{"gene":"PF3D7_1450100","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2014,"finding":"P. falciparum SRP54 is a component of the P. falciparum SRP complex, which is composed of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) and a 303 nt SRP RNA. Transgenic parasites expressing SRP54-GFP chimeric protein showed nucleo-cytoplasmic localization, indicating SRP54 shuttles between nucleus and cytoplasm.","method":"Transgenic parasite lines expressing GFP-chimeric proteins; co-localization fluorescence microscopy; characterization of SRP complex composition","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by live imaging with GFP fusion in transgenic parasites, complex membership established, single lab","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Ivermectin, an inhibitor of importin α/β-mediated nuclear import, blocked the nuclear import of PfSRP polypeptides including SRP54 at submicromolar concentrations and killed parasites, indicating SRP54 nuclear import depends on the importin α/β pathway.","method":"Treatment of transgenic GFP-SRP expressing parasites with ivermectin and other nuclear import/export inhibitors; assessment of subcellular localization and parasite viability","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — pharmacological inhibitor experiment in live transgenic parasites with localization readout, single lab, single method","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"Bioinformatic analysis identified a P. falciparum SRP54 homologue in the P. falciparum genome, placing it as a predicted component of the SRP-mediated co-translational protein translocation pathway alongside SRP RNA, SRP9, SRP14, and SRP19, with a hypothetical SRP receptor partner also predicted.","method":"Bioinformatics/genome analysis","journal":"Archives of biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation in this paper","pmids":["17919451"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum SRP54 is a subunit of the six-polypeptide SRP ribonucleoprotein complex that undergoes nucleo-cytoplasmic shuttling via the importin α/β nuclear import pathway, and pharmacological blockade of this import kills parasites."},"narrative":{"mechanistic_narrative":"PF3D7_1450100 (SRP54) is a subunit of the P. falciparum signal recognition particle, a ribonucleoprotein complex composed of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) assembled on a 303 nt SRP RNA [PMID:24434517]. In transgenic parasites, an SRP54-GFP fusion displays nucleo-cytoplasmic localization, indicating that SRP54 shuttles between the nucleus and cytoplasm [PMID:24434517]. This nuclear import depends on the importin α/β pathway: ivermectin, an inhibitor of importin α/β-mediated import, blocks nuclear entry of SRP polypeptides including SRP54 at submicromolar concentrations and kills parasites [PMID:24434517]. Beyond its membership in the SRP complex and its importin-dependent shuttling behavior, no direct biochemical or functional characterization of SRP54's role in co-translational protein translocation has been established for this gene in the available corpus.","teleology":[{"year":2007,"claim":"Before any experimental work, it was unknown whether P. falciparum encodes SRP machinery; genome analysis established SRP54 as a predicted component of the parasite's SRP-mediated co-translational translocation pathway.","evidence":"Bioinformatic/genome analysis identifying an SRP54 homologue alongside SRP RNA and other SRP subunits","pmids":["17919451"],"confidence":"Low","gaps":["Computational prediction only, no experimental validation of SRP54 function or complex membership","Predicted SRP receptor partner not experimentally confirmed","No demonstration that the homologue is expressed or assembled into a particle"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"To move beyond prediction, the SRP complex was characterized and SRP54's subcellular behavior was determined, establishing it as a bona fide six-polypeptide complex subunit that unexpectedly shuttles between nucleus and cytoplasm.","evidence":"SRP complex composition analysis and live-imaging co-localization of an SRP54-GFP fusion in transgenic parasites","pmids":["24434517"],"confidence":"Medium","gaps":["Single lab, single localization method; no orthogonal confirmation of complex stoichiometry","Functional consequence of nuclear shuttling for SRP54 not defined","No direct evidence that SRP54 performs co-translational targeting in the parasite"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"The route of SRP54 nuclear import was addressed pharmacologically, showing dependence on the importin α/β pathway and linking this trafficking step to parasite viability.","evidence":"Ivermectin and other import/export inhibitor treatment of transgenic GFP-SRP parasites with localization and viability readouts","pmids":["24434517"],"confidence":"Medium","gaps":["Ivermectin effect is pharmacological and may act on multiple importin cargoes, so lethality cannot be attributed solely to SRP54 mislocalization","Direct interaction between SRP54 and importin α/β not demonstrated","The import signal within SRP54 was not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether P. falciparum SRP54 performs the canonical signal-peptide recognition and co-translational translocation activity, and what its nuclear shuttling accomplishes mechanistically.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct assay of SRP54 signal-sequence binding or GTPase/SRP receptor engagement in the parasite","Functional role of nucleo-cytoplasmic shuttling uncharacterized","No genetic loss-of-function data for SRP54 specifically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Signal recognition particle (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72 + 303 nt SRP RNA)"],"partners":["IMPORTIN Α/Β NUCLEAR IMPORT PATHWAY"],"other_free_text":["SRP54-GFP fusion shows nucleo-cytoplasmic shuttling in transgenic P. falciparum [#0]","Ivermectin blocks importin α/β-dependent nuclear import of SRP polypeptides including SRP54 and kills parasites [#1]","SRP54 was initially identified as a predicted SRP component by genome bioinformatics [#2]"]}},"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":["SRP54"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"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":["SRP54"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3569,"output_tokens":828,"usd":0.011564,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5576,"output_tokens":2046,"usd":0.039515,"stage2_stop_reason":"end_turn"},"total_usd":0.051079,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"P. falciparum SRP54 is a component of the P. falciparum SRP complex, which is composed of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) and a 303 nt SRP RNA. Transgenic parasites expressing SRP54-GFP chimeric protein showed nucleo-cytoplasmic localization, indicating SRP54 shuttles between nucleus and cytoplasm.