{"gene":"PF3D7_1216300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2014,"finding":"P. falciparum SRP19 is a component of the P. falciparum SRP ribonucleoprotein complex, which also includes SRP9, SRP14, SRP54, SRP68, SRP72, and a 303 nt SRP RNA. SRP19-GFP chimeric protein shows nucleo-cytoplasmic localization in asexual blood stages, and ivermectin (an importin α/β-mediated nuclear import inhibitor) blocks nuclear import of PfSRP polypeptides including SRP19 at submicromolar concentrations, killing parasites.","method":"Transgenic parasite lines expressing SRP19-GFP chimeric protein; co-localization fluorescence microscopy; pharmacological inhibition with ivermectin","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by live GFP imaging in transgenic parasites plus functional consequence (parasite killing) from ivermectin treatment, single lab, two orthogonal methods","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"SRP19, together with SRP54 and SRP68/72, constitutes the S domain of the P. falciparum SRP, which is responsible for signal recognition and receptor targeting (as opposed to the Alu domain). Co-localization studies in asexual blood stages demonstrated in vivo association of SRP9/14 with SRP19 and SRP54, confirming the in vivo existence of the PfSRP complex.","method":"Co-localization studies in asexual blood stages (referenced as established prior work); cryo-EM, NMR, SAXS of the Alu domain (the paper itself focuses on Alu domain structure, but references SRP19 as S-domain component with in vivo co-localization evidence)","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — co-localization data cited from prior work; the structural paper confirms domain assignment of SRP19 to the S domain but does not itself reconstitute SRP19 function; single method for SRP19 specifically","pmids":["34017052"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"SRP19 was detected in protein interaction cluster 32 in a large-scale P. falciparum interactome study using blue native-polyacrylamide gel electrophoresis coupled with quantitative mass spectrometry, placing it in a protein cluster alongside other parasite proteins in schizonts.","method":"Blue native-PAGE combined with quantitative mass spectrometry and machine learning-based interaction prediction","journal":"Cell reports","confidence":"Low","confidence_rationale":"Tier 4 / Weak — pan-interactome catalog; SRP19 cluster membership is noted but no specific mechanistic experiment was performed on SRP19 itself","pmids":["31390575"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum SRP19 (PF3D7_1216300) is a component of the S domain of the P. falciparum signal recognition particle ribonucleoprotein complex (together with SRP9, SRP14, SRP54, SRP68, SRP72, and a 303 nt SRP RNA), participates in co-translational protein targeting to the ER, and undergoes nucleo-cytoplasmic shuttling in asexual blood stages that can be blocked by ivermectin-mediated inhibition of importin α/β-dependent nuclear import."},"narrative":{"mechanistic_narrative":"PF3D7_1216300 (SRP19) is a constituent of the Plasmodium falciparum signal recognition particle (SRP), a ribonucleoprotein complex comprising SRP9, SRP14, SRP54, SRP68, SRP72 and a 303 nt SRP RNA [PMID:24434517]. Within this assembly, SRP19 belongs to the S domain — together with SRP54 and SRP68/72 — which is responsible for signal recognition and receptor targeting, as distinct from the Alu domain [PMID:34017052]. In vivo co-localization in asexual blood stages demonstrates association of SRP19 with SRP9/14 and SRP54, confirming assembly of the PfSRP complex in the parasite [PMID:34017052]. An SRP19-GFP chimera shows nucleo-cytoplasmic localization in asexual blood stages, and nuclear import of SRP19 (and other PfSRP polypeptides) is blocked by the importin α/β inhibitor ivermectin at submicromolar concentrations, which kills parasites [PMID:24434517]. Beyond its assignment to the SRP complex and S domain and this shuttling behavior, no SRP19-specific molecular mechanism has been reconstituted or characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing that SRP19 is a genuine component of the parasite SRP and that its nuclear import can be pharmacologically disrupted linked an SRP subunit to a druggable trafficking step in the parasite.","evidence":"SRP19-GFP transgenic parasite lines with co-localization microscopy and ivermectin inhibition in P. falciparum asexual blood stages","pmids":["24434517"],"confidence":"Medium","gaps":["The specific molecular activity of SRP19 within the complex was not assayed directly","Whether ivermectin killing is mechanistically attributable to SRP19 import loss specifically, versus general PfSRP disruption, is not resolved","The functional role of nucleo-cytoplasmic shuttling for a canonically cytoplasmic SRP subunit is not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Large-scale interactome profiling placed SRP19 in a defined protein cluster, providing native-complex evidence consistent with its complex membership but no SRP19-directed mechanism.","evidence":"Blue native-PAGE with quantitative mass spectrometry and machine-learning interaction prediction in P. falciparum schizonts","pmids":["31390575"],"confidence":"Low","gaps":["Pan-interactome catalog with no experiment