{"gene":"PF3D7_1212800","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2000,"finding":"The P. falciparum SDHB gene (PF3D7_1212800) encodes a 321-amino-acid iron-sulfur protein (Ip) of 37.8 kDa located on chromosome 12, with a 963-nucleotide single open reading frame. The encoded protein contains a mitochondrial presequence essential for import of nuclear-encoded mitochondrial proteins, and retains almost all conserved amino acids indispensable for substrate binding and catalytic activity of succinate-ubiquinone oxidoreductase (complex II). A unicellular organism-specific deletion was identified in the Ip amino acid sequence. Expression of a 2.4 kb SDHB transcript was confirmed in asynchronous erythrocytic stage cells.","method":"Gene cloning, sequencing, sequence comparison/alignment, and Northern blot detection of transcript in asexual blood stages","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gene cloning with sequence-level functional inference (conserved catalytic residues, mitochondrial targeting sequence identified), transcript confirmed by Northern blot; single lab, no in vitro reconstitution or mutagenesis","pmids":["10779596"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"By complexome profiling (blue-native PAGE coupled to mass spectrometry), P. falciparum SDHB (PF3D7_1212800) was shown to comigrate with SDHA at an apparent molecular mass of ~530 kDa in gametocyte stages, identifying it as a component of a divergent, high-molecular-weight complex II assembly that also includes novel putative subunits not present in opisthokonts.","method":"Complexome profiling (blue-native PAGE fractionation + quantitative mass spectrometry) across asexual blood stages and gametocytes","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complexome profiling provides direct co-migration evidence in native conditions; single study, no reciprocal pulldown or structural validation","pmids":["34155201"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum SDHB (PF3D7_1212800) is a nuclear-encoded, mitochondrially targeted iron-sulfur subunit of complex II (succinate-ubiquinone oxidoreductase) that is transcribed in asexual blood stages, contains conserved catalytic residues for succinate oxidation and iron-sulfur cluster binding, and assembles with SDHA into a divergent ~530 kDa complex in gametocytes; its precise catalytic contributions and the identity of its novel complex II assembly partners remain to be fully characterised."},"narrative":{"mechanistic_narrative":"PF3D7_1212800 (SDHB) is the nuclear-encoded iron-sulfur subunit of Plasmodium falciparum complex II (succinate-ubiquinone oxidoreductase), predicted to contribute to mitochondrial succinate oxidation and expressed as a transcript in asexual erythrocytic stages [PMID:10779596]. The 321-residue protein carries an N-terminal mitochondrial presequence for import and retains nearly all residues conserved for substrate binding and catalysis, while also containing a unicellular-organism-specific sequence deletion that distinguishes it from opisthokont orthologs [PMID:10779596]. In gametocytes, SDHB comigrates with SDHA at ~530 kDa, placing it within a divergent, high-molecular-weight complex II assembly that incorporates novel putative subunits absent from opisthokonts [PMID:34155201]. Beyond this assignment as a complex II iron-sulfur subunit and its assembly with SDHA, the precise catalytic contribution of SDHB and the identities of its novel assembly partners have not been characterized in the available corpus.","teleology":[{"year":2000,"claim":"Establishing whether P. falciparum possesses a canonical complex II iron-sulfur subunit answered whether the parasite encodes the machinery for mitochondrial succinate oxidation and how that subunit is targeted to the mitochondrion.","evidence":"Gene cloning, sequencing and alignment plus Northern blot of asexual blood-stage RNA","pmids":["10779596"],"confidence":"Medium","gaps":["Catalytic activity and iron-sulfur cluster binding were inferred from conserved residues, not tested by mutagenesis or in vitro reconstitution","Mitochondrial import and presequence cleavage were predicted from sequence, not demonstrated experimentally","Functional consequence of the unicellular-organism-specific deletion is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Native complexome analysis addressed how SDHB assembles in vivo, revealing that it partners with SDHA in a divergent, larger-than-canonical complex II containing lineage-specific subunits.","evidence":"Complexome profiling (blue-native PAGE + quantitative mass spectrometry) across asexual blood stages and gametocytes","pmids":["34155201"],"confidence":"Medium","gaps":["Comigration was not corroborated by reciprocal pulldown or structural analysis","The identities of the novel putative subunits in the ~530 kDa complex are not defined","Whether the same assembly forms in asexual stages, and its catalytic activity, are not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How SDHB contributes catalytically to succinate oxidation and what non-canonical proteins constitute its divergent complex II remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct enzymatic or iron-sulfur cluster assay for the P. falciparum protein","Identities and functions of the novel complex II subunits are uncharacterized","No genetic knockout/knockdown phenotype for SDHB in any life stage"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Divergent ~530 kDa complex II (succinate-ubiquinone oxidoreductase) assembly in gametocytes [#1]"],"partners":["SDHA (COMIGRATES IN THE ~530 KDA COMPLEX) [#1]"],"other_free_text":["Encodes a 321-aa, 37.8 kDa iron-sulfur protein on chromosome 12 with an N-terminal mitochondrial presequence [#0]","Retains nearly all conserved substrate-binding/catalytic residues but carries a unicellular-organism-specific sequence deletion [#0]","2.4 kb transcript detected in asynchronous erythrocytic-stage parasites [#0]","Complex includes novel putative subunits not present in opisthokonts [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"10430921","id":"PMC_10430921","title":"A single nuclear transcript encoding mitochondrial RPS14 and SDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins.","date":"1999","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/10430921","citation_count":73,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10779596","id":"PMC_10779596","title":"Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits.","date":"2000","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10779596","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41009722","id":"","title":"Targeting Mitochondrial Function in Plasmodium falciparum: Insight into Antimalarial Drugs and the Emerging Role of Saccharomyces cerevisiae as a Model System.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41009722","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36302692","id":"","title":"The mystery of massive mitochondrial complexes: the apicomplexan respiratory chain.","date":"2022","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/36302692","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39034325","id":"","title":"Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39034325","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34155201","id":"","title":"Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34155201","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32075230","id":"","title":"Heterogeneous Network Model to Identify Potential Associations Between Plasmodium vivax and Human Proteins.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32075230","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32968076","id":"","title":"Genetic screens reveal a central role for heme metabolism in artemisinin susceptibility.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32968076","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28352210","id":"","title":"Proteomic analysis of microparticles isolated from malaria positive blood samples.","date":"2017","source":"Proteome science","url":"https://pubmed.ncbi.nlm.nih.gov/28352210","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26283222","id":"","title":"Anopheles stephensi p38 MAPK signaling regulates innate immunity and bioenergetics during Plasmodium falciparum infection.","date":"2015","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/26283222","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["SDHB"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12038,"output_tokens":798,"usd":0.024042,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5518,"output_tokens":1822,"usd":0.03657,"stage2_stop_reason":"end_turn"},"total_usd":0.060612,"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\": 2000,\n      \"finding\": \"The P. falciparum SDHB gene (PF3D7_1212800) encodes a 321-amino-acid iron-sulfur protein (Ip) of 37.8 kDa located on chromosome 12, with a 963-nucleotide single open reading frame. The encoded protein contains a mitochondrial presequence essential for import of nuclear-encoded mitochondrial proteins, and retains almost all conserved amino acids indispensable for substrate binding and catalytic activity of succinate-ubiquinone oxidoreductase (complex II). A unicellular organism-specific deletion was identified in the Ip amino acid sequence. Expression of a 2.4 kb SDHB transcript was confirmed in asynchronous erythrocytic stage cells.\",\n      \"method\": \"Gene cloning, sequencing, sequence comparison/alignment, and Northern blot detection of transcript in asexual blood stages\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gene cloning with sequence-level functional inference (conserved catalytic residues, mitochondrial targeting sequence identified), transcript confirmed by Northern blot; single lab, no in vitro reconstitution or mutagenesis\",\n      \"pmids\": [\"10779596\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"By complexome profiling (blue-native PAGE coupled to mass spectrometry), P. falciparum SDHB (PF3D7_1212800) was shown to comigrate with SDHA at an apparent molecular mass of ~530 kDa in gametocyte stages, identifying it as a component of a divergent, high-molecular-weight complex II assembly that also includes novel putative subunits not present in opisthokonts.