{"gene":"PF3D7_0729000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2014,"finding":"P. falciparum SRP9 is one of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) that compose the P. falciparum signal recognition particle together with a 303 nt SRP RNA; transgenic parasites expressing SRP9-GFP chimeric protein showed nucleo-cytoplasmic localization, and ivermectin (an importin α/β-mediated nuclear import inhibitor) blocked nuclear import of PfSRP polypeptides including SRP9 at submicromolar concentrations, killing the parasites.","method":"Transgenic parasite lines expressing GFP-chimeric proteins, co-localization fluorescence microscopy, pharmacological inhibition with ivermectin","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional consequence (parasite killing), single lab, two orthogonal methods (live imaging + pharmacological inhibition)","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"The P. falciparum SRP Alu domain, formed by the SRP9/14 heterodimer and Alu RNA, adopts a non-canonical open Y-shaped conformation (rather than the closed loop-loop pseudoknot seen in human/prokaryotic counterparts), as determined by NMR, SAXS, and cryo-EM; cytoplasmic P. falciparum ribosomes recognize both the open PfAlu domain and closed human Alu domain with nanomolar affinity, whereas human ribosomes do not provide high-affinity binding sites for either Alu domain.","method":"NMR, SAXS, cryo-EM structural analysis; ribosome-binding affinity measurements","journal":"Communications biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — three independent structural methods (NMR, SAXS, cryo-EM) plus functional binding assays in a single rigorous study","pmids":["34017052"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum SRP9 (PF3D7_0729000) is a subunit of the six-polypeptide P. falciparum SRP complex that shuttles between nucleus and cytoplasm (nuclear import dependent on importin α/β), and together with SRP14 forms the Alu domain of the SRP, which adopts a distinctive open Y-shaped conformation that nonetheless allows nanomolar-affinity binding to P. falciparum ribosomes, enabling translation retardation during co-translational protein targeting to the ER."},"narrative":{"mechanistic_narrative":"PF3D7_0729000 (SRP9) is a subunit of the six-polypeptide P. falciparum signal recognition particle, which assembles with a 303 nt SRP RNA to mediate co-translational protein targeting [PMID:24434517]. Within this complex, SRP9 partners with SRP14 and Alu RNA to form the Alu domain, which in P. falciparum adopts a non-canonical open Y-shaped conformation rather than the closed loop-loop pseudoknot of human and prokaryotic counterparts; despite this open geometry, the domain binds cytoplasmic P. falciparum ribosomes with nanomolar affinity, a species-specific recognition not reproduced by human ribosomes [PMID:34017052]. In parasites, SRP9-GFP shows nucleo-cytoplasmic distribution, and its nuclear import depends on the importin α/β pathway, since the import inhibitor ivermectin blocks nuclear entry of SRP polypeptides including SRP9 at submicromolar concentrations and kills the parasite [PMID:24434517]. Beyond its role in the SRP Alu domain and its shuttling behavior, no further gene-specific mechanistic detail for SRP9 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing that SRP9 is a bona fide constituent of the parasite SRP and defining its subcellular trafficking answered whether this subunit functions within the P. falciparum SRP and how it reaches its site of action.","evidence":"Transgenic parasites expressing SRP9-GFP with co-localization microscopy and pharmacological nuclear-import inhibition by ivermectin","pmids":["24434517"],"confidence":"Medium","gaps":["Does not resolve which cargo or targeting events SRP9 specifically supports","Killing by ivermectin is not specific to SRP9 and does not isolate its individual contribution","No direct demonstration of SRP9 function in co-translational targeting"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Determining the structure of the SRP9/14-Alu RNA domain resolved whether the parasite Alu domain shares the conserved closed architecture and how it engages ribosomes, revealing a divergent open conformation with species-selective ribosome binding.","evidence":"NMR, SAXS, and cryo-EM structural analysis of the Alu domain with ribosome-binding affinity measurements","pmids":["34017052"],"confidence":"High","gaps":["Does not isolate the individual contribution of SRP9 versus