XDH_HUMAN
ID XDH_HUMAN Reviewed; 1333 AA.
AC P47989; Q16681; Q16712; Q4PJ16;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Xanthine dehydrogenase/oxidase;
DE Includes:
DE RecName: Full=Xanthine dehydrogenase;
DE Short=XD;
DE EC=1.17.1.4 {ECO:0000269|PubMed:8670112};
DE Includes:
DE RecName: Full=Xanthine oxidase;
DE Short=XO;
DE EC=1.17.3.2 {ECO:0000269|PubMed:17301077, ECO:0000269|PubMed:8670112};
DE AltName: Full=Xanthine oxidoreductase;
DE Short=XOR;
GN Name=XDH; Synonyms=XDHA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8224915; DOI=10.1016/0378-1119(93)90652-j;
RA Ichida K., Amaya Y., Noda K., Minoshima S., Hosoya T., Sakai O.,
RA Shimizu N., Nishino T.;
RT "Cloning of the cDNA encoding human xanthine dehydrogenase (oxidase):
RT structural analysis of the protein and chromosomal location of the gene.";
RL Gene 133:279-284(1993).
RN [2]
RP SEQUENCE REVISION TO 191; 231 AND 1150.
RA Ichida K.;
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-172.
RC TISSUE=Liver;
RX PubMed=8135849; DOI=10.1006/bbrc.1994.1328;
RA Xu P., Huecksteadt T.P., Harrison R., Hoidal J.R.;
RT "Molecular cloning, tissue expression of human xanthine dehydrogenase.";
RL Biochem. Biophys. Res. Commun. 199:998-1004(1994).
RN [4]
RP ERRATUM OF PUBMED:8135849.
RX PubMed=7575623; DOI=10.1006/bbrc.1995.2482;
RA Xu P., Huecksteadt T.P., Harrison R., Hoidal J.R.;
RL Biochem. Biophys. Res. Commun. 215:429-429(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RC TISSUE=Small intestine;
RX PubMed=8670112; DOI=10.1042/bj3150235;
RA Saksela M., Raivio K.O.;
RT "Cloning and expression in vitro of human xanthine dehydrogenase/oxidase.";
RL Biochem. J. 315:235-239(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-133; ARG-172; MET-235;
RP MET-395; SER-555; ALA-584; GLN-607; ASN-617; ILE-623; VAL-646; VAL-703;
RP MET-910; LEU-1091; THR-1109; CYS-1176 AND TRP-1296.
RG NIEHS SNPs program;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INVOLVEMENT IN XAN1, AND VARIANT ARG-1150.
RX PubMed=9153281; DOI=10.1172/jci119421;
RA Ichida K., Amaya Y., Kamatani N., Nishino T., Hosoya T., Sakai O.;
RT "Identification of two mutations in human xanthine dehydrogenase gene
RT responsible for classical type I xanthinuria.";
RL J. Clin. Invest. 99:2391-2397(1997).
RN [8]
RP INVOLVEMENT IN XAN1.
RX PubMed=10844591; DOI=10.1046/j.1523-1755.2000.00082.x;
RA Levartovsky D., Lagziel A., Sperling O., Liberman U., Yaron M., Hosoya T.,
RA Ichida K., Peretz H.;
RT "XDH gene mutation is the underlying cause of classical xanthinuria: a
RT second report.";
RL Kidney Int. 57:2215-2220(2000).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF MUTANT VAL-803 IN COMPLEX WITH
RP FAD; 2FE-2S IRON-SULFUR CENTERS; SALICYLATE; MOLYBDOPTERIN AND CALCIUM
RP IONS, COFACTOR, CATALYTIC ACTIVITY, FUNCTION, AND SUBUNIT.
