{"gene":"PF3D7_0320000","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2013,"finding":"I2 (PfI2/PF3D7_0320000) binds to P. falciparum PP1 catalytic subunit (PfPP1c) and inhibits its phosphatase activity in vitro and in vivo; the motifs 12KTISW16 (containing an RVxF-like element) and 102HYNE105 are critical for this inhibitory activity.","method":"Biochemical binding assays, in vitro phosphatase inhibition assays, site-directed mutagenesis of key motifs, Xenopus oocyte microinjection model (germinal vesicle breakdown assay)","journal":"BMC biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro enzymatic assay combined with mutagenesis and in vivo functional model (Xenopus oocyte), single lab but multiple orthogonal methods","pmids":["23837822"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Genetic disruption of the I2 gene in P. falciparum failed to yield viable mutant parasites, indicating an essential role for I2 in blood-stage parasite survival.","method":"Attempted gene disruption by transfection in P. falciparum; absence of viable mutants assessed","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function genetic approach with defined lethality phenotype, but single lab, single method","pmids":["23837822"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"I2 (PfI2) is able to override the G2/M cell cycle checkpoint by inducing germinal vesicle breakdown when microinjected into Xenopus oocytes, linking I2-mediated PP1 inhibition to cell cycle regulation.","method":"Xenopus oocyte microinjection and germinal vesicle breakdown (GVBD) assay","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional cell cycle assay in heterologous model, single lab, single method","pmids":["23837822"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"NMR spectroscopy identified a second PP1-binding site on I2 between residues D94 and T117, containing an 'FxxR/KxR/K' motif; mutations in both the RVxF and FxxR/KxR/K motifs are required to completely abolish the PfI2–PfPP1 interaction, establishing a two-site binding mechanism.","method":"NMR spectroscopy, site-directed mutagenesis of both binding motifs, binding/interaction assays","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — NMR structural mapping combined with mutagenesis and functional assay (GVBD in Xenopus), single lab but multiple orthogonal methods","pmids":["25132288"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Mutation of either the RVxF or the FxxR/KxR/K motif alone in I2 is sufficient to abolish the capacity of I2 to trigger germinal vesicle breakdown in Xenopus oocytes, indicating that the tight two-site association of I2 with PP1 is necessary for its functional activity.","method":"Site-directed mutagenesis of individual motifs followed by Xenopus oocyte GVBD assay","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional mutagenesis in a heterologous cell cycle model, single lab, single functional readout","pmids":["25132288"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Affinity pulldown (mCherry tag) of I2 from P. berghei asexual (schizont) and sexual (gametocyte) stage transgenic parasites followed by mass spectrometry revealed the I2 interactome; nuclear export mediator factor and peptidyl-prolyl cis-trans isomerase were identified as potential targets of the PP1c/I2 complex in both stages.","method":"mCherry-tagged transgenic P. berghei lines, affinity pulldown, mass spectrometry interactome mapping","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single pulldown-MS approach in a single lab; interaction partners identified but not functionally validated for I2 specifically","pmids":["35162991"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"I2 (PF3D7_0320000) is an essential P. falciparum PP1 regulator that binds the PP1 catalytic subunit through a two-site mechanism (RVxF motif and a second FxxR/KxR/K motif spanning residues D94–T117) to inhibit its phosphatase activity, thereby influencing cell cycle progression; interactome mapping in P. berghei further identifies nuclear export mediator factor and peptidyl-prolyl cis-trans isomerase as candidate targets of the PP1c/I2 complex in asexual and sexual stages."