{"gene":"PF3D7_0525400","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2018,"finding":"7-Helix-1 (PF3D7_0525400) accumulates in stress granules of female gametocytes of P. falciparum, where it interacts with ribonucleoprotein components CITH, DOZI, and PABP1, establishing its membership in the stress granule complex.","method":"Co-immunoprecipitation / protein interaction assays; subcellular localization by imaging","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP interactions and direct localization experiments in a single focused study with multiple orthogonal methods (interaction, localization, loss-of-function)","pmids":["30133543"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"7-Helix-1 forms a complex with the RNA-binding protein Puf2 and associates with pfs25-coding mRNA; loss of 7-Helix-1 leads to impaired Pfs25 protein synthesis, placing 7-Helix-1 in the translational regulation pathway of the female-specific antigen Pfs25.","method":"Co-immunoprecipitation/RNA pulldown; loss-of-function (knockout) parasites with protein synthesis readout (Pfs25 levels)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP interaction with Puf2, RNA association assay, and KO phenotype with defined molecular readout, single lab","pmids":["30133543"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Genetic knockout of 7-Helix-1 significantly impairs female gametogenesis and mosquito transmission; this loss-of-function phenotype is mimicked by inhibitors of translation, demonstrating that 7-Helix-1 functions in regulating protein synthesis during the gametocyte-to-gamete transition.","method":"Genetic knockout (loss-of-function) with gametogenesis and transmission phenotype; pharmacological mimicry with translation inhibitors","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype corroborated by pharmacological mimicry, single lab","pmids":["30133543"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum female gametocytes, 7-Helix-1 (PF3D7_0525400) localises to stress granules where it interacts with ribonucleoproteins (CITH, DOZI, PABP1) and the translational regulator Puf2, associates with pfs25 mRNA, and is required for translational regulation of Pfs25 and for female gametogenesis and onward mosquito transmission."},"narrative":{"mechanistic_narrative":"In Plasmodium falciparum female gametocytes, 7-Helix-1 (PF3D7_0525400) is a component of the translational regulatory machinery that governs the gametocyte-to-gamete transition [PMID:30133543]. It accumulates in stress granules, where it interacts with the ribonucleoprotein components CITH, DOZI, and PABP1, establishing its membership in the stress granule complex [PMID:30133543]. 7-Helix-1 additionally forms a complex with the RNA-binding protein Puf2 and associates with pfs25 mRNA, and its loss impairs Pfs25 protein synthesis, placing it in the translational repression/storage pathway of this female-specific antigen [PMID:30133543]. Genetic knockout impairs female gametogenesis and mosquito transmission, a phenotype mimicked by translation inhibitors, indicating that 7-Helix-1 acts through control of protein synthesis during female gamete formation [PMID:30133543]. Beyond its role in this stress-granule/mRNA-storage complex, no further biochemical or structural detail for PF3D7_0525400 has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing where 7-Helix-1 acts and with what partners it was previously unknown; localization and interaction mapping placed it in female gametocyte stress granules bound to core ribonucleoprotein components.","evidence":"Reciprocal co-immunoprecipitation and subcellular imaging in P. falciparum female gametocytes","pmids":["30133543"],"confidence":"Medium","gaps":["The stoichiometry and direct vs. bridged nature of the CITH/DOZI/PABP1 contacts are not resolved","No structural model of 7-Helix-1 or its binding interface","Whether 7-Helix-1 is required for stress granule assembly or merely resides within it is not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"The molecular target of 7-Helix-1 was unknown; linking it to Puf2 and pfs25 mRNA, with loss impairing Pfs25 synthesis, placed 7-Helix-1 in a defined translational regulation pathway for a female-specific transcript.","evidence":"Co-immunoprecipitation/RNA pulldown plus knockout parasites scored for Pfs25 protein levels","pmids":["30133543"],"confidence":"Medium","gaps":["Whether 7-Helix-1 binds pfs25 mRNA directly or via Puf2/RNP partners is unresolved","Whether regulation extends beyond pfs25 to other stored female transcripts is untested","The mechanism by which 7-Helix-1 represses or licenses translation is not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"The cellular consequence of losing 7-Helix-1 was unknown; knockout with pharmacological mimicry established that it functions in protein-synthesis control required