{"gene":"PF3D7_1318800","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2007,"finding":"Bioinformatics analysis identified a homologue of SEC63 (a component of the Sec translocation complex) in the P. falciparum genome, placing PF3D7_1318800 as a putative member of the Sec61αβγ/Sec62/Sec63 translocation machinery involved in co- and post-translational protein translocation into the ER.","method":"Bioinformatics/comparative genomics","journal":"Archives of biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation performed","pmids":["17919451"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"PF3D7_1318800 (referred to as PfSec63) was proposed to be a membrane-bound PfHSP40 co-chaperone that works together with the ER-resident PfHsp70-2 (BiP homologue) and the PfSec61 translocon complex to mediate protein secretion through the ER secretory pathway.","method":"Literature review citing in vitro chaperone assays and pathway analysis of Sec61 complex components","journal":"Frontiers in molecular biosciences","confidence":"Low","confidence_rationale":"Tier 4 / Weak — inference from comparative analysis and prior computational work; no direct experiment on PF3D7_1318800 reported in this abstract","pmids":["26167469"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"In silico molecular docking identified PF3D7_1318800 (PfSec63) as a J-domain protein partner of PfHsp70-2 within the ER, and the PfHsp70-2–PfSec63 complex was used as a target for virtual screening of the Pandemic Response Box drug repurposing library; compounds zoliflodacin and itraconazole were identified as potential stabilizers of this complex, while ezetimibe and a benzo-diazepinone bound preferentially to the J domain of PfSec63.","method":"Molecular docking and molecular dynamics simulation (in silico)","journal":"Frontiers in molecular biosciences","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only; no biochemical or cell-based validation of the PfHsp70-2–PfSec63 interaction or compound effects reported in this abstract","pmids":["37621993"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"PF3D7_1318800 (annotated as PF13_0102, the P. falciparum Sec63 homologue) is a transmembrane ER HSP40 involved in translocation of signal-peptide-containing proteins into the ER; its expression is up-regulated in clinical isolate cluster 2 (active growth/glycolysis state), and interactome network analysis identified two hypothetical protein interactors (MAL8P1.153 and PFI1780w) as partners in the parasite chaperone network.","method":"Expression profiling of clinical isolates combined with cytoscape-based chaperone interactome network construction","journal":"Malaria journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, expression-based network inference; interactors are predicted not experimentally validated by Co-IP or pulldown","pmids":["20719001"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PF3D7_1318800 (Sec63) was described as an auxiliary protein associated with specialized Sec61 translocation channels in the P. falciparum ER that are used specifically for translocation of PEXEL-containing exported proteins (in contrast to canonical Sec61 channels used for PNEP proteins), with plasmepsin V co-associated at these specialized channels.","method":"Review of published genetic and biochemical data on Sec translocon composition","journal":"Life (Basel, Switzerland)","confidence":"Low","confidence_rationale":"Tier 4 / Weak — review-level description citing prior work; no direct experiment on PF3D7_1318800 reported in this abstract","pmids":["34440567"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"In P. knowlesi, PKNH_1419600 (82% sequence identity to PfSec63/PF3D7_1318800) is proposed to be the orthologous ER membrane-bound J-domain protein that activates the ER-lumenal PkHSP70 (PKNH_0715900, homologue of PfHSP70-2/BiP) in the context of protein translocation into the ER, consistent with the established human Sec63–BiP functional relationship.","method":"Comparative genomics and sequence identity analysis (bioinformatics)","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/comparative analysis only; speculative extrapolation from P. falciparum and human data, no experiments in P. knowlesi reported","pmids":["39596368"],"is_preprint":false,"attribution":[{"species":"Plasmodium knowlesi","strain":""}]}],"current_model":"PF3D7_1318800 (PfSec63) is a putative transmembrane ER-resident J-domain protein (HSP40 co-chaperone) that is proposed, based primarily on bioinformatics and in silico analyses, to associate with the PfSec61 translocon and to activate the ER-lumenal chaperone PfHsp70-2 (BiP) during co- and post-translational protein translocation into the ER, including translocation of PEXEL-containing exported proteins; no direct biochemical or structural experiments on PF3D7_1318800 itself have been reported in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1318800 (PfSec63) is a putative transmembrane ER-resident HSP40/J-domain co-chaperone assigned to the Sec-family protein translocation machinery of Plasmodium falciparum on the basis of bioinformatic and comparative-genomics analyses [PMID:17919451, PMID:26167469]. Within this framework it is placed alongside the PfSec61 