{"gene":"PF3D7_0310400","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2004,"finding":"PIESP1 (PF3D7_0310400) was identified as a novel surface protein on Plasmodium falciparum-infected erythrocytes. Surface proteins were fractionated by biotin-streptavidin interaction and analyzed by shotgun proteomics; surface localization was confirmed by confocal microscopy using specific antibodies. PIESP1 was found to be unlikely associated with knobs, and is encoded by a single-copy gene highly conserved across Plasmodium species.","method":"Biotin-streptavidin surface fractionation, shotgun proteomics (MuDPIT), confocal microscopy with specific antibodies","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — orthogonal methods (proteomics + confocal immunofluorescence), single lab, replicated by subsequent studies citing this localization","pmids":["15287581"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"A GFP fusion of PIESP1 (PF3D7_0310400, then called PFC0435w) was detected at the junction of the parasitophorous vacuole membrane (PVM) and the tubovesicular network (TVN), not strictly at the erythrocyte surface as initially reported. The C-terminus of the protein contains a putative ER-retention signal (TDEL), though this was not present in the GFP fusion construct used.","method":"GFP fusion protein expression and live-cell fluorescence microscopy in P. falciparum-infected erythrocytes","journal":"FEMS microbiology reviews (citing van Ooij et al. 2008)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single localization experiment via GFP fusion cited in a review; original paper (van Ooij et al. 2008) not directly in corpus, only described secondhand","pmids":["27587718"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"PIESP1 (PF3D7_0310400) shares 31% protein identity and 50% similarity with human β-1,3-glucosyltransferase (B3GLCT) and possesses a domain with similarity to Fringe, a β-1,3-N-acetylglucosaminyltransferase that glycosylates O-linked fucose, leading to the proposal that PIESP1 may act as the β-1,3-glucosyltransferase that extends O-fucose on TSR domains of CSP and TRAP. PIESP1 was also detected as expressed in P. falciparum salivary gland sporozoites by mass spectrometry.","method":"BLAST homology analysis, mass spectrometry-based proteomics of sporozoites","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 4 / Weak — enzymatic function is computational prediction based on sequence homology; no in vitro assay or mutagenesis performed to confirm glucosyltransferase activity","pmids":["27128092"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Saturation mutagenesis data predict PF3D7_0310400 (PIESP1) to be essential in P. falciparum asexual blood stages, arguing against the hypothesis that PIESP1 functions as the β-1,3-glucosyltransferase responsible for O-fucose elongation (since pofut2 is dispensable). The proposed glucosyltransferase role of PIESP1 was thereby considered unlikely based on this genetic evidence.","method":"Saturation mutagenesis screen (piggyBac/CRISPR-based essentiality data cited from Zhang et al. 2018)","journal":"Parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — essentiality inferred from a genome-wide screen cited secondhand; no direct functional assay of PIESP1 enzymatic activity performed in this paper","pmids":["30773146"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"PIESP1 (PF3D7_0310400) was identified as a high-confidence interacting partner of the P. falciparum ER chaperone PfGRP170 by two independent immunoprecipitation/mass spectrometry approaches. PIESP1 contains a putative ER retention signal (TDEL), suggesting possible ER localization, though its precise subcellular location remains uncertain.","method":"Co-immunoprecipitation / mass spectrometry (two independent IP/MS approaches)","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two independent IP/MS experiments identifying PIESP1 as interacting partner of PfGRP170, single lab","pmids":["31087747"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"The P. berghei ortholog of PIESP1 (PBANKA_0408500) was successfully tagged with 3×HA using the PCR-template CRISPR approach with ~100-bp homology arms; correct integration was confirmed by PCR and western blot, and expression of the tagged protein was confirmed by IFA.","method":"CRISPR-Cas9 epitope tagging, PCR genotyping, western blot, immunofluorescence assay (IFA)","journal":"Nucleic acids research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — tagging and expression confirmation only; no functional or mechanistic result about PIESP1 itself established beyond successful tagging","pmids":["39844455"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PIESP1 (PF3D7_0310400) is a conserved, single-copy Plasmodium falciparum protein localized to the surface of parasite-infected erythrocytes (confirmed by proteomics and immunofluorescence), with a GFP-fusion also detected at the PVM/TVN junction; it contains a fringe-like domain suggesting possible glycosyltransferase activity (proposed but not experimentally confirmed as a β-1,3-glucosyltransferase for TSR O-fucose), physically interacts with the ER chaperone PfGRP170 by co-immunoprecipitation, and is predicted to be essential for asexual blood-stage growth, though its precise molecular function remains uncharacterized."