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Reviewed, UniProtKB/Swiss-Prot P47989 (XDH_HUMAN)

Last modified June 16, 2009. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Xanthine dehydrogenase/oxidase
Including the following 2 domains:
    1- Recommended name:
            Xanthine dehydrogenase
                Short name=XD
              EC=1.17.1.4
    2- Recommended name:
            Xanthine oxidase
                Short name=XO
              EC=1.17.3.2
        Alternative name(s):
            Xanthine oxidoreductase
Gene names
Name: XDH
Synonyms: XDHA
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1333 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

This enzyme can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups.

Catalytic activity

Xanthine + NAD+ + H2O = urate + NADH.

Hypoxanthine + NAD+ + H2O = xanthine + NADH.

Xanthine + H2O + O2 = urate + H2O2.

Cofactor

Binds 2 2Fe-2S clusters.

FAD.

Molybdopterin.

Subunit structure

Homodimer. Interacts with BTN1A1 By similarity.

Subcellular location

Peroxisome.

Involvement in 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. Ref.8 Ref.9 Ref.11 Ref.12

May contribute to adult respiratory stress syndrome (ARDS) and may potentiate influenza infection through an oxygen metabolite-dependent mechanism.

Sequence similarities

Belongs to the xanthine dehydrogenase family.

Contains 1 2Fe-2S ferredoxin-type domain.

Contains 1 FAD-binding PCMH-type domain.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 13331332Xanthine dehydrogenase/oxidase
PRO_0000166084

Regions

Domain4 – 91882Fe-2S ferredoxin-type
Domain229 – 414186FAD-binding PCMH-type

Sites

Metal binding431Iron-sulfur (2Fe-2S) By similarity
Metal binding481Iron-sulfur (2Fe-2S) By similarity
Metal binding511Iron-sulfur (2Fe-2S) By similarity

Amino acid modifications

Modified residue2221Phosphothreonine Ref.7
Glycosylation10741N-linked (GlcNAc...) Ref.10

Natural variations

Natural variant1331E → K: dbSNP rs45447191. Ref.6
VAR_023976
Natural variant1491R → C in XU1. Ref.11
VAR_045900
Natural variant1721G → R: dbSNP rs45523133. Ref.6 Ref.3
VAR_023977
Natural variant2351T → M: dbSNP rs45469499. Ref.6
VAR_023978
Natural variant3951K → M: dbSNP rs34929837. Ref.6
VAR_023979
Natural variant5551P → S: dbSNP rs45577338. Ref.6
VAR_023980
Natural variant5841D → A: dbSNP rs45491693. Ref.6
VAR_023981
Natural variant6071R → Q: dbSNP rs45442092. Ref.6
VAR_023982
Natural variant6171K → N: dbSNP rs45442398. Ref.6
VAR_023983
Natural variant6231T → I: dbSNP rs45448694. Ref.6
VAR_023984
Natural variant6461I → V: dbSNP rs17323225. Ref.6
VAR_023985
Natural variant7031I → V: dbSNP rs17011368. Ref.6
VAR_023986
Natural variant7631L → F in a breast cancer sample; somatic mutation. Ref.13
VAR_035899
Natural variant7911R → G in a breast cancer sample; somatic mutation. Ref.13
VAR_035900
Natural variant9101T → M Ref.6
VAR_023987
Natural variant10911V → L: dbSNP rs45619033. Ref.6
VAR_023988
Natural variant11091N → T: dbSNP rs45547640. Ref.6
VAR_023989
Natural variant11501P → R: dbSNP rs1042036. Ref.8
VAR_045901
Natural variant11761R → C: dbSNP rs45624433. Ref.6
VAR_023990
Natural variant12961R → W: dbSNP rs45564939. Ref.6
VAR_023991

Experimental info

Sequence conflict2591V → E in AAA75287. Ref.3
Sequence conflict333 – 3342QL → HV in AAA75287. Ref.3
Sequence conflict4951H → Q in AAA75287. Ref.3
Sequence conflict515 – 5173FFF → LLL in AAA75287. Ref.3

