{"gene":"PF3D7_1136400","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2014,"finding":"P. falciparum SRP72 (PF3D7_1136400) is one of six polypeptide components (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) of the P. falciparum signal recognition particle ribonucleoprotein complex, which also contains a 303 nt SRP RNA. SRP72-GFP transgenic parasites showed nucleo-cytoplasmic localization, and ivermectin (an inhibitor of importin α/β-mediated nuclear import) blocked nuclear import of PfSRP polypeptides including SRP72 at submicromolar concentrations, killing the parasites.","method":"Transgenic parasite lines expressing SRP72-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 (GFP imaging + pharmacological inhibition)","pmids":["24434517"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"PfSRP72 (PF3D7_1136400) was identified in the cytosolic interactome of PfPRMT5 by mass spectrometry, placing SRP72 as a potential interactor of the type II protein arginine methyltransferase PfPRMT5. The paper notes (as a hypothesis, not experimentally confirmed in P. falciparum) that human SRP68 and SRP72 function as transcriptional regulators regulated by PRMT5.","method":"Interactome/co-immunoprecipitation mass spectrometry of PfPRMT5","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/MS pulldown identifying SRP72 as a candidate interactor; no functional follow-up on SRP72 itself in this paper","pmids":["37349497"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum SRP72 (PF3D7_1136400) is a subunit of the P. falciparum signal recognition particle ribonucleoprotein complex that displays nucleo-cytoplasmic localization in blood-stage parasites, and its nuclear import is mediated via the importin α/β pathway and can be blocked by ivermectin; it has also been detected in the cytosolic interactome of PfPRMT5, but no further mechanistic detail about SRP72's specific molecular function in P. falciparum has been established."},"narrative":{"mechanistic_narrative":"SRP72 (PF3D7_1136400) is one of six polypeptide components of the P. falciparum signal recognition particle (PfSRP) ribonucleoprotein complex, which also contains a 303 nt SRP RNA [PMID:24434517]. In blood-stage parasites, SRP72-GFP displays nucleo-cytoplasmic localization, and its nuclear import — together with that of the other PfSRP polypeptides — is mediated by the importin α/β pathway, as evidenced by the ability of ivermectin to block nuclear import at submicromolar concentrations while killing the parasites [PMID:24434517]. Beyond its membership in the PfSRP complex and this nuclear-import dependence, no specific molecular function has been established for SRP72 in P. falciparum in the available corpus; it has additionally been detected in the cytosolic interactome of the type II protein arginine methyltransferase PfPRMT5 [PMID:37349497].","teleology":[{"year":2014,"claim":"Establishing that P. falciparum encodes an assembled SRP complex answered whether the parasite possesses this ribonucleoprotein machinery and, unexpectedly, placed SRP72 in the nucleus as well as the cytoplasm, revealing an importin-dependent nuclear-import step exploitable pharmacologically.","evidence":"Transgenic SRP72-GFP parasite lines with fluorescence co-localization microscopy and pharmacological inhibition of importin α/β by ivermectin","pmids":["24434517"],"confidence":"Medium","gaps":["The specific molecular activity of SRP72 within the PfSRP complex (e.g. contribution to signal-sequence recognition or translocation) is not defined","The functional purpose of nucleo-cytoplasmic shuttling and nuclear localization of SRP72 is not established","Whether ivermectin acts directly on SRP72 import or on the broader importin pathway is not distinguished for this subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Interactome profiling asked what proteins associate with PfPRMT5 and placed SRP72 among cytosolic candidate interactors, raising the possibility of a regulatory link, though no function of SRP72 itself was tested.","evidence":"Co-immunoprecipitation mass spectrometry of PfPRMT5 in P. falciparum","pmids":["37349497"],"confidence":"Low","gaps":["Single Co-IP/MS pulldown with no functional follow-up on SRP72 and no reciprocal validation","Whether SRP72 is a direct PfPRMT5 interactor or an indirect co-precipitant is unresolved","The transcriptional-regulator role invoked for human SRP68/SRP72 was a hypothesis, not tested for PF3D7_1136400"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular function of SRP72 within the PfSRP complex, the biological significance of its nuclear localization, and the reality and consequence of its association with PfPRMT5 remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct assay of SRP72's biochemical role in co-translational targeting or SRP assembly in P. falciparum","No structural model of PfSRP72 or its contacts within the complex","No functional consequence established for the SRP72–PfPRMT5 association"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["signal recognition particle (PfSRP) ribonucleoprotein complex"],"partners":["PFPRMT5 (CYTOSOLIC INTERACTOME, CANDIDATE)"],"other_free_text":["Nuclear import of SRP72 (with other PfSRP polypeptides) is importin α/β-dependent and blocked by ivermectin at submicromolar concentrations, which kills blood-stage parasites [#0]","PfSRP complex comprises SRP9, SRP14, SRP19, SRP54, SRP68, SRP72 and a 303 nt SRP RNA [#0]"]}},"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":["SRP72"],"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":["SRP72"],"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":["SRP72"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5630,"output_tokens":794,"usd":0.0144,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5450,"output_tokens":1806,"usd":0.0362,"stage2_stop_reason":"end_turn"},"total_usd":0.0506,"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\": \"P. falciparum SRP72 (PF3D7_1136400) is one of six polypeptide components (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) of the P. falciparum signal recognition particle ribonucleoprotein complex, which also contains a 303 nt SRP RNA. SRP72-GFP transgenic parasites showed nucleo-cytoplasmic localization, and ivermectin (an inhibitor of importin α/β-mediated nuclear import) blocked nuclear import of PfSRP polypeptides including SRP72 at submicromolar concentrations, killing the parasites.