Gene Ontology annotation through association of InterPro records with GO terms

Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniPathway vocabulary mapping

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:28508122

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease.

The three recombinant zebrafish uricolytic enzymes convert urate quantitatively to (S)-allantoin.

"A combination of the three enzymes in an appropriate ratio allowed efficient conversion of urate to (S)-allantoin with no accumulation of intermediate metabolites."
Urad catalyses the decarboxylation of OHCU to (S)-allantoin.

"decarboxylation of OHCU to give (S)-allantoin, catalyzed by OHCU decarboxylase (Urad) (Fig."

PMID:17428786

The structure of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase provides insights into the mechanism of uric acid degradation.

The OHCU decarboxylase is a homodimer catalysing the last step of urate degradation.

"describe the 1.8A resolution crystal structure of the homodimeric"
His-67 and Glu-87 are the principal catalytic residues; His-67 protonation sets the (S)-allantoin stereochemistry.

"which His-67 and Glu-87 appear to play a particularly significant role. Glu-87"

file:DANRE/urad/urad-uniprot.txt

UniProtKB entry A1L259 for Danio rerio urad

FUNCTION: Catalyzes the stereoselective decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) to (S)-allantoin.

"FUNCTION: Catalyzes the stereoselective decarboxylation of 2-oxo-4-"
The enzyme is the third (final) step of the urate degradation pathway and is annotated as peroxisomal.

"-!- PATHWAY: Purine metabolism; urate degradation; (S)-allantoin from"

file:DANRE/urad/urad-deep-research-falcon.md

Falcon deep research report on Danio rerio urad (OHCU decarboxylase, A1L259)

Urad is the third enzyme of the three-step uricolysis pathway, decarboxylating OHCU to allantoin downstream of urate oxidase and HIU hydrolase.

"it is the **third enzyme** in the classic three-step uricolysis pathway converting **urate → (S)-allantoin**"
Zebrafish OHCU decarboxylase is a homodimer.

"Zebrafish OHCU decarboxylase (Urad) is a **homodimer**"
The enzyme acts without metal ions or organic cofactors, consistent with a specialized cofactorless uricolysis enzyme.

"it acts **without metal ions or organic cofactors**, consistent with a specialized, cofactorless uricolysis enzyme"
His67 acts as a proton donor controlling stereoselective formation of (S)-allantoin.

"His67** is proposed to act as a **proton donor** in a step that controls **stereoselective formation** of (S)-allantoin"
In zebrafish, Urad has a predicted weak PTS1 (TKL); reporter experiments show predominantly cytoplasmic localization with additional peroxisomal labeling, indicating a weak-but-functional peroxisomal targeting motif.

"D. rerio Urad** has a predicted weak PTS1 (**TKL**) and that EGFP reporter experiments showed **predominantly cytoplasmic localization** with **additional peroxisomal labeling**, indicating the motif is **weak but functional**"
Enzymatic uricolysis stereoselectively produces (S)-allantoin in vivo, whereas uncatalyzed decay yields racemic allantoin.

"in vivo the enzymatic pathway produces the biologically relevant **dextrorotatory (S)-allantoin**"