Secondary structure

1 ............................................................................................................................................................................................................... 1333
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P47989-1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 806FF2C7413F84C5

FASTA1,333146,424
        10         20         30         40         50         60 
MTADKLVFFV NGRKVVEKNA DPETTLLAYL RRKLGLSGTK LGCGEGGCGA CTVMLSKYDR 

        70         80         90        100        110        120 
LQNKIVHFSA NACLAPICSL HHVAVTTVEG IGSTKTRLHP VQERIAKSHG SQCGFCTPGI 

       130        140        150        160        170        180 
VMSMYTLLRN QPEPTMEEIE NAFQGNLCRC TGYRPILQGF RTFARDGGCC GGDGNNPNCC 

       190        200        210        220        230        240 
MNQKKDHSVS LSPSLFKPEE FTPLDPTQEP IFPPELLRLK DTPRKQLRFE GERVTWIQAS 

       250        260        270        280        290        300 
TLKELLDLKA QHPDAKLVVG NTEIGIEMKF KNMLFPMIVC PAWIPELNSV EHGPDGISFG 

       310        320        330        340        350        360 
AACPLSIVEK TLVDAVAKLP AQKTEVFRGV LEQLRWFAGK QVKSVASVGG NIITASPISD 

       370        380        390        400        410        420 
LNPVFMASGA KLTLVSRGTR RTVQMDHTFF PGYRKTLLSP EEILLSIEIP YSREGEYFSA 

       430        440        450        460        470        480 
FKQASRREDD IAKVTSGMRV LFKPGTTEVQ ELALCYGGMA NRTISALKTT QRQLSKLWKE 

       490        500        510        520        530        540 
ELLQDVCAGL AEELHLPPDA PGGMVDFRCT LTLSFFFKFY LTVLQKLGQE NLEDKCGKLD 

       550        560        570        580        590        600 
PTFASATLLF QKDPPADVQL FQEVPKGQSE EDMVGRPLPH LAADMQASGE AVYCDDIPRY 

       610        620        630        640        650        660 
ENELSLRLVT STRAHAKIKS IDTSEAKKVP GFVCFISADD VPGSNITGIC NDETVFAKDK 

       670        680        690        700        710        720 
VTCVGHIIGA VVADTPEHTQ RAAQGVKITY EELPAIITIE DAIKNNSFYG PELKIEKGDL 

       730        740        750        760        770        780 
KKGFSEADNV VSGEIYIGGQ EHFYLETHCT IAVPKGEAGE MELFVSTQNT MKTQSFVAKM 

       790        800        810        820        830        840 
LGVPANRIVV RVKRMGGGFG GKETRSTVVS TAVALAAYKT GRPVRCMLDR DEDMLITGGR 

       850        860        870        880        890        900 
HPFLARYKVG FMKTGTVVAL EVDHFSNVGN TQDLSQSIME RALFHMDNCY KIPNIRGTGR 

       910        920        930        940        950        960 
LCKTNLPSNT AFRGFGGPQG MLIAECWMSE VAVTCGMPAE EVRRKNLYKE GDLTHFNQKL 

       970        980        990       1000       1010       1020 
EGFTLPRCWE ECLASSQYHA RKSEVDKFNK ENCWKKRGLC IIPTKFGISF TVPFLNQAGA 

      1030       1040       1050       1060       1070       1080 
LLHVYTDGSV LLTHGGTEMG QGLHTKMVQV ASRALKIPTS KIYISETSTN TVPNTSPTAA 

      1090       1100       1110       1120       1130       1140 
SVSADLNGQA VYAACQTILK RLEPYKKKNP SGSWEDWVTA AYMDTVSLSA TGFYRTPNLG 

      1150       1160       1170       1180       1190       1200 
YSFETNSGNP FHYFSYGVAC SEVEIDCLTG DHKNLRTDIV MDVGSSLNPA IDIGQVEGAF 

      1210       1220       1230       1240       1250       1260 
VQGLGLFTLE ELHYSPEGSL HTRGPSTYKI PAFGSIPIEF RVSLLRDCPN KKAIYASKAV 

