uox encodes zebrafish urate oxidase/uricase, a peroxisomal enzyme that catalyzes the first oxidative step of purine/urate degradation, converting urate to 5-hydroxyisourate. It functions as a homotetramer.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0019628 urate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: urate catabolic process (GO:0019628) is supported as the direct pathway context for uox. Reason: Uox catalyzes the first step in urate degradation, so this biological-process term is specific and appropriate. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt urate degradation; (S)-allantoin from urate: step 1/3 PMID:36553446 uox KO (uox−/−) larvae file:DANRE/uox/uox-deep-research-falcon.md catalyzes the **first (rate-limiting) step** of oxidative uricolysis/purine catabolism in many non-human vertebrates file:DANRE/uox/uox-deep-research-falcon.md the canonical uricolysis pathway is a **three-enzyme** sequence in which Uox generates **5-hydroxyisourate (HIU)**, followed by HIU hydrolase (Urah) and OHCU decarboxylase (Urad) to yield **(S)-allantoin**. |
| GO:0006145 purine nucleobase catabolic process | IBA GO_REF:0000033 | MODIFY | Summary: purine nucleobase catabolic process (GO:0006145) captures the right pathway area, but urate catabolic process (GO:0019628) is the better supported term. Reason: The annotation should be narrowed from broad purine nucleobase catabolism to the specific urate degradation reaction catalyzed by Uox. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000044668 · urate oxidase (Uox) ancestral node SUPPORTS TRANSFER The node correctly transfers urate-degradation involvement, so the propagation is sound. The problem is granularity: GO:0006145 (purine nucleobase catabolic process) is broader than the specific urate catabolic process (GO:0019628) that Uox catalyzes. UniProtKB:P33282 · Urate oxidase ortholog donor SUPPORTS TRANSFER Characterized urate oxidase ortholog donor supporting the urate-degradation step. Proposed replacements: urate catabolic process Supporting Evidence: file:DANRE/uox/uox-uniprot.txt urate degradation; (S)-allantoin from urate: step 1/3 PMID:36553446 uox KO (uox−/−) larvae |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | ACCEPT | Summary: peroxisome (GO:0005777) is supported for zebrafish uox. Reason: The UniProt record places Uox in the peroxisome, and falcon deep research independently confirms peroxisomal localization via a C-terminal PTS1 (ARM) motif and a zebrafish peroxisomal proteome inventory. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt SUBCELLULAR LOCATION: Peroxisome file:DANRE/uox/uox-deep-research-falcon.md DrUox encodes a C-terminal **ARM** tripeptide corresponding to a **PTS1** motif, indicating peroxisomal matrix import. file:DANRE/uox/uox-deep-research-falcon.md A zebrafish peroxisomal proteome inventory lists Uox (Q6DG85_DANRE) as peroxisomal with PTS1 **ARM**. |
| GO:0004846 urate oxidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: urate oxidase activity (GO:0004846) is the direct catalytic activity of zebrafish uox. Reason: Urate oxidase activity is the specific molecular function supported by biochemical and UniProt evidence. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt Catalyzes the oxidation of uric acid to 5-hydroxyisourate PMID:27922051 A cDNA encoding the complete sequence of zebrafish urate oxidase |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | ACCEPT | Summary: peroxisome (GO:0005777) is supported for zebrafish uox. Reason: The UniProt record places Uox in the peroxisome. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0072523 purine-containing compound catabolic process | IEA GO_REF:0000117 | MODIFY | Summary: purine-containing compound catabolic process (GO:0072523) is too broad for the direct Uox function. Reason: Uox acts specifically in urate degradation rather than purine-containing-compound catabolism generally. Proposed replacements: urate catabolic process Supporting Evidence: file:DANRE/uox/uox-uniprot.txt urate degradation; (S)-allantoin from urate: step 1/3 PMID:36553446 uox KO (uox−/−) larvae |
| GO:0019628 urate catabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: urate catabolic process (GO:0019628) is supported as the direct pathway context for uox. Reason: Uox catalyzes the first step in urate degradation, so this biological-process term is specific and appropriate. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt urate degradation; (S)-allantoin from urate: step 1/3 PMID:36553446 uox KO (uox−/−) larvae |
| GO:0005777 peroxisome | ISS GO_REF:0000024 | ACCEPT | Summary: peroxisome (GO:0005777) is supported for zebrafish uox. Reason: The UniProt record places Uox in the peroxisome. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt SUBCELLULAR LOCATION: Peroxisome |
| GO:0046415 urate metabolic process | IMP PMID:36553446 Uricase-Deficient Larval Zebrafish with Elevated Urate Level... | MODIFY | Summary: urate metabolic process (GO:0046415) is directionally correct but should be narrowed to urate catabolic process. Reason: The mutant phenotype is elevated urate, and the direct biochemical role is catabolic conversion of urate. Proposed replacements: urate catabolic process Supporting Evidence: file:DANRE/uox/uox-uniprot.txt urate degradation; (S)-allantoin from urate: step 1/3 PMID:36553446 uox KO (uox−/−) larvae file:DANRE/uox/uox-deep-research-falcon.md **uox−/−** larvae were viable/fertile with no embryonic mortality reported, had **elevated urate levels**, and showed a **reduced acute inflammatory response** to injected **monosodium urate (MSU) crystals** |