},"narrative":{"mechanistic_narrative":"PIESP1 (PF3D7_0310400) is a conserved, single-copy Plasmodium falciparum protein first identified by surface proteomics of infected erythrocytes, where it localized to the parasite-infected erythrocyte surface and was found to be unlikely associated with knobs [PMID:15287581]. A GFP-fusion of the protein was subsequently detected at the junction of the parasitophorous vacuole membrane and the tubovesicular network rather than strictly at the erythrocyte surface, and the protein carries a putative ER-retention signal (TDEL) [PMID:27587718], consistent with its recovery as a high-confidence interacting partner of the P. falciparum ER chaperone PfGRP170 by two independent immunoprecipitation/mass spectrometry approaches [PMID:31087747]. Genome-wide saturation mutagenesis predicts PIESP1 to be essential in asexual blood stages [PMID:30773146]. Beyond these localization and interaction data, its precise molecular function is uncharacterized in the available corpus: a proposed β-1,3-glucosyltransferase activity based on homology to human B3GLCT and a Fringe-like domain [PMID:27128092] was never confirmed enzymatically and is disfavored by the genetic evidence, since PIESP1 is essential whereas the corresponding fucose-elongation pathway component is dispensable [PMID:30773146].","teleology":[{"year":2004,"claim":"Establishing where PIESP1 acts began with defining it as a novel component of the infected-erythrocyte surface, distinguishing it from knob-associated proteins.","evidence":"Biotin-streptavidin surface fractionation with shotgun proteomics and confocal immunofluorescence in P. falciparum-infected erythrocytes","pmids":["15287581"],"confidence":"Medium","gaps":["Does not define the protein's molecular function","Surface assignment later complicated by a GFP-fusion showing PVM/TVN localization","No topology or membrane-anchoring detail"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"claim":"A GFP-fusion reassigned the protein's steady-state location to the PVM/TVN junction, and identification of a TDEL ER-retention signal raised the question of an ER-associated trafficking role rather than a purely surface function.","evidence":"GFP fusion expression and live-cell fluorescence microscopy (cited secondhand in a review)","pmids":["27587718"],"confidence":"Low","gaps":["Original localization data known only secondhand via review","GFP construct lacked the native TDEL signal, complicating interpretation","Discrepancy with the earlier surface assignment unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Sequence homology to human B3GLCT and a Fringe-like domain prompted a candidate enzymatic identity — a β-1,3-glucosyltransferase extending O-fucose on TSR domains — as a first hypothesis for molecular function.","evidence":"BLAST homology analysis plus mass spectrometry detection in P. falciparum salivary gland sporozoites","pmids":["27128092"],"confidence":"Low","gaps":["Enzymatic activity is a computational prediction only","No in vitro glucosyltransferase assay or mutagenesis","No demonstrated substrate (CSP/TRAP TSR domains) engagement"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Genome-wide essentiality data tested the glucosyltransferase hypothesis genetically and disfavored it, since PIESP1 is predicted essential in asexual blood stages whereas the fucose-elongation component is dispensable.","evidence":"Saturation mutagenesis essentiality data cited from a genome-wide screen","pmids":["30773146"],"confidence":"Low","gaps":["Essentiality inferred from a screen cited secondhand","No direct functional assay of PIESP1 performed","Essentiality does not itself reveal the actual molecular function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Interactome mapping placed PIESP1 in a physical complex with the ER chaperone PfGRP170, providing the first direct molecular partner and reinforcing an ER-associated context consistent with its TDEL signal.","evidence":"Two independent co-immunoprecipitation / mass spectrometry approaches in P. falciparum","pmids":["31087747"],"confidence":"Medium","gaps":["Functional consequence of the PfGRP170 interaction not defined","Whether the interaction reflects chaperone-client or a stable complex is unknown","Subcellular location still not definitively resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"A tractable genetic handle was established for the ortholog, enabling future functional interrogation, though no mechanistic result about the protein was obtained.","evidence":"CRISPR-Cas9 3×HA tagging of the P. berghei ortholog PBANKA_0408500 with PCR, western blot, and IFA confirmation","pmids":["39844455"],"confidence":"Low","gaps":["Only tagging and expression were demonstrated","No functional or localization phenotype reported for the ortholog","Results in P. berghei not yet linked to P. falciparum function"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The actual biochemical activity of PIESP1 and the functional purpose of its interaction with PfGRP170 remain unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimentally validated enzymatic or biochemical activity","Consequence of PfGRP170 