{"gene":"PF3D7_1330500","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2026,"finding":"PF3D7_1330500 (a CTLH domain-containing protein) is a component of the PfGID E3 ubiquitin ligase complex in P. falciparum; deletion of PfGID complex components (including this subunit) causes arrest in gametocyte development and loss of transmission to mosquitoes, establishing its role in the complex's function.","method":"Genetic deletion (loss-of-function) with phenotypic readout (gametocyte developmental arrest, loss of mosquito transmission); complex membership inferred from study of PfGID complex components","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined cellular phenotype (developmental arrest, transmission loss), single lab, but the abstract does not individually distinguish PF3D7_1330500's contribution from that of other complex subunits","pmids":["41986327"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"The PfGID E3 ubiquitin ligase complex (of which PF3D7_1330500 is a component) ubiquitinates two substrates: GD1 (a ZFP36 family RNA-binding protein) and PfDPL (a cryptochrome-like protein), fine-tuning their protein levels to govern gametocyte cell fate programmes.","method":"Targeted ubiquitination assay and substrate identification within the PfGID complex; genetic deletion of complex components with substrate protein-level readout","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — substrate ubiquitination demonstrated within the complex context, single lab; PF3D7_1330500's individual catalytic contribution is not distinguished from other complex members in the abstract","pmids":["41986327"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1330500 is a CTLH domain-containing subunit of the PfGID E3 ubiquitin ligase complex in P. falciparum; the complex ubiquitinates the RNA-binding protein GD1 and the cryptochrome-like protein PfDPL to regulate their protein levels and control gametocyte cell fate programmes, with deletion of complex components causing gametocyte developmental arrest and loss of mosquito transmission."},"narrative":{"mechanistic_narrative":"PF3D7_1330500 is a CTLH domain-containing subunit of the PfGID E3 ubiquitin ligase complex in Plasmodium falciparum, where it contributes to a complex that governs gametocyte developmental progression [PMID:41986327]. Genetic deletion of PfGID complex components, including this subunit, arrests gametocyte development and abolishes transmission to mosquitoes, establishing a role for the complex in the sexual cell-fate programme [PMID:41986327]. Within this complex, the PfGID E3 ligase ubiquitinates the ZFP36-family RNA-binding protein GD1 and the cryptochrome-like protein PfDPL to fine-tune their protein levels [PMID:41986327]. Beyond its membership in the PfGID complex and the shared loss-of-function phenotype, the individual biochemical contribution of PF3D7_1330500 — as distinct from other complex subunits — has not been separately characterized in the available corpus.","teleology":[{"year":2026,"claim":"It was unknown what cellular role PF3D7_1330500 plays; genetic deletion placed it as a functional component of the PfGID E3 ubiquitin ligase complex required for gametocyte development and mosquito transmission.","evidence":"Genetic deletion (loss-of-function) with phenotypic readout of gametocyte developmental arrest and loss of transmission, in the context of studying PfGID complex components","pmids":["41986327"],"confidence":"Medium","gaps":["The abstract does not distinguish PF3D7_1330500's individual contribution from that of other PfGID subunits","No structural or biochemical assignment of a specific role within the complex for this subunit","Whether deletion of this subunit alone reproduces the phenotype is not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"The substrates and downstream logic of the complex were unknown; identification of GD1 and PfDPL as ubiquitination targets linked the PfGID complex to control of gametocyte cell-fate programmes via regulated protein turnover.","evidence":"Targeted ubiquitination and substrate identification within the PfGID complex, with substrate protein-level readout following genetic deletion of complex components","pmids":["41986327"],"confidence":"Medium","gaps":["PF3D7_1330500's individual catalytic or substrate-recognition contribution is not distinguished from other complex members","It is not established whether PF3D7_1330500 directly contacts GD1 or PfDPL","The mechanism by which ubiquitination of these substrates rewires cell fate is not detailed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular function of PF3D7_1330500 within the PfGID complex — its structural placement, whether it confers substrate specificity, and its individual requirement — remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No subunit-resolved biochemistry isolating PF3D7_1330500's role","No structural model of the CTLH subunit within PfGID","No direct binding data between PF3D7_1330500 and identified substrates"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfGID E3 ubiquitin ligase complex"],"partners":["GD1 (ZFP36-FAMILY RNA-BINDING PROTEIN; SUBSTRATE OF THE PFGID COMPLEX)","PFDPL (CRYPTOCHROME-LIKE PROTEIN; SUBSTRATE OF THE PFGID COMPLEX)"],"other_free_text":["PF3D7_1330500 is a CTLH domain-containing subunit of the PfGID complex; deletion of PfGID components arrests gametocyte development and abolishes mosquito transmission [#0].","The individual contribution of PF3D7_1330500 relative to other PfGID subunits is not distinguished in the available corpus [#0, #1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"41986327","id":"PMC_41986327","title":"GID/CTLH E3 ligase complex control cell fate programs for sexual development of Plasmodium falciparum.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41986327","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CTLH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3323,"output_tokens":698,"usd":0.010219,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5270,"output_tokens":1661,"usd":0.033938,"stage2_stop_reason":"end_turn"},"total_usd":0.044157,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2026,\n      \"finding\": \"PF3D7_1330500 (a CTLH domain-containing protein) is a component of the PfGID E3 ubiquitin ligase complex in P. falciparum; deletion of PfGID complex components (including this subunit) causes arrest in gametocyte development and loss of transmission to mosquitoes, establishing its role in the complex's function.