| GO:0004846 urate oxidase activity | IDA PMID:28508122 A Trivalent Enzymatic System for Uricolytic Therapy of HPRT ... | ACCEPT | Summary: urate oxidase activity (GO:0004846) is the direct catalytic activity of zebrafish uox. Reason: Urate oxidase activity is the specific molecular function supported by biochemical and UniProt evidence. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt Catalyzes the oxidation of uric acid to 5-hydroxyisourate PMID:27922051 A cDNA encoding the complete sequence of zebrafish urate oxidase file:DANRE/uox/uox-deep-research-falcon.md Zebrafish Uox catalyzes **oxidation/hydroxylation of urate to HIU**, and is described as the **classical cofactorless Uox** (i.e., it does not require a tightly bound organic cofactor). |
| GO:0004846 urate oxidase activity | IMP PMID:27922051 Catalysis and Structure of Zebrafish Urate Oxidase Provide I... | ACCEPT | Summary: urate oxidase activity (GO:0004846) is the direct catalytic activity of zebrafish uox. Reason: Urate oxidase activity is the specific molecular function supported by biochemical and UniProt evidence. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt Catalyzes the oxidation of uric acid to 5-hydroxyisourate PMID:27922051 A cDNA encoding the complete sequence of zebrafish urate oxidase |
| GO:0051289 protein homotetramerization | IPI PMID:27922051 Catalysis and Structure of Zebrafish Urate Oxidase Provide I... | KEEP AS NON CORE | Summary: protein homotetramerization (GO:0051289) is supported for Uox structure but is not the core gene function. Reason: Tetramer formation describes the enzyme assembly state; it should not displace urate oxidase activity and urate catabolism as the core function. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt SUBUNIT: Homotetramer; dimer of dimers. file:DANRE/uox/uox-deep-research-falcon.md Zebrafish Uox forms a **tetramer** with the **T-fold** architecture typical of classical uricases; the functional active sites occur at subunit interfaces. |
| GO:0004846 urate oxidase activity | IDA PMID:26349049 The identification of an integral membrane, cytochrome c ura... | ACCEPT | Summary: urate oxidase activity (GO:0004846) is the direct catalytic activity of zebrafish uox. Reason: Urate oxidase activity is the specific molecular function supported by biochemical and UniProt evidence. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt Catalyzes the oxidation of uric acid to 5-hydroxyisourate PMID:27922051 A cDNA encoding the complete sequence of zebrafish urate oxidase |
| GO:0004846 urate oxidase activity | IDA PMID:27922051 Catalysis and Structure of Zebrafish Urate Oxidase Provide I... | ACCEPT | Summary: urate oxidase activity (GO:0004846) is the direct catalytic activity of zebrafish uox. Reason: Urate oxidase activity is the specific molecular function supported by biochemical and UniProt evidence. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt Catalyzes the oxidation of uric acid to 5-hydroxyisourate PMID:27922051 A cDNA encoding the complete sequence of zebrafish urate oxidase |
| GO:0019628 urate catabolic process | IDA PMID:27922051 Catalysis and Structure of Zebrafish Urate Oxidase Provide I... | ACCEPT | Summary: urate catabolic process (GO:0019628) is supported as the direct pathway context for uox. Reason: Uox catalyzes the first step in urate degradation, so this biological-process term is specific and appropriate. Supporting Evidence: file:DANRE/uox/uox-uniprot.txt urate degradation; (S)-allantoin from urate: step 1/3 PMID:36553446 uox KO (uox−/−) larvae |
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Download this section (compressed HTML)Q: Why does zebrafish retain a fully functional uricase when hominoids (including humans) have lost urate oxidase activity through pseudogenization?
Q: Is Uox the sole route of urate degradation in zebrafish, or do redundant enzymes contribute to urate homeostasis in larvae and adults?
Experiment: Inject wild-type versus active-site-mutant uox mRNA into uox-/- zebrafish embryos and measure whether urate levels and monosodium urate crystal persistence are normalized.
Hypothesis: Catalytically inactive Uox cannot rescue the elevated-urate phenotype of uox-deficient zebrafish, confirming that urate oxidase activity is the relevant function.
Experiment: Express GFP-tagged Uox with and without candidate targeting-signal mutations in zebrafish cells and assess colocalization with a peroxisomal marker.
Hypothesis: Uox is targeted to the peroxisome via a C-terminal or internal peroxisomal targeting signal.
Experiment: Quantify HIU, OHCU, and allantoin levels and characterize the acute inflammatory response to injected monosodium urate crystals in uox-/- versus wild-type larvae.
Hypothesis: Loss of Uox alters the downstream allantoin pathway and the inflammatory response to urate crystals.
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