Description: Homo sapiens xanthine dehydrogenase (XDH), mRNA. RefSeq Summary (NM_000379): Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism. [provided by RefSeq, Jan 2014]. Transcript (Including UTRs) Position: hg19 chr2:31,557,188-31,637,611 Size: 80,424 Total Exon Count: 36 Strand: - Coding Region Position: hg19 chr2:31,558,824-31,637,532 Size: 78,709 Coding Exon Count: 36
ID:XDH_HUMAN DESCRIPTION: RecName: Full=Xanthine dehydrogenase/oxidase; Includes: RecName: Full=Xanthine dehydrogenase; Short=XD; EC=1.17.1.4; Includes: RecName: Full=Xanthine oxidase; Short=XO; EC=1.17.3.2; AltName: Full=Xanthine oxidoreductase; Short=XOR; FUNCTION: Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro). CATALYTIC ACTIVITY: Hypoxanthine + NAD(+) + H(2)O = xanthine + NADH. CATALYTIC ACTIVITY: Xanthine + H(2)O + O(2) = urate + H(2)O(2). COFACTOR: Binds 2 2Fe-2S clusters. COFACTOR: FAD. COFACTOR: Binds 1 molybdenum ion (molybdopterin) per subunit. ENZYME REGULATION: Can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups (By similarity). SUBUNIT: Homodimer. Interacts with BTN1A1 (By similarity). SUBCELLULAR LOCATION: Cytoplasm (By similarity). Peroxisome (By similarity). Secreted. TISSUE SPECIFICITY: Detected in milk (at protein level). PTM: Subject to partial proteolysis; this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O) (By similarity). PTM: Contains sulfhydryl groups that are easily oxidized (in vitro); this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O) (By similarity). DISEASE: Defects in XDH are the cause of xanthinuria type 1 (XU1) [MIM:278300]. Xanthinuria is characterized by excretion of very large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. XU1 is due to isolated xanthine dehydrogenase. XU1 patients can metabolize allopurinol. SIMILARITY: Belongs to the xanthine dehydrogenase family. SIMILARITY: Contains 1 2Fe-2S ferredoxin-type domain. SIMILARITY: Contains 1 FAD-binding PCMH-type domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/XDH"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/xdh/";
Blood pressure, oxidative stress levels in blood Felipe J Chaves et al. 2007, Xanthine oxidoreductase polymorphisms: influence in blood pressure and oxidative stress levels., Pharmacogenetics and genomics 17(8) : 589-96 2007.
[PubMed 17622935]
Variations in XDH are associated with blood pressure and oxidative stress.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P47989
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004854 xanthine dehydrogenase activity GO:0004855 xanthine oxidase activity GO:0005506 iron ion binding GO:0009055 electron carrier activity GO:0016491 oxidoreductase activity GO:0016614 oxidoreductase activity, acting on CH-OH group of donors GO:0016903 oxidoreductase activity, acting on the aldehyde or oxo group of donors GO:0042803 protein homodimerization activity GO:0043546 molybdopterin cofactor binding GO:0046872 metal ion binding GO:0050660 flavin adenine dinucleotide binding GO:0051536 iron-sulfur cluster binding GO:0051537 2 iron, 2 sulfur cluster binding
Biological Process: GO:0001933 negative regulation of protein phosphorylation GO:0001937 negative regulation of endothelial cell proliferation GO:0006195 purine nucleotide catabolic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007595 lactation GO:0009115 xanthine catabolic process GO:0010629 negative regulation of gene expression GO:0022900 electron transport chain GO:0030856 regulation of epithelial cell differentiation GO:0045602 negative regulation of endothelial cell differentiation GO:0051898 negative regulation of protein kinase B signaling GO:0055114 oxidation-reduction process GO:1900745 positive regulation of p38MAPK cascade GO:1900747 negative regulation of vascular endothelial growth factor signaling pathway GO:2000379 positive regulation of reactive oxygen species metabolic process GO:2001213 negative regulation of vasculogenesis
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
