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Gene Review

UOX  -  urate oxidase

Homo sapiens

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Disease relevance of UOX


High impact information on UOX


Chemical compound and disease context of UOX


Biological context of UOX

  • It is known that murine Uox is expressed only in the liver, whereas human UOX has been inactivated as a pseudogene [9].
  • We suggest that although the inactivation of the hominoid Uox gene was caused by independent nonsense or frameshift mutations, the gene has taken a two-step deterioration process, first in the promoter and second in the coding region during primate evolution [10].
  • Nevertheless, we demonstrate rather strong selective constraint against nonsynonymous sites of the functional Uox gene and argue that this observation is consistent with the fact that the Uox gene is unique in the genome and evolutionarily conserved not only among animals but also among eukaryotes [10].
  • None of the three mutations was present in the gibbon; in contrast, a 13-bp deletion was identified that disrupted the gibbon urate oxidase reading frame [11].
  • The human urate oxidase (E.C. gene, UOX, is assigned to chromosome 1 by Southern analysis of human x hamster cell hybrids [12].

Anatomical context of UOX


Associations of UOX with chemical compounds

  • Urinary glycolate (a metabolic precursor of Ox) always remained below the upper limit of the normal range and did not change between different diets, indicating that changes in UOX x V reflect respective variations in intestinal absorption of Ox [15].
  • Consequently, urate oxidase is used as a protein drug to overcome severe disorders induced by uric acid accumulation [6].
  • We report the identification and purification of a novel enzyme from soybean root nodules that catalyzes the hydrolysis of 5-hydroxyisourate, which is the true product of the urate oxidase reaction [16].
  • A protein drp90 encoded on the leftwards strand of soybean nodule urate oxidase cDNA binds to a regulatory sequence in leghemoglobin C3 gene [17].
  • Cisplatin was administered to normouricemic and hyperuricemic rats (the latter generated by administering the urate oxidase inhibitor, oxonic acid) [18].

Other interactions of UOX

  • The head-to-head organization of DLAD and UOX is conserved in the human genomic sequence [9].
  • We also find that compared with other organisms, the primate functional Uox gene is exceptional in terms of usage of CGA codons which are prone to TGA nonsense mutations [10].
  • The mutant cells exhibited a temperature-sensitive (TS) phenotype on the peroxisomal localizations of the recombinant GFP and urate oxidase appending a genuine peroxisome targeting signal 1 (PTS1), a tripeptide of Ser-Lys-Leu (SKL) at the C-terminus, but did not on that of catalase harboring a divergent PTS1, Lys-Ala-Asn-Leu (KANL) sequence [19].
  • Hemolytic anemia due to G6PD deficiency and urate oxidase in a kidney-transplant patient [20].
  • Catalase, D-amino acid oxidase, and urate oxidase were found to be expressed in mammary carcinoma and in surrounding non-malignant tissue when the postnuclear supernatant fractions prepared from homogenates were assessed by Western blot techniques [21].

