| Identification |
|---|
| HMDB Protein ID
| HMDBP00181 |
| Secondary Accession Numbers
| |
| Name
| Xanthine dehydrogenase/oxidase |
| Synonyms
|
- XD
- XO
- Xanthine dehydrogenase
- Xanthine oxidase
- Xanthine oxidoreductase
|
| Gene Name
| XDH |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Involved in oxidoreductase activity |
| Specific 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).
|
| Pathways
|
- Adenine phosphoribosyltransferase deficiency (APRT)
- Adenosine Deaminase Deficiency
- Adenylosuccinate Lyase Deficiency
- AICA-Ribosiduria
- Azathioprine Action Pathway
- Caffeine metabolism
- Caffeine Metabolism
- Doxorubicin Metabolism Pathway
- Drug metabolism - other enzymes
- Gout or Kelley-Seegmiller Syndrome
- Lesch-Nyhan Syndrome (LNS)
- Mercaptopurine Action Pathway
- Mercaptopurine Metabolism Pathway
- Mitochondrial DNA depletion syndrome
- Molybdenum Cofactor Deficiency
- Myoadenylate deaminase deficiency
- Peroxisome
- Purine metabolism
- Purine metabolism
- Purine Nucleoside Phosphorylase Deficiency
- Thioguanine Action Pathway
- Xanthine Dehydrogenase Deficiency (Xanthinuria)
- Xanthinuria type I
- Xanthinuria type II
|
| Reactions
|
| Hypoxanthine + NAD + Water → Xanthine + NADH |
details
|
| Xanthine + Water + Oxygen → Uric acid + Hydrogen peroxide |
details
|
| Hypoxanthine + NAD + Water → Xanthine + NADH + Hydrogen Ion |
details
|
| Hypoxanthine + Oxygen + Water → Xanthine + Hydrogen peroxide |
details
|
| Xanthine + NAD + Water → Uric acid + NADH + Hydrogen Ion |
details
|
| 1-Methylxanthine + Water + Oxygen → 1-Methyluric acid + Hydrogen peroxide |
details
|
| Paraxanthine + Oxygen + Water → 1,7-Dimethyluric acid + Hydrogen peroxide |
details
|
| Theobromine + Water + Oxygen → 3,7-Dimethyluric acid + Hydrogen peroxide |
details
|
| 7-Methylxanthine + Oxygen + Water → 7-Methyluric acid + Hydrogen peroxide |
details
|
| Mercaptopurine + Water + Oxygen → 6-Thiourate + Hydrogen peroxide |
details
|
|
| GO Classification
|
| Biological Process |
| positive regulation of reactive oxygen species metabolic process |
| purine nucleotide catabolic process |
| activation of cysteine-type endopeptidase activity involved in apoptotic process |
| negative regulation of protein kinase B signaling cascade |
| negative regulation of protein phosphorylation |
| negative regulation of endothelial cell proliferation |
| negative regulation of endothelial cell differentiation |
