{"gene":"PF3D7_0525800","run_date":"2026-09-07T12:57:17+00:00","timeline":{"discoveries":[{"year":2023,"finding":"PfIMC1g (PF3D7_0525800) is essential for P. falciparum asexual blood-stage survival; conditional knockdown demonstrates it is critical for parasite survival post-invasion, establishing a defined role in merozoite intracellular survival distinct from invasion itself.","method":"Conditional knockdown with phenotypic readout (essentiality, post-invasion survival assay)","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean inducible knockdown with defined cellular phenotype (post-invasion survival), single lab but orthogonal approaches (localization + essentiality + stage-specific phenotype)","pmids":["37712738"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfIMC1g (PF3D7_0525800) localizes to the inner membrane complex during asexual blood-stage development, as determined by direct localization experiments evaluating the four asexual-stage alveolins.","method":"Direct subcellular localization (fluorescence microscopy)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization established in single lab study with functional consequence (essentiality) shown in same paper","pmids":["37712738"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"PfIMC1g (PF3D7_0525800) does not require interaction with PfIMC1c to localize properly to the inner membrane complex; alveolin domains of PfIMC1g contain unique signatures for specialized localization rather than a generic mechanism shared across alveolins.","method":"Domain deletion/swap experiments with fluorescence microscopy-based localization readout","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct experimental evidence (domain manipulation + localization), single lab, single study","pmids":["41019501"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"PbIMC1g (ortholog of PF3D7_0525800 in P. berghei) localizes to the IMC in late schizonts, activated gametocytes, and ookinetes; its IMCp domain is required for IMC targeting, while its C-terminus and palmitoylation sites are required for full efficiency of proper IMC targeting.","method":"Fluorescence microscopy (localization), domain deletion analysis, palmitoylation site mutagenesis","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (domain deletion, mutagenesis of palmitoylation sites, fluorescence localization) in single lab","pmids":["39576115"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"PbIMC1g (ortholog of PF3D7_0525800 in P. berghei) interacts with IMC1c, a component of the PHIL1 complex; the core sub-repeat motif 'EKI(V)V(I)EVP' in PbIMC1g is essential for this interaction, as demonstrated by pairwise yeast two-hybrid assays.","method":"Pairwise yeast two-hybrid assay; motif deletion/mutagenesis","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid with motif-level mutagenesis, single lab","pmids":["39576115"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"PbIMC1g (ortholog of PF3D7_0525800 in P. berghei) functions to anchor the glideosome to the subpellicular network; conditional knockdown resulted in defects in schizogony, male gametogenesis, ookinete development, ookinete motility, and mosquito midgut invasion.","method":"Conditional knockdown with multiple phenotypic readouts (schizogony, gametogenesis, ookinete motility, invasion)","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with multiple orthogonal phenotypic readouts across life-cycle stages, single lab","pmids":["39576115"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"IMC1g from Plasmodium vivax can functionally replace PbIMC1g in P. berghei, confirming evolutionary conservation of IMC1g protein function across Plasmodium species.","method":"Functional complementation (heterologous expression of PvIMC1g in P. berghei imc1g knockdown)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional complementation experiment, single lab, single study","pmids":["39576115"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium vivax","strain":""}]}],"current_model":"PF3D7_0525800 (IMC1g) is an essential alveolin/intermediate filament-like protein that localizes to the inner membrane complex via its IMCp domain and palmitoylation sites, interacts with IMC1c through a conserved 'EKI(V)V(I)EVP' sub-repeat motif to anchor the glideosome to the subpellicular network, and is required in P. falciparum for asexual blood-stage survival (particularly post-invasion) and in P. berghei for schizogony, male gametogenesis, ookinete development, and mosquito midgut invasion; its localization to the IMC does not depend on interaction with IMC1c, and its alveolin domain contains unique signatures for compartment-specific targeting rather than a generic shared mechanism."