{"gene":"PF3D7_1321700","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2014,"finding":"PF3D7_1321700 (SF1/PfSF-1), a Serine/Arginine-rich protein, is phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 to -4) on its RS-rich domain; a recombinant PfSF-1 peptide lacking the RS-rich domain was not phosphorylated, demonstrating domain-specific phosphorylation.","method":"In vitro kinase assay with recombinant protein and domain-deletion mutant","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro kinase assay with domain-deletion control, single lab, single method","pmids":["25188378"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"PF3D7_1321700 (SF1/PfSF-1) is predominantly localized to the nucleus of blood stage trophozoites and also detectable in the nucleus of gametocytes.","method":"Subcellular localization assay (immunofluorescence/imaging) in asexual blood stages and gametocytes","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment replicated in body mention of a review (PMID:30782661), single primary lab","pmids":["25188378","30782661"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"The P. berghei orthologue of PF3D7_1321700 (PbSR1, PBANKA_1232100) interacts with nuclear RNA-binding proteins and small nuclear ribonucleoproteins, as well as with cytoplasmic rhoptry proteins RhopH1 (Clag3), RhopH2, and RhopH3, as identified by immunoprecipitation coupled to mass spectrometry. Co-localization of PbSR1 and RhopH2 in the cytoplasm was observed in trophozoites and gametocytes but not in mature schizonts or merozoites.","method":"Immunoprecipitation coupled to mass spectrometry (IP-MS) and live-cell fluorescence co-imaging using GFP/mCherry fusion transgenic parasites","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — IP-MS plus live-cell fluorescence co-imaging, two orthogonal methods, single lab","pmids":["41634752"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]}],"current_model":"PF3D7_1321700 (SF1) is a nuclear SR-type splicing factor in P. falciparum that is phosphorylated on its RS-rich domain by all four PfCLK kinases in vitro; its P. berghei orthologue (PbSR1) localizes predominantly to the nucleus but also co-localizes with rhoptry proteins (RhopH1/2/3) in the cytoplasm of trophozoites and gametocytes, and associates with nuclear RNA-binding proteins and snRNPs as well as cytoplasmic rhoptry complexes as identified by IP-MS."},"narrative":{"mechanistic_narrative":"PF3D7_1321700 (SF1) is a Serine/Arginine-rich (SR-type) splicing factor of Plasmodium falciparum that couples pre-mRNA splicing machinery to regulatory phosphorylation [PMID:25188378, PMID:30782661]. It is phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 to -4) specifically on its RS-rich domain, as a peptide lacking this domain is not phosphorylated [PMID:25188378]. Consistent with a nuclear RNA-processing role, SF1 localizes predominantly to the nucleus in blood-stage trophozoites and is also detectable in the nucleus of gametocytes [PMID:25188378, PMID:30782661]. In P. berghei, the orthologue (PbSR1) associates with nuclear RNA-binding proteins and small nuclear ribonucleoproteins, and unexpectedly also with cytoplasmic rhoptry proteins RhopH1 (Clag3), RhopH2, and RhopH3, with cytoplasmic co-localization of PbSR1 and RhopH2 seen in trophozoites and gametocytes but not in mature schizonts or merozoites [PMID:41634752]. Beyond these phosphorylation, localization, and interaction findings, no catalytic mechanism or direct RNA-substrate specificity has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"Establishing whether SF1 is a regulated substrate of the parasite CLK kinase network showed that its RS-rich domain is the specific target of phosphorylation, placing SF1 downstream of PfCLK signalling.","evidence":"in vitro kinase assay with recombinant PfSF-1 and an RS-domain-deletion mutant, P. falciparum","pmids":["25188378"],"confidence":"Medium","gaps":["in vitro assay only; phosphorylation not demonstrated in living parasites","functional consequence of RS-domain phosphorylation on splicing activity untested","which PfCLK kinase acts physiologically is not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Determining where SF1 acts localized it predominantly to the nucleus in trophozoites and gametocytes, consistent with a role in nuclear RNA processing across asexual and sexual stages.","evidence":"immunofluorescence/imaging localization in asexual blood stages and gametocytes, P. falciparum","pmids":["25188378","30782661"],"confidence":"Medium","gaps":["no direct demonstration of association with spliceosomal RNA in P. falciparum","does not establish target transcripts or splicing events regulated by SF1"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Mapping the interactome of the orthologue defined dual associations — with nuclear RNA-binding proteins/snRNPs and, unexpectedly, with cytoplasmic rhoptry proteins — raising the possibility of a role beyond canonical nuclear splicing.","evidence":"IP-MS plus live-cell GFP/mCherry co-imaging in P. berghei ANKA transgenic parasites (PbSR1)","pmids":["41634752"],"confidence":"Medium","gaps":["rhoptry-protein association shown in P. berghei, not confirmed for P. falciparum SF1","functional significance of the cytoplasmic rhoptry interaction unknown","IP-MS from a single lab without reciprocal or orthogonal biochemical validation of