Peroxisomal NADP+-specific isocitrate dehydrogenase (EC 1.1.1.42) of Saccharomyces cerevisiae, targeted to the peroxisomal matrix by a C-terminal PTS1 (Cys-Lys-Leu). It oxidatively decarboxylates isocitrate to 2-oxoglutarate, regenerating NADPH inside peroxisomes, whose membrane is impermeable to pyridine nucleotides. This NADPH is required by the auxiliary 2,4-dienoyl-CoA reductase during beta-oxidation of unsaturated fatty acids, so idp3 mutants grow poorly on unsaturated but not saturated fatty acids. IDP3 is induced on fatty-acid carbon sources and is the peroxisomal member of three compartment-specific NADP-IDH paralogs (Idp1 mitochondrial, Idp2 cytosolic).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro IPR019818 mapping to Mg2+ binding; Idp3 is a metal-dependent NADP-IDH (by similarity). Reason: Cofactor binding; non-core. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from NADP-IDH node PTN008982454; Idp3 is a member of the eukaryotic cytosolic/peroxisomal NADP-IDH clade with its own experimental support. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IDA PMID:9452501 IDP3 encodes a peroxisomal NADP-dependent isocitrate dehydro... | ACCEPT | Summary: Henke et al. identified Idp3 as the peroxisomal NADP-dependent isocitrate dehydrogenase (abstract-only cache; curator IDA accepted). Supporting Evidence: PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 1.1.1.42 / RHEA:19629 mapping; correct. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0004450 isocitrate dehydrogenase (NADP+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-13) asserting NADP-IDH activity; the activity is correct for Idp3. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) in the yeast Saccharomyces cerevisiae catalyze the NADP(+)-dependent oxidative decarboxylation of isocitrate to form alpha-ketoglutarate. |
| GO:0005737 cytoplasm | HDA PMID:11914276 Subcellular localization of the yeast proteome. | KEEP AS NON CORE | Summary: Kumar et al. genome-wide immunolocalization scored Idp3 as cytoplasmic. Idp3 carries a C-terminal PTS1 (CKL) and is peroxisomal; peroxisomes lie within the cytoplasm, so the term is true but uninformative. Reason: Broad high-throughput location; peroxisomal matrix is the informative compartment. Supporting Evidence: PMID:11914276 By high-throughput immunolocalization of tagged gene products, we have determined the subcellular localization of 2744 yeast proteins. PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0005737 cytoplasm | IDA PMID:15001388 Influence of compartmental localization on the function of y... | KEEP AS NON CORE | Summary: Contreras-Shannon & McAlister-Henn deliberately retargeted Idp3 to the cytosol (by removing targeting information) to test compartment effects; native Idp3 is peroxisomal. Cytoplasm is formally true in that peroxisomes are within the cytoplasm, and the curator saw the full text. Reason: Retained but non-core; the informative location is peroxisomal matrix. Supporting Evidence: PMID:15001388 we exchanged promoters and altered organellar targeting information to obtain expression of IDP2 and IDP3 in mitochondria and of IDP1 and IDP3 in the cytosol. PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) in the yeast Saccharomyces cerevisiae catalyze the NADP(+)-dependent oxidative decarboxylation of isocitrate to form alpha-ketoglutarate. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | MARK AS OVER ANNOTATED | Summary: Detected in the Sickmann mitochondrial proteome. Peroxisomal proteins commonly co-purify with crude yeast mitochondria; Idp3 has a PTS1 and no presequence, and the mitochondrial NADP-IDH is Idp1. Reason: Likely peroxisomal co-purification in an organelle proteome. Supporting Evidence: PMID:14576278 The proteins of highly pure yeast mitochondria were separated by several independent methods and analyzed by tandem MS. PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) in the yeast Saccharomyces cerevisiae catalyze the NADP(+)-dependent oxidative decarboxylation of isocitrate to form alpha-ketoglutarate. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | MARK AS OVER ANNOTATED | Summary: PROMITO mitochondrial proteome detection; same caveat (peroxisomal contamination of mitochondrial preparations). Reason: Likely peroxisomal co-purification in an organelle proteome. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) in the yeast Saccharomyces cerevisiae catalyze the NADP(+)-dependent oxidative decarboxylation of isocitrate to form alpha-ketoglutarate. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | MARK AS OVER ANNOTATED | Summary: Quantitative mitochondrial proteome detection; same caveat as other organelle proteomes. Reason: Likely peroxisomal co-purification in an organelle proteome. Supporting Evidence: PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast grown on fermentative (glucose or galactose) and respiratory (lactate) media. PMID:15001388 Three differentially compartmentalized isozymes of isocitrate dehydrogenase (mitochondrial IDP1, cytosolic IDP2, and peroxisomal IDP3) in the yeast Saccharomyces cerevisiae catalyze the NADP(+)-dependent oxidative decarboxylation of isocitrate to form alpha-ketoglutarate. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA (PTN000214284) propagating mitochondrial location. Yeast partitions NADP-IDH into compartment-specific paralogs; the mitochondrial one is Idp1, and Idp3 is targeted to peroxisomes. Reason: Paralog-level over-propagation; Idp3 is peroxisomal. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000214284 · PANTHER node (mitochondrial NADP-IDH) SUPPORTS SOURCE BUT NOT TARGET Donors include yeast Idp1 (SGD:S000002224) and fly/mouse mitochondrial IDH; S. cerevisiae has a dedicated mitochondrial paralog, so the compartment does not transfer to the extramitochondrial isozymes. Supporting Evidence: PMID:19854152 there are three homologous but genetically distinct and differentially compartmentalized NADP+-dependent isocitrate dehydrogenase isozymes: mitochondrial IDP1 [1], cytosolic IDP2 [2], and peroxisomal IDP3 [3, 4]. PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for peroxisome (PTN002483519); Idp3 is the yeast peroxisomal NADP-IDH and is a donor in its own right. Supporting Evidence: PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0005777 peroxisome | IDA PMID:9452501 IDP3 encodes a peroxisomal NADP-dependent isocitrate dehydro... | ACCEPT | Summary: Henke et al. localised Idp3 to peroxisomes. Supporting Evidence: PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA places the PWY3O-13 IDP reaction in cytosol and attaches all three IDP paralogs; for Idp3 the compartment is the peroxisomal lumen. Reason: Pathway-level compartment assignment wrong for the peroxisomal paralog. Supporting Evidence: PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. PMID:9452501 The impermeability of the peroxisomal membrane for pyrimidine nucleotides led to the question of how the NADPH needed by the reductase is regenerated in the peroxisomal lumen. |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA for TCA cycle from bacterial Icd; Idp3 is peroxisomal and not a TCA-cycle enzyme. Reason: The IBA node (PTN008982454) carries TCA cycle from bacterial Icd (P9WKL1), where NADP-IDH is the TCA isocitrate-oxidising enzyme. In S. cerevisiae the TCA step is catalysed by the mitochondrial NAD+-specific IDH (Idh1/Idh2); the extramitochondrial IDP isozymes are not cycle members. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE Sources checked: UniProtKB:P9WKL1 · Mycobacterium tuberculosis isocitrate dehydrogenase Icd SUPPORTS SOURCE BUT NOT TARGET In bacteria NADP-IDH is the TCA enzyme; eukaryotic extramitochondrial NADP-IDH isozymes are not part of the mitochondrial TCA cycle. Supporting Evidence: PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0006102 isocitrate metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for isocitrate metabolic process; consistent with Idp3 oxidising isocitrate. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0006102 isocitrate metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR004790 mapping to isocitrate metabolic process; correct. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; |
| GO:0006635 fatty acid beta-oxidation | IMP PMID:9452501 IDP3 encodes a peroxisomal NADP-dependent isocitrate dehydro... | ACCEPT | Summary: idp3 deletion mutants grow normally on saturated but poorly on unsaturated fatty acids; Idp3 regenerates intraperoxisomal NADPH for 2,4-dienoyl-CoA reductase (Sps19), an auxiliary beta-oxidation enzyme for unsaturated acyl chains. It contributes the cofactor a beta-oxidation step depends on. Supporting Evidence: PMID:9452501 Yeast cells lacking Idp3p grow normally on saturated fatty acids, but growth is impaired on unsaturated fatty acids, indicating that the peroxisomal Idp3p is involved in their metabolic utilization. PMID:9452501 The impermeability of the peroxisomal membrane for pyrimidine nucleotides led to the question of how the NADPH needed by the reductase is regenerated in the peroxisomal lumen. PMID:9452501 an NADP-dependent isocitrate dehydrogenase, a putative constituent of a peroxisomal NADPH-regenerating redox system. |
| GO:0006739 NADP+ metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA for NADP+ metabolic process; for Idp3 the specific role is regeneration of NADPH inside peroxisomes. Reason: NADPH regeneration is the specific contribution. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000214284 · PANTHER node (NADP-IDH) SUPPORTS TRANSFER Transfer is sound; the term is a general parent of the NADPH-generating role. Proposed replacements: NADPH regeneration Supporting Evidence: PMID:9452501 an NADP-dependent isocitrate dehydrogenase, a putative constituent of a peroxisomal NADPH-regenerating redox system. |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to the oxidoreductase parent class; correct but uninformative. Reason: Parent of GO:0004450. Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | MODIFY | Summary: InterPro family mapping to NAD binding; Idp3 is NADP-dependent. Reason: Wrong nicotinamide cofactor for an NADP-specific IDH. Proposed replacements: NADP binding Supporting Evidence: file:yeast/IDP3/IDP3-uniprot.txt Reaction=D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH; PMID:9452501 We report the identification and functional analysis of the IDP3 gene product, which is a yeast peroxisomal NADP-dependent isocitrate dehydrogenase. |
| GO:0097054 L-glutamate biosynthetic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA from the superpathway of glutamate biosynthesis. Peroxisomal Idp3 functions in NADPH regeneration for unsaturated fatty-acid oxidation; any 2-oxoglutarate it makes is incidental, and glutamate is formed by Gdh/Glt1. Only artificially relocated Idp3 has been shown to support glutamate synthesis. Reason: Superpathway inheritance; not a step of glutamate biosynthesis for the peroxisomal isozyme. Supporting Evidence: PMID:15001388 These studies revealed that the IDP isozymes are functionally interchangeable for glutamate synthesis, although mitochondrial localization has a positive impact on this function during fermentative growth. PMID:9452501 an NADP-dependent isocitrate dehydrogenase, a putative constituent of a peroxisomal NADPH-regenerating redox system. |
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Download this section (compressed HTML)Q: Which shuttle (e.g. isocitrate/2-oxoglutarate exchange) links peroxisomal Idp3 to cytosolic carbon metabolism, and which transporter carries it?
Experiment: Measure peroxisomal NADPH/NADP+ with a targeted biosensor in wild type and idp3 cells on oleate versus petroselinate.
Peroxisomal NADP-dependent isocitrate dehydrogenase; catalyzes oxidation of isocitrate to alpha-ketoglutarate with the formation of NADP(H+), required for growth on unsaturated fatty acids; IDP3 has a paralog, IDP2, that arose from the whole genome duplication
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