RX PubMed=17301077; DOI=10.1093/jb/mvm053;
RA Yamaguchi Y., Matsumura T., Ichida K., Okamoto K., Nishino T.;
RT "Human xanthine oxidase changes its substrate specificity to aldehyde
RT oxidase type upon mutation of amino acid residues in the active site: roles
RT of active site residues in binding and activation of purine substrate.";
RL J. Biochem. 141:513-524(2007).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (3.59 ANGSTROMS) IN COMPLEX WITH FAD AND IRON-SULFUR
RP CENTERS, TISSUE SPECIFICITY, ACTIVITY REGULATION, AND DISULFIDE BONDS.
RA Pearson A.R., Godber B.L.J., Eisenthal R., Taylor G.L., Harrison R.;
RT "Human milk xanthine dehydrogenase is incompletely converted to the oxidase
RT form in the absence of proteolysis. A structural explanation.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [13]
RP VARIANT XAN1 CYS-149.
RX PubMed=11379872; DOI=10.1007/s004390100477;
RA Sakamoto N., Yamamoto T., Moriwaki Y., Teranishi T., Toyoda M., Onishi Y.,
RA Kuroda S., Sakaguchi K., Fujisawa T., Maeda M., Hada T.;
RT "Identification of a new point mutation in the human xanthine dehydrogenase
RT gene responsible for a case of classical type I xanthinuria.";
RL Hum. Genet. 108:279-283(2001).
RN [14]
RP INVOLVEMENT IN XAN1.
RX PubMed=14551354; DOI=10.1093/ndt/gfg385;
RA Gok F., Ichida K., Topaloglu R.;
RT "Mutational analysis of the xanthine dehydrogenase gene in a Turkish family
RT with autosomal recessive classical xanthinuria.";
RL Nephrol. Dial. Transplant. 18:2278-2283(2003).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-763 AND GLY-791.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Key enzyme in purine degradation. Catalyzes the oxidation of
CC hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric
CC acid. Contributes to the generation of reactive oxygen species. Has
CC also low oxidase activity towards aldehydes (in vitro).
CC {ECO:0000269|PubMed:17301077}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + xanthine = H(+) + NADH + urate;
CC Xref=Rhea:RHEA:16669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17712, ChEBI:CHEBI:17775, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.17.1.4;
CC Evidence={ECO:0000269|PubMed:8670112};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hypoxanthine + NAD(+) = H(+) + NADH + xanthine;
CC Xref=Rhea:RHEA:24670, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17368, ChEBI:CHEBI:17712, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.17.1.4;
CC Evidence={ECO:0000269|PubMed:8670112};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O2 + xanthine = H2O2 + urate; Xref=Rhea:RHEA:21132,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:17712, ChEBI:CHEBI:17775; EC=1.17.3.2;
CC Evidence={ECO:0000269|PubMed:17301077, ECO:0000269|PubMed:8670112};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:17301077};
CC Note=Binds 2 [2Fe-2S] clusters. {ECO:0000269|PubMed:17301077};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:17301077};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000269|PubMed:17301077};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000269|PubMed:17301077};
CC -!- ACTIVITY REGULATION: Can be converted from the dehydrogenase form (D)
CC to the oxidase form (O) irreversibly by proteolysis or reversibly
CC through the oxidation of sulfhydryl groups. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with BTN1A1 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P47989; Q9Y3R0-3: GRIP1; NbExp=3; IntAct=EBI-2557331, EBI-12193965;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Peroxisome
CC {ECO:0000250}. Secreted.
CC -!- TISSUE SPECIFICITY: Detected in milk (at protein level).
CC {ECO:0000269|Ref.12}.
CC -!- PTM: Subject to partial proteolysis; this alters the enzyme from the
CC dehydrogenase form (D) to the oxidase form (O). {ECO:0000250}.
CC -!- PTM: Contains sulfhydryl groups that are easily oxidized (in vitro);
CC this alters the enzyme from the dehydrogenase form (D) to the oxidase
CC form (O). {ECO:0000250}.
CC -!- DISEASE: Xanthinuria 1 (XAN1) [MIM:278300]: A disorder characterized by
CC excretion of very large amounts of xanthine in the urine and a tendency
CC to form xanthine stones. Uric acid is strikingly diminished in serum
CC and urine. XAN1 is due to isolated xanthine dehydrogenase deficiency.