      1270       1280       1290       1300       1310       1320 
GEPPLFLAAS IFFAIKDAIR AARAQHTGNN VKELFRLDSP ATPEKIRNAC VDKFTTLCVT 

      1330 
GVPENCKPWS VRV

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References

« Hide 'large scale' references
[1]"Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase): structural analysis of the protein and chromosomal location of the gene."
Ichida K., Amaya Y., Noda K., Minoshima S., Hosoya T., Sakai O., Shimizu N., Nishino T.
Gene 133:279-284(1993) [PubMed: 8224915] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]Ichida K.
Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 191; 231 AND 1150.
[3]"Molecular cloning, tissue expression of human xanthine dehydrogenase."
Xu P., Huecksteadt T.P., Harrison R., Hoidal J.R.
Biochem. Biophys. Res. Commun. 199:998-1004(1994) [PubMed: 8135849] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-172.
Tissue: Liver.
[4]Erratum
Xu P., Huecksteadt T.P., Harrison R., Hoidal J.R.
Biochem. Biophys. Res. Commun. 215:429-429(1995) [PubMed: 7575623] [Abstract]
[5]"Cloning and expression in vitro of human xanthine dehydrogenase/oxidase."
Saksela M., Raivio K.O.
Biochem. J. 315:235-239(1996) [PubMed: 8670112] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Small intestine.
[6]NIEHS SNPs program
Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-133; ARG-172; MET-235; MET-395; SER-555; ALA-584; GLN-607; ASN-617; ILE-623; VAL-646; VAL-703; MET-910; LEU-1091; THR-1109; CYS-1176 AND TRP-1296.
[7]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-222, MASS SPECTROMETRY.
Tissue: Epithelium.
[8]"Identification of two mutations in human xanthine dehydrogenase gene responsible for classical type I xanthinuria."
Ichida K., Amaya Y., Kamatani N., Nishino T., Hosoya T., Sakai O.
J. Clin. Invest. 99:2391-2397(1997) [PubMed: 9153281] [Abstract]
Cited for: INVOLVEMENT IN XU1, VARIANT ARG-1150.
[9]"XDH gene mutation is the underlying cause of classical xanthinuria: a second report."
Levartovsky D., Lagziel A., Sperling O., Liberman U., Yaron M., Hosoya T., Ichida K., Peretz H.
Kidney Int. 57:2215-2220(2000) [PubMed: 10844591] [Abstract]
Cited for: INVOLVEMENT IN XU1.
[10]"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry."
Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.
Proteomics 8:3833-3847(2008) [PubMed: 18780401] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1074, MASS SPECTROMETRY.
Tissue: Milk.
[11]"Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria."
Sakamoto N., Yamamoto T., Moriwaki Y., Teranishi T., Toyoda M., Onishi Y., Kuroda S., Sakaguchi K., Fujisawa T., Maeda M., Hada T.
Hum. Genet. 108:279-283(2001) [PubMed: 11379872] [Abstract]
Cited for: VARIANT XU1 CYS-149.
[12]"Mutational analysis of the xanthine dehydrogenase gene in a Turkish family with autosomal recessive classical xanthinuria."
Gok F., Ichida K., Topaloglu R.
Nephrol. Dial. Transplant. 18:2278-2283(2003) [PubMed: 14551354] [Abstract]
Cited for: INVOLVEMENT IN XU1.
[13]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed: 16959974] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-763 AND GLY-791.
+Additional computationally mapped references.

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Cross-references

Sequence databases

D11456 mRNA. Translation: BAA02013.2.
U06117 mRNA. Translation: AAA75287.1.
U39487 mRNA. Translation: AAB08399.1.
DQ089481 Genomic DNA. Translation: AAY68219.1.
IPIIPI00244391.
PIRXOHUDH. S66573.
RefSeqNP_000370.2.
UniGeneHs.250

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2CKJX-ray3.59A/B/C/D2-1332[»]
2E1QX-ray2.60A/B/C/D2-1332[»]
ModBaseSearch...

PTM databases

PhosphoSiteP47989.

