{"gene":"PF3D7_0934100","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2015,"finding":"P. falciparum XPD (PF3D7_0934100) displays ssDNA-dependent ATPase activity and 5'-to-3' DNA helicase activity, as characterized using recombinant PfXPD protein and its fragments expressed and purified in vitro.","method":"In vitro enzymatic assay with recombinant protein (ssDNA-dependent ATPase assay and DNA helicase translocation assay)","journal":"Protoplasma","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro biochemical assay establishing enzymatic activity, single lab, single study","pmids":["25708921"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"finding":"P. falciparum XPD (PF3D7_0934100) physically interacts with p44 (another TFIIH subunit), as demonstrated by co-localization in the nucleus and direct protein–protein interaction studies using specific antibodies and recombinant proteins, consistent with their membership in a TFIIH-like complex.","method":"Co-localization by immunofluorescence with specific antibodies; protein–protein interaction assay with recombinant PfXPD and Pfp44","journal":"Protoplasma","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-localization plus interaction assay, two complementary methods, single lab","pmids":["25708921"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"finding":"P. falciparum XPD (PF3D7_0934100) localizes to the nucleus during intraerythrocytic blood stages, but during trophozoite and schizont stages both PfXPD and its partner Pfp44 additionally display a distinct cytoplasmic distribution, suggesting functions beyond nuclear transcription/NER at these stages.","method":"Subcellular localization by immunofluorescence with specific antibodies across intraerythrocytic developmental stages","journal":"Protoplasma","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single imaging method, cytoplasmic localization noted but functional consequence not experimentally established","pmids":["25708921"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"finding":"P. falciparum XPD (PF3D7_0934100) is expressed throughout all intraerythrocytic blood stages (rings, trophozoites, schizonts), as detected by stage-specific immunoblotting with specific antibodies; two high molecular weight forms of its partner p44 were also detected.","method":"Stage-specific expression analysis by immunoblotting with specific antibodies","journal":"Protoplasma","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method, expression profiling without mechanistic follow-up","pmids":["25708921"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"finding":"In silico structural modeling of P. falciparum XPD (PF3D7_0934100) as part of a genome-wide NER component analysis indicates its structure is significantly conserved relative to human XPD, supporting its role as a NER component; no functional biochemical experiments were performed in this study.","method":"Bioinformatics: sequence homology search and structural modeling","journal":"DNA repair","confidence":"Low","confidence_rationale":"Tier 4 / Weak — purely computational prediction, no experimental validation","pmids":["25757193"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum XPD (PF3D7_0934100) is a nuclear helicase subunit of TFIIH that possesses ssDNA-dependent ATPase and 5'-to-3' DNA helicase activities in vitro, physically interacts with the TFIIH subunit p44 to form a complex in the nucleus, and is expressed throughout intraerythrocytic blood stages with an additional cytoplasmic distribution during trophozoite and schizont stages whose functional significance is not yet established."},"narrative":{"mechanistic_narrative":"P. falciparum XPD (PF3D7_0934100) is a DNA helicase subunit of a TFIIH-like complex in the malaria parasite [PMID:25708921]. Recombinant PfXPD possesses ssDNA-dependent ATPase activity and 5'-to-3' DNA helicase activity in vitro, establishing it as a catalytically active enzyme [PMID:25708921]. It physically interacts with and co-localizes in the nucleus with the TFIIH subunit p44, consistent with assembly into a TFIIH-like complex [PMID:25708921]. XPD is expressed across all intraerythrocytic blood stages, and while it is nuclear, during trophozoite and schizont stages both XPD and p44 additionally display a cytoplasmic distribution whose functional significance has not been established [PMID:25708921]. Beyond its in vitro enzymatic characterization and its interaction with p44, no downstream role in transcription or nucleotide excision repair has been experimentally demonstrated for PF3D7_0934100 in the available corpus.","teleology":[{"year":2015,"claim":"To determine whether the Plasmodium XPD gene product is a functional enzyme, its intrinsic catalytic activities were tested, establishing PfXPD as a bona fide ATP-driven