},"narrative":{"mechanistic_narrative":"PF3D7_0525800 (IMC1g) is an alveolin-family inner membrane complex (IMC) protein that anchors the glideosome to the subpellicular network and is required for Plasmodium survival and motility across life-cycle stages [PMID:37712738, PMID:39576115]. In P. falciparum, IMC1g localizes to the IMC during asexual blood-stage development and is essential for parasite survival, with conditional knockdown pinpointing a defect post-invasion, indicating a role in merozoite intracellular survival rather than in the invasion event itself [PMID:37712738]. IMC targeting is directed by intrinsic sequence features: its IMCp/alveolin domain carries unique signatures for compartment-specific localization, and this targeting does not depend on interaction with IMC1c [PMID:41019501]; in the P. berghei ortholog, the IMCp domain is required for IMC targeting while the C-terminus and palmitoylation sites contribute to full targeting efficiency [PMID:39576115]. IMC1g interacts with IMC1c, a component of the PHIL1 complex, through a conserved 'EKI(V)V(I)EVP' sub-repeat motif [PMID:39576115]. The protein's function is evolutionarily conserved, as P. vivax IMC1g functionally complements the P. berghei ortholog [PMID:39576115]. Species-specific phenotypes diverge in scope: in P. berghei, knockdown disrupts schizogony, male gametogenesis, ookinete development and motility, and mosquito midgut invasion [PMID:39576115], whereas in P. falciparum the characterized essentiality is in the asexual blood stage [PMID:37712738].","teleology":[{"year":2023,"claim":"Establishing whether IMC1g is functionally required at all, and at which step, distinguished it as an essential factor for intracellular survival rather than for invasion.","evidence":"conditional knockdown with post-invasion survival phenotyping in P. falciparum asexual blood stages","pmids":["37712738"],"confidence":"High","gaps":["the molecular cause of the post-invasion survival defect is not defined","whether the phenotype reflects IMC structural collapse or a downstream signaling failure is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Determining subcellular localization placed IMC1g at the inner membrane complex, connecting its essentiality to IMC biology.","evidence":"fluorescence microscopy localization comparing the four asexual-stage alveolins in P. falciparum","pmids":["37712738"],"confidence":"Medium","gaps":["localization within IMC sub-domains not resolved","dynamics across the asexual cycle not fully mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Mapping IMC targeting determinants in the ortholog showed the IMCp domain drives IMC localization, with C-terminal and palmitoylation contributions to efficiency.","evidence":"domain deletion and palmitoylation-site mutagenesis with fluorescence localization in P. berghei across schizonts, activated gametocytes, and ookinetes","pmids":["39576115"],"confidence":"Medium","gaps":["identity of the palmitoyl transferase acting on IMC1g not established","which IMC binding partner reads the IMCp domain not identified"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"Identifying the IMC1c interaction and its motif dependence defined a molecular link connecting IMC1g to the PHIL1 complex.","evidence":"pairwise yeast two-hybrid with motif deletion/mutagenesis of the 'EKI(V)V(I)EVP' sub-repeat in P. berghei","pmids":["39576115"],"confidence":"Medium","gaps":["interaction not confirmed by orthogonal in-cell or reciprocal co-IP methods","stoichiometry and direct-vs-bridged nature of the IMC1c contact unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"Multi-stage knockdown phenotyping assigned IMC1g a role anchoring the glideosome to the subpellicular network across the parasite life cycle.","evidence":"conditional knockdown with phenotyping of schizogony, male gametogenesis, ookinete development and motility, and midgut invasion in P. berghei","pmids":["39576115"],"confidence":"High","gaps":["direct biochemical demonstration of glideosome tethering not shown","whether motility defects are structural or regulatory is unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"Cross-species complementation demonstrated that IMC1g function is evolutionarily conserved.","evidence":"heterologous expression of P. vivax IMC1g rescuing P. berghei imc1g knockdown","pmids":["39576115"],"confidence":"Medium","gaps":["degree of functional rescue across all life-cycle stages not fully quantified","conservation of the IMC1c interaction motif not directly tested for the P. vivax protein"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium vivax","strain":""}]},{"year":2025,"claim":"Testing whether IMC1c binding was needed for IMC localization separated targeting from complex assembly and revealed IMC1g-intrinsic localization signatures.","evidence":"domain deletion/swap experiments with fluorescence localization readout in P. falciparum","pmids":["41019501"],"confidence":"Medium","gaps":["the specific sequence signatures conferring compartment-specific targeting are not defined at residue level","the receptor or scaffold recognizing these signatures is unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How IMC1g mechanistically bridges the glideosome and subpellicular network, and the molecular basis of its post-invasion