individual partners"],"attribution":[{"species":"Plasmodium berghei","strain":"ANKA"}]},{"year":null,"claim":"The direct RNA substrates, the splicing events SF1 controls, and the biological meaning of its cytoplasmic rhoptry-protein associations remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no identified pre-mRNA targets or splicing phenotype from SF1 depletion","no structural model of SF1 or its RS-domain interactions","mechanistic link between nuclear splicing role and rhoptry-protein association unexplained"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["small nuclear ribonucleoprotein (snRNP) associations (P. berghei PbSR1) [#2]","cytoplasmic rhoptry protein complex: RhopH1/Clag3, RhopH2, RhopH3 (P. berghei PbSR1) [#2]"],"partners":["PFCLK-1, PFCLK-2, PFCLK-3, PFCLK-4 (PHOSPHORYLATE SF1 RS-DOMAIN IN VITRO) [#0]","NUCLEAR RNA-BINDING PROTEINS (P. BERGHEI PBSR1) [#2]","RHOPH1 (CLAG3) [#2]","RHOPH2 [#2]","RHOPH3 [#2]"],"other_free_text":["SF1 is a Serine/Arginine-rich (SR-type) protein; phosphorylation is domain-specific to the RS-rich domain [#0]","Cytoplasmic PbSR1–RhopH2 co-localization is stage-restricted, seen in trophozoites and gametocytes but not mature schizonts or merozoites [#2]","Nuclear localization observed in both asexual trophozoites and gametocytes [#1]"]}},"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":["PfSF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41634752","id":"PMC_41634752","title":"Identification of serine/arginine-rich splicing factor 1-interacting proteins in Plasmodium berghei.","date":"2026","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/41634752","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["splicing factor 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42272758","id":"","title":"The serine-arginine-rich protein PfSR-X2 modulates human malaria parasite gene expression during the intraerythrocytic developmental cycle.","date":"2026","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42272758","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38824128","id":"","title":"An axonemal intron splicing program sustains Plasmodium male development.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38824128","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26525978","id":"","title":"A bioinformatic survey of RNA-binding proteins in Plasmodium.","date":"2015","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/26525978","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SF1"],"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":["SF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25502909","id":"","title":"Evolutionary Dynamics of GLD-1-mRNA complexes in Caenorhabditis nematodes.","date":"2014","source":"Genome biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/25502909","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24312270","id":"","title":"Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24312270","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SF1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11162,"output_tokens":981,"usd":0.024101,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5682,"output_tokens":2330,"usd":0.04333,"stage2_stop_reason":"end_turn"},"total_usd":0.067431,"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\": \"PF3D7_1321700 (SF1/PfSF-1), a Serine/Arginine-rich protein, is phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 to -4) on its RS-rich domain; a recombinant PfSF-1 peptide lacking the RS-rich domain was not phosphorylated, demonstrating domain-specific phosphorylation.\",\n      \"method\": \"In vitro kinase assay with recombinant protein and domain-deletion mutant\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro kinase assay with domain-deletion control, single lab, single method\",\n      \"pmids\": [\"25188378\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"PF3D7_1321700 (SF1/PfSF-1) is predominantly localized to the nucleus of blood stage trophozoites and also detectable in the nucleus of gametocytes.\",\n      \"method\": \"Subcellular localization assay (immunofluorescence/imaging) in asexual blood stages and gametocytes\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment replicated in body mention of a review (PMID:30782661), single primary lab\",\n      \"pmids\": [\"25188378\", \"30782661\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The P. berghei orthologue of PF3D7_1321700 (PbSR1, PBANKA_1232100) interacts with nuclear RNA-binding proteins and small nuclear ribonucleoproteins, as well as with cytoplasmic rhoptry proteins RhopH1 (Clag3), RhopH2, and RhopH3, as identified by immunoprecipitation coupled to mass spectrometry. Co-localization of PbSR1 and RhopH2 in the cytoplasm was observed in trophozoites and gametocytes but not in mature schizonts or merozoites.\",\n      \"method\": \"Immunoprecipitation coupled to mass spectrometry (IP-MS) and live-cell fluorescence co-imaging using GFP/mCherry fusion transgenic parasites\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — IP-MS plus live-cell fluorescence co-imaging, two orthogonal methods, single lab\",\n      \"pmids\": [\"41634752\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1321700 (SF1) is a nuclear SR-type splicing factor in P. falciparum that is phosphorylated on its RS-rich domain by all four PfCLK kinases in vitro; its P. berghei orthologue (PbSR1) localizes predominantly to the nucleus but also co-localizes with rhoptry proteins (RhopH1/2/3) in the cytoplasm of trophozoites and gametocytes, and associates with nuclear RNA-binding proteins and snRNPs as well as cytoplasmic rhoptry complexes as identified by IP-MS.