{"gene":"PF3D7_0910700","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2025,"finding":"ALP5a (PF3D7_0910700) is a subunit of an atypical Arp2/3 complex in Plasmodium. Co-immunoprecipitation of GFP-tagged ARPC1 from activated gametocytes identified ALP5a as an interaction partner, and AlphaFold structural prediction shows ALP5a is structurally similar to human ARP3, with superimposition supporting its assignment as the Arp3-like subunit of this five-subunit complex.","method":"Co-immunoprecipitation (GFP-tag pulldown) from activated P. berghei gametocytes followed by mass spectrometry; AlphaFold3 structural prediction and DALI structural comparison","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP with MS identification, corroborated by structural prediction with DALI alignment, findings independently reported in two papers (PMID:40514561, PMID:41218080)","pmids":["40514561","40828051"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"ALP5a (PF3D7_0910700) localizes to the nucleus in gametocytes and interacts with ALP5b. ALP5a and ALP5b are individually dispensable for P. berghei blood stage development but are simultaneously indispensable for parasite viability, as shown by single and double knockout genetics.","method":"Genetic knockout (single and double deletion), fluorescence localization, co-immunoprecipitation","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockouts with defined phenotypic readouts, direct localization, and protein interaction demonstrated across two independent studies (PMID:41218080, PMID:40514561)","pmids":["41218080"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Deletion of ALP5a (PF3D7_0910700) in P. berghei does not affect actin nucleation, parasite growth, or gametocytemia during blood stages, but causes significantly smaller oocysts that fail to mature, with impaired DNA segregation during male gametogenesis, ultimately blocking malaria transmission.","method":"Genetic knockout with phenotypic analysis across life cycle stages (blood stage growth assays, mosquito infection, oocyst size measurement, DNA segregation assays via microscopy)","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with multiple defined cellular phenotypes across life cycle stages, independently replicated in two separate studies (PMID:41218080, PMID:42629988)","pmids":["41218080","42629988"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"The atypical Arp2/3 complex containing ALP5a (PF3D7_0910700) localizes to endomitotic spindles in male gametocytes and interacts with the kinetochore-associated protein AKiT7. Disruption of Arp2/3 subunits or actin polymerization interferes with kinetochore-spindle association, causing formation of subhaploid gametes.","method":"Co-immunoprecipitation, fluorescence localization, genetic disruption with kinetochore-spindle association readout","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — complex localization by direct imaging, Co-IP identifying AKiT7 interaction, and functional readout from genetic disruption across multiple orthogonal methods in one study","pmids":["40514561"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Two serine positions within the ALP5a sequence were found to be phosphorylated within 60 seconds after activation of male gametogenesis, suggesting post-translational regulation linked to gametogenesis induction signaling.","method":"Phosphoproteomics (cited from Invergo et al. 2017, referenced in the context of ALP5a regulation)","journal":"Cytoskeleton (Hoboken, N.J.)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — phosphosite identification reported as existing data without functional validation of the specific modification's role; single referenced dataset","pmids":["40828051"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"finding":"Deletion of ALP5a (PF3D7_0910700) in P. berghei leads to smaller and fewer oocysts and severely impaired sporozoite formation, without affecting blood stage growth, gametogenesis, or ookinete gliding motility. This indicates ALP5a is required for oocyst development and sporozoite formation steps of mosquito infection.","method":"Genetic knockout with phenotypic characterization across life cycle stages including oocyst counts, oocyst size measurement, sporozoite formation assays, and ookinete gliding assays","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with multiple defined phenotypic readouts across life cycle stages, independently corroborating findings from PMID:41218080","pmids":["42629988"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"ALP5a (PF3D7_0910700) is the Arp3-like subunit of an atypical five-subunit Arp2/3 complex in Plasmodium that localizes to endomitotic spindles in male gametocytes, interacts with ALP5b (Arp2-like), ARPC1, ARPC2, ARPC4, and the kinetochore protein AKiT7, and is required for kinetochore-spindle association and DNA segregation during male gametogenesis, with its loss causing failed oocyst maturation, impaired sporozoite formation, and a complete block in malaria transmission."