translocon and is proposed to function together with the ER-lumenal chaperone PfHsp70-2 (a BiP homologue) to drive co- and post-translational translocation of signal-peptide-containing proteins into the ER [PMID:26167469, PMID:20719001]. It has additionally been described as an auxiliary component of specialized Sec61 channels dedicated to translocation of PEXEL-containing exported proteins, where plasmepsin V is co-associated [PMID:34440567]. Its role as a J-domain activator of PfHsp70-2 has been modeled in silico, and the PfHsp70-2–PfSec63 complex has served as a virtual-screening target [PMID:37621993]. No direct biochemical, genetic, or structural experiment on PF3D7_1318800 itself is present in the available corpus; every claim above rests on computational prediction, expression-based network inference, or review-level extrapolation, and the two candidate interactors (MAL8P1.153 and PFI1780w) reported for it are predicted rather than experimentally validated [PMID:20719001].","teleology":[{"year":2007,"claim":"Establishing whether P. falciparum possesses a Sec63 orthologue was the first step in defining its ER translocation machinery; a genome-wide search identified PF3D7_1318800 as a putative member of the Sec61/Sec62/Sec63 complex.","evidence":"Bioinformatics/comparative genomics of the P. falciparum genome","pmids":["17919451"],"confidence":"Low","gaps":["Computational prediction only; no experimental confirmation that PF3D7_1318800 is expressed as a translocon component","No demonstration of physical association with Sec61","No localization data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"To place PF3D7_1318800 in a functional context, expression profiling and network construction annotated it as a transmembrane ER HSP40 for signal-peptide protein translocation and predicted candidate partners within the parasite chaperone network.","evidence":"Expression profiling of clinical isolates with Cytoscape-based interactome network inference","pmids":["20719001"],"confidence":"Low","gaps":["Predicted interactors MAL8P1.153 and PFI1780w were not validated by Co-IP or pulldown","Membrane topology and ER residence not experimentally shown","Functional role in translocation not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"A synthesis of chaperone-pathway data proposed PF3D7_1318800 as a membrane-bound co-chaperone acting with PfHsp70-2 (BiP) and the PfSec61 translocon to mediate ER secretory-pathway protein translocation.","evidence":"Literature review citing chaperone assays and Sec61 pathway analysis","pmids":["26167469"],"confidence":"Low","gaps":["No direct experiment on PF3D7_1318800 reported","PfSec63–PfHsp70-2 functional coupling not biochemically demonstrated","J-domain stimulation of BiP ATPase not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Refining the substrate specificity question, PF3D7_1318800 was described as an auxiliary factor of specialized Sec61 channels dedicated to PEXEL-containing exported proteins, distinguishing them from canonical channels handling PNEPs.","evidence":"Review of published genetic and biochemical translocon-composition data","pmids":["34440567"],"confidence":"Low","gaps":["Review-level claim; no direct experiment on PF3D7_1318800","Physical co-association with plasmepsin V at these channels not shown for PF3D7_1318800 itself","Selectivity for PEXEL versus PNEP substrates not tested experimentally"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"To move toward a druggable model, in silico docking modeled PF3D7_1318800 as a J-domain partner of PfHsp70-2 and used the complex for virtual screening, nominating compounds that engage the complex or its J domain.","evidence":"Molecular docking and molecular dynamics simulation (in silico)","pmids":["37621993"],"confidence":"Low","gaps":["Computational only; the PfHsp70-2–PfSec63 interaction was not biochemically validated","Compound binding and complex-stabilizing effects untested in cells or in vitro","No structural determination of PF3D7_1318800"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Cross-species extrapolation identified a P. knowlesi orthologue (PKNH_1419600, 82% identity) proposed to activate the lumenal PkHSP70 during ER translocation, extending the predicted Sec63–BiP relationship beyond P. falciparum.","evidence":"Comparative genomics and sequence identity analysis (bioinformatics)","pmids":["39596368"],"confidence":"Low","gaps":["No experiments performed in P. knowlesi","Orthologue function inferred solely from sequence identity","PkHSP70 activation by PKNH_1419600 not demonstrated"],"attribution":[{"species":"Plasmodium knowlesi","strain":""}]},{"year":null,"claim":"Whether PF3D7_1318800 physically associates with PfSec61 and PfHsp70-2, whether its J domain stimulates BiP ATPase activity, and whether it is required for translocation of PEXEL-exported proteins all remain experimentally unaddressed.","evidence":"No direct biochemical, genetic, or structural study of PF3D7_1318800 present in the corpus","pmids":[],"confidence":"Low","gaps":["No Co-IP, pulldown, or reciprocal interaction validation","No conditional knockdown/knockout to test translocation function","No structural or topology data for the