binding uncharacterized","Definitive subcellular localization unresolved across surface vs PVM/TVN vs ER"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfGRP170-containing complex (co-IP/MS)"],"partners":["PFGRP170"],"other_free_text":["Single-copy gene conserved across Plasmodium species [#0]","Predicted essential in P. falciparum asexual blood stages [#3]","Homology to human B3GLCT with a Fringe-like domain; proposed but unconfirmed β-1,3-glucosyltransferase activity, disfavored by essentiality data [#2, #3]","Expressed in P. falciparum salivary gland sporozoites [#2]","P. berghei ortholog PBANKA_0408500 successfully epitope-tagged [#5]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15287581","id":"PMC_15287581","title":"Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15287581","citation_count":145,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39844455","id":"","title":"A scalable CRISPR-Cas9 gene editing system facilitates CRISPR screens in the malaria parasite Plasmodium berghei.","date":"2025","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/39844455","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31087747","id":"","title":"The endoplasmic reticulum chaperone PfGRP170 is essential for asexual development and is linked to stress response in malaria parasites.","date":"2019","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31087747","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31196098","id":"","title":"Clinical expression and antigenic profiles of a Plasmodium vivax vaccine candidate: merozoite surface protein 7 (PvMSP-7).","date":"2019","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/31196098","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30773146","id":"","title":"Protein O- and C-Glycosylation pathways in Toxoplasma gondii and Plasmodium falciparum.","date":"2019","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/30773146","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":false},{"pmid":"28759593","id":"","title":"Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium vivax salivary gland sporozoites.","date":"2017","source":"PLoS neglected tropical diseases","url":"https://pubmed.ncbi.nlm.nih.gov/28759593","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27128092","id":"","title":"Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics.","date":"2016","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/27128092","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27587718","id":"","title":"Host cell remodeling by pathogens: the exomembrane system in Plasmodium-infected erythrocytes.","date":"2016","source":"FEMS microbiology reviews","url":"https://pubmed.ncbi.nlm.nih.gov/27587718","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17519013","id":"","title":"Rapid and specific biotin labelling of the erythrocyte surface antigens of both cultured and ex-vivo Plasmodium parasites.","date":"2007","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/17519013","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18614010","id":"","title":"Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes.","date":"2008","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/18614010","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PIESP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12362,"output_tokens":1924,"usd":0.032973,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7062,"output_tokens":2715,"usd":0.051592,"stage2_stop_reason":"end_turn"},"total_usd":0.084565,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"PIESP1 (PF3D7_0310400) was identified as a novel surface protein on Plasmodium falciparum-infected erythrocytes. Surface proteins were fractionated by biotin-streptavidin interaction and analyzed by shotgun proteomics; surface localization was confirmed by confocal microscopy using specific antibodies. PIESP1 was found to be unlikely associated with knobs, and is encoded by a single-copy gene highly conserved across Plasmodium species.\",\n      \"method\": \"Biotin-streptavidin surface fractionation, shotgun proteomics (MuDPIT), confocal microscopy with specific antibodies\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — orthogonal methods (proteomics + confocal immunofluorescence), single lab, replicated by subsequent studies citing this localization\",\n      \"pmids\": [\"15287581\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"A GFP fusion of PIESP1 (PF3D7_0310400, then called PFC0435w) was detected at the junction of the parasitophorous vacuole membrane (PVM) and the tubovesicular network (TVN), not strictly at the erythrocyte surface as initially reported. The C-terminus of the protein contains a putative ER-retention signal (TDEL), though this was not present in the GFP fusion construct used.