Uox encodes mouse uricase/urate oxidase (EC 1.7.3.3), a uricase-family enzyme that oxidizes urate to 5-hydroxyisourate in the urate degradation branch of purine catabolism. UniProt describes the reaction as urate + oxygen + water producing 5-hydroxyisourate and hydrogen peroxide, and structural and evolutionary evidence supports a cofactor-independent urate oxidase reaction. The conserved primary cellular site is the peroxisome, with additional UniProt-cited evidence for a liver mitochondrial pool; the broader upstream nucleoside and nucleotide catabolic steps are carried out by other enzymes of purine catabolism, not by Uox itself.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0019628 urate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Uox participates in urate catabolism by catalyzing urate oxidation. Reason: Urate oxidation is an early step in urate degradation, consistent with Uox function. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) file:mouse/Uox/Uox-uniprot.txt PATHWAY: Purine metabolism; urate degradation; (S)-allantoin from urate: step 1/3. file:mouse/Uox/Uox-deep-research-falcon.md Falcon places Uox downstream of xanthine dehydrogenase/oxidase in mammalian purine catabolism, where peroxisomal Uox oxidizes urate to 5-hydroxyisourate. |
| GO:0006145 purine nucleobase catabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Uox contributes to purine nucleobase catabolism via the urate degradation step. Reason: Urate is a purine breakdown product; Uox acts downstream in this pathway but is not the sole purine catabolic enzyme. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) file:mouse/Uox/Uox-deep-research-falcon.md Falcon describes Uox as the downstream urate oxidation step in purine catabolism rather than an enzyme acting throughout all purine nucleobase catabolic reactions. |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: Uox localizes to the peroxisomal compartment. Reason: Biochemical fractionation indicates urate oxidase is closely associated with peroxisomes. Supporting Evidence: PMID:3200253 fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment file:mouse/Uox/Uox-uniprot.txt SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:23085393}. file:mouse/Uox/Uox-deep-research-falcon.md Falcon summarizes mammalian Uox as a peroxisomal hepatic uricase. |
| GO:0004846 urate oxidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Uox catalyzes urate oxidation to 5-hydroxyisourate in the urate degradation pathway. Reason: Urate oxidation and uricase activity are described for mouse tissues, matching the specific enzymatic function of Uox. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. file:mouse/Uox/Uox-uniprot.txt Reaction=urate + O2 + H2O = 5-hydroxyisourate + H2O2; EC=1.7.3.3. file:mouse/Uox/Uox-deep-research-falcon.md Falcon describes Uox as a cofactor-independent urate oxidase that catalyzes oxidation of uric acid to 5-hydroxyisourate using molecular oxygen. |
| GO:0004846 urate oxidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Uox catalyzes urate oxidation to 5-hydroxyisourate in the urate degradation pathway. Reason: Urate oxidation and uricase activity are described for mouse tissues, matching the specific enzymatic function of Uox. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt reports a mouse liver mitochondrial pool of Uox, but the conserved and best-supported primary location for uricase is peroxisome. Reason: The UniProt subcellular-location mapping and Nakamura study support retaining the mitochondrial annotation, while Falcon and older fractionation work place the core urate oxidase function in peroxisomes. Supporting Evidence: file:mouse/Uox/Uox-uniprot.txt SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:23085393}. Mitochondrion {ECO:0000269|PubMed:23085393}. file:mouse/Uox/Uox-deep-research-falcon.md Falcon reports that in terrestrial vertebrates, including rodents, uricase resides in peroxisomes and forms a core peroxisomal crystalloid in hepatocytes. |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | ACCEPT | Summary: Uox localizes to the peroxisomal compartment. Reason: Biochemical fractionation indicates urate oxidase is closely associated with peroxisomes. Supporting Evidence: PMID:3200253 fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment |
| GO:0006144 purine nucleobase metabolic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Broad purine nucleobase metabolism term; Uox acts in urate degradation. Reason: Evidence supports urate oxidation within purine metabolism, but the term is broader than the direct reaction. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000043 | MODIFY | Summary: General oxidoreductase activity is correct but too broad for Uox. Reason: Evidence supports the specific urate oxidase activity rather than a generic oxidoreductase term. Proposed replacements: urate oxidase activity Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0004846 urate oxidase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Uox catalyzes urate oxidation to 5-hydroxyisourate in the urate degradation pathway. Reason: Urate oxidation and uricase activity are described for mouse tissues, matching the specific enzymatic function of Uox. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. |
| GO:0005777 peroxisome | ISO GO_REF:0000096 | ACCEPT | Summary: Uox localizes to the peroxisomal compartment. Reason: Biochemical fractionation indicates urate oxidase is closely associated with peroxisomes. Supporting Evidence: PMID:3200253 fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment |
| GO:0019628 urate catabolic process | ISO GO_REF:0000096 | ACCEPT | Summary: Uox participates in urate catabolism by catalyzing urate oxidation. Reason: Urate oxidation is an early step in urate degradation, consistent with Uox function. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0019628 urate catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: Uox participates in urate catabolism by catalyzing urate oxidation. Reason: Urate oxidation is an early step in urate degradation, consistent with Uox function. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0004846 urate oxidase activity | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | ACCEPT | Summary: Uox catalyzes urate oxidation to 5-hydroxyisourate in the urate degradation pathway. Reason: Urate oxidation and uricase activity are described for mouse tissues, matching the specific enzymatic function of Uox. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. |