},"narrative":{"mechanistic_narrative":"ALP5a (PF3D7_0910700) is the Arp3-like subunit of an atypical five-subunit Arp2/3 complex in Plasmodium that supports chromosome segregation during male gametogenesis and downstream mosquito-stage development [PMID:40514561, PMID:40828051]. It was identified as an interaction partner in GFP-ARPC1 co-immunoprecipitations from activated P. berghei gametocytes, and AlphaFold prediction with DALI structural comparison assigned it as the Arp3-like (human ARP3-similar) component of the complex [PMID:40514561, PMID:40828051]. ALP5a localizes to the nucleus in gametocytes and to endomitotic spindles in male gametocytes, where the complex interacts with the kinetochore-associated protein AKiT7; disruption of Arp2/3 subunits or actin polymerization interferes with kinetochore-spindle association and produces subhaploid gametes [PMID:41218080, PMID:40514561]. ALP5a interacts directly with the Arp2-like subunit ALP5b, and while each is individually dispensable for P. berghei blood-stage development, the two are simultaneously indispensable for parasite viability [PMID:41218080]. Deletion of ALP5a leaves blood-stage growth, gametocytemia, and ookinete gliding motility intact but impairs DNA segregation during male gametogenesis and yields smaller, fewer oocysts that fail to mature, with severely impaired sporozoite formation, thereby blocking malaria transmission [PMID:41218080, PMID:42629988]. Beyond its role as a subunit of this atypical Arp2/3 complex and the transmission phenotypes described, no further biochemical detail specific to ALP5a has been characterized in the available corpus.","teleology":[{"year":2025,"claim":"Establishing that ALP5a is a bona fide subunit of a Plasmodium Arp2/3-like complex answered whether this actin-like protein assembles into a defined machine rather than acting alone.","evidence":"GFP-ARPC1 co-immunoprecipitation with mass spectrometry from activated P. berghei gametocytes, plus AlphaFold3 prediction and DALI comparison assigning ALP5a as the Arp3-like subunit","pmids":["40514561","40828051"],"confidence":"High","gaps":["Structural assignment is computational (AlphaFold/DALI), not an experimental structure of the assembled complex","Whether ALP5a possesses nucleation-relevant biochemical activity within the complex is not shown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Localization and genetic interaction with ALP5b defined ALP5a as a nuclear factor whose function is co-dependent on its Arp2-like partner, distinguishing essential from redundant roles.","evidence":"Fluorescence localization, co-immunoprecipitation, and single versus double knockout genetics in P. berghei","pmids":["41218080"],"confidence":"High","gaps":["Molecular basis of the synthetic lethality between ALP5a and ALP5b is not resolved","Whether ALP5a has functions outside the complex is untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Placing the complex on endomitotic spindles and linking it to AKiT7 explained how the complex acts mechanistically — coupling kinetochores to spindles during male gametogenesis.","evidence":"Co-immunoprecipitation identifying AKiT7, fluorescence localization to male gametocyte spindles, and genetic disruption with a kinetochore-spindle association readout","pmids":["40514561"],"confidence":"High","gaps":["Direct binding interface between ALP5a and AKiT7 versus complex-level interaction is not dissected","How the Arp2/3-like complex physically bridges kinetochores to spindles is not defined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Life-cycle knockout phenotyping established where ALP5a is functionally required, showing dispensability in blood stages but a block at oocyst maturation and transmission.","evidence":"Genetic knockout with blood-stage growth, gametocytemia, mosquito infection, oocyst size, and DNA segregation assays in P. berghei","pmids":["41218080","42629988"],"confidence":"High","gaps":["Mechanistic link between impaired DNA segregation and downstream oocyst failure is not fully traced","Whether the transmission block reflects the spindle role alone or additional functions is unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2026,"claim":"Independent knockout characterization refined the developmental defect to oocyst development and sporozoite formation while confirming intact ookinete gliding.","evidence":"Genetic knockout with oocyst counts, oocyst size, sporozoite formation, and ookinete gliding assays in P. berghei","pmids":["42629988"],"confidence":"High","gaps":["Stage-specific molecular events downstream of ALP5a loss during sporogony are not identified","No rescue/complementation reported to formally exclude second-site effects"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"claim":"Identification of two phosphorylated serines within seconds of gametogenesis activation raised the possibility of signaling-linked post-translational control of ALP5a.","evidence":"Phosphoproteomic data referenced in the context of ALP5a regulation (P. berghei)","pmids":["40828051"],"confidence":"Low","gaps":["Functional role of these phosphosites is not validated by mutagenesis","The kinase responsible and the consequence for complex assembly or activity are unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"It remains unknown whether ALP5a has any biochemical activity or role independent of the atypical Arp2/3 complex, and how its predicted structure translates into function in an experimentally determined assembly.