idh1 (UniProt O13696) encodes a subunit of the mitochondrial NAD+-dependent isocitrate dehydrogenase (EC 1.1.1.41), an allosterically regulated hetero-octamer of Idh1 and Idh2 that oxidatively decarboxylates isocitrate to 2-oxoglutarate. This is a rate-controlling step of the TCA cycle and the main mitochondrial source of 2-oxoglutarate for glutamate. Mutants lacking NAD-IDH (glu2, glu3) need glutamate. By analogy to S. cerevisiae, Idh2 is the catalytic subunit and Idh1 the regulatory, AMP-binding one.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Divalent metal (Mg2+/Mn2+) cofactor of the isocitrate dehydrogenase active site; true but subsidiary. Reason: By similarity (ECO:0000250, and UniProtKB:P50213 for the Mg(2+)-binding residue 224) to characterised NAD-dependent isocitrate dehydrogenases, UniProt records an Mg(2+)/Mn(2+) cofactor, one ion per subunit; the protein is in the isocitrate and isopropylmalate dehydrogenase family (Pfam PF00180). No S. pombe-specific metal assay exists. Kept as a non-core cofactor property. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000250}; file:SCHPO/idh1/idh1-uniprot.txt Pfam; PF00180; Iso_dh; 1. |
| GO:0004449 isocitrate dehydrogenase (NAD+) activity | EXP PMID:10975257 Isolation and RNA-binding analysis of NAD+ -isocitrate dehyd... | ACCEPT | Summary: Isolation of S. pombe NAD+-IDH with activity, in a study of its RNA-binding (curator, full text). Supporting Evidence: PMID:10975257 Krebs cycle NAD+ -isocitrate dehydrogenase (Idh) binds to the 5-UTRs of all mitochondrial mRNAs in Saccharomyces cerevisiae. |
| GO:0004449 isocitrate dehydrogenase (NAD+) activity | EXP PMID:7903653 Enzyme defects in glutamate-requiring strains of Schizosacch... | ACCEPT | Summary: NAD-IDH activity is lost in glu2/glu3 glutamate auxotrophs; the hetero-octameric enzyme needs both subunits (contributes_to). Supporting Evidence: PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0004449 isocitrate dehydrogenase (NAD+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent. Reason: The IBA agrees with S. pombe evidence. UniProt's curated catalytic-activity line for this entry rests on PubMed:10975257 (partially purified S. pombe Idh), and glu2/glu3 mutants lack NAD-specific isocitrate dehydrogenase (PMID:7903653). The assayed activity belongs to the Idh1/Idh2 hetero-octamer, so for this subunit it is a contribution to the complex's activity (as in core_functions). Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0004449 isocitrate dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC mapping; consistent. Reason: The EC 1.1.1.41 mapping derives from UniProt's catalytic-activity line, which is experimental for S. pombe Idh (PubMed:10975257); glu2/glu3 mutants lack NAD-specific isocitrate dehydrogenase (PMID:7903653). The activity is that of the Idh1/Idh2 hetero-octamer, to which this subunit contributes. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0005737 cytoplasm | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: ORFeome screen recorded cytoplasmic signal; NAD-IDH is a matrix enzyme. Reason: Single screen observation. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of mitochondrial location. Reason: Root organelle term kept per policy; the claim holds. UniProt curates the location as mitochondrion by similarity and annotates an N-terminal mitochondrial transit peptide (sequence analysis). The matrix sub-compartment is carried by the ISS row. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. file:SCHPO/idh1/idh1-uniprot.txt TRANSIT 1..? |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt/ARBA location mapping; consistent. Reason: Root organelle term kept per policy; the mapping comes from UniProt's curated by-similarity location, and the entry carries an annotated mitochondrial transit peptide. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. file:SCHPO/idh1/idh1-uniprot.txt TRANSIT 1..? |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | ACCEPT | Summary: Matrix location by similarity to S. cerevisiae Idh1/Idh2. Reason: The matrix-specific evidence is the S. cerevisiae ortholog's (P28834), transferred by similarity. For S. pombe the record gives a mitochondrial location by similarity and an N-terminal transit peptide, and the protein has no annotated TRANSMEM feature; together with its TCA-cycle function (which takes place in the matrix) these support the matrix sub-compartment. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. file:SCHPO/idh1/idh1-uniprot.txt TRANSIT 1..? |