essentiality in P. falciparum, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no structural model of IMC1g or its IMC1c interface","no direct biochemical demonstration of glideosome tethering","the full IMC1g interactome beyond IMC1c is uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PHIL1 complex (via interaction with IMC1c) [#4]"],"partners":["IMC1C [#4]"],"other_free_text":["IMC targeting driven by the IMCp/alveolin domain with C-terminal and palmitoylation-site contributions, independent of IMC1c binding [#2, #3]","Interaction with IMC1c requires the conserved 'EKI(V)V(I)EVP' sub-repeat motif [#4]","Essential for P. falciparum asexual blood-stage survival post-invasion [#0]","In P. berghei required for schizogony, male gametogenesis, ookinete development/motility, and mosquito midgut invasion [#5]","Function conserved across Plasmodium species; P. vivax IMC1g complements the P. berghei ortholog [#6]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"20037583","id":"PMC_20037583","title":"Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum.","date":"2009","source":"Nature biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/20037583","citation_count":160,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37712738","id":"PMC_37712738","title":"Essential function of alveolin PfIMC1g in the Plasmodium falciparum asexual blood stage.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37712738","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfIMC1g"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34395314","id":"PMC_34395314","title":"Calcium in the Backstage of Malaria Parasite Biology.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34395314","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1g"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39576115","id":"PMC_39576115","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":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1g","PbIMC1g"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41019501","id":"PMC_41019501","title":"Malaria Cytoskeletal Proteins Require Alveolin-Alveolin Interactions for Differential Localization: Recruitment and Organization of Alveolin Proteins.","date":"2025","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/41019501","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfIMC1g"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39668051","id":"PMC_39668051","title":"IMC1g knockdowns reveal malaria blood-stage alveolin functions.","date":"2024","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/39668051","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IMC1g"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5433,"output_tokens":1809,"usd":0.021717,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6910,"output_tokens":2991,"usd":0.054663,"stage2_stop_reason":"end_turn"},"total_usd":0.0,"stage1_batch_id":"msgbatch_01BW7vvc7h5iV39oJ1MHMzXw","stage2_batch_id":"msgbatch_01Kh5HbgbPXepNfNCbktYkSD","note":"batch pricing = 50% of standard","skipped":true},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"PfIMC1g (PF3D7_0525800) is essential for P. falciparum asexual blood-stage survival; conditional knockdown demonstrates it is critical for parasite survival post-invasion, establishing a defined role in merozoite intracellular survival distinct from invasion itself.\",\n      \"method\": \"Conditional knockdown with phenotypic readout (essentiality, post-invasion survival assay)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean inducible knockdown with defined cellular phenotype (post-invasion survival), single lab but orthogonal approaches (localization + essentiality + stage-specific phenotype)\",\n      \"pmids\": [\"37712738\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfIMC1g (PF3D7_0525800) localizes to the inner membrane complex during asexual blood-stage development, as determined by direct localization experiments evaluating the four asexual-stage alveolins.\",\n      \"method\": \"Direct subcellular localization (fluorescence microscopy)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization established in single lab study with functional consequence (essentiality) shown in same paper\",\n      \"pmids\": [\"37712738\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PfIMC1g (PF3D7_0525800) does not require interaction with PfIMC1c to localize properly to the inner membrane complex; alveolin domains of PfIMC1g contain unique signatures for specialized localization rather than a generic mechanism shared across alveolins.\",\n      \"method\": \"Domain deletion/swap experiments with fluorescence microscopy-based localization readout\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct experimental evidence (domain manipulation + localization), single lab, single study\",\n      \"pmids\": [\"41019501\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PbIMC1g (ortholog of PF3D7_0525800 in P. berghei) localizes to the IMC in late schizonts, activated gametocytes, and ookinetes; its IMCp domain is required for IMC targeting, while its C-terminus and palmitoylation sites are required for full efficiency of proper IMC targeting.