{"gene":"PF3D7_1108600","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":1997,"finding":"ERC (PfERC/PF3D7_1108600) was identified as an endoplasmic reticulum-resident calcium-binding protein in asexual stages of P. falciparum. It contains six EF-hand calcium-binding domains and a C-terminal IDEL ER-retention motif. Calcium-binding activity was confirmed by 45Ca2+-blotting, and ER localization was established by co-localization with the known ER protein Pfgrp by confocal immunofluorescence microscopy. Expression was shown to increase with parasite maturity by immunoblot of synchronized parasites.","method":"45Ca2+-blotting, confocal immunofluorescence co-localization with ER marker Pfgrp, immunoblot of synchronized parasites, partial protein sequencing, gene sequencing","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (45Ca2+-blotting, co-localization, partial protein sequencing, gene sequence analysis) in a single focused study establishing localization and calcium-binding activity","pmids":["9364972"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Conditional knockdown of ERC (PfERC/PF3D7_1108600) in P. falciparum demonstrated it is essential for asexual growth and specifically required for parasite egress. Knockdown prevented rupture of the parasitophorous vacuole membrane (PVM). Mechanistically, ERC knockdown inhibited proteolytic maturation of the subtilisin-like serine protease SUB1. Using double-mutant parasites, ERC was shown to be required for the proteolytic maturation of the aspartic protease plasmepsin X (PMX), which in turn is required for SUB1 cleavage. Processing of substrates downstream of the proteolytic cascade was also inhibited. ERC knockdown did not affect protein trafficking or calcium storage.","method":"Conditional knockdown (inducible knockdown system), double-mutant epistasis analysis, immunofluorescence microscopy, immunoblot for proteolytic maturation, parasitophorous vacuole membrane rupture assay","journal":"mBio","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal genetic epistasis with double mutants, conditional knockdown with defined molecular phenotype (inhibited PMX and SUB1 maturation), multiple orthogonal readouts in one rigorous study","pmids":["32098818"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"ERC (PfERC/PF3D7_1108600) was identified by chemical proteomics as a P. falciparum protein with high affinity for the endoperoxide structure N-346 (a carboxyamino derivative of the antimalarial N-89). ERC protein levels were decreased upon treatment of parasites with N-89 or its hydroxyl derivative N-251, as shown by proteomic expression profiling.","method":"Chemical proteomics (affinity pulldown with endoperoxide-derivatized probe N-346), proteomic expression profiling after drug treatment","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single chemical proteomics pulldown without reciprocal validation or mutagenesis; single lab, single study","pmids":["23061985"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"ERC (PF3D7_1108600) was shown to associate with the ER-resident serpentine receptor SR10 in P. falciparum by co-localization and co-immunoprecipitation assays.","method":"Co-immunoprecipitation, co-localization assay","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single Co-IP and co-localization, single lab, no reciprocal pull-down or functional consequence of the interaction specifically mapped to ERC","pmids":["32890576"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"In P. berghei-infected mice treated with the endoperoxide N-89 transdermally, PbERC (the P. berghei ortholog of ERC/PF3D7_1108600) gene expression was suppressed relative to control. Concurrently, expression of egress-related genes plasmepsin X, subtilisin-like protease 1, and merozoite surface protein 1 was suppressed at 12 h. This is consistent with a functional role for ERC upstream of the egress proteolytic cascade, as established in P. falciparum.","method":"Quantitative real-time PCR of PbERC and egress-related gene expression after transdermal N-89 treatment in P. berghei-infected mice","journal":"Parasitology international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — gene expression measurement only (qRT-PCR), single study, no direct protein-level or mechanistic experiment on ERC function itself","pmids":["39740755"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"ERC (PF3D7_1108600) is an endoplasmic reticulum-resident protein with six EF-hand calcium-binding domains and a C-terminal IDEL retention motif that is essential for asexual blood-stage growth of P. falciparum; it acts as a key early regulator of the egress proteolytic cascade by being required for the proteolytic maturation of the aspartic protease plasmepsin X, which in turn enables maturation of the subtilisin-like protease SUB1 and rupture of the parasitophorous vacuole membrane, while being dispensable for protein trafficking or calcium storage."},"narrative":{"mechanistic_narrative":"ERC (PF3D7_1108600) is an endoplasmic reticulum-resident calcium-binding protein of P. falciparum that functions as an essential early regulator of the parasite egress proteolytic cascade [PMID:9364972, PMID:32098818]. It carries six EF-hand calcium-binding domains and a C-terminal IDEL ER-retention motif; its calcium-binding activity was confirmed directly and its ER residence established by co-localization with the ER marker Pfgrp, with expression rising as parasites mature [PMID:9364972]. Conditional knockdown showed ERC is required for asexual blood-stage growth and specifically for rupture of the parasitophorous vacuole membrane during egress; mechanistically, ERC is required for proteolytic maturation of the aspartic protease plasmepsin X, which in turn enables maturation of the subtilisin-like protease SUB1 and processing of downstream cascade substrates, while ERC loss does not affect protein trafficking or calcium storage [PMID:32098818]. Beyond its role upstream of this proteolytic cascade, ERC has been reported to associate with the ER-resident serpentine receptor SR10 [PMID:32890576], but the functional consequence of this interaction for ERC has not been characterized in the available corpus.","teleology":[{"year":1997,"claim":"Established that PF3D7_1108600 is a genuine ER-resident calcium-binding protein, defining its subcellular niche and biochemical activity before any functional role was known.","evidence":"45Ca2+-blotting, confocal co-localization with ER marker Pfgrp, and partial protein/gene sequencing in P. falciparum asexual stages","pmids":["9364972"],"confidence":"High","gaps":["No cellular or growth phenotype tested at this stage","Functional purpose of calcium binding not addressed","Interaction partners unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Linked ERC to endoperoxide antimalarial action by identifying it as a high-affinity binder of an endoperoxide probe, raising the possibility it is a drug-relevant target.","evidence":"Chemical proteomics affinity pulldown with endoperoxide probe N-346 and proteomic expression profiling after N-89/N-251 treatment in P. falciparum","pmids":["23061985"],"confidence":"Medium","gaps":["Single pulldown without reciprocal validation or mutagenesis","Direct binding site not mapped","Whether the interaction is causal for drug action untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Defined the essential function of ERC by placing it upstream of the egress proteolytic cascade, answering what this ER calcium-binding protein actually does for the parasite.","evidence":"Conditional knockdown, double-mutant epistasis, immunoblot of PMX and SUB1 maturation, and PVM rupture assay in P. falciparum","pmids":["32098818"],"confidence":"High","gaps":["Molecular mechanism by which ERC promotes PMX maturation unresolved","Whether ERC calcium binding is required for the egress function untested","Direct physical link between ERC and PMX not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Identified a physical partner for ERC, the ER-resident serpentine receptor SR10, hinting at a protein-interaction context within the ER.","evidence":"Co-immunoprecipitation and co-localization assays in P. falciparum","pmids":["32890576"],"confidence":"Medium","gaps":["Single Co-IP without reciprocal pull-down","Functional consequence of the interaction for ERC not mapped","Relationship of SR10 binding to the egress role unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Extended the egress-cascade model to a rodent malaria system by showing endoperoxide treatment coordinately suppresses PbERC and downstream egress-gene transcripts.","evidence":"qRT-PCR of PbERC, plasmepsin X, SUB1, and MSP1 after transdermal N-89 treatment in P. berghei-infected mice","pmids":["39740755"],"confidence":"Low","gaps":["Expression measurement only; no protein-level or mechanistic assay on ERC function","Cannot distinguish direct effect on ERC from general drug-induced stress","Ortholog function not independently validated by genetics in P. berghei"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The molecular mechanism by which an ER calcium-binding protein controls proteolytic maturation of plasmepsin X, and the role of its calcium binding and SR10 interaction in that process, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural or biochemical account of how ERC enables PMX maturation","Contribution of the six EF-hands / calcium binding to egress function untested","Whether SR10 association participates in the egress pathway unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["SR10 (ER-RESIDENT SERPENTINE RECEPTOR; CO-IP AND CO-LOCALIZATION) [#3]","PLASMEPSIN X (PMX; ERC REQUIRED FOR ITS PROTEOLYTIC MATURATION) [#1]","SUB1 (SUBTILISIN-LIKE PROTEASE MATURED DOWNSTREAM OF ERC VIA PMX) [#1]"],"other_free_text":["Contains six EF-hand calcium-binding domains and a C-terminal IDEL ER-retention motif [#0].","Essential for asexual blood-stage growth and specifically required for parasitophorous vacuole membrane rupture during egress [#1].","Dispensable for protein trafficking and calcium storage despite its ER localization and calcium-binding activity [#1].","Identified as a high-affinity binder of the endoperoxide antimalarial probe N-346; ERC levels decrease upon N-89/N-251 treatment [#2].","In P. berghei, the PbERC ortholog transcript and egress-gene transcripts (PMX, SUB1, MSP1) are suppressed by transdermal endoperoxide N-89 treatment [#4]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"10648803","id":"PMC_10648803","title":"The CREC family, a novel family of multiple EF-hand, low-affinity Ca(2+)-binding proteins localised to the secretory pathway of mammalian cells.","date":"2000","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/10648803","citation_count":132,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ERC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9364972","id":"PMC_9364972","title":"Identification of an endoplasmic reticulum-resident calcium-binding protein with multiple EF-hand motifs in asexual stages of Plasmodium falciparum.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9364972","citation_count":66,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ERC","endoplasmic reticulum-resident calcium binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23061985","id":"PMC_23061985","title":"Plasmodium falciparum endoplasmic reticulum-resident calcium binding protein is a possible target of synthetic antimalarial endoperoxides, N-89 and N-251.","date":"2012","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/23061985","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["endoplasmic reticulum-resident calcium binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32098818","id":"PMC_32098818","title":"An Endoplasmic Reticulum CREC Family Protein Regulates the Egress Proteolytic Cascade in Malaria Parasites.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32098818","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9497061","id":"PMC_9497061","title":"Plasmodium falciparum Pfs40, renamed Pf39, is localized to an intracellular membrane-bound compartment and is not sexual stage-specific.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9497061","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"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":["ERC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33202000","id":"PMC_33202000","title":"A proteomic glimpse into the effect of antimalarial drugs on Plasmodium falciparum proteome towards highlighting possible therapeutic targets.","date":"2021","source":"Pathogens and disease","url":"https://pubmed.ncbi.nlm.nih.gov/33202000","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["endoplasmic reticulum-resident calcium binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32890576","id":"PMC_32890576","title":"The endoplasmic reticulum-resident serpentine receptor SR10 has important functions for asexual and sexual blood stage development of Plasmodium falciparum.","date":"2020","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/32890576","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ERC"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31377318","id":"PMC_31377318","title":"Genomic and biological features of Plasmodium falciparum resistance against antimalarial endoperoxide N-89.","date":"2019","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/31377318","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["endoplasmic reticulum-resident calcium binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39740755","id":"PMC_39740755","title":"The antimalarial activity of transdermal N-89 mediated by inhibiting ERC gene expression in P. Berghei-infected mice.","date":"2024","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/39740755","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ERC","endoplasmic reticulum-resident calcium binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7506,"output_tokens":1700,"usd":0.024009,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6756,"output_tokens":2613,"usd":0.049552,"stage2_stop_reason":"end_turn"},"total_usd":0.073561,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1997,\n      \"finding\": \"ERC (PfERC/PF3D7_1108600) was identified as an endoplasmic reticulum-resident calcium-binding protein in asexual stages of P. falciparum. It contains six EF-hand calcium-binding domains and a C-terminal IDEL ER-retention motif. Calcium-binding activity was confirmed by 45Ca2+-blotting, and ER localization was established by co-localization with the known ER protein Pfgrp by confocal immunofluorescence microscopy. Expression was shown to increase with parasite maturity by immunoblot of synchronized parasites.\",\n      \"method\": \"45Ca2+-blotting, confocal immunofluorescence co-localization with ER marker Pfgrp, immunoblot of synchronized parasites, partial protein sequencing, gene sequencing\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (45Ca2+-blotting, co-localization, partial protein sequencing, gene sequence analysis) in a single focused study establishing localization and calcium-binding activity\",\n      \"pmids\": [\"9364972\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Conditional knockdown of ERC (PfERC/PF3D7_1108600) in P. falciparum demonstrated it is essential for asexual growth and specifically required for parasite egress. Knockdown prevented rupture of the parasitophorous vacuole membrane (PVM). Mechanistically, ERC knockdown inhibited proteolytic maturation of the subtilisin-like serine protease SUB1. Using double-mutant parasites, ERC was shown to be required for the proteolytic maturation of the aspartic protease plasmepsin X (PMX), which in turn is required for SUB1 cleavage. Processing of substrates downstream of the proteolytic cascade was also inhibited. ERC knockdown did not affect protein trafficking or calcium storage.