\",\n      \"method\": \"GFP fusion protein expression and live-cell fluorescence microscopy in P. falciparum-infected erythrocytes\",\n      \"journal\": \"FEMS microbiology reviews (citing van Ooij et al. 2008)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single localization experiment via GFP fusion cited in a review; original paper (van Ooij et al. 2008) not directly in corpus, only described secondhand\",\n      \"pmids\": [\"27587718\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"PIESP1 (PF3D7_0310400) shares 31% protein identity and 50% similarity with human β-1,3-glucosyltransferase (B3GLCT) and possesses a domain with similarity to Fringe, a β-1,3-N-acetylglucosaminyltransferase that glycosylates O-linked fucose, leading to the proposal that PIESP1 may act as the β-1,3-glucosyltransferase that extends O-fucose on TSR domains of CSP and TRAP. PIESP1 was also detected as expressed in P. falciparum salivary gland sporozoites by mass spectrometry.\",\n      \"method\": \"BLAST homology analysis, mass spectrometry-based proteomics of sporozoites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — enzymatic function is computational prediction based on sequence homology; no in vitro assay or mutagenesis performed to confirm glucosyltransferase activity\",\n      \"pmids\": [\"27128092\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Saturation mutagenesis data predict PF3D7_0310400 (PIESP1) to be essential in P. falciparum asexual blood stages, arguing against the hypothesis that PIESP1 functions as the β-1,3-glucosyltransferase responsible for O-fucose elongation (since pofut2 is dispensable). The proposed glucosyltransferase role of PIESP1 was thereby considered unlikely based on this genetic evidence.\",\n      \"method\": \"Saturation mutagenesis screen (piggyBac/CRISPR-based essentiality data cited from Zhang et al. 2018)\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — essentiality inferred from a genome-wide screen cited secondhand; no direct functional assay of PIESP1 enzymatic activity performed in this paper\",\n      \"pmids\": [\"30773146\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PIESP1 (PF3D7_0310400) was identified as a high-confidence interacting partner of the P. falciparum ER chaperone PfGRP170 by two independent immunoprecipitation/mass spectrometry approaches. PIESP1 contains a putative ER retention signal (TDEL), suggesting possible ER localization, though its precise subcellular location remains uncertain.\",\n      \"method\": \"Co-immunoprecipitation / mass spectrometry (two independent IP/MS approaches)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two independent IP/MS experiments identifying PIESP1 as interacting partner of PfGRP170, single lab\",\n      \"pmids\": [\"31087747\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The P. berghei ortholog of PIESP1 (PBANKA_0408500) was successfully tagged with 3×HA using the PCR-template CRISPR approach with ~100-bp homology arms; correct integration was confirmed by PCR and western blot, and expression of the tagged protein was confirmed by IFA.\",\n      \"method\": \"CRISPR-Cas9 epitope tagging, PCR genotyping, western blot, immunofluorescence assay (IFA)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — tagging and expression confirmation only; no functional or mechanistic result about PIESP1 itself established beyond successful tagging\",\n      \"pmids\": [\"39844455\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PIESP1 (PF3D7_0310400) is a conserved, single-copy Plasmodium falciparum protein localized to the surface of parasite-infected erythrocytes (confirmed by proteomics and immunofluorescence), with a GFP-fusion also detected at the PVM/TVN junction; it contains a fringe-like domain suggesting possible glycosyltransferase activity (proposed but not experimentally confirmed as a β-1,3-glucosyltransferase for TSR O-fucose), physically interacts with the ER chaperone PfGRP170 by co-immunoprecipitation, and is predicted to be essential for asexual blood-stage growth, though its precise molecular function remains uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PIESP1 (PF3D7_0310400) is a conserved, single-copy Plasmodium falciparum protein first identified by surface proteomics of infected erythrocytes, where it localized to the parasite-infected erythrocyte surface and was found to be unlikely associated with knobs [#0]. A GFP-fusion of the protein was subsequently detected at the junction of the parasitophorous vacuole membrane and the tubovesicular network rather than strictly at the erythrocyte surface, and the protein carries a putative ER-retention signal (TDEL) [#1], consistent with its recovery as a high-confidence interacting partner of the P. falciparum ER chaperone PfGRP170 by two independent immunoprecipitation/mass spectrometry approaches [#4]. Genome-wide saturation mutagenesis predicts PIESP1 to be essential in asexual blood stages [#3]. Beyond these localization and interaction data, its precise molecular function is uncharacterized in the available corpus: a proposed β-1,3-glucosyltransferase activity based on homology to human B3GLCT and a Fringe-like domain [#2] was never confirmed enzymatically and is disfavored by the genetic evidence, since PIESP1 is essential whereas the corresponding fucose-elongation pathway component is dispensable [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing where PIESP1 acts began with defining it as a novel component of the infected-erythrocyte surface, distinguishing it from knob-associated proteins.