\",\n      \"method\": \"Fluorescence microscopy (localization), domain deletion analysis, palmitoylation site mutagenesis\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (domain deletion, mutagenesis of palmitoylation sites, fluorescence localization) in single lab\",\n      \"pmids\": [\"39576115\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PbIMC1g (ortholog of PF3D7_0525800 in P. berghei) interacts with IMC1c, a component of the PHIL1 complex; the core sub-repeat motif 'EKI(V)V(I)EVP' in PbIMC1g is essential for this interaction, as demonstrated by pairwise yeast two-hybrid assays.\",\n      \"method\": \"Pairwise yeast two-hybrid assay; motif deletion/mutagenesis\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid with motif-level mutagenesis, single lab\",\n      \"pmids\": [\"39576115\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PbIMC1g (ortholog of PF3D7_0525800 in P. berghei) functions to anchor the glideosome to the subpellicular network; conditional knockdown resulted in defects in schizogony, male gametogenesis, ookinete development, ookinete motility, and mosquito midgut invasion.\",\n      \"method\": \"Conditional knockdown with multiple phenotypic readouts (schizogony, gametogenesis, ookinete motility, invasion)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with multiple orthogonal phenotypic readouts across life-cycle stages, single lab\",\n      \"pmids\": [\"39576115\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"IMC1g from Plasmodium vivax can functionally replace PbIMC1g in P. berghei, confirming evolutionary conservation of IMC1g protein function across Plasmodium species.\",\n      \"method\": \"Functional complementation (heterologous expression of PvIMC1g in P. berghei imc1g knockdown)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional complementation experiment, single lab, single study\",\n      \"pmids\": [\"39576115\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}, {\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0525800 (IMC1g) is an essential alveolin/intermediate filament-like protein that localizes to the inner membrane complex via its IMCp domain and palmitoylation sites, interacts with IMC1c through a conserved 'EKI(V)V(I)EVP' sub-repeat motif to anchor the glideosome to the subpellicular network, and is required in P. falciparum for asexual blood-stage survival (particularly post-invasion) and in P. berghei for schizogony, male gametogenesis, ookinete development, and mosquito midgut invasion; its localization to the IMC does not depend on interaction with IMC1c, and its alveolin domain contains unique signatures for compartment-specific targeting rather than a generic shared mechanism.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0525800 (IMC1g) is an alveolin-family inner membrane complex (IMC) protein that anchors the glideosome to the subpellicular network and is required for Plasmodium survival and motility across life-cycle stages [#0, #5]. In P. falciparum, IMC1g localizes to the IMC during asexual blood-stage development and is essential for parasite survival, with conditional knockdown pinpointing a defect post-invasion, indicating a role in merozoite intracellular survival rather than in the invasion event itself [#0, #1]. IMC targeting is directed by intrinsic sequence features: its IMCp/alveolin domain carries unique signatures for compartment-specific localization, and this targeting does not depend on interaction with IMC1c [#2]; in the P. berghei ortholog, the IMCp domain is required for IMC targeting while the C-terminus and palmitoylation sites contribute to full targeting efficiency [#3]. IMC1g interacts with IMC1c, a component of the PHIL1 complex, through a conserved 'EKI(V)V(I)EVP' sub-repeat motif [#4]. The protein's function is evolutionarily conserved, as P. vivax IMC1g functionally complements the P. berghei ortholog [#6]. Species-specific phenotypes diverge in scope: in P. berghei, knockdown disrupts schizogony, male gametogenesis, ookinete development and motility, and mosquito midgut invasion [#5], whereas in P. falciparum the characterized essentiality is in the asexual blood stage [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing whether IMC1g is functionally required at all, and at which step, distinguished it as an essential factor for intracellular survival rather than for invasion.\",\n      \"evidence\": \"conditional knockdown with post-invasion survival phenotyping in P. falciparum asexual blood stages\",\n      \"pmids\": [\"37712738\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"the molecular cause of the post-invasion survival defect is not defined\", \"whether the phenotype reflects IMC structural collapse or a downstream signaling failure is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Determining subcellular localization placed IMC1g at the inner membrane complex, connecting its essentiality to IMC biology.