| negative regulation of vascular endothelial growth factor signaling pathway |
| negative regulation of vasculogenesis |
| positive regulation of p38MAPK cascade |
| xanthine catabolic process |
| lactation |
| negative regulation of gene expression |
| Cellular Component |
| cytosol |
| extracellular region |
| peroxisome |
| Function |
| ion binding |
| cation binding |
| metal ion binding |
| binding |
| catalytic activity |
| transition metal ion binding |
| oxidoreductase activity, acting on ch or ch2 groups |
| nucleoside binding |
| purine nucleoside binding |
| adenyl nucleotide binding |
| electron carrier activity |
| metal cluster binding |
| iron-sulfur cluster binding |
| iron ion binding |
| molybdenum ion binding |
| oxidoreductase activity, acting on ch or ch2 groups, oxygen as acceptor |
| xanthine oxidase activity |
| oxidoreductase activity, acting on ch or ch2 groups, nad or nadp as acceptor |
| xanthine dehydrogenase activity |
| oxidoreductase activity |
| fad or fadh2 binding |
| Molecular Function |
| electron carrier activity |
| 2 iron, 2 sulfur cluster binding |
| molybdopterin cofactor binding |
| UDP-N-acetylmuramate dehydrogenase activity |
| xanthine dehydrogenase activity |
| iron ion binding |
| xanthine oxidase activity |
| flavin adenine dinucleotide binding |
| Process |
| metabolic process |
| oxidation reduction |
|
| Cellular Location
|
- Cytoplasm
- Peroxisome
- Secreted
|
| Gene Properties |
|---|
| Chromosome Location
| 2 |
| Locus
| 2p23.1 |
| SNPs
| XDH |
| Gene Sequence
|
>4002 bp
ATGACAGCAGACAAATTGGTTTTCTTTGTGAATGGCAGAAAGGTGGTGGAGAAAAATGCA
GATCCAGAGACAACCCTTTTGGCCTACCTGAGAAGAAAGTTGGGGCTGAGTGGAACCAAG
CTCGGCTGTGGAGAGGGGGGCTGCGGGGCTTGCACAGTGATGCTCTCCAAGTATGATCGT
CTGCAGAACAAGATCGTCCACTTTTCTGCCAATGCCTGCCTGGCCCCCATCTGCTCCTTG
CACCATGTTGCAGTGACAACTGTGGAAGGAATAGGAAGCACCAAGACGAGGCTGCATCCT
GTGCAGGAGAGAATTGCCAAAAGCCACGGCTCCCAGTGCGGGTTCTGCACCCCTGGCATC
GTCATGAGTATGTACACACTGCTCCGGAATCAGCCCGAGCCCACCATGGAGGAGATTGAG
AATGCCTTCCAAGGAAATCTGTGCCGCTGCACAGGCTACAGACCCATCCTCCAGGGCTTC
CGGACCTTTGCCAGGGATGGTGGATGCTGTGGAGGAGATGGGAATAATCCAAATTGCTGC
ATGAACCAGAAGAAAGACCACTCAGTCAGCCTCTCGCCATCTTTATTCAAACCAGAGGAG
TTCACGCCCCTGGATCCAACCCAGGAGCCCATTTTTCCCCCAGAGTTGCTGAGGCTGAAA
GACACTCCTCGGAAGCAGCTGCGATTTGAAGGGGAGCGTGTGACGTGGATACAGGCCTCA
ACCCTCAAGGAGCTGCTGGACCTCAAGGCTCAGCACCCTGACGCCAAGCTGGTCGTGGGG
AACACGGAGATTGGCATTGAGATGAAGTTCAAGAATATGCTGTTTCCTATGATTGTCTGC