Proteomic databases

PeptideAtlasP47989.
PRIDEP47989.

Genome annotation databases

EnsemblENSG00000158125. Homo sapiens. [Contig view]
GeneID7498.
KEGGhsa:7498.
NMPDRfig|9606.3.peg.17717.

Organism-specific databases

GeneCardsGC02M031470.
H-InvDBHIX0023973.
HIX0030009.
HGNCHGNC:12805. XDH.
HPACAB009518.
MIM278300. phenotype.
607633. gene.
Orphanet3467. Xanthinuria.
PharmGKBPA37404.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP47989.
HOVERGENP47989.
OMAP47989. LLFQKDP.

Enzyme and pathway databases

BRENDA1.17.1.4. 247.
1.17.3.2. 247.
ReactomeREACT_1698. Nucleotide metabolism.

Gene expression databases

ArrayExpressP47989.
BgeeP47989.
CleanExHS_XDH.
GermOnlineENSG00000158125. Homo sapiens.

Family and domain databases

InterProIPR002888. 2Fe-2S_bd.
IPR006058. 2Fe2S_fd_BS.
IPR000674. Ald_Oxase/Xan_DH_a/b.
IPR016208. Ald_Oxase/xanthine_DH.
IPR008274. AldOxase/xan_DH_Mopterin-bd.
IPR012675. b-grasp_ferredoxin-like.
IPR005107. CO_DH_flav_C.
IPR016169. CO_DH_flavot_FAD-bd_sub2.
IPR016166. FAD-bd_2.
IPR016167. FAD-bd_2_sub1.
IPR001041. Ferredoxin.
IPR002346. Mopterin_DH_FAD-bd.
IPR000572. OxRdtase_Mopterin-bd.
IPR014309. Xanthine_DH_Mopterin-bd_su.
IPR014307. Xanthine_DH_ssu.
[Graphical view]
Gene3DG3DSA:3.30.365.10. Ald_xan_DH_mo_bd. 2 hits.
G3DSA:3.90.1170.50. Aldxan_DH_hamm. 1 hit.
G3DSA:3.30.390.50. CO_DH_flav_C. 1 hit.
G3DSA:3.30.465.10. CO_DH_flavoprot_FAD-bd_sub2. 1 hit.
G3DSA:3.30.43.10. FAD-binding_2_sub1. 1 hit.
G3DSA:3.10.20.30. Ferredoxin_fold. 1 hit.
PfamPF01315. Ald_Xan_dh_C. 1 hit.
PF02738. Ald_Xan_dh_C2. 1 hit.
PF03450. CO_deh_flav_C. 1 hit.
PF00941. FAD_binding_5. 1 hit.
PF00111. Fer2. 1 hit.
PF01799. Fer2_2. 1 hit.
[Graphical view]
PIRSFPIRSF000127. Xanthine_DH. 1 hit.
ProDomPD186071. 2Fe-2S_bind. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsTIGR02963. xanthine_xdhA. 1 hit.
TIGR02965. xanthine_xdhB. 1 hit.
PROSITEPS00197. 2FE2S_FER_1. 1 hit.
PS51085. 2FE2S_FER_2. 1 hit.
PS51387. FAD_PCMH. 1 hit.
PS00559. MOLYBDOPTERIN_EUK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00437. Allopurinol.
DB01136. Carvedilol.
DB00694. Daunorubicin.
DB00746. Deferoxamine.
DB01189. Desflurane.
DB00170. Menadione.
DB01033. Mercaptopurine.
DB00563. Methotrexate.
DB00157. NADH.
DB00336. Nitrofurazone.
DB01113. Papaverine.
DB01168. Procarbazine.
DB00339. Pyrazinamide.
DB00049. Rasburicase.
DB00127. Spermine.
DB00831. Trifluoperazine.
DB00163. Vitamin E.
NextBio29364.
SOURCESearch...

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Entry information

Entry nameXDH_HUMAN
AccessionPrimary (citable) accession number: P47989
Secondary accession number(s): Q16681, Q16712, Q4PJ16
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: June 16, 2009
This is version 99 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents