Mitochondrial NADP+-specific isocitrate dehydrogenase (EC 1.1.1.42) of Saccharomyces cerevisiae, a homodimeric enzyme imported via an N-terminal mitochondrial presequence. IDP1 catalyses the Mg2+/Mn2+-dependent oxidative decarboxylation of D-threo-isocitrate to 2-oxoglutarate, CO2 and NADPH in the mitochondrial matrix. It is one of three NADP-IDH isozymes (mitochondrial IDP1, cytosolic IDP2, peroxisomal IDP3) and is distinct from the NAD+-specific heterooctameric IDH (IDH1/IDH2) that carries TCA-cycle flux. IDP1 is constitutively expressed, is dispensable for growth and respiration, and does not substitute for IDH in the TCA cycle; its roles are provision of mitochondrial NADPH and an ancillary supply of 2-oxoglutarate for glutamate synthesis (idp1 idh double mutants are glutamate auxotrophs on glucose).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro isocitrate/isopropylmalate DH conserved-site mapping to magnesium ion binding; NADP-IDHs require a divalent cation (Mg2+ or Mn2+) for catalysis. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: NADP-IDH IBA from PTN008982454, seeded by many NADP-IDHs including IDP1 (SGD:S000002224), IDP2 and IDP3. Core function. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IDA PMID:15574419 Kinetic properties and metabolic contributions of yeast mito... | ACCEPT | Summary: His-tagged IDP1 was expressed, purified and kinetically characterised (Km for isocitrate and cofactors). Core function. Supporting Evidence: PMID:15574419 histidine-tagged forms of yeast mitochondrial (IDP1) and cytosolic (IDP2) enzymes were expressed and purified |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated assignment via EC 1.1.1.42 / RHEA:19629 and NADP-IDH InterPro family; correct. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IMP PMID:8099357 Function and expression of yeast mitochondrial NAD- and NADP... | ACCEPT | Summary: IDP1 disruption removes the mitochondrial NADP-specific IDH; with idh it causes glutamate auxotrophy on glucose. Correct. Supporting Evidence: PMID:8099357 The two mitochondrial isozymes, IDH and IDP1, are NAD- and NADP-specific, respectively. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways superpathway of glutamate biosynthesis assigns EC 1.1.1.42 to IDP1. The activity is correct for IDP1 (the compartment assigned by the pathway is not; see cytosol row). |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: IPI with the ER-lumenal Hsp70 KAR2/BiP (P16474) from the Gavin et al. 2006 AP-MS complex survey. A mitochondrial matrix enzyme co-purifying with an ER chaperone has no clear functional meaning, and 'protein binding' is uninformative. Reason: Uninformative protein binding term; partner in a different compartment, likely a post-lysis or folding association. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Mitochondrial proteome (Sickmann et al. 2003); correct. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteome (Reinders et al. 2006); correct. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Quantitative mitochondrial proteome/phosphoproteome (Renvoise et al. 2014); correct. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion IBA from PTN000214284 with IDP1 itself among the seeds; correct. |
| GO:0005739 mitochondrion | IDA PMID:15001388 Influence of compartmental localization on the function of y... | ACCEPT | Summary: Studies relocating IDP isozymes treat IDP1 as the mitochondrial isozyme, and showed mitochondrial location favours its glutamate-synthesis function during fermentative growth. Core location. Supporting Evidence: PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location (Mitochondrion; transit peptide experimentally mapped) mapping; correct. |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | REMOVE | Summary: Peroxisome IBA from PTN002483519, seeded by peroxisomal NADP-IDHs (human IDH1, rat, yeast IDP3 SGD:S000004954). In S. cerevisiae the peroxisomal isozyme is the paralog IDP3; IDP1 carries an experimentally mapped mitochondrial presequence and is consistently described as the mitochondrial isozyme. Reason: Paralog-specific localisation (IDP3) propagated to the mitochondrial isozyme; target evidence places IDP1 in mitochondria. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN002483519 · PTN002483519 SUPPORTS SOURCE BUT NOT TARGET Seeds include the peroxisomal yeast paralog IDP3; IDP1 is mitochondrial. Supporting Evidence: PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways superpathway of glutamate biosynthesis (PWY3O-13) places the NADP-IDH step in the cytosol and attaches IDP1 to it. IDP1 is the mitochondrial isozyme (experimentally mapped presequence); the cytosolic NADP-IDH is IDP2. Reason: Pathway-to-GO conversion assigned the cytosolic compartment of the pathway step to the mitochondrial paralog; contradicted by target-specific localisation evidence. Supporting Evidence: PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | REMOVE | Summary: TCA cycle IBA from PTN008982454, seeded only by M. tuberculosis Icd (P9WKL1), where NADP-IDH is the TCA enzyme. In yeast the TCA-cycle isocitrate step is carried out by NAD-IDH (IDH1/IDH2); idp1 disruptants respire normally and IDP1 expression does not follow TCA-cycle (carbon-source) regulation. Reason: Target-specific genetic evidence shows IDP1 does not participate in TCA-cycle-based respiration. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN008982454 · PTN008982454 SUPPORTS SOURCE BUT NOT TARGET Sole TCA-cycle seed is a bacterial NADP-IDH; in yeast the TCA step is NAD-IDH. Supporting Evidence: PMID:8099357 These results strongly suggest that IDP1 is incapable of participating in tricarboxylic acid cycle-based respiration despite its mitochondrial location. |
| GO:0006102 isocitrate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Isocitrate metabolic process IBA from PTN008982454 seeded by IDP2/IDP3 and others; correct, IDP1 oxidises isocitrate. |
| GO:0006102 isocitrate metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro NADP-IDH family mapping; correct. |
| GO:0006739 NADP+ metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: NADP+ metabolic process IBA from PTN000214284; the reaction reduces NADP+ to NADPH in the matrix, and NADPH supply is considered IDP1's main function. |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | TOO GENERAL | Summary: Generic CH-OH oxidoreductase (NAD or NADP acceptor) from InterPro conserved site; correct parent. Reason: Less specific parent of GO:0004450. |
| GO:0042645 mitochondrial nucleoid | IDA PMID:15692048 Aconitase couples metabolic regulation to mitochondrial DNA ... | KEEP AS NON CORE | Summary: Identified among mtDNA nucleoid-associated proteins in a screen focused on aconitase (Chen et al. 2005; abstract-only). Many abundant matrix enzymes co-purify with nucleoids; no nucleoid function of IDP1 is known. Reason: Curator-assigned association from a nucleoid proteomic screen; not the functional location. |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | REMOVE | Summary: InterPro conserved-site mapping to NAD binding. IDP1 is NADP-specific; NAD binding is incorrect for this protein (the family includes NAD-dependent members). Reason: Cofactor specificity contradicted by experimental characterisation (NADP-specific). Supporting Evidence: PMID:8099357 The two mitochondrial isozymes, IDH and IDP1, are NAD- and NADP-specific, respectively. |
| GO:0097054 L-glutamate biosynthetic process | IGI PMID:15574419 Kinetic properties and metabolic contributions of yeast mito... | KEEP AS NON CORE | Summary: IGI with IDH (SGD:S000004982); overexpressed IDP1 partly rescues the glutamate auxotrophy of IDH loss, and idp1 idh double mutants require glutamate on glucose. IDP1 supplies the 2-oxoglutarate precursor; the glutamate-forming steps are carried out by GDH1/GDH3/GLT1. Curator experimental annotation retained. Reason: Ancillary precursor supply to glutamate biosynthesis rather than a glutamate-forming step. Supporting Evidence: PMID:15574419 these results suggest an ancillary role for IDP1 in cellular glutamate synthesis |
| GO:0097054 L-glutamate biosynthetic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: Inherited from the YeastPathways superpathway of glutamate biosynthesis. As above, IDP1 supplies 2-oxoglutarate but does not form glutamate. Reason: Superpathway-level, precursor-supply role; ancillary. |
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