CCAGCCTGGATCCCTGAGCTGAATTCGGTAGAACATGGACCCGACGGTATCTCCTTTGGA
GCTGCTTGCCCCCTGAGCATTGTGGAAAAAACCCTGGTGGATGCTGTTGCTAAGCTTCCT
GCCCAAAAGACAGAGGTGTTCAGAGGGGTCCTGGAGCAGCTGCGCTGGTTTGCTGGGAAG
CAAGTCAAGTCTGTGGCGTCCGTTGGAGGGAACATCATCACTGCCAGCCCCATCTCCGAC
CTCAACCCCGTGTTCATGGCCAGTGGGGCCAAGCTGACACTTGTGTCCAGAGGCACCAGG
AGAACTGTCCAGATGGACCACACCTTCTTCCCTGGCTACAGAAAGACCCTGCTGAGCCCG
GAGGAGATACTGCTCTCCATAGAGATCCCCTACAGCAGGGAGGGGGAGTATTTCTCAGCA
TTCAAGCAGGCCTCCCGGAGAGAAGATGACATTGCCAAGGTAACCAGTGGCATGAGAGTT
TTATTCAAGCCAGGAACCACAGAGGTACAGGAGCTGGCCCTTTGCTATGGTGGAATGGCC
AACAGAACCATCTCAGCCCTCAAGACCACTCAGAGGCAGCTTTCCAAGCTCTGGAAGGAG
GAGCTGCTGCAGGACGTGTGTGCAGGACTGGCAGAGGAGCTGCATCTGCCTCCCGATGCC
CCTGGTGGCATGGTGGACTTCCGGTGCACCCTCACCCTCAGCTTCTTCTTCAAGTTCTAC
CTGACAGTCCTTCAGAAGCTGGGCCAAGAGAACCTGGAAGACAAGTGTGGTAAACTGGAC
CCCACTTTCGCCAGTGCAACTTTACTGTTTCAGAAAGACCCCCCAGCCGATGTCCAGCTC
TTCCAAGAGGTGCCCAAGGGTCAGTCTGAGGAGGACATGGTGGGCCGGCCCCTGCCCCAC
CTGGCAGCGGACATGCAGGCCTCTGGTGAGGCCGTGTACTGTGACGACATTCCTCGCTAC
GAGAATGAGCTGTCTCTCCGGCTGGTCACCAGCACCCGGGCCCACGCCAAGATCAAGTCC
ATAGATACATCAGAAGCTAAGAAGGTTCCAGGGTTTGTTTGTTTCATTTCCGCTGATGAT
GTTCCTGGGAGTAACATAACTGGAATTTGTAATGATGAGACAGTCTTTGCGAAGGATAAG
GTTACTTGTGTTGGGCATATCATTGGTGCTGTGGTTGCTGACACCCCGGAACACACACAG
AGAGCTGCCCAAGGGGTGAAAATCACCTATGAAGAACTACCAGCCATTATCACAATTGAG
GATGCTATAAAGAACAACTCCTTTTATGGACCTGAGCTGAAGATCGAGAAAGGGGACCTA
AAGAAGGGGTTTTCCGAAGCAGATAATGTTGTGTCAGGGGAGATATACATCGGTGGCCAA
GAGCACTTCTACCTGGAGACTCACTGCACCATTGCTGTTCCAAAAGGCGAGGCAGGGGAG
ATGGAGCTCTTTGTGTCTACACAGAACACCATGAAGACCCAGAGCTTTGTTGCAAAAATG
TTGGGGGTTCCAGCAAACCGGATTGTGGTTCGAGTGAAGAGAATGGGAGGAGGCTTTGGA
GGCAAGGAGACCCGGAGCACTGTGGTGTCCACGGCAGTGGCCCTGGCTGCATATAAGACC
GGCCGCCCTGTGCGATGCATGCTGGACCGTGATGAGGACATGCTGATAACTGGTGGCAGA
CATCCCTTCCTGGCCAGATACAAGGTTGGCTTCATGAAGACTGGGACAGTTGTGGCTCTT
GAGGTGGACCACTTCAGCAATGTGGGGAACACCCAGGATCTCTCTCAGAGTATTATGGAA
CGAGCTTTATTCCACATGGACAACTGCTATAAAATCCCCAACATCCGGGGCACTGGGCGG
CTGTGCAAAACCAACCTTCCCTCCAACACGGCCTTCCGGGGCTTTGGGGGGCCCCAGGGG
ATGCTCATTGCCGAGTGCTGGATGAGTGAAGTTGCAGTGACCTGTGGGATGCCTGCAGAG
GAGGTGCGGAGAAAAAACCTGTACAAAGAAGGGGACCTGACACACTTCAACCAGAAGCTT
GAGGGTTTCACCTTGCCCAGATGCTGGGAAGAATGCCTAGCAAGCTCTCAGTATCATGCT
CGGAAGAGTGAGGTTGACAAGTTCAACAAGGAGAATTGTTGGAAAAAGAGAGGATTGTGC
ATAATTCCCACCAAGTTTGGAATAAGCTTCACAGTTCCTTTTCTGAATCAGGCAGGAGCC
CTACTTCATGTGTACACAGATGGCTCTGTGCTGCTGACCCACGGGGGGACTGAGATGGGC
CAAGGCCTTCATACCAAAATGGTCCAGGTGGCCAGTAGAGCTCTGAAAATCCCCACCTCT
AAGATTTATATCAGCGAGACAAGCACTAACACTGTGCCCAACACCTCTCCCACGGCTGCC