\",\n      \"method\": \"Conditional knockdown (inducible knockdown system), double-mutant epistasis analysis, immunofluorescence microscopy, immunoblot for proteolytic maturation, parasitophorous vacuole membrane rupture assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal genetic epistasis with double mutants, conditional knockdown with defined molecular phenotype (inhibited PMX and SUB1 maturation), multiple orthogonal readouts in one rigorous study\",\n      \"pmids\": [\"32098818\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ERC (PfERC/PF3D7_1108600) was identified by chemical proteomics as a P. falciparum protein with high affinity for the endoperoxide structure N-346 (a carboxyamino derivative of the antimalarial N-89). ERC protein levels were decreased upon treatment of parasites with N-89 or its hydroxyl derivative N-251, as shown by proteomic expression profiling.\",\n      \"method\": \"Chemical proteomics (affinity pulldown with endoperoxide-derivatized probe N-346), proteomic expression profiling after drug treatment\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single chemical proteomics pulldown without reciprocal validation or mutagenesis; single lab, single study\",\n      \"pmids\": [\"23061985\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ERC (PF3D7_1108600) was shown to associate with the ER-resident serpentine receptor SR10 in P. falciparum by co-localization and co-immunoprecipitation assays.\",\n      \"method\": \"Co-immunoprecipitation, co-localization assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP and co-localization, single lab, no reciprocal pull-down or functional consequence of the interaction specifically mapped to ERC\",\n      \"pmids\": [\"32890576\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In P. berghei-infected mice treated with the endoperoxide N-89 transdermally, PbERC (the P. berghei ortholog of ERC/PF3D7_1108600) gene expression was suppressed relative to control. Concurrently, expression of egress-related genes plasmepsin X, subtilisin-like protease 1, and merozoite surface protein 1 was suppressed at 12 h. This is consistent with a functional role for ERC upstream of the egress proteolytic cascade, as established in P. falciparum.\",\n      \"method\": \"Quantitative real-time PCR of PbERC and egress-related gene expression after transdermal N-89 treatment in P. berghei-infected mice\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — gene expression measurement only (qRT-PCR), single study, no direct protein-level or mechanistic experiment on ERC function itself\",\n      \"pmids\": [\"39740755\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"ERC (PF3D7_1108600) is an endoplasmic reticulum-resident protein with six EF-hand calcium-binding domains and a C-terminal IDEL retention motif that is essential for asexual blood-stage growth of P. falciparum; it acts as a key early regulator of the egress proteolytic cascade by being required for the proteolytic maturation of the aspartic protease plasmepsin X, which in turn enables maturation of the subtilisin-like protease SUB1 and rupture of the parasitophorous vacuole membrane, while being dispensable for protein trafficking or calcium storage.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ERC (PF3D7_1108600) is an endoplasmic reticulum-resident calcium-binding protein of P. falciparum that functions as an essential early regulator of the parasite egress proteolytic cascade [#0, #1]. It carries six EF-hand calcium-binding domains and a C-terminal IDEL ER-retention motif; its calcium-binding activity was confirmed directly and its ER residence established by co-localization with the ER marker Pfgrp, with expression rising as parasites mature [#0]. Conditional knockdown showed ERC is required for asexual blood-stage growth and specifically for rupture of the parasitophorous vacuole membrane during egress; mechanistically, ERC is required for proteolytic maturation of the aspartic protease plasmepsin X, which in turn enables maturation of the subtilisin-like protease SUB1 and processing of downstream cascade substrates, while ERC loss does not affect protein trafficking or calcium storage [#1]. Beyond its role upstream of this proteolytic cascade, ERC has been reported to associate with the ER-resident serpentine receptor SR10 [#3], but the functional consequence of this interaction for ERC has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1997,\n      \"claim\": \"Established that PF3D7_1108600 is a genuine ER-resident calcium-binding protein, defining its subcellular niche and biochemical activity before any functional role was known.