{"gene":"PF3D7_1006200","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2011,"finding":"ALBA3 (PfAlba3) binds to DNA non-specifically at the minor groove, and acetylation of its N-terminal lysine residue lowers its DNA-binding affinity. In vitro, PfAlba3 inhibits transcription by binding to DNA. PfSir2A (a nuclear-localized deacetylase) interacts with PfAlba3 and deacetylates its N-terminal lysine residue. PfAlba3 co-localizes with PfSir2A at the nuclear periphery and is found in telomeric and subtelomeric regions by FISH, ChIP, and ChIP-ReChIP analyses. It also binds to var gene promoters. The protein is expressed in all erythrocytic stages and exists predominantly in the acetylated form.","method":"DNA-binding assays (EMSA), in vitro transcription inhibition assay, acetylation/deacetylation assays, co-immunoprecipitation with PfSir2A, immunofluorescence/co-localization, FISH, ChIP, ChIP-ReChIP","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal methods (in vitro binding and transcription assays, co-IP, ChIP/ReChIP, FISH, localization) in a single study establishing enzymatic regulation and genomic targeting","pmids":["22006844"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"ALBA3 (PfAlba3) is one of three PfAlba paralogs isolated as part of a molecular complex associated with the TARE6 subtelomeric region; EMSAs showed PfAlbas bind to TARE6 repeats and to single-stranded RNA, with different binding preferences among paralogs. In early blood stages PfAlba proteins are enriched at the nuclear periphery and partially co-localize with PfSir2; at the trophozoite–schizont transition they are also detectable in the cytoplasm in a punctate pattern.","method":"Molecular complex isolation (affinity purification), EMSA with TARE6 DNA and ssRNA probes, immunofluorescence/co-localization, subcellular fractionation/stage-specific imaging","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — reciprocal complex isolation and EMSA with multiple orthogonal methods, single lab; ALBA3-specific contribution inferred within a multi-paralog study","pmids":["22167473"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"ALBA3 (PfAlba3) is identified as one of 16 major protein components of the DOZI/CITH messenger ribonucleoprotein (mRNP) complex purified from Plasmodium berghei gametocytes by affinity purification coupled with mass spectrometry. This mRNP contains translationally silent transcripts and integrates eIF4E and poly(A)-binding protein but excludes P-body RNA degradation factors and translation-initiation-promoting eIF4G.","method":"Affinity purification coupled with mass spectrometry (AP-MS) from gametocyte lysates","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — rigorous AP-MS identification in a well-characterised complex, but ALBA3-specific functional role within the complex not separately validated; single study","pmids":["20169188"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2025,"finding":"Ectopic overexpression of ALBA3 (PfAlba3) from an episome under a strong constitutive promoter strongly reduced P. falciparum intra-erythrocytic development (IED) growth and impaired stage transitions. RNA-seq of PfAlba3-overexpressing strains revealed significant misregulation of mRNAs encoding virulence factors (including erythrocyte invasion genes) and a general repression of var gene expression, linking ALBA3 to subtelomeric chromatin biology and mutually exclusive PfEMP1 expression.","method":"Episomal overexpression, growth assays, RNA-seq differential gene expression analysis","journal":"Microbiology spectrum","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — overexpression with specific phenotypic readout and transcriptome-wide analysis, two orthogonal methods (growth and RNA-seq), single lab","pmids":["39868986"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"ALBA3 (PF3D7_1006200) is a DNA/RNA-binding protein expressed throughout P. falciparum intra-erythrocytic development that binds DNA at the minor groove and telomeric/subtelomeric chromatin (including var gene promoters); its DNA-binding affinity is reduced by acetylation of an N-terminal lysine and restored by the deacetylase PfSir2A with which it co-localizes at the nuclear periphery; it is also a component of the DOZI/CITH translationally silent mRNP complex in P. berghei gametocytes; and its overexpression in P. falciparum impairs intra-erythrocytic growth and stage transitions, accompanied by misregulation of virulence-factor mRNAs and general repression of var gene expression."