\",\n      \"method\": \"Genetic deletion (loss-of-function) with phenotypic readout (gametocyte developmental arrest, loss of mosquito transmission); complex membership inferred from study of PfGID complex components\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined cellular phenotype (developmental arrest, transmission loss), single lab, but the abstract does not individually distinguish PF3D7_1330500's contribution from that of other complex subunits\",\n      \"pmids\": [\"41986327\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The PfGID E3 ubiquitin ligase complex (of which PF3D7_1330500 is a component) ubiquitinates two substrates: GD1 (a ZFP36 family RNA-binding protein) and PfDPL (a cryptochrome-like protein), fine-tuning their protein levels to govern gametocyte cell fate programmes.\",\n      \"method\": \"Targeted ubiquitination assay and substrate identification within the PfGID complex; genetic deletion of complex components with substrate protein-level readout\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — substrate ubiquitination demonstrated within the complex context, single lab; PF3D7_1330500's individual catalytic contribution is not distinguished from other complex members in the abstract\",\n      \"pmids\": [\"41986327\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1330500 is a CTLH domain-containing subunit of the PfGID E3 ubiquitin ligase complex in P. falciparum; the complex ubiquitinates the RNA-binding protein GD1 and the cryptochrome-like protein PfDPL to regulate their protein levels and control gametocyte cell fate programmes, with deletion of complex components causing gametocyte developmental arrest and loss of mosquito transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1330500 is a CTLH domain-containing subunit of the PfGID E3 ubiquitin ligase complex in Plasmodium falciparum, where it contributes to a complex that governs gametocyte developmental progression [#0]. Genetic deletion of PfGID complex components, including this subunit, arrests gametocyte development and abolishes transmission to mosquitoes, establishing a role for the complex in the sexual cell-fate programme [#0]. Within this complex, the PfGID E3 ligase ubiquitinates the ZFP36-family RNA-binding protein GD1 and the cryptochrome-like protein PfDPL to fine-tune their protein levels [#1]. Beyond its membership in the PfGID complex and the shared loss-of-function phenotype, the individual biochemical contribution of PF3D7_1330500 — as distinct from other complex subunits — has not been separately characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2026,\n      \"claim\": \"It was unknown what cellular role PF3D7_1330500 plays; genetic deletion placed it as a functional component of the PfGID E3 ubiquitin ligase complex required for gametocyte development and mosquito transmission.\",\n      \"evidence\": \"Genetic deletion (loss-of-function) with phenotypic readout of gametocyte developmental arrest and loss of transmission, in the context of studying PfGID complex components\",\n      \"pmids\": [\"41986327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The abstract does not distinguish PF3D7_1330500's individual contribution from that of other PfGID subunits\",\n        \"No structural or biochemical assignment of a specific role within the complex for this subunit\",\n        \"Whether deletion of this subunit alone reproduces the phenotype is not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"The substrates and downstream logic of the complex were unknown; identification of GD1 and PfDPL as ubiquitination targets linked the PfGID complex to control of gametocyte cell-fate programmes via regulated protein turnover.\",\n      \"evidence\": \"Targeted ubiquitination and substrate identification within the PfGID complex, with substrate protein-level readout following genetic deletion of complex components\",\n      \"pmids\": [\"41986327\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"PF3D7_1330500's individual catalytic or substrate-recognition contribution is not distinguished from other complex members\",\n        \"It is not established whether PF3D7_1330500 directly contacts GD1 or PfDPL\",\n        \"The mechanism by which ubiquitination of these substrates rewires cell fate is not detailed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function of PF3D7_1330500 within the PfGID complex — its structural placement, whether it confers substrate specificity, and its individual requirement — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No subunit-resolved biochemistry isolating PF3D7_1330500's role\",\n        \"No structural model of the CTLH subunit within PfGID\",\n        \"No direct binding data between PF3D7_1330500 and identified substrates\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0061630\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016567\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0043934\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"PfGID E3 ubiquitin ligase complex\"\n    ],\n    \"partners\": [\n      \"GD1 (ZFP36-family RNA-binding protein; substrate of the PfGID complex)\",\n      \"PfDPL (cryptochrome-like protein; substrate of the PfGID complex)\"\n    ],\n    \"other_free_text\": [\n      \"PF3D7_1330500 is a CTLH domain-containing subunit of the PfGID complex; deletion of PfGID components arrests gametocyte development and abolishes mosquito transmission [#0].\",\n      \"The individual contribution of PF3D7_1330500 relative to other PfGID subunits is not distinguished in the available corpus [#0, #1].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1330500","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_0927200). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1330500","name":null,"product":"CTLH domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1345500","name":null,"product":"CTLH domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1269900","name":null,"product":"CTLH domain-containing protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}