| GO:0006099 tricarboxylic acid cycle | EXP PMID:37164017 Optimization of energy production and central carbon metabol... | ACCEPT | Summary: 13C tracing in S. pombe versus S. japonicus shows that S. pombe runs a respiratory, oxidative TCA cycle (curator, full text). Supporting Evidence: PMID:37164017 Here, we use two related fission yeasts, Schizosaccharomyces pombe and Schizosaccharomyces japonicus, as a comparative model system. PMID:37164017 We show that although S. japonicus does not respire oxygen, unlike S. pombe, it is capable of efficient NADH oxidation, amino acid synthesis, and ATP generation. |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; TCA cycle step. Reason: Consistent with UniProt's curated function statement (experimental, PubMed:10975257) and with the loss of NAD-specific isocitrate dehydrogenase in glu2/glu3 glutamate auxotrophs (PMID:7903653). Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Performs an essential role in the oxidative function of the citric acid cycle. PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/UniPathway mapping; consistent. Reason: The InterPro IPR004434 (NAD-dependent isocitrate dehydrogenase) membership underlying the mapping is confirmed by S. pombe evidence, UniProt's curated experimental function statement. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt InterPro; IPR004434; Isocitrate_DH_NAD. file:SCHPO/idh1/idh1-uniprot.txt Performs an essential role in the oxidative function of the citric acid cycle. |
| GO:0006099 tricarboxylic acid cycle | IMP PMID:7903653 Enzyme defects in glutamate-requiring strains of Schizosacch... | ACCEPT | Summary: glu2/glu3 mutants lacking NAD-IDH need glutamate, consistent with a blocked TCA flux to 2-oxoglutarate. Supporting Evidence: PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0006102 isocitrate metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference; isocitrate metabolism is a broad description of the step catalysed by the Idh1/Idh2 complex. Reason: True. The S. pombe NAD+-isocitrate dehydrogenase, of which Idh1 is a subunit, oxidatively decarboxylates isocitrate (UniProt catalytic activity, ECO:0000269 PubMed:10975257), and the protein lies in the NAD-dependent isocitrate dehydrogenase clade (InterPro IPR004434) that the PAINT node covers. No more specific descendant of this term fits the step better, and the TCA cycle row carries the main process, so it is kept as non-core. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; file:SCHPO/idh1/idh1-uniprot.txt InterPro; IPR004434; Isocitrate_DH_NAD. |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro-derived parent of the specific activity, which is already annotated. Reason: The generic NAD(P) CH-OH oxidoreductase term is correct but general; the specific activity, isocitrate dehydrogenase (NAD+) (EC 1.1.1.41), is shown for S. pombe Idh (UniProt catalytic activity, ECO:0000269 PubMed:10975257) and fits the NAD-specific isocitrate dehydrogenase family signature (InterPro IPR004434). The gene already carries GO:0004449. Proposed replacements: isocitrate dehydrogenase (NAD+) activity Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; file:SCHPO/idh1/idh1-uniprot.txt InterPro; IPR004434; Isocitrate_DH_NAD. |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: NAD+ is the cosubstrate of the Idh1/Idh2 isocitrate dehydrogenase; subsidiary to the dehydrogenase activity. Reason: NAD+ is a substrate of the reaction assigned to S. pombe Idh (UniProt catalytic activity, ECO:0000269 PubMed:10975257), and Idh1 belongs to the NAD-specific isocitrate dehydrogenase family (InterPro IPR004434). Whether NAD binds this subunit or its Idh2 partner in the hetero-octamer is not established for S. pombe, so the row is kept as non-core. Supporting Evidence: file:SCHPO/idh1/idh1-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; file:SCHPO/idh1/idh1-uniprot.txt InterPro; IPR004434; Isocitrate_DH_NAD. |
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