\",\n      \"method\": \"Complexome profiling (blue-native PAGE fractionation + quantitative mass spectrometry) across asexual blood stages and gametocytes\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complexome profiling provides direct co-migration evidence in native conditions; single study, no reciprocal pulldown or structural validation\",\n      \"pmids\": [\"34155201\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum SDHB (PF3D7_1212800) is a nuclear-encoded, mitochondrially targeted iron-sulfur subunit of complex II (succinate-ubiquinone oxidoreductase) that is transcribed in asexual blood stages, contains conserved catalytic residues for succinate oxidation and iron-sulfur cluster binding, and assembles with SDHA into a divergent ~530 kDa complex in gametocytes; its precise catalytic contributions and the identity of its novel complex II assembly partners remain to be fully characterised.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1212800 (SDHB) is the nuclear-encoded iron-sulfur subunit of Plasmodium falciparum complex II (succinate-ubiquinone oxidoreductase), predicted to contribute to mitochondrial succinate oxidation and expressed as a transcript in asexual erythrocytic stages [#0]. The 321-residue protein carries an N-terminal mitochondrial presequence for import and retains nearly all residues conserved for substrate binding and catalysis, while also containing a unicellular-organism-specific sequence deletion that distinguishes it from opisthokont orthologs [#0]. In gametocytes, SDHB comigrates with SDHA at ~530 kDa, placing it within a divergent, high-molecular-weight complex II assembly that incorporates novel putative subunits absent from opisthokonts [#1]. Beyond this assignment as a complex II iron-sulfur subunit and its assembly with SDHA, the precise catalytic contribution of SDHB and the identities of its novel assembly partners have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing whether P. falciparum possesses a canonical complex II iron-sulfur subunit answered whether the parasite encodes the machinery for mitochondrial succinate oxidation and how that subunit is targeted to the mitochondrion.\",\n      \"evidence\": \"Gene cloning, sequencing and alignment plus Northern blot of asexual blood-stage RNA\",\n      \"pmids\": [\"10779596\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Catalytic activity and iron-sulfur cluster binding were inferred from conserved residues, not tested by mutagenesis or in vitro reconstitution\",\n        \"Mitochondrial import and presequence cleavage were predicted from sequence, not demonstrated experimentally\",\n        \"Functional consequence of the unicellular-organism-specific deletion is unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Native complexome analysis addressed how SDHB assembles in vivo, revealing that it partners with SDHA in a divergent, larger-than-canonical complex II containing lineage-specific subunits.\",\n      \"evidence\": \"Complexome profiling (blue-native PAGE + quantitative mass spectrometry) across asexual blood stages and gametocytes\",\n      \"pmids\": [\"34155201\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Comigration was not corroborated by reciprocal pulldown or structural analysis\",\n        \"The identities of the novel putative subunits in the ~530 kDa complex are not defined\",\n        \"Whether the same assembly forms in asexual stages, and its catalytic activity, are not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How SDHB contributes catalytically to succinate oxidation and what non-canonical proteins constitute its divergent complex II remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct enzymatic or iron-sulfur cluster assay for the P. falciparum protein\",\n        \"Identities and functions of the novel complex II subunits are uncharacterized\",\n        \"No genetic knockout/knockdown phenotype for SDHB in any life stage\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008177\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0051537\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0045273\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006099\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"Divergent ~530 kDa complex II (succinate-ubiquinone oxidoreductase) assembly in gametocytes [#1]\"\n    ],\n    \"partners\": [\n      \"SDHA (comigrates in the ~530 kDa complex) [#1]\"\n    ],\n    \"other_free_text\": [\n      \"Encodes a 321-aa, 37.8 kDa iron-sulfur protein on chromosome 12 with an N-terminal mitochondrial presequence [#0]\",\n      \"Retains nearly all conserved substrate-binding/catalytic residues but carries a unicellular-organism-specific sequence deletion [#0]\",\n      \"2.4 kb transcript detected in asynchronous erythrocytic-stage parasites [#0]\",\n      \"Complex includes novel putative subunits not present in opisthokonts [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1212800","name":null,"product":"succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1428800","name":null,"product":"succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1432200","name":null,"product":"succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"SDHB","evaluation":null}