for female gametogenesis and onward transmission.","evidence":"Genetic knockout with gametogenesis and mosquito-transmission phenotype, corroborated by translation-inhibitor mimicry in P. falciparum","pmids":["30133543"],"confidence":"Medium","gaps":["The single-lab knockout phenotype awaits independent confirmation","Whether the transmission defect is fully attributable to Pfs25 loss or reflects broader translational dysregulation is unclear","Male gametocyte requirement, if any, is not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether 7-Helix-1 has an intrinsic biochemical activity (e.g. direct RNA binding or a scaffolding function via its 7-helix architecture) versus a purely structural role within the stress-granule RNP remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No reconstituted biochemistry defining a direct molecular activity","No structural characterization of the 7-helix fold in this protein","Full mRNA regulon and interactome beyond the reported partners are uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Stress granule ribonucleoprotein complex (with CITH, DOZI, PABP1)","Puf2-containing mRNA regulatory complex associated with pfs25 mRNA"],"partners":["CITH","DOZI","PABP1","PUF2"],"other_free_text":["Associates with pfs25-coding mRNA and is required for Pfs25 protein synthesis in female gametocytes.","Knockout impairs female gametogenesis and mosquito transmission in P. falciparum; phenotype mimicked by translation inhibitors.","Corpus establishes only its membership in a female-gametocyte stress-granule/translational-regulation complex; no independent biochemical or structural characterization of PF3D7_0525400 is present."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30133543","id":"PMC_30133543","title":"A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum.","date":"2018","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/30133543","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3441,"output_tokens":884,"usd":0.011791,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5526,"output_tokens":2144,"usd":0.040615,"stage2_stop_reason":"end_turn"},"total_usd":0.052406,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"7-Helix-1 (PF3D7_0525400) accumulates in stress granules of female gametocytes of P. falciparum, where it interacts with ribonucleoprotein components CITH, DOZI, and PABP1, establishing its membership in the stress granule complex.\",\n      \"method\": \"Co-immunoprecipitation / protein interaction assays; subcellular localization by imaging\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP interactions and direct localization experiments in a single focused study with multiple orthogonal methods (interaction, localization, loss-of-function)\",\n      \"pmids\": [\"30133543\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"7-Helix-1 forms a complex with the RNA-binding protein Puf2 and associates with pfs25-coding mRNA; loss of 7-Helix-1 leads to impaired Pfs25 protein synthesis, placing 7-Helix-1 in the translational regulation pathway of the female-specific antigen Pfs25.\",\n      \"method\": \"Co-immunoprecipitation/RNA pulldown; loss-of-function (knockout) parasites with protein synthesis readout (Pfs25 levels)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP interaction with Puf2, RNA association assay, and KO phenotype with defined molecular readout, single lab\",\n      \"pmids\": [\"30133543\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Genetic knockout of 7-Helix-1 significantly impairs female gametogenesis and mosquito transmission; this loss-of-function phenotype is mimicked by inhibitors of translation, demonstrating that 7-Helix-1 functions in regulating protein synthesis during the gametocyte-to-gamete transition.\",\n      \"method\": \"Genetic knockout (loss-of-function) with gametogenesis and transmission phenotype; pharmacological mimicry with translation inhibitors\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype corroborated by pharmacological mimicry, single lab\",\n      \"pmids\": [\"30133543\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"In P. falciparum female gametocytes, 7-Helix-1 (PF3D7_0525400) localises to stress granules where it interacts with ribonucleoproteins (CITH, DOZI, PABP1) and the translational regulator Puf2, associates with pfs25 mRNA, and is required for translational regulation of Pfs25 and for female gametogenesis and onward mosquito transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"In Plasmodium falciparum female gametocytes, 7-Helix-1 (PF3D7_0525400) is a component of the translational regulatory machinery that governs the gametocyte-to-gamete transition [#0, #2]. It accumulates in stress granules, where it interacts with the ribonucleoprotein components CITH, DOZI, and PABP1, establishing its membership in the stress granule complex [#0]. 