},"narrative":{"mechanistic_narrative":"ALBA3 (PF3D7_1006200) is a DNA/RNA-binding protein expressed across all intra-erythrocytic stages of Plasmodium falciparum that couples chromatin-level DNA binding to the control of subtelomeric virulence-gene expression [PMID:22006844, PMID:39868986]. It binds DNA non-specifically at the minor groove and inhibits transcription in vitro, with this activity governed by reversible acetylation: acetylation of an N-terminal lysine lowers DNA-binding affinity, and the nuclear deacetylase PfSir2A interacts with ALBA3, removes this modification, and co-localizes with it at the nuclear periphery [PMID:22006844]. ALBA3 occupies telomeric and subtelomeric chromatin, including var gene promoters, and also binds TARE6 subtelomeric repeats and single-stranded RNA, placing it at the interface of chromatin structure and RNA metabolism [PMID:22006844, PMID:22167473]. Consistent with a regulatory role in virulence-gene control, episomal overexpression of ALBA3 impairs intra-erythrocytic growth and stage transitions and misregulates virulence-factor mRNAs while generally repressing var gene expression [PMID:39868986]. In P. berghei gametocytes, ALBA3 is a component of the translationally silent DOZI/CITH mRNP complex, indicating an additional role in post-transcriptional mRNA storage [PMID:20169188]. Beyond these findings, the structural basis of DNA binding and the direct molecular consequences of ALBA3 within the DOZI/CITH complex have not been characterized in the available corpus.","teleology":[{"year":2010,"claim":"The question of whether ALBA3 participates in post-transcriptional gene regulation was addressed by defining the composition of the translationally silent mRNP that stores maternal transcripts in gametocytes.","evidence":"Affinity purification coupled with mass spectrometry of the DOZI/CITH complex from P. berghei gametocyte lysates","pmids":["20169188"],"confidence":"Medium","gaps":["ALBA3-specific functional role within the DOZI/CITH complex was not separately validated","shown in P. berghei; not demonstrated for the P. falciparum ortholog","no mechanism for how ALBA3 contributes to translational silencing"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"claim":"How ALBA3 engages DNA and how that engagement is regulated was established by defining its minor-groove binding, transcription-inhibitory activity, acetylation-dependent affinity, and its regulation by and co-localization with PfSir2A at telomeric/subtelomeric chromatin.","evidence":"EMSA DNA-binding and in vitro transcription assays, acetylation/deacetylation assays, co-IP with PfSir2A, immunofluorescence, FISH, ChIP and ChIP-ReChIP in P. falciparum","pmids":["22006844"],"confidence":"High","gaps":["no structural model of the ALBA3–DNA interaction","functional consequence of PfSir2A-mediated deacetylation on var gene regulation in vivo not directly tested","specific N-terminal lysine residue and its stoichiometry in vivo not fully resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Whether ALBA3 acts as part of a nucleic-acid-binding complex at subtelomeres and whether it binds RNA was addressed by isolating it in a TARE6-associated complex and testing binding across DNA and RNA substrates.","evidence":"Molecular complex isolation, EMSA with TARE6 DNA and ssRNA probes, and stage-specific immunofluorescence in P. falciparum (multi-paralog study)","pmids":["22167473"],"confidence":"Medium","gaps":["ALBA3-specific contribution inferred within a multi-paralog Alba study","in vivo relevance of ssRNA binding not established","identity of other complex components binding TARE6 not resolved for ALBA3 specifically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The functional consequence of altered ALBA3 dosage was tested to link its chromatin binding to virulence-gene output, showing it controls growth, stage transitions, and var gene expression.","evidence":"Episomal overexpression under a constitutive promoter with growth assays and RNA-seq differential expression analysis in P. falciparum","pmids":["39868986"],"confidence":"Medium","gaps":["overexpression phenotype does not establish the loss-of-function/endogenous requirement","whether var repression is a direct chromatin effect or an indirect consequence not resolved","single lab, single experimental strategy"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether ALBA3's chromatin-binding and mRNP-associated functions are mechanistically integrated, and how the PfSir2A-acetylation switch governs var gene silencing in vivo, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no endogenous loss-of-function characterization of ALBA3 in P. falciparum","structural basis of minor-groove DNA binding unknown","direct in vivo link between acetylation state and var promoter regulation not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["DOZI/CITH translationally silent mRNP complex (P. berghei)","TARE6-associated subtelomeric nucleoprotein complex (P. falciparum)"],"partners":["PFSIR2A (DEACETYLASE; INTERACTS WITH AND DEACETYLATES ALBA3 N-TERMINAL LYSINE)"],"other_free_text":["DNA-binding affinity regulated by reversible acetylation of an N-terminal lysine; predominantly acetylated in vivo [#0]","Binds var gene promoters and telomeric/subtelomeric chromatin including TARE6 