POX1 (FOX1) encodes acyl-CoA oxidase (EC 1.3.3.6), the first enzyme of peroxisomal fatty acid beta-oxidation in Saccharomyces cerevisiae and the only acyl-CoA oxidase gene in this yeast. The FAD-containing enzyme oxidises a 2,3-saturated acyl-CoA with molecular oxygen to the trans-2-enoyl-CoA, and the hydrogen peroxide produced is removed by peroxisomal catalase. Pox1p is a homo-oligomeric matrix protein. It lacks both PTS1 and PTS2 signals and is imported into peroxisomes by direct binding of an internal region to the N-terminal part of the receptor Pex5p. POX1 transcription is strongly induced by oleate, and disruption impairs growth on fatty acids as the sole carbon source. Pox1p also converts blue light into a hydrogen peroxide signal: in its absence the light-induced rise in cytosolic H2O2 is much reduced, and the peroxiredoxin Tsa1 and thioredoxins relay this signal to counteract PKA-dependent phosphorylation and so drive nucleocytoplasmic oscillation of the stress transcription factor Msn2.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003997 acyl-CoA oxidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000097533 (ACOX clade), with mammalian ACOX1 among the donors. Pox1p is the single acyl-CoA oxidase of S. cerevisiae, so the inherited activity is correct. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0003997 acyl-CoA oxidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from InterPro ACOX signatures, RHEA:38959 and EC 1.3.3.6. This is the correct reaction for Pox1p. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0003997 acyl-CoA oxidase activity | ISA PMID:2189786 Structure and transcriptional control of the Saccharomyces c... | ACCEPT | Summary: Dmochowska et al. identified POX1 by sequence alignment with the Candida tropicalis POX4/POX5 acyl-CoA oxidases (about 40% identity). The pox1 disruption impairs growth on oleate, which supports the assigned activity. Supporting Evidence: PMID:2189786 We have cloned the Saccharomyces cerevisiae gene coding for the peroxisomal enzyme: fatty acyl-CoA oxidase (POX) PMID:2189786 The gene (named POX1) is unique in S. cerevisiae and has been identified through homology with the POX4 and POX5 genes of Candida tropicalis PMID:2189786 A disruption of the POX1 coding sequence diminishes the ability of yeast cells to grow on oleic acid as a sole carbon source |
| GO:0003997 acyl-CoA oxidase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from YEAST-FAO-PWY for the acyl-CoA + O2 -> trans-2-enoyl-CoA + H2O2 step (EC 1.3.3.6). This is precisely the Pox1p reaction. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0005504 fatty acid binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA from PTN000097533, based on rat ACOX/ACAD fatty-acid-binding annotations. Acyl-CoA oxidases bind acyl-CoA thioesters as substrates, not free fatty acids, and substrate binding is part of the catalytic activity rather than a separate function. No data show free fatty acid binding by Pox1p. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000097533 · PTN000097533 SUPPORTS SOURCE BUT NOT TARGET Rat donor fatty-acid-binding annotations reflect acyl-CoA substrate binding; the substrate is an acyl-CoA thioester, not a free fatty acid. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0005504 fatty acid binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro IPR034171 (ACOX, C-terminal) to 'fatty acid binding' mapping. The protein's substrate is acyl-CoA, so this is an over-annotation for the same reason as the IBA. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Michaelis et al. proteome-wide affinity-enrichment MS, which recorded an interaction with the ribosomal stalk protein RPP0 (P05317). This is a single high-throughput association with a very abundant ribosomal protein, has no biological follow-up, and the 'protein binding' term says nothing about Pox1p function. Removed; this does not assert the association is false. Supporting Evidence: PMID:37968396 high-throughput method using highly reproducible affinity enrichment coupled to file:yeast/POX1/POX1-uniprot.txt P13711; P05317: RPP0; NbExp=2; IntAct=EBI-3999, EBI-15447; |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000097533), with SGD:S000003173 (POX1) among the descendants. Pox1p is a peroxisomal enzyme. Supporting Evidence: PMID:11967269 Here we demonstrate that peroxisomal import of Pox1p is nevertheless dependent on binding to Pex5p, the PTS1 import receptor file:yeast/POX1/POX1-uniprot.txt SUBCELLULAR LOCATION: Peroxisome. |
| GO:0005777 peroxisome | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/SubCell mapping to peroxisome. This is correct and is confirmed by import studies. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt SUBCELLULAR LOCATION: Peroxisome. PMID:11967269 Here we demonstrate that peroxisomal import of Pox1p is nevertheless dependent on binding to Pex5p, the PTS1 import receptor |
| GO:0005782 peroxisomal matrix | IDA PMID:11967269 Saccharomyces cerevisiae acyl-CoA oxidase follows a novel, n... | ACCEPT | Summary: Klein et al. showed Pex5p-dependent import of Pox1p into the peroxisomal matrix through an internal non-PTS1 binding site. This places it in the matrix where beta-oxidation occurs. Supporting Evidence: PMID:11967269 Here we demonstrate that peroxisomal import of Pox1p is nevertheless dependent on binding to Pex5p, the PTS1 import receptor |