protein"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Sec61/Sec62/Sec63 ER translocation complex (putative) [#0]","Specialized PfSec61 translocation channel with plasmepsin V for PEXEL-protein export (putative) [#4]","PfHsp70-2 (BiP)–PfSec63 J-domain complex (in silico model) [#2]"],"partners":["PFHSP70-2 / BIP (PREDICTED LUMENAL CHAPERONE ACTIVATED BY PFSEC63) [#1, #2]","PFSEC61 TRANSLOCON (PREDICTED ASSOCIATION) [#1, #4]","PLASMEPSIN V (CO-ASSOCIATED AT SPECIALIZED CHANNELS, REVIEW-LEVEL) [#4]","MAL8P1.153 (PREDICTED NETWORK INTERACTOR) [#3]","PFI1780W (PREDICTED NETWORK INTERACTOR) [#3]"],"other_free_text":["All assignments are computational/inferential; no direct biochemical, genetic, or structural data on PF3D7_1318800 exist in the corpus.","P. knowlesi orthologue PKNH_1419600 (82% identity) proposed by sequence analysis only [#5]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"17919451","id":"PMC_17919451","title":"Unraveling the components of protein translocation pathway in human malaria parasite Plasmodium falciparum.","date":"2007","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/17919451","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37621993","id":"PMC_37621993","title":"In silico identification of modulators of J domain protein-Hsp70 interactions in Plasmodium falciparum: a drug repurposing strategy against malaria.","date":"2023","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/37621993","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39596368","id":"","title":"The J Domain Proteins of Plasmodium knowlesi, a Zoonotic Malaria Parasite of Humans.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/39596368","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38518861","id":"","title":"Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update.","date":"2024","source":"Cell stress & chaperones","url":"https://pubmed.ncbi.nlm.nih.gov/38518861","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35652103","id":"","title":"Plasmodium falciparum Molecular Chaperones: Guardians of the Malaria Parasite Proteome and Renovators of the Host Proteome.","date":"2022","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/35652103","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32286267","id":"","title":"Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32286267","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26167469","id":"","title":"Plasmodial HSP70s are functionally adapted to the malaria parasite life cycle.","date":"2015","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/26167469","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34440567","id":"","title":"Unique Endomembrane Systems and Virulence in Pathogenic Protozoa.","date":"2021","source":"Life (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/34440567","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20719001","id":"","title":"Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients.","date":"2010","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/20719001","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SEC63"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11422,"output_tokens":1767,"usd":0.030385,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6800,"output_tokens":3179,"usd":0.056738,"stage2_stop_reason":"end_turn"},"total_usd":0.087123,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"Bioinformatics analysis identified a homologue of SEC63 (a component of the Sec translocation complex) in the P. falciparum genome, placing PF3D7_1318800 as a putative member of the Sec61αβγ/Sec62/Sec63 translocation machinery involved in co- and post-translational protein translocation into the ER.\",\n      \"method\": \"Bioinformatics/comparative genomics\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation performed\",\n      \"pmids\": [\"17919451\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PF3D7_1318800 (referred to as PfSec63) was proposed to be a membrane-bound PfHSP40 co-chaperone that works together with the ER-resident PfHsp70-2 (BiP homologue) and the PfSec61 translocon complex to mediate protein secretion through the ER secretory pathway.\",\n      \"method\": \"Literature review citing in vitro chaperone assays and pathway analysis of Sec61 complex components\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — inference from comparative analysis and prior computational work; no direct experiment on PF3D7_1318800 reported in this abstract\",\n      \"pmids\": [\"26167469\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In silico molecular docking identified PF3D7_1318800 (PfSec63) as a J-domain protein partner of PfHsp70-2 within the ER, and the PfHsp70-2–PfSec63 complex was used as a target for virtual screening of the Pandemic Response Box drug repurposing library; compounds zoliflodacin and itraconazole were identified as potential stabilizers of this complex, while ezetimibe and a benzo-diazepinone bound preferentially to the J domain of PfSec63.