7-Helix-1 additionally forms a complex with the RNA-binding protein Puf2 and associates with pfs25 mRNA, and its loss impairs Pfs25 protein synthesis, placing it in the translational repression/storage pathway of this female-specific antigen [#1]. Genetic knockout impairs female gametogenesis and mosquito transmission, a phenotype mimicked by translation inhibitors, indicating that 7-Helix-1 acts through control of protein synthesis during female gamete formation [#2]. Beyond its role in this stress-granule/mRNA-storage complex, no further biochemical or structural detail for PF3D7_0525400 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing where 7-Helix-1 acts and with what partners it was previously unknown; localization and interaction mapping placed it in female gametocyte stress granules bound to core ribonucleoprotein components.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation and subcellular imaging in P. falciparum female gametocytes\",\n      \"pmids\": [\"30133543\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The stoichiometry and direct vs. bridged nature of the CITH/DOZI/PABP1 contacts are not resolved\",\n        \"No structural model of 7-Helix-1 or its binding interface\",\n        \"Whether 7-Helix-1 is required for stress granule assembly or merely resides within it is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The molecular target of 7-Helix-1 was unknown; linking it to Puf2 and pfs25 mRNA, with loss impairing Pfs25 synthesis, placed 7-Helix-1 in a defined translational regulation pathway for a female-specific transcript.\",\n      \"evidence\": \"Co-immunoprecipitation/RNA pulldown plus knockout parasites scored for Pfs25 protein levels\",\n      \"pmids\": [\"30133543\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether 7-Helix-1 binds pfs25 mRNA directly or via Puf2/RNP partners is unresolved\",\n        \"Whether regulation extends beyond pfs25 to other stored female transcripts is untested\",\n        \"The mechanism by which 7-Helix-1 represses or licenses translation is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"The cellular consequence of losing 7-Helix-1 was unknown; knockout with pharmacological mimicry established that it functions in protein-synthesis control required for female gametogenesis and onward transmission.\",\n      \"evidence\": \"Genetic knockout with gametogenesis and mosquito-transmission phenotype, corroborated by translation-inhibitor mimicry in P. falciparum\",\n      \"pmids\": [\"30133543\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The single-lab knockout phenotype awaits independent confirmation\",\n        \"Whether the transmission defect is fully attributable to Pfs25 loss or reflects broader translational dysregulation is unclear\",\n        \"Male gametocyte requirement, if any, is not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether 7-Helix-1 has an intrinsic biochemical activity (e.g. direct RNA binding or a scaffolding function via its 7-helix architecture) versus a purely structural role within the stress-granule RNP remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reconstituted biochemistry defining a direct molecular activity\",\n        \"No structural characterization of the 7-helix fold in this protein\",\n        \"Full mRNA regulon and interactome beyond the reported partners are uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0010494\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006417\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0007276\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"Stress granule ribonucleoprotein complex (with CITH, DOZI, PABP1)\",\n      \"Puf2-containing mRNA regulatory complex associated with pfs25 mRNA\"\n    ],\n    \"partners\": [\n      \"CITH\",\n      \"DOZI\",\n      \"PABP1\",\n      \"Puf2\"\n    ],\n    \"other_free_text\": [\n      \"Associates with pfs25-coding mRNA and is required for Pfs25 protein synthesis in female gametocytes.\",\n      \"Knockout impairs female gametogenesis and mosquito transmission in P. falciparum; phenotype mimicked by translation inhibitors.\",\n      \"Corpus establishes only its membership in a female-gametocyte stress-granule/translational-regulation complex; no independent biochemical or structural characterization of PF3D7_0525400 is present.\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0525400","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0320800, PF3D7_0417100, PF3D7_1224300). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0525400","name":null,"product":"7-helix-1 protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1240200","name":null,"product":"7-helix-1 protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1007400","name":null,"product":"7-helix-1 protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}