| GO:0006149 deoxyinosine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0006157 deoxyadenosine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0006161 deoxyguanosine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0006147 guanine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0009114 hypoxanthine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0006148 inosine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0006154 adenosine catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0004846 urate oxidase activity | IDA PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxida... | ACCEPT | Summary: Uox catalyzes urate oxidation to 5-hydroxyisourate in the urate degradation pathway. Reason: Urate oxidation and uricase activity are described for mouse tissues, matching the specific enzymatic function of Uox. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. |
| GO:0009115 xanthine catabolic process | IDA PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxida... | UNDECIDED | Summary: Cannot be adjudicated here: PMID:4207016 is cached abstract-only. Prior observation, not a verdict: Uox is uricase, not xanthine oxidase. Reason: PMID:4207016 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: The cited study distinguishes xanthine oxidase from uricase; Uox activity is specific to urate oxidation. Supporting Evidence: PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. |
| GO:0006204 IMP catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0046059 dAMP catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0005777 peroxisome | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | ACCEPT | Summary: Uox localizes to the peroxisomal compartment. Reason: Biochemical fractionation indicates urate oxidase is closely associated with peroxisomes. Supporting Evidence: PMID:3200253 fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment |
| GO:0046038 GMP catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0005777 peroxisome | IDA PMID:3200253 On the compartmentalization of catalase, fatty acyl-CoA oxid... | ACCEPT | Summary: Uox localizes to the peroxisomal compartment. Reason: Biochemical fractionation indicates urate oxidase is closely associated with peroxisomes. Supporting Evidence: PMID:3200253 fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment |
| GO:0006196 AMP catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0046055 dGMP catabolic process | IDA PMID:16462750 Completing the uric acid degradation pathway through phyloge... | REMOVE | Summary: Uox catalyzes urate oxidation and does not directly carry out upstream nucleoside catabolic steps. Reason: The available evidence describes urate oxidation, not deoxyadenosine/inosine/guanine or nucleotide catabolic reactions. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0005829 cytosol | TAS Reactome:R-MMU-9033925 | MARK AS OVER ANNOTATED | Summary: Reactome notes Pex5l binding to Uox, but this does not establish cytosolic residence as a primary location. Reason: The evidence is interaction-based and does not specify stable cytosolic localization for Uox. Supporting Evidence: Reactome:R-MMU-9033925 Pex5l binds monomeric Acox1 and monomeric Uox in preference to dimeric Acox1 and tetrameric Uox (Freitas et al. 2015) |
| GO:0005739 mitochondrion | HDA PMID:14651853 Integrated analysis of protein composition, tissue diversity... | KEEP AS NON CORE | Summary: The original HDA record comes from a mitochondrial proteome survey; UniProt separately cites a mouse liver study supporting a mitochondrial Uox pool. Reason: Retain as non-core because mitochondrial Uox has some protein-level support, but it is not the conserved primary localization emphasized by uricase pathway and localization literature. Supporting Evidence: PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver file:mouse/Uox/Uox-uniprot.txt SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:23085393}. Mitochondrion {ECO:0000269|PubMed:23085393}. |
| GO:0005777 peroxisome | TAS PMID:11461119 Peroxisome proliferator-activated receptor alpha-responsive ... | ACCEPT | Summary: Uox localizes to the peroxisomal compartment. Reason: PMID:11461119 reports peroxisome proliferation-related expression; peroxisomal localization is supported by fractionation data. Supporting Evidence: PMID:3200253 fatty acyl-CoA oxidase and urate oxidase both of which were indicated as showing a closer association with the peroxisomal compartment |
| GO:0006144 purine nucleobase metabolic process | TAS PMID:11461119 Peroxisome proliferator-activated receptor alpha-responsive ... | KEEP AS NON CORE | Summary: Broad purine nucleobase metabolism term; Uox acts in urate degradation. Reason: PMID:11461119 is expression-focused; functional support comes from urate oxidation evidence. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) |
| GO:0004846 urate oxidase activity | TAS PMID:11461119 Peroxisome proliferator-activated receptor alpha-responsive ... | ACCEPT | Summary: Uox catalyzes urate oxidation to 5-hydroxyisourate in the urate degradation pathway. Reason: PMID:11461119 reports expression changes; enzymatic activity is supported by other studies. Supporting Evidence: PMID:16462750 two proteins encoded by mouse genes catalyze two consecutive steps following urate oxidation to 5-hydroxyisourate (HIU) PMID:4207016 Developmental changes of adenosine deaminase, xanthine oxidase, and uricase in mouse tissues. |
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Download this section (compressed HTML)Q: What fraction of endogenous mouse liver Uox activity is mitochondrial under normal, fasted, or SIRT5-perturbed conditions, compared with the peroxisomal pool?
Suggested experts: urate metabolism biochemists, peroxisome and mitochondrial proteomics experts
Q: Should the MGI annotations to specific upstream nucleoside, nucleotide, and xanthine catabolic processes be retired or replaced by urate catabolic process for Uox?
Suggested experts: GO biological process curators, mouse genome annotation curators
Experiment: Quantitatively fractionate mouse liver peroxisomes, mitochondria, and cytosol under fed and fasted conditions, measuring endogenous Uox protein, peroxisomal and mitochondrial marker purity, and urate oxidase activity in each fraction.
Hypothesis: Most endogenous Uox activity resides in peroxisomes, with any mitochondrial pool representing a smaller and condition-dependent non-core localization.
Type: Endogenous localization and activity fractionation
Experiment: In Uox-null and rescued mouse hepatocytes, trace labeled urate, xanthine, inosine, and AMP into 5-hydroxyisourate/allantoin-pathway products while assaying xanthine oxidase separately.
Hypothesis: Uox loss specifically blocks urate-to-5-hydroxyisourate conversion and does not directly impair upstream nucleoside, nucleotide, or xanthine catabolic reactions except through pathway accumulation.
Type: Purine pathway specificity curation assay
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