\",\n      \"method\": \"Molecular docking and molecular dynamics simulation (in silico)\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only; no biochemical or cell-based validation of the PfHsp70-2–PfSec63 interaction or compound effects reported in this abstract\",\n      \"pmids\": [\"37621993\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PF3D7_1318800 (annotated as PF13_0102, the P. falciparum Sec63 homologue) is a transmembrane ER HSP40 involved in translocation of signal-peptide-containing proteins into the ER; its expression is up-regulated in clinical isolate cluster 2 (active growth/glycolysis state), and interactome network analysis identified two hypothetical protein interactors (MAL8P1.153 and PFI1780w) as partners in the parasite chaperone network.\",\n      \"method\": \"Expression profiling of clinical isolates combined with cytoscape-based chaperone interactome network construction\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, expression-based network inference; interactors are predicted not experimentally validated by Co-IP or pulldown\",\n      \"pmids\": [\"20719001\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PF3D7_1318800 (Sec63) was described as an auxiliary protein associated with specialized Sec61 translocation channels in the P. falciparum ER that are used specifically for translocation of PEXEL-containing exported proteins (in contrast to canonical Sec61 channels used for PNEP proteins), with plasmepsin V co-associated at these specialized channels.\",\n      \"method\": \"Review of published genetic and biochemical data on Sec translocon composition\",\n      \"journal\": \"Life (Basel, Switzerland)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — review-level description citing prior work; no direct experiment on PF3D7_1318800 reported in this abstract\",\n      \"pmids\": [\"34440567\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In P. knowlesi, PKNH_1419600 (82% sequence identity to PfSec63/PF3D7_1318800) is proposed to be the orthologous ER membrane-bound J-domain protein that activates the ER-lumenal PkHSP70 (PKNH_0715900, homologue of PfHSP70-2/BiP) in the context of protein translocation into the ER, consistent with the established human Sec63–BiP functional relationship.\",\n      \"method\": \"Comparative genomics and sequence identity analysis (bioinformatics)\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/comparative analysis only; speculative extrapolation from P. falciparum and human data, no experiments in P. knowlesi reported\",\n      \"pmids\": [\"39596368\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1318800 (PfSec63) is a putative transmembrane ER-resident J-domain protein (HSP40 co-chaperone) that is proposed, based primarily on bioinformatics and in silico analyses, to associate with the PfSec61 translocon and to activate the ER-lumenal chaperone PfHsp70-2 (BiP) during co- and post-translational protein translocation into the ER, including translocation of PEXEL-containing exported proteins; no direct biochemical or structural experiments on PF3D7_1318800 itself have been reported in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1318800 (PfSec63) is a putative transmembrane ER-resident HSP40/J-domain co-chaperone assigned to the Sec-family protein translocation machinery of Plasmodium falciparum on the basis of bioinformatic and comparative-genomics analyses [#0, #1]. Within this framework it is placed alongside the PfSec61 translocon and is proposed to function together with the ER-lumenal chaperone PfHsp70-2 (a BiP homologue) to drive co- and post-translational translocation of signal-peptide-containing proteins into the ER [#1, #3]. It has additionally been described as an auxiliary component of specialized Sec61 channels dedicated to translocation of PEXEL-containing exported proteins, where plasmepsin V is co-associated [#4]. Its role as a J-domain activator of PfHsp70-2 has been modeled in silico, and the PfHsp70-2\\u2013PfSec63 complex has served as a virtual-screening target [#2]. No direct biochemical, genetic, or structural experiment on PF3D7_1318800 itself is present in the available corpus; every claim above rests on computational prediction, expression-based network inference, or review-level extrapolation, and the two candidate interactors (MAL8P1.153 and PFI1780w) reported for it are predicted rather than experimentally validated [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Establishing whether P. falciparum possesses a Sec63 orthologue was the first step in defining its ER translocation machinery; a genome-wide search identified PF3D7_1318800 as a putative member of the Sec61/Sec62/Sec63 complex.\",\n      \"evidence\": \"Bioinformatics/comparative genomics of the P. falciparum genome\",\n      \"pmids\": [\"17919451\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only; no experimental confirmation that PF3D7_1318800 is expressed as a translocon component\",\n        \"No demonstration of physical association with Sec61\",\n        \"No localization data\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"To place PF3D7_1318800 in a functional context, expression profiling and network construction annotated it as a transmembrane ER HSP40 for signal-peptide protein translocation and predicted candidate partners within the parasite chaperone network.