repeats [#0, #1]","Overexpression represses var gene expression and misregulates virulence-factor/erythrocyte-invasion mRNAs, impairing intra-erythrocytic growth and stage transitions [#3]","DOZI/CITH association shown in P. berghei gametocytes; chromatin/DNA-binding and PfSir2A regulation shown in P. falciparum [#0, #1, #2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"10693754","id":"PMC_10693754","title":"A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum.","date":"2000","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10693754","citation_count":234,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20169188","id":"PMC_20169188","title":"Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20169188","citation_count":216,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21811616","id":"PMC_21811616","title":"Alba-domain proteins of Trypanosoma brucei are cytoplasmic RNA-binding proteins that interact with the translation machinery.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21811616","citation_count":106,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALBA3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26525978","id":"PMC_26525978","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":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22006844","id":"PMC_22006844","title":"Identification and molecular characterization of an Alba-family protein from human malaria parasite Plasmodium falciparum.","date":"2011","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/22006844","citation_count":60,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfALBA3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22167473","id":"PMC_22167473","title":"PfAlbas constitute a new eukaryotic DNA/RNA-binding protein family in malaria parasites.","date":"2011","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/22167473","citation_count":60,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27230797","id":"PMC_27230797","title":"Translational regulation in blood stages of the malaria parasite Plasmodium spp.: systems-wide studies pave the way.","date":"2016","source":"Wiley interdisciplinary reviews. RNA","url":"https://pubmed.ncbi.nlm.nih.gov/27230797","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28787542","id":"PMC_28787542","title":"ALBA4 modulates its stage-specific interactions and specific mRNA fates during Plasmodium yoelii growth and transmission.","date":"2017","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28787542","citation_count":38,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39868986","id":"PMC_39868986","title":"Ectopic overexpression of Plasmodium falciparum DNA-/RNA-binding Alba proteins misregulates virulence gene homeostasis during asexual blood development.","date":"2025","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/39868986","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfALBA3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41107154","id":"PMC_41107154","title":"Pink or blue: sex determination in malaria gametocytes.","date":"2025","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/41107154","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RNA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7821,"output_tokens":1571,"usd":0.023514,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6542,"output_tokens":2888,"usd":0.052455,"stage2_stop_reason":"end_turn"},"total_usd":0.075969,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"ALBA3 (PfAlba3) binds to DNA non-specifically at the minor groove, and acetylation of its N-terminal lysine residue lowers its DNA-binding affinity. In vitro, PfAlba3 inhibits transcription by binding to DNA. PfSir2A (a nuclear-localized deacetylase) interacts with PfAlba3 and deacetylates its N-terminal lysine residue. PfAlba3 co-localizes with PfSir2A at the nuclear periphery and is found in telomeric and subtelomeric regions by FISH, ChIP, and ChIP-ReChIP analyses. It also binds to var gene promoters. The protein is expressed in all erythrocytic stages and exists predominantly in the acetylated form.\",\n      \"method\": \"DNA-binding assays (EMSA), in vitro transcription inhibition assay, acetylation/deacetylation assays, co-immunoprecipitation with PfSir2A, immunofluorescence/co-localization, FISH, ChIP, ChIP-ReChIP\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal methods (in vitro binding and transcription assays, co-IP, ChIP/ReChIP, FISH, localization) in a single study establishing enzymatic regulation and genomic targeting\",\n      \"pmids\": [\"22006844\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ALBA3 (PfAlba3) is one of three PfAlba paralogs isolated as part of a molecular complex associated with the TARE6 subtelomeric region; EMSAs showed PfAlbas bind to TARE6 repeats and to single-stranded RNA, with different binding preferences among paralogs. In early blood stages PfAlba proteins are enriched at the nuclear periphery and partially co-localize with PfSir2; at the trophozoite–schizont transition they are also detectable in the cytoplasm in a punctate pattern.