\",\n      \"evidence\": \"fluorescence microscopy localization comparing the four asexual-stage alveolins in P. falciparum\",\n      \"pmids\": [\"37712738\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"localization within IMC sub-domains not resolved\", \"dynamics across the asexual cycle not fully mapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Mapping IMC targeting determinants in the ortholog showed the IMCp domain drives IMC localization, with C-terminal and palmitoylation contributions to efficiency.\",\n      \"evidence\": \"domain deletion and palmitoylation-site mutagenesis with fluorescence localization in P. berghei across schizonts, activated gametocytes, and ookinetes\",\n      \"pmids\": [\"39576115\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"identity of the palmitoyl transferase acting on IMC1g not established\", \"which IMC binding partner reads the IMCp domain not identified\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying the IMC1c interaction and its motif dependence defined a molecular link connecting IMC1g to the PHIL1 complex.\",\n      \"evidence\": \"pairwise yeast two-hybrid with motif deletion/mutagenesis of the 'EKI(V)V(I)EVP' sub-repeat in P. berghei\",\n      \"pmids\": [\"39576115\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"interaction not confirmed by orthogonal in-cell or reciprocal co-IP methods\", \"stoichiometry and direct-vs-bridged nature of the IMC1c contact unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Multi-stage knockdown phenotyping assigned IMC1g a role anchoring the glideosome to the subpellicular network across the parasite life cycle.\",\n      \"evidence\": \"conditional knockdown with phenotyping of schizogony, male gametogenesis, ookinete development and motility, and midgut invasion in P. berghei\",\n      \"pmids\": [\"39576115\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"direct biochemical demonstration of glideosome tethering not shown\", \"whether motility defects are structural or regulatory is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Cross-species complementation demonstrated that IMC1g function is evolutionarily conserved.\",\n      \"evidence\": \"heterologous expression of P. vivax IMC1g rescuing P. berghei imc1g knockdown\",\n      \"pmids\": [\"39576115\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"degree of functional rescue across all life-cycle stages not fully quantified\", \"conservation of the IMC1c interaction motif not directly tested for the P. vivax protein\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}, {\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Testing whether IMC1c binding was needed for IMC localization separated targeting from complex assembly and revealed IMC1g-intrinsic localization signatures.\",\n      \"evidence\": \"domain deletion/swap experiments with fluorescence localization readout in P. falciparum\",\n      \"pmids\": [\"41019501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"the specific sequence signatures conferring compartment-specific targeting are not defined at residue level\", \"the receptor or scaffold recognizing these signatures is unidentified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How IMC1g mechanistically bridges the glideosome and subpellicular network, and the molecular basis of its post-invasion essentiality in P. falciparum, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"no structural model of IMC1g or its IMC1c interface\", \"no direct biochemical demonstration of glideosome tethering\", \"the full IMC1g interactome beyond IMC1c is uncharacterized\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}, {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0071973\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"PHIL1 complex (via interaction with IMC1c) [#4]\"\n    ],\n    \"partners\": [\n      \"IMC1c [#4]\"\n    ],\n    \"other_free_text\": [\n      \"IMC targeting driven by the IMCp/alveolin domain with C-terminal and palmitoylation-site contributions, independent of IMC1c binding [#2, #3]\",\n      \"Interaction with IMC1c requires the conserved 'EKI(V)V(I)EVP' sub-repeat motif [#4]\",\n      \"Essential for P. falciparum asexual blood-stage survival post-invasion [#0]\",\n      \"In P. berghei required for schizogony, male gametogenesis, ookinete development/motility, and mosquito midgut invasion [#5]\",\n      \"Function conserved across Plasmodium species; P. vivax IMC1g complements the P. berghei ortholog [#6]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0525800","name":null,"product":"inner membrane complex protein 1g","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1240600","name":null,"product":"inner membrane complex protein 1g, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1007000","name":null,"product":"inner membrane complex protein 1g, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IMC1g","evaluation":null}