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimental structure of the assembled complex","No defined enzymatic or nucleation activity attributed to ALP5a itself","Human ortholog function not established from this corpus"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Atypical five-subunit Arp2/3 complex (Arp3-like subunit)"],"partners":["ALP5B (ARP2-LIKE SUBUNIT)","ARPC1","ARPC2","ARPC4","AKIT7 (KINETOCHORE-ASSOCIATED PROTEIN)"],"other_free_text":["Individually dispensable for P. berghei blood-stage development but synthetically essential with ALP5b for parasite viability [#1]","Required for DNA segregation during male gametogenesis, oocyst maturation, and sporozoite formation; loss blocks malaria transmission [#2, #5]","Two serine residues phosphorylated within 60 s of gametogenesis activation (Low confidence, unvalidated) [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"41218080","id":"PMC_41218080","title":"Plasmodium actin-like proteins are essential for DNA segregation during male gametogenesis and malaria transmission.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41218080","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALP5a"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42629988","id":"PMC_42629988","title":"Plasmodium Actin-Like Proteins 3 and 5a Are Required for Subsequent Steps of Mosquito Infection.","date":"2026","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42629988","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALP5a","actin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40514561","id":"","title":"An atypical Arp2/3 complex is required for Plasmodium DNA segregation and malaria transmission.","date":"2025","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/40514561","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALP5a"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40828051","id":"","title":"Discovery of an Atypical Arp2/3 Complex in Malaria Parasites Sheds New Light on Nuclear Actin.","date":"2025","source":"Cytoskeleton (Hoboken, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/40828051","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALP5a"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6113,"output_tokens":1822,"usd":0.022835,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6872,"output_tokens":2911,"usd":0.053567,"stage2_stop_reason":"end_turn"},"total_usd":0.076402,"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\": 2025,\n      \"finding\": \"ALP5a (PF3D7_0910700) is a subunit of an atypical Arp2/3 complex in Plasmodium. Co-immunoprecipitation of GFP-tagged ARPC1 from activated gametocytes identified ALP5a as an interaction partner, and AlphaFold structural prediction shows ALP5a is structurally similar to human ARP3, with superimposition supporting its assignment as the Arp3-like subunit of this five-subunit complex.\",\n      \"method\": \"Co-immunoprecipitation (GFP-tag pulldown) from activated P. berghei gametocytes followed by mass spectrometry; AlphaFold3 structural prediction and DALI structural comparison\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP with MS identification, corroborated by structural prediction with DALI alignment, findings independently reported in two papers (PMID:40514561, PMID:41218080)\",\n      \"pmids\": [\"40514561\", \"40828051\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ALP5a (PF3D7_0910700) localizes to the nucleus in gametocytes and interacts with ALP5b. ALP5a and ALP5b are individually dispensable for P. berghei blood stage development but are simultaneously indispensable for parasite viability, as shown by single and double knockout genetics.\",\n      \"method\": \"Genetic knockout (single and double deletion), fluorescence localization, co-immunoprecipitation\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockouts with defined phenotypic readouts, direct localization, and protein interaction demonstrated across two independent studies (PMID:41218080, PMID:40514561)\",\n      \"pmids\": [\"41218080\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Deletion of ALP5a (PF3D7_0910700) in P. berghei does not affect actin nucleation, parasite growth, or gametocytemia during blood stages, but causes significantly smaller oocysts that fail to mature, with impaired DNA segregation during male gametogenesis, ultimately blocking malaria transmission.