performed specifically on SRP19","Cluster membership does not establish direct binding partners for SRP19"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Domain assignment resolved SRP19 to the S domain of the PfSRP responsible for signal recognition and receptor targeting, distinguishing its functional context from the Alu domain.","evidence":"Structural study focused on the Alu domain (cryo-EM/NMR/SAXS) referencing prior in vivo co-localization of SRP19 with SRP9/14 and SRP54 in P. falciparum asexual blood stages","pmids":["34017052"],"confidence":"Medium","gaps":["The paper did not reconstitute or structurally resolve SRP19 itself","Direct demonstration of SRP19's contribution to signal recognition in the parasite is absent"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The SRP19-specific molecular function — its RNA-binding and role in assembling or stabilizing the S domain and enabling co-translational ER targeting in P. falciparum — remains uncharacterized experimentally.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstitution of SRP19 activity or direct binding assay in the corpus","No genetic knockout/knockdown phenotype for SRP19 specifically","No structural model of SRP19 within the PfSRP"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Signal recognition particle (PfSRP: SRP9, SRP14, SRP19, SRP54, SRP68, SRP72, 303 nt SRP RNA)","SRP S domain (SRP19, SRP54, SRP68/72)"],"partners":["SRP9","SRP14","SRP54","SRP68","SRP72"],"other_free_text":["Nucleo-cytoplasmic shuttling of SRP19-GFP in asexual blood stages; nuclear import blocked by importin α/β inhibitor ivermectin, which kills parasites [#0]","Detected in P. falciparum interactome cluster 32 by BN-PAGE/quantitative MS in schizonts [#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":["SRP19"],"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":["SRP19"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38890312","id":"","title":"Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38890312","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP19"],"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":["SRP19"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31390575","id":"","title":"Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.","date":"2019","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/31390575","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRP19"],"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":["SRP19"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7544,"output_tokens":1044,"usd":0.019146,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5844,"output_tokens":2047,"usd":0.040197,"stage2_stop_reason":"end_turn"},"total_usd":0.059343,"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\": 2014,\n      \"finding\": \"P. falciparum SRP19 is a component of the P. falciparum SRP ribonucleoprotein complex, which also includes SRP9, SRP14, SRP54, SRP68, SRP72, and a 303 nt SRP RNA. SRP19-GFP chimeric protein shows nucleo-cytoplasmic localization in asexual blood stages, and ivermectin (an importin α/β-mediated nuclear import inhibitor) blocks nuclear import of PfSRP polypeptides including SRP19 at submicromolar concentrations, killing parasites.\",\n      \"method\": \"Transgenic parasite lines expressing SRP19-GFP chimeric protein; co-localization fluorescence microscopy; pharmacological inhibition with ivermectin\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by live GFP imaging in transgenic parasites plus functional consequence (parasite killing) from ivermectin treatment, single lab, two orthogonal methods\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"SRP19, together with SRP54 and SRP68/72, constitutes the S domain of the P. falciparum SRP, which is responsible for signal recognition and receptor targeting (as opposed to the Alu domain). Co-localization studies in asexual blood stages demonstrated in vivo association of SRP9/14 with SRP19 and SRP54, confirming the in vivo existence of the PfSRP complex.\",\n      \"method\": \"Co-localization studies in asexual blood stages (referenced as established prior work); cryo-EM, NMR, SAXS of the Alu domain (the paper itself focuses on Alu domain structure, but references SRP19 as S-domain component with in vivo co-localization evidence)\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — co-localization data cited from prior work; the structural paper confirms domain assignment of SRP19 to the S domain but does not itself reconstitute SRP19 function; single method for SRP19 specifically\",\n      \"pmids\": [\"34017052\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"SRP19 was detected in protein interaction cluster 32 in a large-scale P. falciparum interactome study using blue native-polyacrylamide gel electrophoresis coupled with quantitative mass spectrometry, placing it in a protein cluster alongside other parasite proteins in schizonts.