CC Patients can metabolize allopurinol. {ECO:0000269|PubMed:10844591,
CC ECO:0000269|PubMed:11379872, ECO:0000269|PubMed:14551354,
CC ECO:0000269|PubMed:9153281}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/xdh/";
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DR EMBL; D11456; BAA02013.2; -; mRNA.
DR EMBL; U06117; AAA75287.1; -; mRNA.
DR EMBL; U39487; AAB08399.1; -; mRNA.
DR EMBL; DQ089481; AAY68219.1; -; Genomic_DNA.
DR CCDS; CCDS1775.1; -.
DR PIR; S66573; XOHUDH.
DR RefSeq; NP_000370.2; NM_000379.3.
DR PDB; 2CKJ; X-ray; 3.59 A; A/B/C/D=2-1333.
DR PDB; 2E1Q; X-ray; 2.60 A; A/B/C/D=1-1333.
DR PDBsum; 2CKJ; -.
DR PDBsum; 2E1Q; -.
DR AlphaFoldDB; P47989; -.
DR SMR; P47989; -.
DR BioGRID; 113335; 18.
DR CORUM; P47989; -.
DR IntAct; P47989; 4.
DR STRING; 9606.ENSP00000368727; -.
DR BindingDB; P47989; -.
DR ChEMBL; CHEMBL1929; -.
DR DrugBank; DB00640; Adenosine.
DR DrugBank; DB00041; Aldesleukin.
DR DrugBank; DB00437; Allopurinol.
DR DrugBank; DB00993; Azathioprine.
DR DrugBank; DB00958; Carboplatin.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB00856; Chlorphenesin.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB00746; Deferoxamine.
DR DrugBank; DB03328; Dioxo(sulfanyl)molybdenum.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB03516; Eniluracil.
DR DrugBank; DB12466; Favipiravir.
DR DrugBank; DB04854; Febuxostat.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB04335; Inosine.
DR DrugBank; DB01020; Isosorbide mononitrate.
DR DrugBank; DB00583; Levocarnitine.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB01033; Mercaptopurine.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03841; Niraxostat.
DR DrugBank; DB00336; Nitrofural.
DR DrugBank; DB05262; Oxypurinol.
DR DrugBank; DB06478; Porfiromycin.
DR DrugBank; DB01168; Procarbazine.
DR DrugBank; DB00339; Pyrazinamide.
DR DrugBank; DB00127; Spermine.
DR DrugBank; DB01685; Topiroxostat.
DR DrugBank; DB00831; Trifluoperazine.
DR DrugCentral; P47989; -.
DR GuidetoPHARMACOLOGY; 2646; -.
DR iPTMnet; P47989; -.
DR PhosphoSitePlus; P47989; -.
DR BioMuta; XDH; -.
DR DMDM; 2506326; -.
DR EPD; P47989; -.
DR jPOST; P47989; -.
DR MassIVE; P47989; -.
DR MaxQB; P47989; -.
DR PaxDb; P47989; -.
DR PeptideAtlas; P47989; -.
DR PRIDE; P47989; -.
DR ProteomicsDB; 55829; -.
DR Antibodypedia; 4018; 273 antibodies from 35 providers.
DR DNASU; 7498; -.
DR Ensembl; ENST00000379416.4; ENSP00000368727.3; ENSG00000158125.10.
DR GeneID; 7498; -.
DR KEGG; hsa:7498; -.
DR MANE-Select; ENST00000379416.4; ENSP00000368727.3; NM_000379.4; NP_000370.2.
DR UCSC; uc002rnv.2; human.
DR CTD; 7498; -.
DR DisGeNET; 7498; -.
DR GeneCards; XDH; -.
DR HGNC; HGNC:12805; XDH.
DR HPA; ENSG00000158125; Group enriched (breast, intestine, liver).
DR MalaCards; XDH; -.