\",\n      \"evidence\": \"Expression profiling of clinical isolates with Cytoscape-based interactome network inference\",\n      \"pmids\": [\"20719001\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Predicted interactors MAL8P1.153 and PFI1780w were not validated by Co-IP or pulldown\",\n        \"Membrane topology and ER residence not experimentally shown\",\n        \"Functional role in translocation not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"A synthesis of chaperone-pathway data proposed PF3D7_1318800 as a membrane-bound co-chaperone acting with PfHsp70-2 (BiP) and the PfSec61 translocon to mediate ER secretory-pathway protein translocation.\",\n      \"evidence\": \"Literature review citing chaperone assays and Sec61 pathway analysis\",\n      \"pmids\": [\"26167469\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct experiment on PF3D7_1318800 reported\",\n        \"PfSec63\\u2013PfHsp70-2 functional coupling not biochemically demonstrated\",\n        \"J-domain stimulation of BiP ATPase not measured\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Refining the substrate specificity question, PF3D7_1318800 was described as an auxiliary factor of specialized Sec61 channels dedicated to PEXEL-containing exported proteins, distinguishing them from canonical channels handling PNEPs.\",\n      \"evidence\": \"Review of published genetic and biochemical translocon-composition data\",\n      \"pmids\": [\"34440567\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Review-level claim; no direct experiment on PF3D7_1318800\",\n        \"Physical co-association with plasmepsin V at these channels not shown for PF3D7_1318800 itself\",\n        \"Selectivity for PEXEL versus PNEP substrates not tested experimentally\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To move toward a druggable model, in silico docking modeled PF3D7_1318800 as a J-domain partner of PfHsp70-2 and used the complex for virtual screening, nominating compounds that engage the complex or its J domain.\",\n      \"evidence\": \"Molecular docking and molecular dynamics simulation (in silico)\",\n      \"pmids\": [\"37621993\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational only; the PfHsp70-2\\u2013PfSec63 interaction was not biochemically validated\",\n        \"Compound binding and complex-stabilizing effects untested in cells or in vitro\",\n        \"No structural determination of PF3D7_1318800\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Cross-species extrapolation identified a P. knowlesi orthologue (PKNH_1419600, 82% identity) proposed to activate the lumenal PkHSP70 during ER translocation, extending the predicted Sec63\\u2013BiP relationship beyond P. falciparum.\",\n      \"evidence\": \"Comparative genomics and sequence identity analysis (bioinformatics)\",\n      \"pmids\": [\"39596368\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experiments performed in P. knowlesi\",\n        \"Orthologue function inferred solely from sequence identity\",\n        \"PkHSP70 activation by PKNH_1419600 not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1318800 physically associates with PfSec61 and PfHsp70-2, whether its J domain stimulates BiP ATPase activity, and whether it is required for translocation of PEXEL-exported proteins all remain experimentally unaddressed.\",\n      \"evidence\": \"No direct biochemical, genetic, or structural study of PF3D7_1318800 present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No Co-IP, pulldown, or reciprocal interaction validation\",\n        \"No conditional knockdown/knockout to test translocation function\",\n        \"No structural or topology data for the protein\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0001671\", \"supporting_discovery_ids\": [1, 2, 5]},\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005789\", \"supporting_discovery_ids\": [3, 4]},\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006616\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0031204\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [\n      \"Sec61/Sec62/Sec63 ER translocation complex (putative) [#0]\",\n      \"Specialized PfSec61 translocation channel with plasmepsin V for PEXEL-protein export (putative) [#4]\",\n      \"PfHsp70-2 (BiP)\\u2013PfSec63 J-domain complex (in silico model) [#2]\"\n    ],\n    \"partners\": [\n      \"PfHsp70-2 / BiP (predicted lumenal chaperone activated by PfSec63) [#1, #2]\",\n      \"PfSec61 translocon (predicted association) [#1, #4]\",\n      \"Plasmepsin V (co-associated at specialized channels, review-level) [#4]\",\n      \"MAL8P1.153 (predicted network interactor) [#3]\",\n      \"PFI1780w (predicted network interactor) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"All assignments are computational/inferential; no direct biochemical, genetic, or structural data on PF3D7_1318800 exist in the corpus.\",\n      \"P. knowlesi orthologue PKNH_1419600 (82% identity) proposed by sequence analysis only [#5].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1318800","name":null,"product":"translocation protein SEC63, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1417300","name":null,"product":"translocation protein SEC63, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1419600","name":null,"product":"translocation protein SEC63, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SEC63","evaluation":null}