\",\n      \"method\": \"Molecular complex isolation (affinity purification), EMSA with TARE6 DNA and ssRNA probes, immunofluorescence/co-localization, subcellular fractionation/stage-specific imaging\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — reciprocal complex isolation and EMSA with multiple orthogonal methods, single lab; ALBA3-specific contribution inferred within a multi-paralog study\",\n      \"pmids\": [\"22167473\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ALBA3 (PfAlba3) is identified as one of 16 major protein components of the DOZI/CITH messenger ribonucleoprotein (mRNP) complex purified from Plasmodium berghei gametocytes by affinity purification coupled with mass spectrometry. This mRNP contains translationally silent transcripts and integrates eIF4E and poly(A)-binding protein but excludes P-body RNA degradation factors and translation-initiation-promoting eIF4G.\",\n      \"method\": \"Affinity purification coupled with mass spectrometry (AP-MS) from gametocyte lysates\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — rigorous AP-MS identification in a well-characterised complex, but ALBA3-specific functional role within the complex not separately validated; single study\",\n      \"pmids\": [\"20169188\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Ectopic overexpression of ALBA3 (PfAlba3) from an episome under a strong constitutive promoter strongly reduced P. falciparum intra-erythrocytic development (IED) growth and impaired stage transitions. RNA-seq of PfAlba3-overexpressing strains revealed significant misregulation of mRNAs encoding virulence factors (including erythrocyte invasion genes) and a general repression of var gene expression, linking ALBA3 to subtelomeric chromatin biology and mutually exclusive PfEMP1 expression.\",\n      \"method\": \"Episomal overexpression, growth assays, RNA-seq differential gene expression analysis\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — overexpression with specific phenotypic readout and transcriptome-wide analysis, two orthogonal methods (growth and RNA-seq), single lab\",\n      \"pmids\": [\"39868986\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ALBA3 (PF3D7_1006200) is a DNA/RNA-binding protein expressed throughout P. falciparum intra-erythrocytic development that binds DNA at the minor groove and telomeric/subtelomeric chromatin (including var gene promoters); its DNA-binding affinity is reduced by acetylation of an N-terminal lysine and restored by the deacetylase PfSir2A with which it co-localizes at the nuclear periphery; it is also a component of the DOZI/CITH translationally silent mRNP complex in P. berghei gametocytes; and its overexpression in P. falciparum impairs intra-erythrocytic growth and stage transitions, accompanied by misregulation of virulence-factor mRNAs and general repression of var gene expression.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ALBA3 (PF3D7_1006200) is a DNA/RNA-binding protein expressed across all intra-erythrocytic stages of Plasmodium falciparum that couples chromatin-level DNA binding to the control of subtelomeric virulence-gene expression [#0, #3]. It binds DNA non-specifically at the minor groove and inhibits transcription in vitro, with this activity governed by reversible acetylation: acetylation of an N-terminal lysine lowers DNA-binding affinity, and the nuclear deacetylase PfSir2A interacts with ALBA3, removes this modification, and co-localizes with it at the nuclear periphery [#0]. ALBA3 occupies telomeric and subtelomeric chromatin, including var gene promoters, and also binds TARE6 subtelomeric repeats and single-stranded RNA, placing it at the interface of chromatin structure and RNA metabolism [#0, #1]. Consistent with a regulatory role in virulence-gene control, episomal overexpression of ALBA3 impairs intra-erythrocytic growth and stage transitions and misregulates virulence-factor mRNAs while generally repressing var gene expression [#3]. In P. berghei gametocytes, ALBA3 is a component of the translationally silent DOZI/CITH mRNP complex, indicating an additional role in post-transcriptional mRNA storage [#2]. Beyond these findings, the structural basis of DNA binding and the direct molecular consequences of ALBA3 within the DOZI/CITH complex have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"The question of whether ALBA3 participates in post-transcriptional gene regulation was addressed by defining the composition of the translationally silent mRNP that stores maternal transcripts in gametocytes.