DR MIM; 278300; phenotype.
DR MIM; 607633; gene.
DR neXtProt; NX_P47989; -.
DR OpenTargets; ENSG00000158125; -.
DR Orphanet; 93601; Xanthinuria type I.
DR PharmGKB; PA37404; -.
DR VEuPathDB; HostDB:ENSG00000158125; -.
DR eggNOG; KOG0430; Eukaryota.
DR GeneTree; ENSGT00950000183114; -.
DR HOGENOM; CLU_001681_1_2_1; -.
DR InParanoid; P47989; -.
DR OMA; DIGYVWG; -.
DR OrthoDB; 48717at2759; -.
DR PhylomeDB; P47989; -.
DR TreeFam; TF353036; -.
DR BioCyc; MetaCyc:HS08270-MON; -.
DR BRENDA; 1.17.1.4; 2681.
DR BRENDA; 1.17.3.2; 2681.
DR PathwayCommons; P47989; -.
DR Reactome; R-HSA-74259; Purine catabolism.
DR Reactome; R-HSA-8851680; Butyrophilin (BTN) family interactions.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR SABIO-RK; P47989; -.
DR SignaLink; P47989; -.
DR BioGRID-ORCS; 7498; 12 hits in 1068 CRISPR screens.
DR ChiTaRS; XDH; human.
DR EvolutionaryTrace; P47989; -.
DR GeneWiki; Xanthine_dehydrogenase; -.
DR GenomeRNAi; 7498; -.
DR Pharos; P47989; Tclin.
DR PRO; PR:P47989; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P47989; protein.
DR Bgee; ENSG00000158125; Expressed in jejunal mucosa and 124 other tissues.
DR Genevisible; P47989; HS.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0070674; F:hypoxanthine dehydrogenase activity; IDA:MGI.
DR GO; GO:0070675; F:hypoxanthine oxidase activity; IEA:Ensembl.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0043546; F:molybdopterin cofactor binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0004854; F:xanthine dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0004855; F:xanthine oxidase activity; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006154; P:adenosine catabolic process; IEA:Ensembl.
DR GO; GO:0000255; P:allantoin metabolic process; IDA:MGI.
DR GO; GO:0006196; P:AMP catabolic process; IDA:MGI.
DR GO; GO:0046059; P:dAMP catabolic process; IEA:Ensembl.
DR GO; GO:0006157; P:deoxyadenosine catabolic process; IEA:Ensembl.
DR GO; GO:0006161; P:deoxyguanosine catabolic process; IEA:Ensembl.
DR GO; GO:0006149; P:deoxyinosine catabolic process; IDA:MGI.
DR GO; GO:0046055; P:dGMP catabolic process; IEA:Ensembl.
DR GO; GO:0046038; P:GMP catabolic process; IEA:Ensembl.
DR GO; GO:0006147; P:guanine catabolic process; IEA:Ensembl.
DR GO; GO:0009114; P:hypoxanthine catabolic process; IDA:MGI.
DR GO; GO:0006204; P:IMP catabolic process; IDA:MGI.
DR GO; GO:0006148; P:inosine catabolic process; IDA:MGI.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IEA:Ensembl.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0045602; P:negative regulation of endothelial cell differentiation; IDA:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IDA:UniProtKB.
DR GO; GO:2001213; P:negative regulation of vasculogenesis; IDA:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB.
DR GO; GO:0009115; P:xanthine catabolic process; IDA:UniProtKB.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR002888; 2Fe-2S-bd.
DR InterPro; IPR036884; 2Fe-2S-bd_dom_sf.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR006058; 2Fe2S_fd_BS.
DR InterPro; IPR000674; Ald_Oxase/Xan_DH_a/b.
DR InterPro; IPR036856; Ald_Oxase/Xan_DH_a/b_sf.
DR InterPro; IPR016208; Ald_Oxase/xanthine_DH.
DR InterPro; IPR008274; AldOxase/xan_DH_Mopterin-bd.
