{"gene":"PF3D7_0302100","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2010,"finding":"SRPK1 (PfSRPK1) inhibits RNA splicing when incubated with parasite nuclear extracts, and phosphorylates PfSR1 (a putative P. falciparum splicing factor) as a substrate; PfSRPK1 modulates PfSR1's RNA-binding activity. Early in parasite development, PfSRPK1 and PfSR1 co-localize in the nucleus.","method":"In vitro splicing inhibition assay with parasite nuclear extracts; substrate phosphorylation assay; RNA-binding assay; subcellular fractionation/localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro kinase assay and splicing inhibition assay establish substrate and activity, but single lab, single study","pmids":["20870716"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Genetic deletion of PfSRPK1 in P. falciparum causes: (i) reduced merozoite formation during asexual schizogony; (ii) a complete block in male gamete differentiation, abolishing parasite transmission to mosquitoes. RNA-seq of pfsrpk1− stage V gametocytes revealed altered splicing and transcript abundance of genes involved in microtubule/cilium morphogenesis, cyclic nucleotide metabolism, signaling (including PfMAP2), lipid metabolism, osmophilic bodies, and crystalloid components, consistent with a role for SRPK1 in transcript homeostasis.","method":"Gene knockout (pfsrpk1− parasites); mosquito transmission assays; RNA-seq of stage V gametocytes","journal":"Microbiology spectrum","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean knockout with defined cellular and transmission phenotypes, supplemented by RNA-seq pathway analysis, single lab but multiple orthogonal readouts","pmids":["36094218"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]},{"year":2017,"finding":"In P. berghei, a homolog of SRPK1 participates in phosphoregulation during male gametogenesis within the first minute of gametocyte activation. Genetic disruption of SRPK1 in P. berghei produces a distinct phosphoproteomic signature, implicating SRPK1 in specific phosphorylation events during the rapid cell cycle of male gametogenesis.","method":"Time-course phosphoproteomics; genetic mutant analysis (phosphoproteome of SRPK1 mutant vs. wild-type)","journal":"Cell reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phosphoproteomics with genetic mutant in P. berghei, two orthogonal approaches, single lab","pmids":["29141230"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"In P. berghei male gametogenesis, SRPK1 localizes to the cytoplasmic compartment (distinct from CDPK4 and MAP2 which are nuclear), and immunoprecipitation identifies SRPK1 interacting partners involved in RNA translation. Absence of SRPK1 causes severe defects in axoneme formation, placing SRPK1 in a pathway controlling cytoplasmic RNA translation during endomitosis.","method":"Live-cell imaging (localization); immunoprecipitation of interacting partners; ultrastructure expansion microscopy and transmission electron microscopy of knockout parasites","journal":"Life science alliance","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal localization and Co-IP with morphological phenotype in knockout, single lab but multiple orthogonal methods","pmids":["40127922"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"finding":"A nonsense (stop codon) mutation in SRPK1 was positively selected during in vitro culture adaptation of P. falciparum clinical isolates, indicating that loss-of-function of SRPK1 confers a fitness advantage in laboratory culture conditions.","method":"Longitudinal genome sequencing of cultured clinical isolates; selection of emergent SNPs","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genomic observation of loss-of-function allele selection; no direct functional assay of SRPK1 activity","pmids":["28117431"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"SRPK1 loss-of-function mutations (nonsense mutants) independently emerged during culture adaptation in multiple West African P. falciparum isolates, replicating the earlier finding that SRPK1 is a convergent target for culture adaptation.","method":"Longitudinal genome sequencing of cultured clinical isolates","journal":"Microbial genomics","confidence":"Low","confidence_rationale":"Tier 3 / Moderate — replicated genomic observation across independent isolates but no direct functional assay","pmids":["37204422"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfSRPK1 (PF3D7_0302100) is a serine/threonine protein kinase that localizes to the nucleus early in asexual development and to the cytoplasm during male gametogenesis; it phosphorylates the splicing factor PfSR1 to modulate its RNA-binding activity and inhibits pre-mRNA splicing in nuclear extracts, while genetic deletion in P. falciparum causes reduced merozoite formation during schizogony and a complete block in male gamete formation and mosquito transmission, with transcriptomic evidence linking SRPK1 to regulation of splicing and transcript abundance for genes controlling microtubule/axoneme morphogenesis and signaling."