{"gene":"PF3D7_0621900","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2014,"finding":"PfSRP68 (PF3D7_0621900) is one of six polypeptide subunits (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) that together with a 303 nt SRP RNA constitute the P. falciparum signal recognition particle ribonucleoprotein complex.","method":"Transgenic parasite lines expressing SRP-GFP chimeric proteins; co-localization studies","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — GFP tagging and co-localization in transgenic parasites; single lab but multiple SRP subunits examined together; complex membership demonstrated indirectly through co-localization rather than biochemical co-IP or reconstitution","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"SRP68 (PF3D7_0621900) displays nucleo-cytoplasmic (shuttling) localization in asexual blood-stage P. falciparum parasites, as shown by GFP-chimera imaging.","method":"Transgenic parasite lines expressing SRP68-GFP chimeric protein; fluorescence co-localization microscopy","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct live-cell imaging of GFP-tagged protein, single lab, localization established but functional consequence not independently validated","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Nuclear import of PfSRP polypeptides including SRP68 is inhibited by ivermectin (an inhibitor of importin α/β-mediated nuclear import) at submicromolar concentrations, blocking nucleo-cytoplasmic shuttling and killing parasites.","method":"Treatment of transgenic SRP-GFP parasite lines with ivermectin; fluorescence microscopy to monitor nuclear import; parasite viability assay","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pharmacological perturbation with phenotypic readout in transgenic lines; importin pathway implicated but direct binding not demonstrated; single lab","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"SRP68 (PF3D7_0621900) was detected in the cytosolic interactome of PfPRMT5 by co-immunoprecipitation/mass spectrometry, placing it in a potential interaction with the parasite's type II protein arginine methyltransferase; the biological significance of this association in P. falciparum was not experimentally resolved beyond detection.","method":"Co-immunoprecipitation followed by mass spectrometry (interactome study of PfPRMT5)","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP/MS experiment; SRP68 mentioned as a detected interactor with no functional follow-up; authors explicitly note it is speculative","pmids":["37349497"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"In P. falciparum, SRP68 (PF3D7_0621900) is a subunit of the six-polypeptide, ~303 nt RNA-containing signal recognition particle ribonucleoprotein complex that targets proteins to the ER; it undergoes importin α/β-dependent nucleo-cytoplasmic shuttling that can be blocked by ivermectin at submicromolar concentrations, and it was detected in the cytosolic interactome of PfPRMT5, though its precise mechanistic role beyond SRP complex membership remains uncharacterized."},"narrative":{"mechanistic_narrative":"SRP68 (PF3D7_0621900) is one of six polypeptide subunits that, together with a 303 nt SRP RNA, constitute the P. falciparum signal recognition particle ribonucleoprotein complex implicated in protein targeting [PMID:24434517]. In asexual blood-stage parasites, GFP-chimera imaging shows SRP68 undergoes nucleo-cytoplasmic shuttling [PMID:24434517], and this trafficking depends on importin α/β-mediated nuclear import: submicromolar ivermectin blocks nuclear import of SRP polypeptides including SRP68 and kills parasites [PMID:24434517]. Beyond its membership in the SRP complex and this shuttling behavior, the specific mechanistic role of SRP68 has not been characterized in the available corpus; a single co-IP/MS study also detected it in the cytosolic interactome of PfPRMT5 without functional resolution [PMID:37349497].","teleology":[{"year":2014,"claim":"Establishing whether P. falciparum encodes a canonical SRP machinery answered whether SRP68 exists as a defined complex subunit rather than an isolated protein.","evidence":"GFP-chimera expression and co-localization of six SRP subunits with a 303 nt SRP RNA in transgenic parasites","pmids":["24434517"],"confidence":"Medium","gaps":["Complex membership inferred from co-localization, not biochemical co-IP or reconstitution","Direct role of SRP68 within the complex (e.g. RNA or subunit binding) not resolved","No substrate or targeting activity demonstrated for SRP68 itself"],"attribution":[]},{"year":2014,"claim":"Determining SRP68's subcellular distribution addressed whether the protein is confined to the cytosol or traffics to the nucleus, an unusual property for an SRP subunit.","evidence":"Live-cell fluorescence microscopy of SRP68-GFP chimera in asexual blood-stage parasites","pmids":["24434517"],"confidence":"Medium","gaps":["Functional consequence of nuclear shuttling for SRP68 not established","Whether shuttling reflects SRP assembly or an independent role is unknown"],"attribution":[]},{"year":2014,"claim":"Testing ivermectin sensitivity addressed the mechanism of SRP68 nuclear entry and its druggability, linking shuttling to the importin pathway.","evidence":"Ivermectin treatment of SRP-GFP transgenic lines with imaging of nuclear import and parasite viability assay","pmids":["24434517"],"confidence":"Medium","gaps":["Direct binding of SRP68 to importin α/β not demonstrated","Whether killing is caused specifically by loss of SRP68 nuclear import versus broader effects is unresolved"],"attribution":[]},{"year":2023,"claim":"Interactome profiling of PfPRMT5 asked whether SRP68 