TCTGTCAGCGCTGACCTCAATGGACAGGCCGTCTATGCGGCTTGTCAGACCATCTTGAAA
AGGCTGGAACCCTACAAGAAGAAGAATCCCAGTGGCTCCTGGGAAGACTGGGTCACAGCT
GCCTACATGGACACAGTGAGCTTGTCTGCCACTGGGTTTTATAGAACACCCAATCTGGGC
TACAGCTTTGAGACTAACTCAGGGAACCCCTTCCACTACTTCAGCTATGGGGTGGCTTGC
TCTGAAGTAGAAATCGACTGCCTAACAGGAGATCATAAGAACCTCCGCACAGATATTGTC
ATGGATGTTGGCTCCAGTCTAAACCCTGCCATTGATATTGGACAGGTGGAAGGGGCATTT
GTCCAGGGCCTTGGCCTCTTCACCCTAGAGGAGCTACACTATTCCCCCGAGGGGAGCCTG
CACACCCGTGGCCCTAGCACCTACAAGATCCCGGCATTTGGCAGCATCCCCATTGAGTTC
AGGGTGTCCCTGCTCCGCGACTGCCCCAACAAGAAGGCCATCTATGCATCGAAGGCTGTT
GGAGAGCCGCCCCTCTTCCTGGCTGCTTCTATCTTCTTTGCCATCAAAGATGCCATCCGT
GCAGCTCGAGCTCAGCACACAGGTAATAACGTGAAGGAACTCTTCCGGCTAGACAGCCCT
GCCACCCCGGAGAAGATCCGCAATGCCTGCGTGGACAAGTTCACCACCCTGTGTGTCACT
GGTGTCCCAGAAAACTGCAAACCCTGGTCTGTGAGGGTCTAA
|
| Protein Properties |
|---|
| Number of Residues
| 1333 |
| Molecular Weight
| 146422.99 |
| Theoretical pI
| 7.663 |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
>Xanthine dehydrogenase/oxidase
MTADKLVFFVNGRKVVEKNADPETTLLAYLRRKLGLSGTKLGCGEGGCGACTVMLSKYDR
LQNKIVHFSANACLAPICSLHHVAVTTVEGIGSTKTRLHPVQERIAKSHGSQCGFCTPGI
VMSMYTLLRNQPEPTMEEIENAFQGNLCRCTGYRPILQGFRTFARDGGCCGGDGNNPNCC
MNQKKDHSVSLSPSLFKPEEFTPLDPTQEPIFPPELLRLKDTPRKQLRFEGERVTWIQAS
TLKELLDLKAQHPDAKLVVGNTEIGIEMKFKNMLFPMIVCPAWIPELNSVEHGPDGISFG
AACPLSIVEKTLVDAVAKLPAQKTEVFRGVLEQLRWFAGKQVKSVASVGGNIITASPISD
LNPVFMASGAKLTLVSRGTRRTVQMDHTFFPGYRKTLLSPEEILLSIEIPYSREGEYFSA
FKQASRREDDIAKVTSGMRVLFKPGTTEVQELALCYGGMANRTISALKTTQRQLSKLWKE
ELLQDVCAGLAEELHLPPDAPGGMVDFRCTLTLSFFFKFYLTVLQKLGQENLEDKCGKLD
PTFASATLLFQKDPPADVQLFQEVPKGQSEEDMVGRPLPHLAADMQASGEAVYCDDIPRY
ENELSLRLVTSTRAHAKIKSIDTSEAKKVPGFVCFISADDVPGSNITGICNDETVFAKDK
VTCVGHIIGAVVADTPEHTQRAAQGVKITYEELPAIITIEDAIKNNSFYGPELKIEKGDL
KKGFSEADNVVSGEIYIGGQEHFYLETHCTIAVPKGEAGEMELFVSTQNTMKTQSFVAKM
LGVPANRIVVRVKRMGGGFGGKETRSTVVSTAVALAAYKTGRPVRCMLDRDEDMLITGGR
HPFLARYKVGFMKTGTVVALEVDHFSNVGNTQDLSQSIMERALFHMDNCYKIPNIRGTGR
LCKTNLPSNTAFRGFGGPQGMLIAECWMSEVAVTCGMPAEEVRRKNLYKEGDLTHFNQKL
EGFTLPRCWEECLASSQYHARKSEVDKFNKENCWKKRGLCIIPTKFGISFTVPFLNQAGA
LLHVYTDGSVLLTHGGTEMGQGLHTKMVQVASRALKIPTSKIYISETSTNTVPNTSPTAA
SVSADLNGQAVYAACQTILKRLEPYKKKNPSGSWEDWVTAAYMDTVSLSATGFYRTPNLG
YSFETNSGNPFHYFSYGVACSEVEIDCLTGDHKNLRTDIVMDVGSSLNPAIDIGQVEGAF
VQGLGLFTLEELHYSPEGSLHTRGPSTYKIPAFGSIPIEFRVSLLRDCPNKKAIYASKAV
GEPPLFLAASIFFAIKDAIRAARAQHTGNNVKELFRLDSPATPEKIRNACVDKFTTLCVT
GVPENCKPWSVRV
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| P47989 |
| UniProtKB/Swiss-Prot Entry Name