| GO:0005829 cytosol | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA from YEAST-FAO-PWY assigns the fatty acid oxidation pathway to the cytosol. Yeast beta-oxidation is exclusively peroxisomal, and Pox1p is a Pex5p-imported matrix enzyme. The cytosolic location is wrong for this activity. Supporting Evidence: PMID:11967269 Here we demonstrate that peroxisomal import of Pox1p is nevertheless dependent on binding to Pex5p, the PTS1 import receptor file:yeast/POX1/POX1-uniprot.txt PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation. |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR012258 (acyl-CoA oxidase) mapping to fatty acid metabolic process. This is correct but too general: Pox1p acts in peroxisomal beta-oxidation using acyl-CoA oxidase. Proposed replacements: fatty acid beta-oxidation using acyl-CoA oxidase Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation. |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro mapping to fatty acid beta-oxidation. This is correct. The more precise child GO:0033540 is also annotated. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation. PMID:12819196 Synthesis of polyhydroxyalkanoate was dependent on the beta-oxidation enzymes acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase multifunctional protein |
| GO:0006635 fatty acid beta-oxidation | IMP PMID:12819196 Futile cycling of intermediates of fatty acid biosynthesis t... | ACCEPT | Summary: Marchesini and Poirier: synthesis of polyhydroxyalkanoate from beta-oxidation intermediates requires acyl-CoA oxidase, so Pox1p catalyses the first step of the cycle in vivo. Supporting Evidence: PMID:12819196 Synthesis of polyhydroxyalkanoate was dependent on the beta-oxidation enzymes acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase multifunctional protein |
| GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors | IEA GO_REF:0000002 | MODIFY | Summary: InterPro acyl-CoA dehydrogenase/oxidase fold signatures mapping to the generic CH-CH oxidoreductase parent. The specific activity is acyl-CoA oxidase (O2 as acceptor). Proposed replacements: acyl-CoA oxidase activity Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0019395 fatty acid oxidation | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways RCA from YEAST-FAO-PWY (fatty acid oxidation). This is correct but general. The specific process is beta-oxidation using acyl-CoA oxidase. Proposed replacements: fatty acid beta-oxidation using acyl-CoA oxidase Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation. |
| GO:0033540 fatty acid beta-oxidation using acyl-CoA oxidase | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000097533) to the oxidase-type beta-oxidation process. This is the most precise process term for Pox1p. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation. file:yeast/POX1/POX1-uniprot.txt Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2; |
| GO:0033540 fatty acid beta-oxidation using acyl-CoA oxidase | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro IPR034171 and UniPathway UPA00661 mapping. This is correct for the yeast peroxisomal oxidase-initiated beta-oxidation. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation. |
| GO:0050660 flavin adenine dinucleotide binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA FAD binding. Pox1p is an FAD-dependent flavoenzyme, so the term is correct, but cofactor binding is part of the oxidase activity rather than a separate core function. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro IPR037069 (acyl-CoA dehydrogenase/oxidase N-terminal) mapping to FAD binding. The term is correct (FAD cofactor) and non-core. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; |
| GO:0071949 FAD binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro IPR012258/IPR034171 mapping to FAD binding (GO:0071949). The term is correct for this flavoprotein but is a cofactor property, so non-core. Supporting Evidence: file:yeast/POX1/POX1-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; |
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Download this section (compressed HTML)Q: What is the chain-length specificity of S. cerevisiae Pox1p, given that it is the only acyl-CoA oxidase and must handle all straight-chain substrates entering beta-oxidation?
Experiment: Purify recombinant Pox1p and measure kinetic parameters with saturated and unsaturated acyl-CoAs of C4 to C22 using an H2O2-coupled assay.
Hypothesis: Pox1p has broad acyl-CoA chain-length specificity that covers the whole beta-oxidation spiral
Type: enzyme kinetics
Fatty-acyl coenzyme A oxidase; involved in the fatty acid beta-oxidation pathway; localized to the peroxisomal matrix; component of a light sensing pathway, converting light into a hydrogen peroxide signal, modulating nucleo-cytoplasmic shuttling of stress-responsive transcription factor, Msn2p
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