{"gene":"PF3D7_0503300","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2014,"finding":"PfSRSF12 (PF3D7_0503300) is localized predominantly to the nucleus of blood stage trophozoites and is also detectable in the nucleus of gametocytes, as determined by immunolocalization experiments.","method":"Immunolocalization / subcellular fractionation in P. falciparum blood stages and gametocytes","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment reported in a peer-reviewed study with multiple SR proteins examined, single lab","pmids":["25188378"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Recombinantly expressed PfSRSF12 (PF3D7_0503300) RS-rich domain is phosphorylated in vitro by all four PfCLK kinases (PfCLK-1, -2, -3, -4); a control peptide lacking the RS-rich domain was not phosphorylated, demonstrating that the RS domain is required for phosphorylation.","method":"In vitro kinase assay using recombinant RS-domain-containing PfSRSF12 protein and recombinant PfCLK-1 through -4","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro kinase assay with domain-deletion control, peer-reviewed single lab but with rigorous biochemical validation","pmids":["25188378"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0503300 (SRSF12) is a nuclear SR protein in P. falciparum blood stage trophozoites and gametocytes whose RS-rich domain is directly phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 through -4), implicating it as a downstream substrate of these kinases in pre-mRNA processing regulation."},"narrative":{"mechanistic_narrative":"PF3D7_0503300 (SRSF12) is a serine/arginine-rich splicing factor of Plasmodium falciparum that localizes predominantly to the nucleus of blood stage trophozoites and is also present in the nucleus of gametocytes [PMID:25188378]. Its RS-rich domain is a direct in vitro substrate of all four P. falciparum CLK kinases (PfCLK-1 through -4), and this phosphorylation strictly requires the RS domain, positioning SRSF12 as a downstream target of CLK-mediated regulation of pre-mRNA processing [PMID:25188378]. Beyond its nuclear localization and CLK-dependent RS-domain phosphorylation, no further mechanistic detail — including RNA targets, splicing activity, or interaction partners — has been characterized for SRSF12 in the available corpus.","teleology":[{"year":2014,"claim":"To establish where SRSF12 could act, its subcellular distribution was resolved, showing a nuclear residence consistent with a role in pre-mRNA processing across asexual and sexual stages.","evidence":"Immunolocalization and subcellular fractionation in P. falciparum blood stage trophozoites and gametocytes","pmids":["25188378"],"confidence":"Medium","gaps":["No RNA substrates or splicing targets identified","No interaction partners or spliceosome association demonstrated","Localization not resolved across all life-cycle stages"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"To connect SRSF12 to an upstream regulatory kinase, its RS-rich domain was tested as a phosphorylation substrate, establishing it as a direct in vitro target of all four PfCLK kinases and defining the RS domain as the required phosphoacceptor region.","evidence":"In vitro kinase assay with recombinant RS-domain-containing PfSRSF12 and recombinant PfCLK-1 through -4, using an RS-domain-lacking control peptide","pmids":["25188378"],"confidence":"High","gaps":["Phosphorylation not demonstrated in vivo in the parasite","Functional consequence of RS-domain phosphorylation on splicing activity unknown","Which specific residues within the RS domain are phosphorylated is not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what RNA transcripts SRSF12 processes, whether its CLK-dependent phosphorylation regulates its activity or localization in vivo, and what role it plays in asexual proliferation or gametocyte development.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo functional or genetic characterization of SRSF12","No defined splicing targets or transcriptome-level effect","No structural model of the SRSF12–CLK interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFCLK-1 (KINASE ACTING ON SRSF12 RS DOMAIN IN VITRO) [#1]","PFCLK-2 (KINASE ACTING ON SRSF12 RS DOMAIN IN VITRO) [#1]","PFCLK-3 (KINASE ACTING ON SRSF12 RS DOMAIN IN VITRO) [#1]","PFCLK-4 (KINASE ACTING ON SRSF12 RS DOMAIN IN VITRO) [#1]"],"other_free_text":["SRSF12 phosphorylation by PfCLK kinases requires its RS-rich domain; a control peptide lacking the RS domain is not phosphorylated [#1]","SRSF12 is nuclear in both blood stage trophozoites and gametocytes [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"25188378","id":"PMC_25188378","title":"Inhibition of the SR protein-phosphorylating CLK kinases of Plasmodium falciparum impairs blood stage replication and malaria transmission.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25188378","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSRSF12"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30782661","id":"","title":"Alternative Splicing in Apicomplexan Parasites.","date":"2019","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/30782661","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRSF12"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4453,"output_tokens":616,"usd":0.0113,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5190,"output_tokens":1631,"usd":0.033363,"stage2_stop_reason":"end_turn"},"total_usd":0.044663,"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\": \"PfSRSF12 (PF3D7_0503300) is localized predominantly to the nucleus of blood stage trophozoites and is also detectable in the nucleus of gametocytes, as determined by immunolocalization experiments.