SRP14 to the open conformation or ribosome binding","Functional consequence of the open geometry for translation retardation in living parasites not demonstrated","Structural basis of the P. falciparum ribosome selectivity not defined at residue level"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular role of SRP9 within the Alu domain, its individual contribution to ribosome binding and translation retardation, and any function outside the SRP complex remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No subunit-resolved dissection of SRP9 within the Alu heterodimer","No direct evidence linking SRP9 to translation elongation arrest in vivo","No characterization of SRP9 function independent of the SRP complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Signal recognition particle (six-polypeptide SRP9/SRP14/SRP19/SRP54/SRP68/SRP72 with 303 nt SRP RNA)","SRP Alu domain (SRP9/14 heterodimer with Alu RNA)"],"partners":["SRP14","SRP RNA / ALU RNA","SRP19","SRP54","SRP68","SRP72","IMPORTIN Α/Β (NUCLEAR IMPORT)","P. FALCIPARUM CYTOPLASMIC RIBOSOME"],"other_free_text":["Nuclear import of SRP9 is ivermectin-sensitive, and ivermectin treatment kills P. falciparum [#0]","The P. falciparum Alu domain adopts a non-canonical open Y-shaped conformation distinct from the closed human/prokaryotic architecture [#1]","Ribosome recognition of the Alu domain is species-selective: P. falciparum ribosomes bind both open PfAlu and closed human Alu domains at nanomolar affinity, whereas human ribosomes do not [#1]"]}},"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":["SRP9"],"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":["SRP9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34017052","id":"PMC_34017052","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":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4002,"output_tokens":777,"usd":0.011831,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5465,"output_tokens":2018,"usd":0.038887,"stage2_stop_reason":"end_turn"},"total_usd":0.050718,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"P. falciparum SRP9 is one of six polypeptides (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) that compose the P. falciparum signal recognition particle together with a 303 nt SRP RNA; transgenic parasites expressing SRP9-GFP chimeric protein showed nucleo-cytoplasmic localization, and ivermectin (an importin α/β-mediated nuclear import inhibitor) blocked nuclear import of PfSRP polypeptides including SRP9 at submicromolar concentrations, killing the parasites.\",\n      \"method\": \"Transgenic parasite lines expressing GFP-chimeric proteins, co-localization fluorescence microscopy, pharmacological inhibition with ivermectin\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional consequence (parasite killing), single lab, two orthogonal methods (live imaging + pharmacological inhibition)\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The P. falciparum SRP Alu domain, formed by the SRP9/14 heterodimer and Alu RNA, adopts a non-canonical open Y-shaped conformation (rather than the closed loop-loop pseudoknot seen in human/prokaryotic counterparts), as determined by NMR, SAXS, and cryo-EM; cytoplasmic P. falciparum ribosomes recognize both the open PfAlu domain and closed human Alu domain with nanomolar affinity, whereas human ribosomes do not provide high-affinity binding sites for either Alu domain.\",\n      \"method\": \"NMR, SAXS, cryo-EM structural analysis; ribosome-binding affinity measurements\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — three independent structural methods (NMR, SAXS, cryo-EM) plus functional binding assays in a single rigorous study\",\n      \"pmids\": [\"34017052\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum SRP9 (PF3D7_0729000) is a subunit of the six-polypeptide P. falciparum SRP complex that shuttles between nucleus and cytoplasm (nuclear import dependent on importin α/β), and together with SRP14 forms the Alu domain of the SRP, which adopts a distinctive open Y-shaped conformation that nonetheless allows nanomolar-affinity binding to P. falciparum ribosomes, enabling translation retardation during co-translational protein targeting to the ER.