DNA helicase.","evidence":"In vitro ssDNA-dependent ATPase and 5'-to-3' DNA helicase assays with recombinant PfXPD protein and fragments","pmids":["25708921"],"confidence":"Medium","gaps":["No physiological substrate or in vivo activity demonstrated","Helicase polarity and processivity characterized only in vitro with recombinant protein","No structural basis for the ATPase/helicase activity resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"claim":"To place PfXPD within a molecular assembly, its physical association with another TFIIH subunit was tested, establishing that XPD partners with p44 in a TFIIH-like complex.","evidence":"Nuclear co-localization by immunofluorescence and direct protein-protein interaction assay using recombinant PfXPD and Pfp44 with specific antibodies","pmids":["25708921"],"confidence":"Medium","gaps":["Full TFIIH complex composition and stoichiometry in P. falciparum not defined","Functional consequence of the XPD-p44 interaction (e.g. helicase regulation) not tested","Interaction mapped without reciprocal or endogenous complex isolation"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"claim":"To assess when and where XPD acts, its stage-specific expression and subcellular distribution were profiled, revealing constitutive blood-stage expression and an unexpected cytoplasmic pool alongside p44 at later stages.","evidence":"Stage-specific immunoblotting and immunofluorescence localization across rings, trophozoites, and schizonts","pmids":["25708921"],"confidence":"Low","gaps":["Functional significance of trophozoite/schizont cytoplasmic localization not experimentally established","Single imaging method, single lab","No genetic perturbation to link expression pattern to a biological role"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2015,"claim":"To predict whether PfXPD contributes to DNA repair, its structure was computationally compared to human XPD, supporting conservation consistent with a nucleotide excision repair role.","evidence":"Bioinformatic sequence homology and structural modeling within a genome-wide NER component survey; no biochemical experiments","pmids":["25757193"],"confidence":"Low","gaps":["Purely computational prediction with no experimental validation","No demonstrated participation of PfXPD in NER in the parasite","Conservation modeling does not establish in vivo function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PfXPD functions in nucleotide excision repair or basal transcription in vivo, and what its cytoplasmic pool does at trophozoite and schizont stages, remains unresolved.","evidence":"No genetic knockout, conditional knockdown, or in vivo functional assay reported in the corpus","pmids":[],"confidence":"Low","gaps":["No loss-of-function/essentiality data for PF3D7_0934100","No demonstrated substrate or pathway assignment in vivo","Cytoplasmic function undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TFIIH-like transcription factor complex (XPD-p44)"],"partners":["P44 (TFIIH SUBUNIT)"],"other_free_text":["Recombinant PfXPD displays ssDNA-dependent ATPase and 5'-to-3' DNA helicase activity in vitro [#0]","Expressed throughout ring, trophozoite, and schizont intraerythrocytic stages [#3]","Cytoplasmic distribution of XPD and p44 at trophozoite/schizont stages of undetermined function [#2]","In silico structural conservation with human XPD supports a predicted NER role; not experimentally validated [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16042788","id":"PMC_16042788","title":"Prediction of the general transcription factors associated with RNA polymerase II in Plasmodium falciparum: conserved features and differences relative to other eukaryotes.","date":"2005","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/16042788","citation_count":101,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TFIIH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25757193","id":"PMC_25757193","title":"Comparative insight into nucleotide excision repair components of Plasmodium falciparum.","date":"2015","source":"DNA repair","url":"https://pubmed.ncbi.nlm.nih.gov/25757193","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TFIIH"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25708921","id":"PMC_25708921","title":"Plasmodium falciparum XPD translocates in 5' to 3' direction, is expressed throughout the blood stages, and interacts with p44.","date":"2015","source":"Protoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/25708921","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["XPD","TFIIH","PfXPD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4477,"output_tokens":1316,"usd":0.016585,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6187,"output_tokens":2421,"usd":0.04573,"stage2_stop_reason":"end_turn"},"total_usd":0.062315,"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\": 2015,\n      \"finding\": \"P. falciparum XPD (PF3D7_0934100) displays ssDNA-dependent ATPase activity and 5'-to-3' DNA helicase activity, as characterized using recombinant PfXPD protein and its fragments expressed and purified in vitro.