\",\n      \"method\": \"Immunolocalization / subcellular fractionation in P. falciparum blood stages and gametocytes\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment reported in a peer-reviewed study with multiple SR proteins examined, single lab\",\n      \"pmids\": [\"25188378\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Recombinantly expressed PfSRSF12 (PF3D7_0503300) RS-rich domain is phosphorylated in vitro by all four PfCLK kinases (PfCLK-1, -2, -3, -4); a control peptide lacking the RS-rich domain was not phosphorylated, demonstrating that the RS domain is required for phosphorylation.\",\n      \"method\": \"In vitro kinase assay using recombinant RS-domain-containing PfSRSF12 protein and recombinant PfCLK-1 through -4\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinase assay with domain-deletion control, peer-reviewed single lab but with rigorous biochemical validation\",\n      \"pmids\": [\"25188378\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0503300 (SRSF12) is a nuclear SR protein in P. falciparum blood stage trophozoites and gametocytes whose RS-rich domain is directly phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 through -4), implicating it as a downstream substrate of these kinases in pre-mRNA processing regulation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0503300 (SRSF12) is a serine/arginine-rich splicing factor of Plasmodium falciparum that localizes predominantly to the nucleus of blood stage trophozoites and is also present in the nucleus of gametocytes [#0]. Its RS-rich domain is a direct in vitro substrate of all four P. falciparum CLK kinases (PfCLK-1 through -4), and this phosphorylation strictly requires the RS domain, positioning SRSF12 as a downstream target of CLK-mediated regulation of pre-mRNA processing [#1]. Beyond its nuclear localization and CLK-dependent RS-domain phosphorylation, no further mechanistic detail — including RNA targets, splicing activity, or interaction partners — has been characterized for SRSF12 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"To establish where SRSF12 could act, its subcellular distribution was resolved, showing a nuclear residence consistent with a role in pre-mRNA processing across asexual and sexual stages.\",\n      \"evidence\": \"Immunolocalization and subcellular fractionation in P. falciparum blood stage trophozoites and gametocytes\",\n      \"pmids\": [\"25188378\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No RNA substrates or splicing targets identified\",\n        \"No interaction partners or spliceosome association demonstrated\",\n        \"Localization not resolved across all life-cycle stages\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"To connect SRSF12 to an upstream regulatory kinase, its RS-rich domain was tested as a phosphorylation substrate, establishing it as a direct in vitro target of all four PfCLK kinases and defining the RS domain as the required phosphoacceptor region.\",\n      \"evidence\": \"In vitro kinase assay with recombinant RS-domain-containing PfSRSF12 and recombinant PfCLK-1 through -4, using an RS-domain-lacking control peptide\",\n      \"pmids\": [\"25188378\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Phosphorylation not demonstrated in vivo in the parasite\",\n        \"Functional consequence of RS-domain phosphorylation on splicing activity unknown\",\n        \"Which specific residues within the RS domain are phosphorylated is not mapped\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what RNA transcripts SRSF12 processes, whether its CLK-dependent phosphorylation regulates its activity or localization in vivo, and what role it plays in asexual proliferation or gametocyte development.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in vivo functional or genetic characterization of SRSF12\",\n        \"No defined splicing targets or transcriptome-level effect\",\n        \"No structural model of the SRSF12–CLK interaction\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0030621\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006397\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfCLK-1 (kinase acting on SRSF12 RS domain in vitro) [#1]\",\n      \"PfCLK-2 (kinase acting on SRSF12 RS domain in vitro) [#1]\",\n      \"PfCLK-3 (kinase acting on SRSF12 RS domain in vitro) [#1]\",\n      \"PfCLK-4 (kinase acting on SRSF12 RS domain in vitro) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"SRSF12 phosphorylation by PfCLK kinases requires its RS-rich domain; a control peptide lacking the RS domain is not phosphorylated [#1]\",\n      \"SRSF12 is nuclear in both blood stage trophozoites and gametocytes [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0503300","name":null,"product":"serine/arginine-rich splicing factor 12","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1103000","name":null,"product":"serine/arginine-rich splicing factor 12, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1030300","name":null,"product":"serine/arginine-rich splicing factor 12, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRSF12","evaluation":null}