\",\n      \"evidence\": \"Biotin-streptavidin surface fractionation with shotgun proteomics and confocal immunofluorescence in P. falciparum-infected erythrocytes\",\n      \"pmids\": [\"15287581\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not define the protein's molecular function\", \"Surface assignment later complicated by a GFP-fusion showing PVM/TVN localization\", \"No topology or membrane-anchoring detail\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"A GFP-fusion reassigned the protein's steady-state location to the PVM/TVN junction, and identification of a TDEL ER-retention signal raised the question of an ER-associated trafficking role rather than a purely surface function.\",\n      \"evidence\": \"GFP fusion expression and live-cell fluorescence microscopy (cited secondhand in a review)\",\n      \"pmids\": [\"27587718\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Original localization data known only secondhand via review\", \"GFP construct lacked the native TDEL signal, complicating interpretation\", \"Discrepancy with the earlier surface assignment unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Sequence homology to human B3GLCT and a Fringe-like domain prompted a candidate enzymatic identity — a β-1,3-glucosyltransferase extending O-fucose on TSR domains — as a first hypothesis for molecular function.\",\n      \"evidence\": \"BLAST homology analysis plus mass spectrometry detection in P. falciparum salivary gland sporozoites\",\n      \"pmids\": [\"27128092\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Enzymatic activity is a computational prediction only\", \"No in vitro glucosyltransferase assay or mutagenesis\", \"No demonstrated substrate (CSP/TRAP TSR domains) engagement\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Genome-wide essentiality data tested the glucosyltransferase hypothesis genetically and disfavored it, since PIESP1 is predicted essential in asexual blood stages whereas the fucose-elongation component is dispensable.\",\n      \"evidence\": \"Saturation mutagenesis essentiality data cited from a genome-wide screen\",\n      \"pmids\": [\"30773146\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Essentiality inferred from a screen cited secondhand\", \"No direct functional assay of PIESP1 performed\", \"Essentiality does not itself reveal the actual molecular function\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Interactome mapping placed PIESP1 in a physical complex with the ER chaperone PfGRP170, providing the first direct molecular partner and reinforcing an ER-associated context consistent with its TDEL signal.\",\n      \"evidence\": \"Two independent co-immunoprecipitation / mass spectrometry approaches in P. falciparum\",\n      \"pmids\": [\"31087747\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the PfGRP170 interaction not defined\", \"Whether the interaction reflects chaperone-client or a stable complex is unknown\", \"Subcellular location still not definitively resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A tractable genetic handle was established for the ortholog, enabling future functional interrogation, though no mechanistic result about the protein was obtained.\",\n      \"evidence\": \"CRISPR-Cas9 3×HA tagging of the P. berghei ortholog PBANKA_0408500 with PCR, western blot, and IFA confirmation\",\n      \"pmids\": [\"39844455\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Only tagging and expression were demonstrated\", \"No functional or localization phenotype reported for the ortholog\", \"Results in P. berghei not yet linked to P. falciparum function\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The actual biochemical activity of PIESP1 and the functional purpose of its interaction with PfGRP170 remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No experimentally validated enzymatic or biochemical activity\", \"Consequence of PfGRP170 binding uncharacterized\", \"Definitive subcellular localization unresolved across surface vs PVM/TVN vs ER\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"infected erythrocyte surface\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"PVM/TVN junction\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"endoplasmic reticulum (predicted via TDEL retention signal)\", \"supporting_discovery_ids\": [1, 4]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"PfGRP170-containing complex (co-IP/MS)\"],\n    \"partners\": [\"PfGRP170\"],\n    \"other_free_text\": [\n      \"Single-copy gene conserved across Plasmodium species [#0]\",\n      \"Predicted essential in P. falciparum asexual blood stages [#3]\",\n      \"Homology to human B3GLCT with a Fringe-like domain; proposed but unconfirmed β-1,3-glucosyltransferase activity, disfavored by essentiality data [#2, #3]\",\n      \"Expressed in P. falciparum salivary gland sporozoites [#2]\",\n      \"P. berghei ortholog PBANKA_0408500 successfully epitope-tagged [#5]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0310400","name":null,"product":"parasite-infected erythrocyte surface protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0408500","name":null,"product":"parasite-infected erythrocyte surface protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0832300","name":null,"product":"conserved Plasmodium protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PIESP1","evaluation":null}