associates with the arginine methyltransferase machinery, hinting at a possible regulatory link.","evidence":"Co-immunoprecipitation/mass spectrometry of the PfPRMT5 cytosolic interactome","pmids":["37349497"],"confidence":"Low","gaps":["Single co-IP/MS detection with no reciprocal validation","Biological significance of the association not experimentally resolved","No evidence SRP68 is a methylation substrate"],"attribution":[]},{"year":null,"claim":"The direct molecular function of SRP68 within the SRP complex and the purpose of its nuclear shuttling remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No biochemical reconstitution of SRP68 within the complex","No identified binding partners within the complex confirmed by direct interaction","Functional role of nucleo-cytoplasmic shuttling uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Signal recognition particle (SRP9/SRP14/SRP19/SRP54/SRP68/SRP72 + 303 nt SRP RNA)"],"partners":["PFPRMT5 (DETECTED IN INTERACTOME, UNVALIDATED)","IMPORTIN Α/Β (INFERRED FROM IVERMECTIN SENSITIVITY)"],"other_free_text":["Nuclear import of SRP68 is blocked by submicromolar ivermectin, which kills parasites [#2].","SRP68 complex membership shown by GFP co-localization rather than biochemical co-IP or reconstitution [#0].","The precise mechanistic role of SRP68 beyond SRP complex membership is uncharacterized in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24434517","id":"PMC_24434517","title":"Plasmodium falciparum signal recognition particle components and anti-parasitic effect of ivermectin in blocking nucleo-cytoplasmic shuttling of SRP.","date":"2014","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/24434517","citation_count":51,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP68"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41387489","id":"","title":"Novel zoonotic cases of Plasmodium simium from São Paulo with a reference genome of the Brazilian strain.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41387489","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP68"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37349497","id":"","title":"A type II protein arginine methyltransferase regulates merozoite invasion in Plasmodium falciparum.","date":"2023","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/37349497","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP68"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34017052","id":"","title":"Structural analysis of the SRP Alu domain from Plasmodium falciparum reveals a non-canonical open conformation.","date":"2021","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/34017052","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP68"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27381095","id":"","title":"The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum.","date":"2016","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/27381095","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP68"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"14720308","id":"","title":"Identification and comparative analysis of components from the signal recognition particle in protozoa and fungi.","date":"2004","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/14720308","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP68"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9003,"output_tokens":1166,"usd":0.022249,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6010,"output_tokens":1885,"usd":0.038587,"stage2_stop_reason":"end_turn"},"total_usd":0.060836,"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\": 2014,\n      \"finding\": \"PfSRP68 (PF3D7_0621900) is one of six polypeptide subunits (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) that together with a 303 nt SRP RNA constitute the P. falciparum signal recognition particle ribonucleoprotein complex.\",\n      \"method\": \"Transgenic parasite lines expressing SRP-GFP chimeric proteins; co-localization studies\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — GFP tagging and co-localization in transgenic parasites; single lab but multiple SRP subunits examined together; complex membership demonstrated indirectly through co-localization rather than biochemical co-IP or reconstitution\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"SRP68 (PF3D7_0621900) displays nucleo-cytoplasmic (shuttling) localization in asexual blood-stage P. falciparum parasites, as shown by GFP-chimera imaging.\",\n      \"method\": \"Transgenic parasite lines expressing SRP68-GFP chimeric protein; fluorescence co-localization microscopy\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct live-cell imaging of GFP-tagged protein, single lab, localization established but functional consequence not independently validated\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Nuclear import of PfSRP polypeptides including SRP68 is inhibited by ivermectin (an inhibitor of importin α/β-mediated nuclear import) at submicromolar concentrations, blocking nucleo-cytoplasmic shuttling and killing parasites.\",\n      \"method\": \"Treatment of transgenic SRP-GFP parasite lines with ivermectin; fluorescence microscopy to monitor nuclear import; parasite viability assay\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pharmacological perturbation with phenotypic readout in transgenic lines; importin pathway implicated but direct binding not demonstrated; single lab\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SRP68 (PF3D7_0621900) was detected in the cytosolic interactome of PfPRMT5 by co-immunoprecipitation/mass spectrometry, placing it in a potential interaction with the parasite's type II protein arginine methyltransferase; the biological significance of this association in P. falciparum was not experimentally resolved beyond detection.