},"narrative":{"mechanistic_narrative":"SRPK1 (PF3D7_0302100) is a serine/threonine protein kinase that couples RNA processing and translation to developmental transitions across the Plasmodium life cycle [PMID:20870716, PMID:36094218]. In P. falciparum, PfSRPK1 phosphorylates the putative splicing factor PfSR1, with which it co-localizes in the nucleus early in development, and it inhibits pre-mRNA splicing in parasite nuclear extracts while modulating PfSR1's RNA-binding activity [PMID:20870716]. Genetic deletion in P. falciparum reduces merozoite formation during asexual schizogony and completely blocks male gamete differentiation, abolishing transmission to mosquitoes; transcriptomic analysis of knockout stage V gametocytes shows altered splicing and transcript abundance for genes governing microtubule/cilium morphogenesis, cyclic nucleotide metabolism, and signaling, consistent with a role in transcript homeostasis [PMID:36094218]. In P. berghei, the ortholog acts within the first minute of male gametocyte activation, generating a distinct phosphoproteomic signature during the rapid cell cycle of gametogenesis [PMID:29141230]; there it localizes to the cytoplasm (unlike the nuclear CDPK4 and MAP2), interacts with partners implicated in RNA translation, and its loss produces severe axoneme defects, placing SRPK1 in a cytoplasmic translational control pathway during endomitosis [PMID:40127922]. Beyond these findings, the kinase's direct substrate repertoire outside PfSR1 has not been characterized in the available corpus.","teleology":[{"year":2010,"claim":"Establishing what molecular process SRPK1 acts on: the finding that PfSRPK1 phosphorylates the splicing factor PfSR1 and inhibits splicing defined SRPK1 as a regulator of RNA processing rather than an uncharacterized kinase.","evidence":"In vitro splicing inhibition and kinase assays with parasite nuclear extracts, plus RNA-binding and co-localization assays, in P. falciparum","pmids":["20870716"],"confidence":"Medium","gaps":["single lab, single study without independent replication","no in-cell demonstration that SRPK1-dependent PfSR1 phosphorylation controls specific transcripts","substrate repertoire beyond PfSR1 unaddressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Placing SRPK1 temporally and functionally in male gametogenesis: phosphoproteomics of a P. berghei mutant showed SRPK1 drives specific phosphorylation events within the first minute of activation, linking it to the rapid gametogenesis cell cycle.","evidence":"Time-course phosphoproteomics comparing SRPK1 mutant and wild-type P. berghei gametocytes","pmids":["29141230"],"confidence":"Medium","gaps":["direct kinase-substrate relationships not resolved from phosphoproteome correlation","single lab","does not distinguish direct from indirect phosphorylation targets"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"Testing SRPK1 dispensability in laboratory culture: convergent selection of a nonsense mutation during in vitro adaptation indicated loss-of-function confers a fitness advantage under culture, implying SRPK1's essential roles lie outside asexual culture growth.","evidence":"Longitudinal genome sequencing of cultured P. falciparum clinical isolates tracking emergent SNPs","pmids":["28117431"],"confidence":"Low","gaps":["genomic observation only, no direct functional assay of the mutant allele","mechanism of the fitness advantage unknown","does not establish SRPK1's normal function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Defining the cellular consequences of SRPK1 loss in P. falciparum: knockout phenotyping showed reduced merozoite formation and a complete transmission block via failed male gametogenesis, tying SRPK1 to transcript homeostasis of morphogenesis and signaling genes.","evidence":"Gene knockout, mosquito transmission assays, and RNA-seq of stage V gametocytes in P. falciparum NF54","pmids":["36094218"],"confidence":"High","gaps":["RNA-seq changes do not distinguish direct splicing targets from downstream effects","kinase substrates mediating the phenotype not identified","single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]},{"year":2023,"claim":"Confirming convergent culture selection of SRPK1 loss-of-function: independent emergence of nonsense mutations across multiple West African isolates reproduced the earlier observation that SRPK1 is a repeatable target of culture adaptation.","evidence":"Longitudinal genome sequencing of independent cultured P. falciparum clinical isolates","pmids":["37204422"],"confidence":"Low","gaps":["genomic observation only, no functional assay","does not clarify the mechanistic basis of the fitness cost of intact SRPK1 in culture"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Refining the subcellular context and pathway of SRPK1 in gametogenesis: cytoplasmic localization, Co-IP with translation-associated partners, and axoneme defects in knockouts placed P. berghei SRPK1 in a cytoplasmic RNA-translation pathway during endomitosis.","evidence":"Live-cell imaging, immunoprecipitation of interactors, and ultrastructure expansion microscopy/TEM of P. berghei knockout parasites","pmids":["40127922"],"confidence":"Medium","gaps":["Co-IP interactors not reciprocally validated or functionally tested","how a cytoplasmic kinase controls translation mechanistically is unresolved","relationship between the nuclear splicing role and cytoplasmic translation role not reconciled"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The direct in vivo substrate set of SRPK1 beyond PfSR1, and how its distinct nuclear (splicing) and cytoplasmic (translation) activities are coordinated across developmental stages, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no comprehensive direct-substrate map","mechanism switching kinase between nuclear and