. falciparum\", \"Does not distinguish direct dependency from general IMC disruption\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic function of GAPM3 itself—whether it is required for glideosome assembly, motility, or invasion—remains unresolved because no direct loss-of-function study of GAPM3 has been reported.\",\n      \"evidence\": \"No timeline discovery directly perturbs GAPM3 and measures a phenotype\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No GAPM3 knockout/knockdown phenotype\", \"No structural model of the oligomer or its motor/cytoskeleton contacts\", \"Molecular activity beyond structural anchoring undefined\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020039\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0018345\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"GAPM heteromeric complex with two related six-transmembrane GAPM-family proteins [#1]\",\n      \"MyoA-GFP glideosome/actin-myosin motor co-purifying complex [#0, #3]\",\n      \"PHIL1/IMC1g-associated IMC complex [#4, #5]\"\n    ],\n    \"partners\": [\n      \"cytoskeletal alveolin proteins [#0]\",\n      \"actin-myosin (MyoA) glideosome motor [#0, #3]\",\n      \"two related GAPM-family six-transmembrane proteins [#1]\",\n      \"PhIL1 [#4]\",\n      \"IMC1g (P. berghei) [#5]\"\n    ],\n    \"other_free_text\": [\n      \"Forms highly SDS-resistant oligomeric complexes [#0]\",\n      \"Palmitoylated in asexual stages [#2]\",\n      \"IMC localization and protein stability depend on an intact PHIL1 complex (shown via IMC1g depletion in P. berghei) [#5]\",\n      \"No direct GAPM3 loss-of-function phenotype reported in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1406800","name":null,"product":"glideosome associated protein with multiple membrane spans 3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1035400","name":null,"product":"glideosome associated protein with multiple membrane spans 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1351300","name":null,"product":"glideosome associated protein with multiple membrane spans 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GAPM3","evaluation":null}