\",\n      \"evidence\": \"45Ca2+-blotting, confocal co-localization with ER marker Pfgrp, and partial protein/gene sequencing in P. falciparum asexual stages\",\n      \"pmids\": [\"9364972\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No cellular or growth phenotype tested at this stage\",\n        \"Functional purpose of calcium binding not addressed\",\n        \"Interaction partners unidentified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linked ERC to endoperoxide antimalarial action by identifying it as a high-affinity binder of an endoperoxide probe, raising the possibility it is a drug-relevant target.\",\n      \"evidence\": \"Chemical proteomics affinity pulldown with endoperoxide probe N-346 and proteomic expression profiling after N-89/N-251 treatment in P. falciparum\",\n      \"pmids\": [\"23061985\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single pulldown without reciprocal validation or mutagenesis\",\n        \"Direct binding site not mapped\",\n        \"Whether the interaction is causal for drug action untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined the essential function of ERC by placing it upstream of the egress proteolytic cascade, answering what this ER calcium-binding protein actually does for the parasite.\",\n      \"evidence\": \"Conditional knockdown, double-mutant epistasis, immunoblot of PMX and SUB1 maturation, and PVM rupture assay in P. falciparum\",\n      \"pmids\": [\"32098818\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism by which ERC promotes PMX maturation unresolved\",\n        \"Whether ERC calcium binding is required for the egress function untested\",\n        \"Direct physical link between ERC and PMX not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified a physical partner for ERC, the ER-resident serpentine receptor SR10, hinting at a protein-interaction context within the ER.\",\n      \"evidence\": \"Co-immunoprecipitation and co-localization assays in P. falciparum\",\n      \"pmids\": [\"32890576\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP without reciprocal pull-down\",\n        \"Functional consequence of the interaction for ERC not mapped\",\n        \"Relationship of SR10 binding to the egress role unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Extended the egress-cascade model to a rodent malaria system by showing endoperoxide treatment coordinately suppresses PbERC and downstream egress-gene transcripts.\",\n      \"evidence\": \"qRT-PCR of PbERC, plasmepsin X, SUB1, and MSP1 after transdermal N-89 treatment in P. berghei-infected mice\",\n      \"pmids\": [\"39740755\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Expression measurement only; no protein-level or mechanistic assay on ERC function\",\n        \"Cannot distinguish direct effect on ERC from general drug-induced stress\",\n        \"Ortholog function not independently validated by genetics in P. berghei\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular mechanism by which an ER calcium-binding protein controls proteolytic maturation of plasmepsin X, and the role of its calcium binding and SR10 interaction in that process, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural or biochemical account of how ERC enables PMX maturation\",\n        \"Contribution of the six EF-hands / calcium binding to egress function untested\",\n        \"Whether SR10 association participates in the egress pathway unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005509\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005788\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0035891\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"SR10 (ER-resident serpentine receptor; co-IP and co-localization) [#3]\",\n      \"Plasmepsin X (PMX; ERC required for its proteolytic maturation) [#1]\",\n      \"SUB1 (subtilisin-like protease matured downstream of ERC via PMX) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"Contains six EF-hand calcium-binding domains and a C-terminal IDEL ER-retention motif [#0].\",\n      \"Essential for asexual blood-stage growth and specifically required for parasitophorous vacuole membrane rupture during egress [#1].\",\n      \"Dispensable for protein trafficking and calcium storage despite its ER localization and calcium-binding activity [#1].\",\n      \"Identified as a high-affinity binder of the endoperoxide antimalarial probe N-346; ERC levels decrease upon N-89/N-251 treatment [#2].\",\n      \"In P. berghei, the PbERC ortholog transcript and egress-gene transcripts (PMX, SUB1, MSP1) are suppressed by transdermal endoperoxide N-89 treatment [#4].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1108600","name":null,"product":"endoplasmic reticulum-resident calcium binding protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0938400","name":null,"product":"endoplasmic reticulum-resident calcium binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0906200","name":null,"product":"endoplasmic reticulum-resident calcium binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ERC","evaluation":null}