cytoplasmic roles unknown","structural basis of substrate recognition uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFSR1 (SUBSTRATE; P. FALCIPARUM) [#0]","RNA TRANSLATION-ASSOCIATED INTERACTORS IDENTIFIED BY CO-IP (P. BERGHEI) [#3]"],"other_free_text":["Knockout in P. falciparum blocks male gamete formation and mosquito transmission and reduces merozoite formation [#1].","In P. berghei, loss causes severe axoneme formation defects [#3].","Loss-of-function nonsense mutations are convergently selected during in vitro culture adaptation of P. falciparum clinical isolates [#4, #5].","P. falciparum PfSRPK1 is nuclear early in development, whereas the P. berghei ortholog is cytoplasmic during male gametogenesis, distinct from the nuclear CDPK4 and MAP2 [#0, #3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15479470","id":"PMC_15479470","title":"Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote.","date":"2004","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/15479470","citation_count":421,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22127061","id":"PMC_22127061","title":"Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum.","date":"2011","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/22127061","citation_count":288,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28117431","id":"PMC_28117431","title":"Culture adaptation of malaria parasites selects for convergent loss-of-function mutants.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28117431","citation_count":61,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29141230","id":"PMC_29141230","title":"Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium Gamete Formation.","date":"2017","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29141230","citation_count":50,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20870716","id":"PMC_20870716","title":"PfSRPK1, a novel splicing-related kinase from Plasmodium falciparum.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20870716","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfSRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36094218","id":"PMC_36094218","title":"PfSRPK1 Regulates Asexual Blood Stage Schizogony and Is Essential for Male Gamete Formation.","date":"2022","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/36094218","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRPK1","PfSRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40127922","id":"PMC_40127922","title":"Divergent Plasmodium kinases drive MTOC, kinetochore and axoneme organisation in male gametogenesis.","date":"2025","source":"Life science alliance","url":"https://pubmed.ncbi.nlm.nih.gov/40127922","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37204422","id":"PMC_37204422","title":"Genomic variation during culture adaptation of genetically complex Plasmodium falciparum clinical isolates.","date":"2023","source":"Microbial genomics","url":"https://pubmed.ncbi.nlm.nih.gov/37204422","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37535401","id":"PMC_37535401","title":"Plasmodium microtubule-binding protein EB1 is critical for partitioning of nuclei in male gametogenesis.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37535401","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SRPK1","PfSRPK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7156,"output_tokens":1741,"usd":0.023792,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6902,"output_tokens":3239,"usd":0.057743,"stage2_stop_reason":"end_turn"},"total_usd":0.081535,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"SRPK1 (PfSRPK1) inhibits RNA splicing when incubated with parasite nuclear extracts, and phosphorylates PfSR1 (a putative P. falciparum splicing factor) as a substrate; PfSRPK1 modulates PfSR1's RNA-binding activity. Early in parasite development, PfSRPK1 and PfSR1 co-localize in the nucleus.\",\n      \"method\": \"In vitro splicing inhibition assay with parasite nuclear extracts; substrate phosphorylation assay; RNA-binding assay; subcellular fractionation/localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro kinase assay and splicing inhibition assay establish substrate and activity, but single lab, single study\",\n      \"pmids\": [\"20870716\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Genetic deletion of PfSRPK1 in P. falciparum causes: (i) reduced merozoite formation during asexual schizogony; (ii) a complete block in male gamete differentiation, abolishing parasite transmission to mosquitoes. RNA-seq of pfsrpk1− stage V gametocytes revealed altered splicing and transcript abundance of genes involved in microtubule/cilium morphogenesis, cyclic nucleotide metabolism, signaling (including PfMAP2), lipid metabolism, osmophilic bodies, and crystalloid components, consistent with a role for SRPK1 in transcript homeostasis.\",\n      \"method\": \"Gene knockout (pfsrpk1− parasites); mosquito transmission assays; RNA-seq of stage V gametocytes\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockout with defined cellular and transmission phenotypes, supplemented by RNA-seq pathway analysis, single lab but multiple orthogonal readouts\",\n      \"pmids\": [\"36094218\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In P. berghei, a homolog of SRPK1 participates in phosphoregulation during male gametogenesis within the first minute of gametocyte activation. Genetic disruption of SRPK1 in P. berghei produces a distinct phosphoproteomic signature, implicating SRPK1 in specific phosphorylation events during the rapid cell cycle of male gametogenesis.