\",\n      \"method\": \"Genetic knockout with phenotypic analysis across life cycle stages (blood stage growth assays, mosquito infection, oocyst size measurement, DNA segregation assays via microscopy)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with multiple defined cellular phenotypes across life cycle stages, independently replicated in two separate studies (PMID:41218080, PMID:42629988)\",\n      \"pmids\": [\"41218080\", \"42629988\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The atypical Arp2/3 complex containing ALP5a (PF3D7_0910700) localizes to endomitotic spindles in male gametocytes and interacts with the kinetochore-associated protein AKiT7. Disruption of Arp2/3 subunits or actin polymerization interferes with kinetochore-spindle association, causing formation of subhaploid gametes.\",\n      \"method\": \"Co-immunoprecipitation, fluorescence localization, genetic disruption with kinetochore-spindle association readout\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — complex localization by direct imaging, Co-IP identifying AKiT7 interaction, and functional readout from genetic disruption across multiple orthogonal methods in one study\",\n      \"pmids\": [\"40514561\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Two serine positions within the ALP5a sequence were found to be phosphorylated within 60 seconds after activation of male gametogenesis, suggesting post-translational regulation linked to gametogenesis induction signaling.\",\n      \"method\": \"Phosphoproteomics (cited from Invergo et al. 2017, referenced in the context of ALP5a regulation)\",\n      \"journal\": \"Cytoskeleton (Hoboken, N.J.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — phosphosite identification reported as existing data without functional validation of the specific modification's role; single referenced dataset\",\n      \"pmids\": [\"40828051\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Deletion of ALP5a (PF3D7_0910700) in P. berghei leads to smaller and fewer oocysts and severely impaired sporozoite formation, without affecting blood stage growth, gametogenesis, or ookinete gliding motility. This indicates ALP5a is required for oocyst development and sporozoite formation steps of mosquito infection.\",\n      \"method\": \"Genetic knockout with phenotypic characterization across life cycle stages including oocyst counts, oocyst size measurement, sporozoite formation assays, and ookinete gliding assays\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with multiple defined phenotypic readouts across life cycle stages, independently corroborating findings from PMID:41218080\",\n      \"pmids\": [\"42629988\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ALP5a (PF3D7_0910700) is the Arp3-like subunit of an atypical five-subunit Arp2/3 complex in Plasmodium that localizes to endomitotic spindles in male gametocytes, interacts with ALP5b (Arp2-like), ARPC1, ARPC2, ARPC4, and the kinetochore protein AKiT7, and is required for kinetochore-spindle association and DNA segregation during male gametogenesis, with its loss causing failed oocyst maturation, impaired sporozoite formation, and a complete block in malaria transmission.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ALP5a (PF3D7_0910700) is the Arp3-like subunit of an atypical five-subunit Arp2/3 complex in Plasmodium that supports chromosome segregation during male gametogenesis and downstream mosquito-stage development [#0, #3]. It was identified as an interaction partner in GFP-ARPC1 co-immunoprecipitations from activated P. berghei gametocytes, and AlphaFold prediction with DALI structural comparison assigned it as the Arp3-like (human ARP3-similar) component of the complex [#0]. ALP5a localizes to the nucleus in gametocytes and to endomitotic spindles in male gametocytes, where the complex interacts with the kinetochore-associated protein AKiT7; disruption of Arp2/3 subunits or actin polymerization interferes with kinetochore-spindle association and produces subhaploid gametes [#1, #3]. ALP5a interacts directly with the Arp2-like subunit ALP5b, and while each is individually dispensable for P. berghei blood-stage development, the two are simultaneously indispensable for parasite viability [#1]. Deletion of ALP5a leaves blood-stage growth, gametocytemia, and ookinete gliding motility intact but impairs DNA segregation during male gametogenesis and yields smaller, fewer oocysts that fail to mature, with severely impaired sporozoite formation, thereby blocking malaria transmission [#2, #5]. Beyond its role as a subunit of this atypical Arp2/3 complex and the transmission phenotypes described, no further biochemical detail specific to ALP5a has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Establishing that ALP5a is a bona fide subunit of a Plasmodium Arp2/3-like complex answered whether this actin-like protein assembles into a defined machine rather than acting alone.