\",\n      \"evidence\": \"Affinity purification coupled with mass spectrometry of the DOZI/CITH complex from P. berghei gametocyte lysates\",\n      \"pmids\": [\"20169188\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ALBA3-specific functional role within the DOZI/CITH complex was not separately validated\",\n        \"shown in P. berghei; not demonstrated for the P. falciparum ortholog\",\n        \"no mechanism for how ALBA3 contributes to translational silencing\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"How ALBA3 engages DNA and how that engagement is regulated was established by defining its minor-groove binding, transcription-inhibitory activity, acetylation-dependent affinity, and its regulation by and co-localization with PfSir2A at telomeric/subtelomeric chromatin.\",\n      \"evidence\": \"EMSA DNA-binding and in vitro transcription assays, acetylation/deacetylation assays, co-IP with PfSir2A, immunofluorescence, FISH, ChIP and ChIP-ReChIP in P. falciparum\",\n      \"pmids\": [\"22006844\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"no structural model of the ALBA3\\u2013DNA interaction\",\n        \"functional consequence of PfSir2A-mediated deacetylation on var gene regulation in vivo not directly tested\",\n        \"specific N-terminal lysine residue and its stoichiometry in vivo not fully resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Whether ALBA3 acts as part of a nucleic-acid-binding complex at subtelomeres and whether it binds RNA was addressed by isolating it in a TARE6-associated complex and testing binding across DNA and RNA substrates.\",\n      \"evidence\": \"Molecular complex isolation, EMSA with TARE6 DNA and ssRNA probes, and stage-specific immunofluorescence in P. falciparum (multi-paralog study)\",\n      \"pmids\": [\"22167473\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ALBA3-specific contribution inferred within a multi-paralog Alba study\",\n        \"in vivo relevance of ssRNA binding not established\",\n        \"identity of other complex components binding TARE6 not resolved for ALBA3 specifically\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The functional consequence of altered ALBA3 dosage was tested to link its chromatin binding to virulence-gene output, showing it controls growth, stage transitions, and var gene expression.\",\n      \"evidence\": \"Episomal overexpression under a constitutive promoter with growth assays and RNA-seq differential expression analysis in P. falciparum\",\n      \"pmids\": [\"39868986\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"overexpression phenotype does not establish the loss-of-function/endogenous requirement\",\n        \"whether var repression is a direct chromatin effect or an indirect consequence not resolved\",\n        \"single lab, single experimental strategy\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether ALBA3's chromatin-binding and mRNP-associated functions are mechanistically integrated, and how the PfSir2A-acetylation switch governs var gene silencing in vivo, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"no endogenous loss-of-function characterization of ALBA3 in P. falciparum\",\n        \"structural basis of minor-groove DNA binding unknown\",\n        \"direct in vivo link between acetylation state and var promoter regulation not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0003727\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0003690\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0043565\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0034399\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0000781\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0017148\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0006342\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"complexes\": [\n      \"DOZI/CITH translationally silent mRNP complex (P. berghei)\",\n      \"TARE6-associated subtelomeric nucleoprotein complex (P. falciparum)\"\n    ],\n    \"partners\": [\n      \"PfSir2A (deacetylase; interacts with and deacetylates ALBA3 N-terminal lysine)\"\n    ],\n    \"other_free_text\": [\n      \"DNA-binding affinity regulated by reversible acetylation of an N-terminal lysine; predominantly acetylated in vivo [#0]\",\n      \"Binds var gene promoters and telomeric/subtelomeric chromatin including TARE6 repeats [#0, #1]\",\n      \"Overexpression represses var gene expression and misregulates virulence-factor/erythrocyte-invasion mRNAs, impairing intra-erythrocytic growth and stage transitions [#3]\",\n      \"DOZI/CITH association shown in P. berghei gametocytes; chromatin/DNA-binding and PfSir2A regulation shown in P. falciparum [#0, #1, #2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1006200","name":null,"product":"DNA/RNA-binding protein Alba 3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1204400","name":null,"product":"DNA/RNA-binding protein Alba 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0805000","name":null,"product":"DNA/RNA-binding protein Alba 3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ALBA3","evaluation":null}