\",\n      \"method\": \"Co-immunoprecipitation followed by mass spectrometry (interactome study of PfPRMT5)\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP/MS experiment; SRP68 mentioned as a detected interactor with no functional follow-up; authors explicitly note it is speculative\",\n      \"pmids\": [\"37349497\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"In P. falciparum, SRP68 (PF3D7_0621900) is a subunit of the six-polypeptide, ~303 nt RNA-containing signal recognition particle ribonucleoprotein complex that targets proteins to the ER; it undergoes importin α/β-dependent nucleo-cytoplasmic shuttling that can be blocked by ivermectin at submicromolar concentrations, and it was detected in the cytosolic interactome of PfPRMT5, though its precise mechanistic role beyond SRP complex membership remains uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SRP68 (PF3D7_0621900) is one of six polypeptide subunits that, together with a 303 nt SRP RNA, constitute the P. falciparum signal recognition particle ribonucleoprotein complex implicated in protein targeting [#0]. In asexual blood-stage parasites, GFP-chimera imaging shows SRP68 undergoes nucleo-cytoplasmic shuttling [#1], and this trafficking depends on importin \\u03b1/\\u03b2-mediated nuclear import: submicromolar ivermectin blocks nuclear import of SRP polypeptides including SRP68 and kills parasites [#2]. Beyond its membership in the SRP complex and this shuttling behavior, the specific mechanistic role of SRP68 has not been characterized in the available corpus; a single co-IP/MS study also detected it in the cytosolic interactome of PfPRMT5 without functional resolution [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing whether P. falciparum encodes a canonical SRP machinery answered whether SRP68 exists as a defined complex subunit rather than an isolated protein.\",\n      \"evidence\": \"GFP-chimera expression and co-localization of six SRP subunits with a 303 nt SRP RNA in transgenic parasites\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Complex membership inferred from co-localization, not biochemical co-IP or reconstitution\", \"Direct role of SRP68 within the complex (e.g. RNA or subunit binding) not resolved\", \"No substrate or targeting activity demonstrated for SRP68 itself\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Determining SRP68's subcellular distribution addressed whether the protein is confined to the cytosol or traffics to the nucleus, an unusual property for an SRP subunit.\",\n      \"evidence\": \"Live-cell fluorescence microscopy of SRP68-GFP chimera in asexual blood-stage parasites\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of nuclear shuttling for SRP68 not established\", \"Whether shuttling reflects SRP assembly or an independent role is unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Testing ivermectin sensitivity addressed the mechanism of SRP68 nuclear entry and its druggability, linking shuttling to the importin pathway.\",\n      \"evidence\": \"Ivermectin treatment of SRP-GFP transgenic lines with imaging of nuclear import and parasite viability assay\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding of SRP68 to importin \\u03b1/\\u03b2 not demonstrated\", \"Whether killing is caused specifically by loss of SRP68 nuclear import versus broader effects is unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Interactome profiling of PfPRMT5 asked whether SRP68 associates with the arginine methyltransferase machinery, hinting at a possible regulatory link.\",\n      \"evidence\": \"Co-immunoprecipitation/mass spectrometry of the PfPRMT5 cytosolic interactome\",\n      \"pmids\": [\"37349497\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single co-IP/MS detection with no reciprocal validation\", \"Biological significance of the association not experimentally resolved\", \"No evidence SRP68 is a methylation substrate\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of SRP68 within the SRP complex and the purpose of its nuclear shuttling remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No biochemical reconstitution of SRP68 within the complex\", \"No identified binding partners within the complex confirmed by direct interaction\", \"Functional role of nucleo-cytoplasmic shuttling uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006614\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006606\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"Signal recognition particle (SRP9/SRP14/SRP19/SRP54/SRP68/SRP72 + 303 nt SRP RNA)\"],\n    \"partners\": [\"PfPRMT5 (detected in interactome, unvalidated)\", \"importin \\u03b1/\\u03b2 (inferred from ivermectin sensitivity)\"],\n    \"other_free_text\": [\n      \"Nuclear import of SRP68 is blocked by submicromolar ivermectin, which kills parasites [#2].\",\n      \"SRP68 complex membership shown by GFP co-localization rather than biochemical co-IP or reconstitution [#0].\",\n      \"The precise mechanistic role of SRP68 beyond SRP complex membership is uncharacterized in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0621900","name":null,"product":"signal recognition particle subunit SRP68, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1120800","name":null,"product":"signal recognition particle subunit SRP68, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1128300","name":null,"product":"signal recognition particle subunit SRP68, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRP68","evaluation":null}