\",\n      \"method\": \"Transgenic parasite lines expressing SRP72-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 (GFP imaging + pharmacological inhibition)\",\n      \"pmids\": [\"24434517\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"PfSRP72 (PF3D7_1136400) was identified in the cytosolic interactome of PfPRMT5 by mass spectrometry, placing SRP72 as a potential interactor of the type II protein arginine methyltransferase PfPRMT5. The paper notes (as a hypothesis, not experimentally confirmed in P. falciparum) that human SRP68 and SRP72 function as transcriptional regulators regulated by PRMT5.\",\n      \"method\": \"Interactome/co-immunoprecipitation mass spectrometry of PfPRMT5\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/MS pulldown identifying SRP72 as a candidate interactor; no functional follow-up on SRP72 itself in this paper\",\n      \"pmids\": [\"37349497\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum SRP72 (PF3D7_1136400) is a subunit of the P. falciparum signal recognition particle ribonucleoprotein complex that displays nucleo-cytoplasmic localization in blood-stage parasites, and its nuclear import is mediated via the importin α/β pathway and can be blocked by ivermectin; it has also been detected in the cytosolic interactome of PfPRMT5, but no further mechanistic detail about SRP72's specific molecular function in P. falciparum has been established.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"SRP72 (PF3D7_1136400) is one of six polypeptide components of the P. falciparum signal recognition particle (PfSRP) ribonucleoprotein complex, which also contains a 303 nt SRP RNA [#0]. In blood-stage parasites, SRP72-GFP displays nucleo-cytoplasmic localization, and its nuclear import — together with that of the other PfSRP polypeptides — is mediated by the importin \\u03b1/\\u03b2 pathway, as evidenced by the ability of ivermectin to block nuclear import at submicromolar concentrations while killing the parasites [#0]. Beyond its membership in the PfSRP complex and this nuclear-import dependence, no specific molecular function has been established for SRP72 in P. falciparum in the available corpus; it has additionally been detected in the cytosolic interactome of the type II protein arginine methyltransferase PfPRMT5 [#1].\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing that P. falciparum encodes an assembled SRP complex answered whether the parasite possesses this ribonucleoprotein machinery and, unexpectedly, placed SRP72 in the nucleus as well as the cytoplasm, revealing an importin-dependent nuclear-import step exploitable pharmacologically.\",\n      \"evidence\": \"Transgenic SRP72-GFP parasite lines with fluorescence co-localization microscopy and pharmacological inhibition of importin \\u03b1/\\u03b2 by ivermectin\",\n      \"pmids\": [\"24434517\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"The specific molecular activity of SRP72 within the PfSRP complex (e.g. contribution to signal-sequence recognition or translocation) is not defined\",\n        \"The functional purpose of nucleo-cytoplasmic shuttling and nuclear localization of SRP72 is not established\",\n        \"Whether ivermectin acts directly on SRP72 import or on the broader importin pathway is not distinguished for this subunit\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Interactome profiling asked what proteins associate with PfPRMT5 and placed SRP72 among cytosolic candidate interactors, raising the possibility of a regulatory link, though no function of SRP72 itself was tested.\",\n      \"evidence\": \"Co-immunoprecipitation mass spectrometry of PfPRMT5 in P. falciparum\",\n      \"pmids\": [\"37349497\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Single Co-IP/MS pulldown with no functional follow-up on SRP72 and no reciprocal validation\",\n        \"Whether SRP72 is a direct PfPRMT5 interactor or an indirect co-precipitant is unresolved\",\n        \"The transcriptional-regulator role invoked for human SRP68/SRP72 was a hypothesis, not tested for PF3D7_1136400\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function of SRP72 within the PfSRP complex, the biological significance of its nuclear localization, and the reality and consequence of its association with PfPRMT5 remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No direct assay of SRP72's biochemical role in co-translational targeting or SRP assembly in P. falciparum\",\n        \"No structural model of PfSRP72 or its contacts within the complex\",\n        \"No functional consequence established for the SRP72\\u2013PfPRMT5 association\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006614\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"signal recognition particle (PfSRP) ribonucleoprotein complex\"\n    ],\n    \"partners\": [\n      \"PfPRMT5 (cytosolic interactome, candidate)\"\n    ],\n    \"other_free_text\": [\n      \"Nuclear import of SRP72 (with other PfSRP polypeptides) is importin \\u03b1/\\u03b2-dependent and blocked by ivermectin at submicromolar concentrations, which kills blood-stage parasites [#0]\",\n      \"PfSRP complex comprises SRP9, SRP14, SRP19, SRP54, SRP68, SRP72 and a 303 nt SRP RNA [#0]\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1136400","name":null,"product":"signal recognition particle subunit SRP72, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0912200","name":null,"product":"signal recognition particle subunit SRP72, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0934600","name":null,"product":"signal recognition particle subunit SRP72, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRP72","evaluation":null}