DR InterPro; IPR037165; AldOxase/xan_DH_Mopterin-bd_sf.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR005107; CO_DH_flav_C.
DR InterPro; IPR036683; CO_DH_flav_C_dom_sf.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR002346; Mopterin_DH_FAD-bd.
DR InterPro; IPR022407; OxRdtase_Mopterin_BS.
DR InterPro; IPR014307; Xanthine_DH_ssu.
DR PANTHER; PTHR11908; PTHR11908; 1.
DR Pfam; PF01315; Ald_Xan_dh_C; 1.
DR Pfam; PF02738; Ald_Xan_dh_C2; 1.
DR Pfam; PF03450; CO_deh_flav_C; 1.
DR Pfam; PF00941; FAD_binding_5; 1.
DR Pfam; PF00111; Fer2; 1.
DR Pfam; PF01799; Fer2_2; 1.
DR PIRSF; PIRSF000127; Xanthine_DH; 1.
DR SMART; SM01008; Ald_Xan_dh_C; 1.
DR SMART; SM01092; CO_deh_flav_C; 1.
DR SUPFAM; SSF47741; SSF47741; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR SUPFAM; SSF54665; SSF54665; 1.
DR SUPFAM; SSF55447; SSF55447; 1.
DR SUPFAM; SSF56003; SSF56003; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR TIGRFAMs; TIGR02963; xanthine_xdhA; 1.
DR PROSITE; PS00197; 2FE2S_FER_1; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
DR PROSITE; PS00559; MOLYBDOPTERIN_EUK; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 3D-structure; Cytoplasm; Disease variant; Disulfide bond; FAD;
KW Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum; NAD;
KW Oxidoreductase; Peroxisome; Reference proteome; Secreted.
FT CHAIN 1..1333
FT /note="Xanthine dehydrogenase/oxidase"
FT /id="PRO_0000166084"
FT DOMAIN 4..91
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 229..414
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1262
FT /note="Proton acceptor"
FT BINDING 43
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT BINDING 48
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT BINDING 51
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT BINDING 73
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT BINDING 113
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT BINDING 116
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT BINDING 148
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT BINDING 150
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT BINDING 257..264
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17301077, ECO:0000269|Ref.12"
FT BINDING 337
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17301077, ECO:0000269|Ref.12"
FT BINDING 347..351
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17301077, ECO:0000269|Ref.12"
FT BINDING 360
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17301077, ECO:0000269|Ref.12"
FT BINDING 404
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 422
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17301077, ECO:0000269|Ref.12"
FT BINDING 768
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT BINDING 799
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT BINDING 803
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 881
FT /ligand="substrate"
FT BINDING 913
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT BINDING 915
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 1011
FT /ligand="substrate"
FT BINDING 1080
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT DISULFID 509..1318
FT /note="In oxidase form"
FT /evidence="ECO:0000269|Ref.12"
FT DISULFID 536..993
FT /note="In oxidase form"
FT /evidence="ECO:0000269|Ref.12"
FT VARIANT 133
FT /note="E -> K (in dbSNP:rs45447191)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023976"
FT VARIANT 149
FT /note="R -> C (in XAN1; dbSNP:rs72549369)"
FT /evidence="ECO:0000269|PubMed:11379872"
FT /id="VAR_045900"
FT VARIANT 172
FT /note="G -> R (in dbSNP:rs45523133)"
FT /evidence="ECO:0000269|PubMed:8135849, ECO:0000269|Ref.6"
FT /id="VAR_023977"
FT VARIANT 235
FT /note="T -> M (in dbSNP:rs45469499)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023978"
FT VARIANT 395
FT /note="K -> M (in dbSNP:rs34929837)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023979"
FT VARIANT 555
FT /note="P -> S (in dbSNP:rs45577338)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023980"
FT VARIANT 584
FT /note="D -> A (in dbSNP:rs45491693)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023981"
FT VARIANT 607
FT /note="R -> Q (in dbSNP:rs45442092)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023982"
FT VARIANT 617
FT /note="K -> N (in dbSNP:rs45442398)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023983"
FT VARIANT 623
FT /note="T -> I (in dbSNP:rs45448694)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023984"
FT VARIANT 646
FT /note="I -> V (in dbSNP:rs17323225)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023985"
FT VARIANT 703
FT /note="I -> V (in dbSNP:rs17011368)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023986"
FT VARIANT 763
FT /note="L -> F (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035899"
FT VARIANT 791
FT /note="R -> G (in a breast cancer sample; somatic mutation;
FT dbSNP:rs775646772)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035900"
FT VARIANT 910
FT /note="T -> M (in dbSNP:rs669884)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023987"
FT VARIANT 1091
FT /note="V -> L (in dbSNP:rs45619033)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023988"
FT VARIANT 1109
FT /note="N -> T (in dbSNP:rs45547640)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023989"
FT VARIANT 1150
FT /note="P -> R (in dbSNP:rs1042036)"
FT /evidence="ECO:0000269|PubMed:9153281"
FT /id="VAR_045901"
FT VARIANT 1176
FT /note="R -> C (in dbSNP:rs45624433)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023990"
FT VARIANT 1296
FT /note="R -> W (in dbSNP:rs45564939)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023991"
FT MUTAGEN 803
FT /note="E->V: Strongly decreased activity towards xanthine
FT and hypoxanthine. Increased affinity and activity towards
FT aromatic aldehydes."
FT MUTAGEN 881
FT /note="R->M: Abolishes xanthine oxidase activity."
FT CONFLICT 259
FT /note="V -> E (in Ref. 3; AAA75287)"