\",\n      \"method\": \"Transgenic parasite lines expressing GFP-chimeric proteins; co-localization fluorescence microscopy; characterization of SRP complex composition\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by live imaging with GFP fusion in transgenic parasites, complex membership established, single lab\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Ivermectin, an inhibitor of importin α/β-mediated nuclear import, blocked the nuclear import of PfSRP polypeptides including SRP54 at submicromolar concentrations and killed parasites, indicating SRP54 nuclear import depends on the importin α/β pathway.\",\n      \"method\": \"Treatment of transgenic GFP-SRP expressing parasites with ivermectin and other nuclear import/export inhibitors; assessment of subcellular localization and parasite viability\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — pharmacological inhibitor experiment in live transgenic parasites with localization readout, single lab, single method\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Bioinformatic analysis identified a P. falciparum SRP54 homologue in the P. falciparum genome, placing it as a predicted component of the SRP-mediated co-translational protein translocation pathway alongside SRP RNA, SRP9, SRP14, and SRP19, with a hypothetical SRP receptor partner also predicted.\",\n      \"method\": \"Bioinformatics/genome analysis\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation in this paper\",\n      \"pmids\": [\"17919451\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum SRP54 is a subunit of the six-polypeptide SRP ribonucleoprotein complex that undergoes nucleo-cytoplasmic shuttling via the importin α/β nuclear import pathway, and pharmacological blockade of this import kills parasites.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1450100 (SRP54) is a subunit of the P. falciparum signal recognition particle, a ribonucleoprotein complex composed of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) assembled on a 303 nt SRP RNA [#0]. In transgenic parasites, an SRP54-GFP fusion displays nucleo-cytoplasmic localization, indicating that SRP54 shuttles between the nucleus and cytoplasm [#0]. This nuclear import depends on the importin \\u03b1/\\u03b2 pathway: ivermectin, an inhibitor of importin \\u03b1/\\u03b2-mediated import, blocks nuclear entry of SRP polypeptides including SRP54 at submicromolar concentrations and kills parasites [#1]. Beyond its membership in the SRP complex and its importin-dependent shuttling behavior, no direct biochemical or functional characterization of SRP54's role in co-translational protein translocation has been established for this gene in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Before any experimental work, it was unknown whether P. falciparum encodes SRP machinery; genome analysis established SRP54 as a predicted component of the parasite's SRP-mediated co-translational translocation pathway.\",\n      \"evidence\": \"Bioinformatic/genome analysis identifying an SRP54 homologue alongside SRP RNA and other SRP subunits\",\n      \"pmids\": [\"17919451\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, no experimental validation of SRP54 function or complex membership\",\n        \"Predicted SRP receptor partner not experimentally confirmed\",\n        \"No demonstration that the homologue is expressed or assembled into a particle\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To move beyond prediction, the SRP complex was characterized and SRP54's subcellular behavior was determined, establishing it as a bona fide six-polypeptide complex subunit that unexpectedly shuttles between nucleus and cytoplasm.\",\n      \"evidence\": \"SRP complex composition analysis and live-imaging co-localization of an SRP54-GFP fusion in transgenic parasites\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single localization method; no orthogonal confirmation of complex stoichiometry\",\n        \"Functional consequence of nuclear shuttling for SRP54 not defined\",\n        \"No direct evidence that SRP54 performs co-translational targeting in the parasite\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"The route of SRP54 nuclear import was addressed pharmacologically, showing dependence on the importin \\u03b1/\\u03b2 pathway and linking this trafficking step to parasite viability.\",\n      \"evidence\": \"Ivermectin and other import/export inhibitor treatment of transgenic GFP-SRP parasites with localization and viability readouts\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Ivermectin effect is pharmacological and may act on multiple importin cargoes, so lethality cannot be attributed solely to SRP54 mislocalization\",\n        \"Direct interaction between SRP54 and importin \\u03b1/\\u03b2 not demonstrated\",\n        \"The import signal within SRP54 was not mapped\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether P. falciparum SRP54 performs the canonical signal-peptide recognition and co-translational translocation activity, and what its nuclear shuttling accomplishes mechanistically.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct assay of SRP54 signal-sequence binding or GTPase/SRP receptor engagement in the parasite\",\n        \"Functional role of nucleo-cytoplasmic shuttling uncharacterized\",\n        \"No genetic loss-of-function data for SRP54 specifically\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006614\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0006606\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"Signal recognition particle (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72 + 303 nt SRP RNA)\"\n    ],\n    \"partners\": [\n      \"importin \\u03b1/\\u03b2 nuclear import pathway\"\n    ],\n    \"other_free_text\": [\n      \"SRP54-GFP fusion shows nucleo-cytoplasmic shuttling in transgenic P. falciparum [#0]\",\n      \"Ivermectin blocks importin \\u03b1/\\u03b2-dependent nuclear import of SRP polypeptides including SRP54 and kills parasites [#1]\",\n      \"SRP54 was initially identified as a predicted SRP component by genome bioinformatics [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1450100","name":null,"product":"signal recognition particle subunit SRP54","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1313800","name":null,"product":"signal recognition particle subunit SRP54, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1232000","name":null,"product":"signal recognition particle subunit SRP54, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRP54","evaluation":null}