Analytical, diagnostic and therapeutic context of UOX


  1. Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-Hodgkin's lymphoma: results of the GRAAL1 (Groupe d'Etude des Lymphomes de l'Adulte Trial on Rasburicase Activity in Adult Lymphoma) study. Coiffier, B., Mounier, N., Bologna, S., Fermé, C., Tilly, H., Sonet, A., Christian, B., Casasnovas, O., Jourdan, E., Belhadj, K., Herbrecht, R. J. Clin. Oncol. (2003) [Pubmed]
  2. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma. Pui, C.H., Mahmoud, H.H., Wiley, J.M., Woods, G.M., Leverger, G., Camitta, B., Hastings, C., Blaney, S.M., Relling, M.V., Reaman, G.H. J. Clin. Oncol. (2001) [Pubmed]
  3. Treatment by design in leukemia, a meeting report, Philadelphia, Pennsylvania, December 2002. Larson, R.A., Daley, G.Q., Schiffer, C.A., Porcu, P., Pui, C.H., Marie, J.P., Steelman, L.S., Bertrand, F.E., McCubrey, J.A. Leukemia (2003) [Pubmed]
  4. Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies. Pui, C.H., Relling, M.V., Lascombes, F., Harrison, P.L., Struxiano, A., Mondesir, J.M., Ribeiro, R.C., Sandlund, J.T., Rivera, G.K., Evans, W.E., Mahmoud, H.H. Leukemia (1997) [Pubmed]
  5. Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. Scott, G.S., Spitsin, S.V., Kean, R.B., Mikheeva, T., Koprowski, H., Hooper, D.C. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Crystal structure of the protein drug urate oxidase-inhibitor complex at 2.05 A resolution. Colloc'h, N., el Hajji, M., Bachet, B., L'Hermite, G., Schiltz, M., Prangé, T., Castro, B., Mornon, J.P. Nat. Struct. Biol. (1997) [Pubmed]
  7. A radiochemical-high-performance liquid chromatographic assay for urate oxidase in human plasma. Greenberg, M.L., Hershfield, M.S. Anal. Biochem. (1989) [Pubmed]
  8. Protective effect of urate oxidase on uric acid induced-monocyte apoptosis. Bordoni, V., De Cal, M., Rassu, M., Cazzavillan, S., Segala, C., Bonello, M., Ranishta, R., Andrikos, E., Yavuz, A., Salvatori, G., Galloni, E., Bolgan, I., Bellomo, R., Levin, N., Ronco, C. Current drug discovery technologies. (2005) [Pubmed]
  9. Isolation and characterization of the DLAD/Dlad genes, which lie head-to-head with the genes for urate oxidase. Shiokawa, D., Tanuma, S.I. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  10. Loss of urate oxidase activity in hominoids and its evolutionary implications. Oda, M., Satta, Y., Takenaka, O., Takahata, N. Mol. Biol. Evol. (2002) [Pubmed]
  11. Two independent mutational events in the loss of urate oxidase during hominoid evolution. Wu, X.W., Muzny, D.M., Lee, C.C., Caskey, C.T. J. Mol. Evol. (1992) [Pubmed]
  12. Localization of the human urate oxidase gene (UOX) to 1p22. Yeldandi, A.V., Patel, Y.D., Liao, M., Kao, F.T., Rao, M.S., Reddy, J.K., Le Beau, M.M. Cytogenet. Cell Genet. (1992) [Pubmed]
  13. Uric acid degrading enzymes, urate oxidase and allantoinase, are associated with different subcellular organelles in frog liver and kidney. Usuda, N., Hayashi, S., Fujiwara, S., Noguchi, T., Nagata, T., Rao, M.S., Alvares, K., Reddy, J.K., Yeldandi, A.V. J. Cell. Sci. (1994) [Pubmed]
  14. A study of some mitochondrial and peroxisomal enzymes in human colonic adenocarcinoma. Sun, A.S., Sepkowitz, K., Geller, S.A. Lab. Invest. (1981) [Pubmed]
  15. High-calcium intake abolishes hyperoxaluria and reduces urinary crystallization during a 20-fold normal oxalate load in humans. Hess, B., Jost, C., Zipperle, L., Takkinen, R., Jaeger, P. Nephrol. Dial. Transplant. (1998) [Pubmed]
  16. Identification and purification of hydroxyisourate hydrolase, a novel ureide-metabolizing enzyme. Sarma, A.D., Serfozo, P., Kahn, K., Tipton, P.A. J. Biol. Chem. (1999) [Pubmed]
  17. A protein drp90 encoded on the leftwards strand of soybean nodule urate oxidase cDNA binds to a regulatory sequence in leghemoglobin C3 gene. Bergmann, J.E., Preddie, E., Cortes, L., Brousseau, R. Nucleic Acids Res. (1991) [Pubmed]
  18. Effect of elevated serum uric acid on cisplatin-induced acute renal failure. Roncal, C.A., Mu, W., Croker, B., Reungjui, S., Ouyang, X., Tabah-Fisch, I., Johnson, R.J., Ahsan Ejaz, A. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  19. Temperature-sensitive phenotype of Chinese hamster ovary cells defective in PEX5 gene. Ito, R., Huang, Y., Yao, C., Shimozawa, N., Suzuki, Y., Kondo, N., Imanaka, T., Usuda, N., Ito, M. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  20. Hemolytic anemia due to G6PD deficiency and urate oxidase in a kidney-transplant patient. Ducros, J., Saingra, S., Rampal, M., Coulange, C., Barbe, M.C., Verzetti, G. Clin. Nephrol. (1991) [Pubmed]
  21. Peroxisomal enzymes in normal and tumoral human breast. el Bouhtoury, F., Keller, J.M., Colin, S., Parache, R.M., Dauça, M. J. Pathol. (1992) [Pubmed]
  22. Primary hyperoxaluria 1: catch up growth and normalization of oxaluria 6 years after hepatorenal transplantation in a prepubertal boy. Walden, U., Böswald, M., Dörr, H.G., Ruder, H. Eur. J. Pediatr. (1999) [Pubmed]
  23. Urate-oxidase in the prevention and treatment of metabolic complications in patients with B-cell lymphoma and leukemia, treated in the Société Française d'Oncologie Pédiatrique LMB89 protocol. Patte, C., Sakiroglu, C., Ansoborlo, S., Baruchel, A., Plouvier, E., Pacquement, H., Babin-Boilletot, A. Ann. Oncol. (2002) [Pubmed]
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