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_0729000 (SRP9) is a subunit of the six-polypeptide P. falciparum signal recognition particle, which assembles with a 303 nt SRP RNA to mediate co-translational protein targeting [#0]. Within this complex, SRP9 partners with SRP14 and Alu RNA to form the Alu domain, which in P. falciparum adopts a non-canonical open Y-shaped conformation rather than the closed loop-loop pseudoknot of human and prokaryotic counterparts; despite this open geometry, the domain binds cytoplasmic P. falciparum ribosomes with nanomolar affinity, a species-specific recognition not reproduced by human ribosomes [#1]. In parasites, SRP9-GFP shows nucleo-cytoplasmic distribution, and its nuclear import depends on the importin \\u03b1/\\u03b2 pathway, since the import inhibitor ivermectin blocks nuclear entry of SRP polypeptides including SRP9 at submicromolar concentrations and kills the parasite [#0]. Beyond its role in the SRP Alu domain and its shuttling behavior, no further gene-specific mechanistic detail for SRP9 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that SRP9 is a bona fide constituent of the parasite SRP and defining its subcellular trafficking answered whether this subunit functions within the P. falciparum SRP and how it reaches its site of action.\",\n      \"evidence\": \"Transgenic parasites expressing SRP9-GFP with co-localization microscopy and pharmacological nuclear-import inhibition by ivermectin\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not resolve which cargo or targeting events SRP9 specifically supports\",\n        \"Killing by ivermectin is not specific to SRP9 and does not isolate its individual contribution\",\n        \"No direct demonstration of SRP9 function in co-translational targeting\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Determining the structure of the SRP9/14-Alu RNA domain resolved whether the parasite Alu domain shares the conserved closed architecture and how it engages ribosomes, revealing a divergent open conformation with species-selective ribosome binding.\",\n      \"evidence\": \"NMR, SAXS, and cryo-EM structural analysis of the Alu domain with ribosome-binding affinity measurements\",\n      \"pmids\": [\"34017052\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not isolate the individual contribution of SRP9 versus SRP14 to the open conformation or ribosome binding\",\n        \"Functional consequence of the open geometry for translation retardation in living parasites not demonstrated\",\n        \"Structural basis of the P. falciparum ribosome selectivity not defined at residue level\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular role of SRP9 within the Alu domain, its individual contribution to ribosome binding and translation retardation, and any function outside the SRP complex remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No subunit-resolved dissection of SRP9 within the Alu heterodimer\",\n        \"No direct evidence linking SRP9 to translation elongation arrest in vivo\",\n        \"No characterization of SRP9 function independent of the SRP complex\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0043022\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0008312\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006614\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006606\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"Signal recognition particle (six-polypeptide SRP9/SRP14/SRP19/SRP54/SRP68/SRP72 with 303 nt SRP RNA)\",\n      \"SRP Alu domain (SRP9/14 heterodimer with Alu RNA)\"\n    ],\n    \"partners\": [\n      \"SRP14\",\n      \"SRP RNA / Alu RNA\",\n      \"SRP19\",\n      \"SRP54\",\n      \"SRP68\",\n      \"SRP72\",\n      \"importin \\u03b1/\\u03b2 (nuclear import)\",\n      \"P. falciparum cytoplasmic ribosome\"\n    ],\n    \"other_free_text\": [\n      \"Nuclear import of SRP9 is ivermectin-sensitive, and ivermectin treatment kills P. falciparum [#0]\",\n      \"The P. falciparum Alu domain adopts a non-canonical open Y-shaped conformation distinct from the closed human/prokaryotic architecture [#1]\",\n      \"Ribosome recognition of the Alu domain is species-selective: P. falciparum ribosomes bind both open PfAlu and closed human Alu domains at nanomolar affinity, whereas human ribosomes do not [#1]\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0729000","name":null,"product":"signal recognition particle subunit SRP9","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0213100","name":null,"product":"signal recognition particle subunit SRP9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0213600","name":null,"product":"signal recognition particle subunit SRP9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRP9","evaluation":null}