\",\n      \"method\": \"Blue native-PAGE combined with quantitative mass spectrometry and machine learning-based interaction prediction\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — pan-interactome catalog; SRP19 cluster membership is noted but no specific mechanistic experiment was performed on SRP19 itself\",\n      \"pmids\": [\"31390575\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum SRP19 (PF3D7_1216300) is a component of the S domain of the P. falciparum signal recognition particle ribonucleoprotein complex (together with SRP9, SRP14, SRP54, SRP68, SRP72, and a 303 nt SRP RNA), participates in co-translational protein targeting to the ER, and undergoes nucleo-cytoplasmic shuttling in asexual blood stages that can be blocked by ivermectin-mediated inhibition of importin α/β-dependent nuclear import.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1216300 (SRP19) is a constituent of the Plasmodium falciparum signal recognition particle (SRP), a ribonucleoprotein complex comprising SRP9, SRP14, SRP54, SRP68, SRP72 and a 303 nt SRP RNA [#0]. Within this assembly, SRP19 belongs to the S domain — together with SRP54 and SRP68/72 — which is responsible for signal recognition and receptor targeting, as distinct from the Alu domain [#1]. In vivo co-localization in asexual blood stages demonstrates association of SRP19 with SRP9/14 and SRP54, confirming assembly of the PfSRP complex in the parasite [#1]. An SRP19-GFP chimera shows nucleo-cytoplasmic localization in asexual blood stages, and nuclear import of SRP19 (and other PfSRP polypeptides) is blocked by the importin \\u03b1/\\u03b2 inhibitor ivermectin at submicromolar concentrations, which kills parasites [#0]. Beyond its assignment to the SRP complex and S domain and this shuttling behavior, no SRP19-specific molecular mechanism has been reconstituted or characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that SRP19 is a genuine component of the parasite SRP and that its nuclear import can be pharmacologically disrupted linked an SRP subunit to a druggable trafficking step in the parasite.\",\n      \"evidence\": \"SRP19-GFP transgenic parasite lines with co-localization microscopy and ivermectin inhibition in P. falciparum asexual blood stages\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific molecular activity of SRP19 within the complex was not assayed directly\",\n        \"Whether ivermectin killing is mechanistically attributable to SRP19 import loss specifically, versus general PfSRP disruption, is not resolved\",\n        \"The functional role of nucleo-cytoplasmic shuttling for a canonically cytoplasmic SRP subunit is not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Large-scale interactome profiling placed SRP19 in a defined protein cluster, providing native-complex evidence consistent with its complex membership but no SRP19-directed mechanism.\",\n      \"evidence\": \"Blue native-PAGE with quantitative mass spectrometry and machine-learning interaction prediction in P. falciparum schizonts\",\n      \"pmids\": [\"31390575\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Pan-interactome catalog with no experiment performed specifically on SRP19\",\n        \"Cluster membership does not establish direct binding partners for SRP19\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Domain assignment resolved SRP19 to the S domain of the PfSRP responsible for signal recognition and receptor targeting, distinguishing its functional context from the Alu domain.\",\n      \"evidence\": \"Structural study focused on the Alu domain (cryo-EM/NMR/SAXS) referencing prior in vivo co-localization of SRP19 with SRP9/14 and SRP54 in P. falciparum asexual blood stages\",\n      \"pmids\": [\"34017052\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The paper did not reconstitute or structurally resolve SRP19 itself\",\n        \"Direct demonstration of SRP19's contribution to signal recognition in the parasite is absent\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The SRP19-specific molecular function — its RNA-binding and role in assembling or stabilizing the S domain and enabling co-translational ER targeting in P. falciparum — remains uncharacterized experimentally.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No reconstitution of SRP19 activity or direct binding assay in the corpus\",\n        \"No genetic knockout/knockdown phenotype for SRP19 specifically\",\n        \"No structural model of SRP19 within the PfSRP\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\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\": [1]}\n    ],\n    \"complexes\": [\n      \"Signal recognition particle (PfSRP: SRP9, SRP14, SRP19, SRP54, SRP68, SRP72, 303 nt SRP RNA)\",\n      \"SRP S domain (SRP19, SRP54, SRP68/72)\"\n    ],\n    \"partners\": [\n      \"SRP9\",\n      \"SRP14\",\n      \"SRP54\",\n      \"SRP68\",\n      \"SRP72\"\n    ],\n    \"other_free_text\": [\n      \"Nucleo-cytoplasmic shuttling of SRP19-GFP in asexual blood stages; nuclear import blocked by importin \\u03b1/\\u03b2 inhibitor ivermectin, which kills parasites [#0]\",\n      \"Detected in P. falciparum interactome cluster 32 by BN-PAGE/quantitative MS in schizonts [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1216300","name":null,"product":"signal recognition particle subunit SRP19","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1432000","name":null,"product":"signal recognition particle subunit SRP19, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1435900","name":null,"product":"signal recognition particle subunit SRP19, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRP19","evaluation":null}