\",\n      \"method\": \"In vitro enzymatic assay with recombinant protein (ssDNA-dependent ATPase assay and DNA helicase translocation assay)\",\n      \"journal\": \"Protoplasma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro biochemical assay establishing enzymatic activity, single lab, single study\",\n      \"pmids\": [\"25708921\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"P. falciparum XPD (PF3D7_0934100) physically interacts with p44 (another TFIIH subunit), as demonstrated by co-localization in the nucleus and direct protein–protein interaction studies using specific antibodies and recombinant proteins, consistent with their membership in a TFIIH-like complex.\",\n      \"method\": \"Co-localization by immunofluorescence with specific antibodies; protein–protein interaction assay with recombinant PfXPD and Pfp44\",\n      \"journal\": \"Protoplasma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-localization plus interaction assay, two complementary methods, single lab\",\n      \"pmids\": [\"25708921\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"P. falciparum XPD (PF3D7_0934100) localizes to the nucleus during intraerythrocytic blood stages, but during trophozoite and schizont stages both PfXPD and its partner Pfp44 additionally display a distinct cytoplasmic distribution, suggesting functions beyond nuclear transcription/NER at these stages.\",\n      \"method\": \"Subcellular localization by immunofluorescence with specific antibodies across intraerythrocytic developmental stages\",\n      \"journal\": \"Protoplasma\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single imaging method, cytoplasmic localization noted but functional consequence not experimentally established\",\n      \"pmids\": [\"25708921\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"P. falciparum XPD (PF3D7_0934100) is expressed throughout all intraerythrocytic blood stages (rings, trophozoites, schizonts), as detected by stage-specific immunoblotting with specific antibodies; two high molecular weight forms of its partner p44 were also detected.\",\n      \"method\": \"Stage-specific expression analysis by immunoblotting with specific antibodies\",\n      \"journal\": \"Protoplasma\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method, expression profiling without mechanistic follow-up\",\n      \"pmids\": [\"25708921\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In silico structural modeling of P. falciparum XPD (PF3D7_0934100) as part of a genome-wide NER component analysis indicates its structure is significantly conserved relative to human XPD, supporting its role as a NER component; no functional biochemical experiments were performed in this study.\",\n      \"method\": \"Bioinformatics: sequence homology search and structural modeling\",\n      \"journal\": \"DNA repair\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — purely computational prediction, no experimental validation\",\n      \"pmids\": [\"25757193\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum XPD (PF3D7_0934100) is a nuclear helicase subunit of TFIIH that possesses ssDNA-dependent ATPase and 5'-to-3' DNA helicase activities in vitro, physically interacts with the TFIIH subunit p44 to form a complex in the nucleus, and is expressed throughout intraerythrocytic blood stages with an additional cytoplasmic distribution during trophozoite and schizont stages whose functional significance is not yet established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"P. falciparum XPD (PF3D7_0934100) is a DNA helicase subunit of a TFIIH-like complex in the malaria parasite [#0, #1]. Recombinant PfXPD possesses ssDNA-dependent ATPase activity and 5'-to-3' DNA helicase activity in vitro, establishing it as a catalytically active enzyme [#0]. It physically interacts with and co-localizes in the nucleus with the TFIIH subunit p44, consistent with assembly into a TFIIH-like complex [#1]. XPD is expressed across all intraerythrocytic blood stages, and while it is nuclear, during trophozoite and schizont stages both XPD and p44 additionally display a cytoplasmic distribution whose functional significance has not been established [#2, #3]. Beyond its in vitro enzymatic characterization and its interaction with p44, no downstream role in transcription or nucleotide excision repair has been experimentally demonstrated for PF3D7_0934100 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"To determine whether the Plasmodium XPD gene product is a functional enzyme, its intrinsic catalytic activities were tested, establishing PfXPD as a bona fide ATP-driven DNA helicase.