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1321700 (SF1) is a Serine/Arginine-rich (SR-type) splicing factor of Plasmodium falciparum that couples pre-mRNA splicing machinery to regulatory phosphorylation [#0, #1]. It is phosphorylated in vitro by all four P. falciparum CLK kinases (PfCLK-1 to -4) specifically on its RS-rich domain, as a peptide lacking this domain is not phosphorylated [#0]. Consistent with a nuclear RNA-processing role, SF1 localizes predominantly to the nucleus in blood-stage trophozoites and is also detectable in the nucleus of gametocytes [#1]. In P. berghei, the orthologue (PbSR1) associates with nuclear RNA-binding proteins and small nuclear ribonucleoproteins, and unexpectedly also with cytoplasmic rhoptry proteins RhopH1 (Clag3), RhopH2, and RhopH3, with cytoplasmic co-localization of PbSR1 and RhopH2 seen in trophozoites and gametocytes but not in mature schizonts or merozoites [#2]. Beyond these phosphorylation, localization, and interaction findings, no catalytic mechanism or direct RNA-substrate specificity has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing whether SF1 is a regulated substrate of the parasite CLK kinase network showed that its RS-rich domain is the specific target of phosphorylation, placing SF1 downstream of PfCLK signalling.\",\n      \"evidence\": \"in vitro kinase assay with recombinant PfSF-1 and an RS-domain-deletion mutant, P. falciparum\",\n      \"pmids\": [\"25188378\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"in vitro assay only; phosphorylation not demonstrated in living parasites\",\n        \"functional consequence of RS-domain phosphorylation on splicing activity untested\",\n        \"which PfCLK kinase acts physiologically is not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Determining where SF1 acts localized it predominantly to the nucleus in trophozoites and gametocytes, consistent with a role in nuclear RNA processing across asexual and sexual stages.\",\n      \"evidence\": \"immunofluorescence/imaging localization in asexual blood stages and gametocytes, P. falciparum\",\n      \"pmids\": [\"25188378\", \"30782661\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"no direct demonstration of association with spliceosomal RNA in P. falciparum\",\n        \"does not establish target transcripts or splicing events regulated by SF1\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Mapping the interactome of the orthologue defined dual associations \\u2014 with nuclear RNA-binding proteins/snRNPs and, unexpectedly, with cytoplasmic rhoptry proteins \\u2014 raising the possibility of a role beyond canonical nuclear splicing.\",\n      \"evidence\": \"IP-MS plus live-cell GFP/mCherry co-imaging in P. berghei ANKA transgenic parasites (PbSR1)\",\n      \"pmids\": [\"41634752\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"rhoptry-protein association shown in P. berghei, not confirmed for P. falciparum SF1\",\n        \"functional significance of the cytoplasmic rhoptry interaction unknown\",\n        \"IP-MS from a single lab without reciprocal or orthogonal biochemical validation of individual partners\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"ANKA\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct RNA substrates, the splicing events SF1 controls, and the biological meaning of its cytoplasmic rhoptry-protein associations remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"no identified pre-mRNA targets or splicing phenotype from SF1 depletion\",\n        \"no structural model of SF1 or its RS-domain interactions\",\n        \"mechanistic link between nuclear splicing role and rhoptry-protein association unexplained\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0004674\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0008380\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\n      \"small nuclear ribonucleoprotein (snRNP) associations (P. berghei PbSR1) [#2]\",\n      \"cytoplasmic rhoptry protein complex: RhopH1/Clag3, RhopH2, RhopH3 (P. berghei PbSR1) [#2]\"\n    ],\n    \"partners\": [\n      \"PfCLK-1, PfCLK-2, PfCLK-3, PfCLK-4 (phosphorylate SF1 RS-domain in vitro) [#0]\",\n      \"nuclear RNA-binding proteins (P. berghei PbSR1) [#2]\",\n      \"RhopH1 (Clag3) [#2]\",\n      \"RhopH2 [#2]\",\n      \"RhopH3 [#2]\"\n    ],\n    \"other_free_text\": [\n      \"SF1 is a Serine/Arginine-rich (SR-type) protein; phosphorylation is domain-specific to the RS-rich domain [#0]\",\n      \"Cytoplasmic PbSR1\\u2013RhopH2 co-localization is stage-restricted, seen in trophozoites and gametocytes but not mature schizonts or merozoites [#2]\",\n      \"Nuclear localization observed in both asexual trophozoites and gametocytes [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1321700","name":null,"product":"splicing factor 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1337100","name":null,"product":"splicing factor 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1207100","name":null,"product":"splicing factor 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SF1","evaluation":null}