\",\n      \"method\": \"Time-course phosphoproteomics; genetic mutant analysis (phosphoproteome of SRPK1 mutant vs. wild-type)\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phosphoproteomics with genetic mutant in P. berghei, two orthogonal approaches, single lab\",\n      \"pmids\": [\"29141230\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In P. berghei male gametogenesis, SRPK1 localizes to the cytoplasmic compartment (distinct from CDPK4 and MAP2 which are nuclear), and immunoprecipitation identifies SRPK1 interacting partners involved in RNA translation. Absence of SRPK1 causes severe defects in axoneme formation, placing SRPK1 in a pathway controlling cytoplasmic RNA translation during endomitosis.\",\n      \"method\": \"Live-cell imaging (localization); immunoprecipitation of interacting partners; ultrastructure expansion microscopy and transmission electron microscopy of knockout parasites\",\n      \"journal\": \"Life science alliance\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal localization and Co-IP with morphological phenotype in knockout, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"40127922\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"A nonsense (stop codon) mutation in SRPK1 was positively selected during in vitro culture adaptation of P. falciparum clinical isolates, indicating that loss-of-function of SRPK1 confers a fitness advantage in laboratory culture conditions.\",\n      \"method\": \"Longitudinal genome sequencing of cultured clinical isolates; selection of emergent SNPs\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genomic observation of loss-of-function allele selection; no direct functional assay of SRPK1 activity\",\n      \"pmids\": [\"28117431\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"SRPK1 loss-of-function mutations (nonsense mutants) independently emerged during culture adaptation in multiple West African P. falciparum isolates, replicating the earlier finding that SRPK1 is a convergent target for culture adaptation.\",\n      \"method\": \"Longitudinal genome sequencing of cultured clinical isolates\",\n      \"journal\": \"Microbial genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — replicated genomic observation across independent isolates but no direct functional assay\",\n      \"pmids\": [\"37204422\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfSRPK1 (PF3D7_0302100) is a serine/threonine protein kinase that localizes to the nucleus early in asexual development and to the cytoplasm during male gametogenesis; it phosphorylates the splicing factor PfSR1 to modulate its RNA-binding activity and inhibits pre-mRNA splicing in nuclear extracts, while genetic deletion in P. falciparum causes reduced merozoite formation during schizogony and a complete block in male gamete formation and mosquito transmission, with transcriptomic evidence linking SRPK1 to regulation of splicing and transcript abundance for genes controlling microtubule/axoneme morphogenesis and signaling.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SRPK1 (PF3D7_0302100) is a serine/threonine protein kinase that couples RNA processing and translation to developmental transitions across the Plasmodium life cycle [#0, #1]. In P. falciparum, PfSRPK1 phosphorylates the putative splicing factor PfSR1, with which it co-localizes in the nucleus early in development, and it inhibits pre-mRNA splicing in parasite nuclear extracts while modulating PfSR1's RNA-binding activity [#0]. Genetic deletion in P. falciparum reduces merozoite formation during asexual schizogony and completely blocks male gamete differentiation, abolishing transmission to mosquitoes; transcriptomic analysis of knockout stage V gametocytes shows altered splicing and transcript abundance for genes governing microtubule/cilium morphogenesis, cyclic nucleotide metabolism, and signaling, consistent with a role in transcript homeostasis [#1]. In P. berghei, the ortholog acts within the first minute of male gametocyte activation, generating a distinct phosphoproteomic signature during the rapid cell cycle of gametogenesis [#2]; there it localizes to the cytoplasm (unlike the nuclear CDPK4 and MAP2), interacts with partners implicated in RNA translation, and its loss produces severe axoneme defects, placing SRPK1 in a cytoplasmic translational control pathway during endomitosis [#3]. Beyond these findings, the kinase's direct substrate repertoire outside PfSR1 has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Establishing what molecular process SRPK1 acts on: the finding that PfSRPK1 phosphorylates the splicing factor PfSR1 and inhibits splicing defined SRPK1 as a regulator of RNA processing rather than an uncharacterized kinase.\",\n      \"evidence\": \"In vitro splicing inhibition and kinase assays with parasite nuclear extracts, plus RNA-binding and co-localization assays, in P. falciparum\",\n      \"pmids\": [\"20870716\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single lab, single study without independent replication\",\n        \"no in-cell demonstration that SRPK1-dependent PfSR1 phosphorylation controls specific transcripts\",\n        \"substrate repertoire beyond PfSR1 unaddressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placing SRPK1 temporally and functionally in male gametogenesis: phosphoproteomics of a P. berghei mutant showed SRPK1 drives specific phosphorylation events within the first minute of activation, linking it to the rapid gametogenesis cell cycle.