| XDH_HUMAN |
| PDB IDs
|
|
| GenBank Gene ID
| D11456 |
| GeneCard ID
| XDH |
| GenAtlas ID
| XDH |
| HGNC ID
| HGNC:12805 |
| References |
|---|
| General References
| - Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
- Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
- Ichida K, Amaya Y, Noda K, Minoshima S, Hosoya T, Sakai O, Shimizu N, Nishino T: Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene. Gene. 1993 Nov 15;133(2):279-84. [PubMed:8224915 ]
- Xu P, Huecksteadt TP, Harrison R, Hoidal JR: Molecular cloning, tissue expression of human xanthine dehydrogenase. Biochem Biophys Res Commun. 1994 Mar 15;199(2):998-1004. [PubMed:8135849 ]
- Xu P, Huecksteadt TP, Harrison R, Hoidal JR: Molecular cloning, tissue expression of human xanthine dehydrogenase. Biochem Biophys Res Commun. 1995 Oct 4;215(1):429. [PubMed:7575623 ]
- Saksela M, Raivio KO: Cloning and expression in vitro of human xanthine dehydrogenase/oxidase. Biochem J. 1996 Apr 1;315 ( Pt 1):235-9. [PubMed:8670112 ]
- Ichida K, Amaya Y, Kamatani N, Nishino T, Hosoya T, Sakai O: Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria. J Clin Invest. 1997 May 15;99(10):2391-7. [PubMed:9153281 ]
- Levartovsky D, Lagziel A, Sperling O, Liberman U, Yaron M, Hosoya T, Ichida K, Peretz H: XDH gene mutation is the underlying cause of classical xanthinuria: a second report. Kidney Int. 2000 Jun;57(6):2215-20. [PubMed:10844591 ]
- Picariello G, Ferranti P, Mamone G, Roepstorff P, Addeo F: Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry. Proteomics. 2008 Sep;8(18):3833-47. doi: 10.1002/pmic.200701057. [PubMed:18780401 ]
- Yamaguchi Y, Matsumura T, Ichida K, Okamoto K, Nishino T: Human xanthine oxidase changes its substrate specificity to aldehyde oxidase type upon mutation of amino acid residues in the active site: roles of active site residues in binding and activation of purine substrate. J Biochem. 2007 Apr;141(4):513-24. Epub 2007 Feb 14. [PubMed:17301077 ]
- Sakamoto N, Yamamoto T, Moriwaki Y, Teranishi T, Toyoda M, Onishi Y, Kuroda S, Sakaguchi K, Fujisawa T, Maeda M, Hada T: Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria. Hum Genet. 2001 Apr;108(4):279-83. [PubMed:11379872 ]
- Gok F, Ichida K, Topaloglu R: Mutational analysis of the xanthine dehydrogenase gene in a Turkish family with autosomal recessive classical xanthinuria. Nephrol Dial Transplant. 2003 Nov;18(11):2278-83. [PubMed:14551354 ]
|