\",\n      \"evidence\": \"GFP-ARPC1 co-immunoprecipitation with mass spectrometry from activated P. berghei gametocytes, plus AlphaFold3 prediction and DALI comparison assigning ALP5a as the Arp3-like subunit\",\n      \"pmids\": [\"40514561\", \"40828051\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural assignment is computational (AlphaFold/DALI), not an experimental structure of the assembled complex\", \"Whether ALP5a possesses nucleation-relevant biochemical activity within the complex is not shown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Localization and genetic interaction with ALP5b defined ALP5a as a nuclear factor whose function is co-dependent on its Arp2-like partner, distinguishing essential from redundant roles.\",\n      \"evidence\": \"Fluorescence localization, co-immunoprecipitation, and single versus double knockout genetics in P. berghei\",\n      \"pmids\": [\"41218080\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of the synthetic lethality between ALP5a and ALP5b is not resolved\", \"Whether ALP5a has functions outside the complex is untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Placing the complex on endomitotic spindles and linking it to AKiT7 explained how the complex acts mechanistically — coupling kinetochores to spindles during male gametogenesis.\",\n      \"evidence\": \"Co-immunoprecipitation identifying AKiT7, fluorescence localization to male gametocyte spindles, and genetic disruption with a kinetochore-spindle association readout\",\n      \"pmids\": [\"40514561\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding interface between ALP5a and AKiT7 versus complex-level interaction is not dissected\", \"How the Arp2/3-like complex physically bridges kinetochores to spindles is not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Life-cycle knockout phenotyping established where ALP5a is functionally required, showing dispensability in blood stages but a block at oocyst maturation and transmission.\",\n      \"evidence\": \"Genetic knockout with blood-stage growth, gametocytemia, mosquito infection, oocyst size, and DNA segregation assays in P. berghei\",\n      \"pmids\": [\"41218080\", \"42629988\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanistic link between impaired DNA segregation and downstream oocyst failure is not fully traced\", \"Whether the transmission block reflects the spindle role alone or additional functions is unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Independent knockout characterization refined the developmental defect to oocyst development and sporozoite formation while confirming intact ookinete gliding.\",\n      \"evidence\": \"Genetic knockout with oocyst counts, oocyst size, sporozoite formation, and ookinete gliding assays in P. berghei\",\n      \"pmids\": [\"42629988\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stage-specific molecular events downstream of ALP5a loss during sporogony are not identified\", \"No rescue/complementation reported to formally exclude second-site effects\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of two phosphorylated serines within seconds of gametogenesis activation raised the possibility of signaling-linked post-translational control of ALP5a.\",\n      \"evidence\": \"Phosphoproteomic data referenced in the context of ALP5a regulation (P. berghei)\",\n      \"pmids\": [\"40828051\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Functional role of these phosphosites is not validated by mutagenesis\", \"The kinase responsible and the consequence for complex assembly or activity are unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether ALP5a has any biochemical activity or role independent of the atypical Arp2/3 complex, and how its predicted structure translates into function in an experimentally determined assembly.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No experimental structure of the assembled complex\", \"No defined enzymatic or nucleation activity attributed to ALP5a itself\", \"Human ortholog function not established from this corpus\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005200\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005819\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007059\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0007140\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\n      \"Atypical five-subunit Arp2/3 complex (Arp3-like subunit)\"\n    ],\n    \"partners\": [\n      \"ALP5b (Arp2-like subunit)\",\n      \"ARPC1\",\n      \"ARPC2\",\n      \"ARPC4\",\n      \"AKiT7 (kinetochore-associated protein)\"\n    ],\n    \"other_free_text\": [\n      \"Individually dispensable for P. berghei blood-stage development but synthetically essential with ALP5b for parasite viability [#1]\",\n      \"Required for DNA segregation during male gametogenesis, oocyst maturation, and sporozoite formation; loss blocks malaria transmission [#2, #5]\",\n      \"Two serine residues phosphorylated within 60 s of gametogenesis activation (Low confidence, unvalidated) [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0910700","name":null,"product":"actin-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0811800","name":null,"product":"actin-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0708700","name":null,"product":"actin-like protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ALP5a","evaluation":null}