\",\n      \"evidence\": \"Time-course phosphoproteomics comparing SRPK1 mutant and wild-type P. berghei gametocytes\",\n      \"pmids\": [\"29141230\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"direct kinase-substrate relationships not resolved from phosphoproteome correlation\",\n        \"single lab\",\n        \"does not distinguish direct from indirect phosphorylation targets\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Testing SRPK1 dispensability in laboratory culture: convergent selection of a nonsense mutation during in vitro adaptation indicated loss-of-function confers a fitness advantage under culture, implying SRPK1's essential roles lie outside asexual culture growth.\",\n      \"evidence\": \"Longitudinal genome sequencing of cultured P. falciparum clinical isolates tracking emergent SNPs\",\n      \"pmids\": [\"28117431\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"genomic observation only, no direct functional assay of the mutant allele\",\n        \"mechanism of the fitness advantage unknown\",\n        \"does not establish SRPK1's normal function\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defining the cellular consequences of SRPK1 loss in P. falciparum: knockout phenotyping showed reduced merozoite formation and a complete transmission block via failed male gametogenesis, tying SRPK1 to transcript homeostasis of morphogenesis and signaling genes.\",\n      \"evidence\": \"Gene knockout, mosquito transmission assays, and RNA-seq of stage V gametocytes in P. falciparum NF54\",\n      \"pmids\": [\"36094218\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"RNA-seq changes do not distinguish direct splicing targets from downstream effects\",\n        \"kinase substrates mediating the phenotype not identified\",\n        \"single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Confirming convergent culture selection of SRPK1 loss-of-function: independent emergence of nonsense mutations across multiple West African isolates reproduced the earlier observation that SRPK1 is a repeatable target of culture adaptation.\",\n      \"evidence\": \"Longitudinal genome sequencing of independent cultured P. falciparum clinical isolates\",\n      \"pmids\": [\"37204422\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"genomic observation only, no functional assay\",\n        \"does not clarify the mechanistic basis of the fitness cost of intact SRPK1 in culture\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Refining the subcellular context and pathway of SRPK1 in gametogenesis: cytoplasmic localization, Co-IP with translation-associated partners, and axoneme defects in knockouts placed P. berghei SRPK1 in a cytoplasmic RNA-translation pathway during endomitosis.\",\n      \"evidence\": \"Live-cell imaging, immunoprecipitation of interactors, and ultrastructure expansion microscopy/TEM of P. berghei knockout parasites\",\n      \"pmids\": [\"40127922\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-IP interactors not reciprocally validated or functionally tested\",\n        \"how a cytoplasmic kinase controls translation mechanistically is unresolved\",\n        \"relationship between the nuclear splicing role and cytoplasmic translation role not reconciled\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct in vivo substrate set of SRPK1 beyond PfSR1, and how its distinct nuclear (splicing) and cytoplasmic (translation) activities are coordinated across developmental stages, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no comprehensive direct-substrate map\",\n        \"mechanism switching kinase between nuclear and cytoplasmic roles unknown\",\n        \"structural basis of substrate recognition uncharacterized\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004674\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0004672\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0008380\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0007140\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0060271\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfSR1 (substrate; P. falciparum) [#0]\",\n      \"RNA translation-associated interactors identified by Co-IP (P. berghei) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Knockout in P. falciparum blocks male gamete formation and mosquito transmission and reduces merozoite formation [#1].\",\n      \"In P. berghei, loss causes severe axoneme formation defects [#3].\",\n      \"Loss-of-function nonsense mutations are convergently selected during in vitro culture adaptation of P. falciparum clinical isolates [#4, #5].\",\n      \"P. falciparum PfSRPK1 is nuclear early in development, whereas the P. berghei ortholog is cytoplasmic during male gametogenesis, distinct from the nuclear CDPK4 and MAP2 [#0, #3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0302100","name":null,"product":"serine/threonine protein kinase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0401100","name":null,"product":"serine/threonine protein kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0840600","name":null,"product":"serine/threonine protein kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SRPK1","evaluation":null}