\",\n      \"evidence\": \"In vitro ssDNA-dependent ATPase and 5'-to-3' DNA helicase assays with recombinant PfXPD protein and fragments\",\n      \"pmids\": [\"25708921\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No physiological substrate or in vivo activity demonstrated\",\n        \"Helicase polarity and processivity characterized only in vitro with recombinant protein\",\n        \"No structural basis for the ATPase/helicase activity resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To place PfXPD within a molecular assembly, its physical association with another TFIIH subunit was tested, establishing that XPD partners with p44 in a TFIIH-like complex.\",\n      \"evidence\": \"Nuclear co-localization by immunofluorescence and direct protein-protein interaction assay using recombinant PfXPD and Pfp44 with specific antibodies\",\n      \"pmids\": [\"25708921\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Full TFIIH complex composition and stoichiometry in P. falciparum not defined\",\n        \"Functional consequence of the XPD-p44 interaction (e.g. helicase regulation) not tested\",\n        \"Interaction mapped without reciprocal or endogenous complex isolation\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To assess when and where XPD acts, its stage-specific expression and subcellular distribution were profiled, revealing constitutive blood-stage expression and an unexpected cytoplasmic pool alongside p44 at later stages.\",\n      \"evidence\": \"Stage-specific immunoblotting and immunofluorescence localization across rings, trophozoites, and schizonts\",\n      \"pmids\": [\"25708921\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Functional significance of trophozoite/schizont cytoplasmic localization not experimentally established\",\n        \"Single imaging method, single lab\",\n        \"No genetic perturbation to link expression pattern to a biological role\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To predict whether PfXPD contributes to DNA repair, its structure was computationally compared to human XPD, supporting conservation consistent with a nucleotide excision repair role.\",\n      \"evidence\": \"Bioinformatic sequence homology and structural modeling within a genome-wide NER component survey; no biochemical experiments\",\n      \"pmids\": [\"25757193\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational prediction with no experimental validation\",\n        \"No demonstrated participation of PfXPD in NER in the parasite\",\n        \"Conservation modeling does not establish in vivo function\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PfXPD functions in nucleotide excision repair or basal transcription in vivo, and what its cytoplasmic pool does at trophozoite and schizont stages, remains unresolved.\",\n      \"evidence\": \"No genetic knockout, conditional knockdown, or in vivo functional assay reported in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function/essentiality data for PF3D7_0934100\",\n        \"No demonstrated substrate or pathway assignment in vivo\",\n        \"Cytoplasmic function undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003678\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0043139\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008026\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0043142\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005675\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006289\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0006367\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"TFIIH-like transcription factor complex (XPD-p44)\"\n    ],\n    \"partners\": [\n      \"p44 (TFIIH subunit)\"\n    ],\n    \"other_free_text\": [\n      \"Recombinant PfXPD displays ssDNA-dependent ATPase and 5'-to-3' DNA helicase activity in vitro [#0]\",\n      \"Expressed throughout ring, trophozoite, and schizont intraerythrocytic stages [#3]\",\n      \"Cytoplasmic distribution of XPD and p44 at trophozoite/schizont stages of undetermined function [#2]\",\n      \"In silico structural conservation with human XPD supports a predicted NER role; not experimentally validated [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0934100","name":null,"product":"TFIIH basal transcription factor complex helicase XPD subunit","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0834900","name":null,"product":"TFIIH basal transcription factor complex helicase XPD subunit, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0732800","name":null,"product":"TFIIH basal transcription factor complex helicase XPD subunit, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"XPD","evaluation":null}