},"narrative":{"mechanistic_narrative":"I2 (PF3D7_0320000) is an essential regulator of the Plasmodium falciparum type-1 protein phosphatase catalytic subunit (PfPP1c), binding PfPP1c and inhibiting its phosphatase activity in vitro and in vivo [PMID:23837822]. Binding occurs through a two-site mechanism: an N-terminal RVxF-like element within the 12KTISW16 motif together with the 102HYNE105 region [PMID:23837822], and a second PP1-binding site between residues D94 and T117 containing an 'FxxR/KxR/K' motif mapped by NMR, such that mutation of both motifs is required to fully abolish the PfI2–PfPP1 interaction while mutation of either motif alone abrogates I2 function [PMID:25132288]. Through this PP1 inhibition I2 is linked to cell cycle control, overriding the G2/M checkpoint to induce germinal vesicle breakdown when microinjected into Xenopus oocytes [PMID:23837822]. Attempted gene disruption failed to yield viable parasites, establishing I2 as essential for blood-stage survival [PMID:23837822]. In P. berghei, affinity pulldown-mass spectrometry of tagged I2 across asexual and sexual stages identified nuclear export mediator factor and a peptidyl-prolyl cis-trans isomerase as candidate targets of the PP1c/I2 complex [PMID:35162991]. Beyond these findings, the downstream substrates and cellular pathways controlled by the I2/PP1c complex have not been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing whether P. falciparum encodes a functional PP1 inhibitor, this work showed that I2 directly binds and inhibits the PfPP1 catalytic subunit through defined sequence motifs.","evidence":"In vitro phosphatase inhibition and binding assays with site-directed mutagenesis of the 12KTISW16 and 102HYNE105 motifs","pmids":["23837822"],"confidence":"High","gaps":["Native substrates dephosphorylated by PP1c that are affected by I2 not identified","Structural basis of inhibition not resolved at this stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"To test physiological importance, gene disruption was attempted and failed, defining I2 as essential for blood-stage parasite survival.","evidence":"Attempted targeted gene disruption by transfection in P. falciparum with assessment of viable mutants","pmids":["23837822"],"confidence":"Medium","gaps":["Single method (failed disruption) does not distinguish essentiality from locus inaccessibility","Conditional knockdown to define the essential function not performed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"To connect I2-mediated PP1 inhibition to a cellular process, I2 was shown to override the G2/M checkpoint, linking it to cell cycle regulation.","evidence":"Xenopus oocyte microinjection and germinal vesicle breakdown (GVBD) assay","pmids":["23837822"],"confidence":"Medium","gaps":["Cell cycle role demonstrated only in a heterologous oocyte system","Direct role in parasite cell cycle progression not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Resolving how I2 engages PP1, NMR mapping revealed a second binding site (D94–T117, FxxR/KxR/K motif), establishing a two-site binding mechanism required to fully abolish the interaction.","evidence":"NMR spectroscopy with site-directed mutagenesis of both binding motifs and interaction assays","pmids":["25132288"],"confidence":"High","gaps":["No co-complex crystal structure of I2 bound to PfPP1c","Whether the two sites bind sequentially or cooperatively not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Establishing functional requirement of each site, mutation of either the RVxF or FxxR/KxR/K motif alone abolished I2's ability to trigger GVBD, showing tight two-site association is necessary for activity.","evidence":"Site-directed mutagenesis of individual motifs followed by Xenopus oocyte GVBD assay","pmids":["25132288"],"confidence":"Medium","gaps":["Functional readout limited to heterologous oocyte assay","Contribution of each motif to inhibition in the parasite not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"To identify downstream targets of the complex, interactome mapping of tagged I2 across asexual and sexual stages nominated nuclear export mediator factor and a peptidyl-prolyl cis-trans isomerase as candidate PP1c/I2 partners.","evidence":"mCherry-tagged transgenic P. berghei schizont and gametocyte lines, affinity pulldown and mass spectrometry","pmids":["35162991"],"confidence":"Medium","gaps":["Candidate partners not functionally validated as I2-specific interactors","Whether these are direct I2 contacts or bridged through PP1c not resolved","Shown in P. berghei, not confirmed in P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The endogenous substrates dephosphorylated by the I2/PP1c complex and the pathway by which I2 controls parasite cell cycle progression in vivo remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No parasite substrate directly linked to I2-regulated PP1 activity","In-parasite cell cycle function inferred only from heterologous assays","Regulation of I2 activity itself uncharacterized"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PP1c/I2 complex (PfPP1c–PfI2)"],"partners":["PFPP1C (P. FALCIPARUM PROTEIN PHOSPHATASE 1 CATALYTIC SUBUNIT)","NUCLEAR EXPORT MEDIATOR FACTOR (CANDIDATE PP1C/I2 TARGET, P. BERGHEI)","PEPTIDYL-PROLYL CIS-TRANS ISOMERASE (CANDIDATE PP1C/I2 TARGET, P. BERGHEI)"],"other_free_text":["Two-site PP1-binding mechanism: RVxF-like element within 12KTISW16 plus 102HYNE105, and a second FxxR/KxR/K motif spanning residues D94–T117 [#0, #3].","Essential for P. falciparum blood-stage survival by failed gene disruption [#1].","Interactome partners identified in P. berghei; not yet confirmed in P. falciparum [#5]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23837822","id":"PMC_23837822","title":"Plasmodium falciparum encodes a conserved active inhibitor-2 for Protein Phosphatase type 1: perspectives for novel anti-plasmodial therapy.","date":"2013","source":"BMC biology","url":"https://pubmed.ncbi.nlm.nih.gov/23837822","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfI2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25132288","id":"PMC_25132288","title":"Identification of a Plasmodium falciparum inhibitor-2 motif involved in the binding and regulation activity of protein phosphatase type 1.","date":"2014","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/25132288","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfI2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35336160","id":"PMC_35336160","title":"Deciphering the Role of Protein Phosphatases in Apicomplexa: The Future of Innovative Therapeutics?","date":"2022","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/35336160","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35162991","id":"PMC_35162991","title":"Mapping PP1c and Its Inhibitor 2 Interactomes Reveals Conserved and Specific Networks in Asexual and Sexual Stages of Plasmodium.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35162991","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"citation_expansion","match_terms":["fwd_cite"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4870,"output_tokens":1637,"usd":0.019582,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6648,"output_tokens":2826,"usd":0.051945,"stage2_stop_reason":"end_turn"},"total_usd":0.071527,"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\": 2013,\n      \"finding\": \"I2 (PfI2/PF3D7_0320000) binds to P. falciparum PP1 catalytic subunit (PfPP1c) and inhibits its phosphatase activity in vitro and in vivo; the motifs 12KTISW16 (containing an RVxF-like element) and 102HYNE105 are critical for this inhibitory activity.\",\n      \"method\": \"Biochemical binding assays, in vitro phosphatase inhibition assays, site-directed mutagenesis of key motifs, Xenopus oocyte microinjection model (germinal vesicle breakdown assay)\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro enzymatic assay combined with mutagenesis and in vivo functional model (Xenopus oocyte), single lab but multiple orthogonal methods\",\n      \"pmids\": [\"23837822\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Genetic disruption of the I2 gene in P. falciparum failed to yield viable mutant parasites, indicating an essential role for I2 in blood-stage parasite survival.\",\n      \"method\": \"Attempted gene disruption by transfection in P. falciparum; absence of viable mutants assessed\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function genetic approach with defined lethality phenotype, but single lab, single method\",\n      \"pmids\": [\"23837822\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"I2 (PfI2) is able to override the G2/M cell cycle checkpoint by inducing germinal vesicle breakdown when microinjected into Xenopus oocytes, linking I2-mediated PP1 inhibition to cell cycle regulation.\",\n      \"method\": \"Xenopus oocyte microinjection and germinal vesicle breakdown (GVBD) assay\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional cell cycle assay in heterologous model, single lab, single method\",\n      \"pmids\": [\"23837822\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"NMR spectroscopy identified a second PP1-binding site on I2 between residues D94 and T117, containing an 'FxxR/KxR/K' motif; mutations in both the RVxF and FxxR/KxR/K motifs are required to completely abolish the PfI2–PfPP1 interaction, establishing a two-site binding mechanism.\",\n      \"method\": \"NMR spectroscopy, site-directed mutagenesis of both binding motifs, binding/interaction assays\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — NMR structural mapping combined with mutagenesis and functional assay (GVBD in Xenopus), single lab but multiple orthogonal methods\",\n      \"pmids\": [\"25132288\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Mutation of either the RVxF or the FxxR/KxR/K motif alone in I2 is sufficient to abolish the capacity of I2 to trigger germinal vesicle breakdown in Xenopus oocytes, indicating that the tight two-site association of I2 with PP1 is necessary for its functional activity.\",\n      \"method\": \"Site-directed mutagenesis of individual motifs followed by Xenopus oocyte GVBD assay\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional mutagenesis in a heterologous cell cycle model, single lab, single functional readout\",\n      \"pmids\": [\"25132288\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Affinity pulldown (mCherry tag) of I2 from P. berghei asexual (schizont) and sexual (gametocyte) stage transgenic parasites followed by mass spectrometry revealed the I2 interactome; nuclear export mediator factor and peptidyl-prolyl cis-trans isomerase were identified as potential targets of the PP1c/I2 complex in both stages.\",\n      \"method\": \"mCherry-tagged transgenic P. berghei lines, affinity pulldown, mass spectrometry interactome mapping\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single pulldown-MS approach in a single lab; interaction partners identified but not functionally validated for I2 specifically\",\n      \"pmids\": [\"35162991\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"I2 (PF3D7_0320000) is an essential P. falciparum PP1 regulator that binds the PP1 catalytic subunit through a two-site mechanism (RVxF motif and a second FxxR/KxR/K motif spanning residues D94–T117) to inhibit its phosphatase activity, thereby influencing cell cycle progression; interactome mapping in P. berghei further identifies nuclear export mediator factor and peptidyl-prolyl cis-trans isomerase as candidate targets of the PP1c/I2 complex in asexual and sexual stages.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"I2 (PF3D7_0320000) is an essential regulator of the Plasmodium falciparum type-1 protein phosphatase catalytic subunit (PfPP1c), binding PfPP1c and inhibiting its phosphatase activity in vitro and in vivo [#0]. Binding occurs through a two-site mechanism: an N-terminal RVxF-like element within the 12KTISW16 motif together with the 102HYNE105 region [#0], and a second PP1-binding site between residues D94 and T117 containing an 'FxxR/KxR/K' motif mapped by NMR, such that mutation of both motifs is required to fully abolish the PfI2\\u2013PfPP1 interaction while mutation of either motif alone abrogates I2 function [#3, #4]. Through this PP1 inhibition I2 is linked to cell cycle control, overriding the G2/M checkpoint to induce germinal vesicle breakdown when microinjected into Xenopus oocytes [#2]. Attempted gene disruption failed to yield viable parasites, establishing I2 as essential for blood-stage survival [#1]. In P. berghei, affinity pulldown-mass spectrometry of tagged I2 across asexual and sexual stages identified nuclear export mediator factor and a peptidyl-prolyl cis-trans isomerase as candidate targets of the PP1c/I2 complex [#5]. Beyond these findings, the downstream substrates and cellular pathways controlled by the I2/PP1c complex have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing whether P. falciparum encodes a functional PP1 inhibitor, this work showed that I2 directly binds and inhibits the PfPP1 catalytic subunit through defined sequence motifs.\",\n      \"evidence\": \"In vitro phosphatase inhibition and binding assays with site-directed mutagenesis of the 12KTISW16 and 102HYNE105 motifs\",\n      \"pmids\": [\"23837822\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Native substrates dephosphorylated by PP1c that are affected by I2 not identified\", \"Structural basis of inhibition not resolved at this stage\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"To test physiological importance, gene disruption was attempted and failed, defining I2 as essential for blood-stage parasite survival.\",\n      \"evidence\": \"Attempted targeted gene disruption by transfection in P. falciparum with assessment of viable mutants\",\n      \"pmids\": [\"23837822\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single method (failed disruption) does not distinguish essentiality from locus inaccessibility\", \"Conditional knockdown to define the essential function not performed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"To connect I2-mediated PP1 inhibition to a cellular process, I2 was shown to override the G2/M checkpoint, linking it to cell cycle regulation.\",\n      \"evidence\": \"Xenopus oocyte microinjection and germinal vesicle breakdown (GVBD) assay\",\n      \"pmids\": [\"23837822\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cell cycle role demonstrated only in a heterologous oocyte system\", \"Direct role in parasite cell cycle progression not shown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Resolving how I2 engages PP1, NMR mapping revealed a second binding site (D94\\u2013T117, FxxR/KxR/K motif), establishing a two-site binding mechanism required to fully abolish the interaction.\",\n      \"evidence\": \"NMR spectroscopy with site-directed mutagenesis of both binding motifs and interaction assays\",\n      \"pmids\": [\"25132288\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No co-complex crystal structure of I2 bound to PfPP1c\", \"Whether the two sites bind sequentially or cooperatively not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Establishing functional requirement of each site, mutation of either the RVxF or FxxR/KxR/K motif alone abolished I2's ability to trigger GVBD, showing tight two-site association is necessary for activity.\",\n      \"evidence\": \"Site-directed mutagenesis of individual motifs followed by Xenopus oocyte GVBD assay\",\n      \"pmids\": [\"25132288\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional readout limited to heterologous oocyte assay\", \"Contribution of each motif to inhibition in the parasite not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To identify downstream targets of the complex, interactome mapping of tagged I2 across asexual and sexual stages nominated nuclear export mediator factor and a peptidyl-prolyl cis-trans isomerase as candidate PP1c/I2 partners.\",\n      \"evidence\": \"mCherry-tagged transgenic P. berghei schizont and gametocyte lines, affinity pulldown and mass spectrometry\",\n      \"pmids\": [\"35162991\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Candidate partners not functionally validated as I2-specific interactors\", \"Whether these are direct I2 contacts or bridged through PP1c not resolved\", \"Shown in P. berghei, not confirmed in P. falciparum\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The endogenous substrates dephosphorylated by the I2/PP1c complex and the pathway by which I2 controls parasite cell cycle progression in vivo remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No parasite substrate directly linked to I2-regulated PP1 activity\", \"In-parasite cell cycle function inferred only from heterologous assays\", \"Regulation of I2 activity itself uncharacterized\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004865\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0019212\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0008157\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [2, 4]},\n      {\"term_id\": \"GO:0000086\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"PP1c/I2 complex (PfPP1c\\u2013PfI2)\"\n    ],\n    \"partners\": [\n      \"PfPP1c (P. falciparum protein phosphatase 1 catalytic subunit)\",\n      \"nuclear export mediator factor (candidate PP1c/I2 target, P. berghei)\",\n      \"peptidyl-prolyl cis-trans isomerase (candidate PP1c/I2 target, P. berghei)\"\n    ],\n    \"other_free_text\": [\n      \"Two-site PP1-binding mechanism: RVxF-like element within 12KTISW16 plus 102HYNE105, and a second FxxR/KxR/K motif spanning residues D94\\u2013T117 [#0, #3].\",\n      \"Essential for P. falciparum blood-stage survival by failed gene disruption [#1].\",\n      \"Interactome partners identified in P. berghei; not yet confirmed in P. falciparum [#5].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0320000","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 3 cited papers name other catalogue genes (PF3D7_1414400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0320000","name":null,"product":"protein phosphatase inhibitor 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1218500","name":null,"product":"protein phosphatase inhibitor 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0821200","name":null,"product":"protein phosphatase inhibitor 2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"I2","evaluation":null}