FT /evidence="ECO:0000305"
FT CONFLICT 333..334
FT /note="QL -> HV (in Ref. 3; AAA75287)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="H -> Q (in Ref. 3; AAA75287)"
FT /evidence="ECO:0000305"
FT CONFLICT 515..517
FT /note="FFF -> LLL (in Ref. 3; AAA75287)"
FT /evidence="ECO:0000305"
FT STRAND 6..10
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 26..32
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 117..130
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 136..141
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 149..151
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 154..160
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 214..218
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 235..238
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 264..270
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 294..300
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 305..318
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 325..335
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 340..345
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 348..354
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 362..367
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 371..375
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 403..410
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 416..423
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 425..429
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 433..442
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 448..465
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 467..471
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 472..475
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 480..493
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 505..529
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 541..543
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 544..547
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 556..560
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 583..587
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 594..596
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 604..610
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 612..622
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 626..628
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 632..637
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 638..640
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 645..648
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 653..656
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 659..661
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 667..675
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 676..684
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 687..692
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 699..705
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 708..718
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 720..726
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 728..737
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 749..754
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 761..765
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 770..781
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 785..787
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 788..793
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 799..802
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 807..820
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 824..827
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 830..837
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 843..851
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 857..871
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 875..884
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 893..903
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 913..916
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 917..935
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 939..945
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 965..976
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 978..991
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 993..1009
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1013..1015
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1017..1024
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1030..1035
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1039..1041
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1043..1055
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1059..1061
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 1069..1071
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1083..1108
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1114..1123
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1129..1135
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 1143..1146
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1152..1166
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 1167..1169
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1172..1182
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1189..1208
FT /evidence="ECO:0007829|PDB:2E1Q"
FT TURN 1225..1227
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1233..1235
FT /evidence="ECO:0007829|PDB:2E1Q"
FT STRAND 1238..1244
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1254..1256
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1263..1268
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1269..1286
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1303..1309
FT /evidence="ECO:0007829|PDB:2E1Q"
FT HELIX 1315..1317
FT /evidence="ECO:0007829|PDB:2E1Q"
SQ SEQUENCE 1333 AA; 146424 MW; 806FF2C7413F84C5 CRC64;
MTADKLVFFV NGRKVVEKNA DPETTLLAYL RRKLGLSGTK LGCGEGGCGA CTVMLSKYDR
LQNKIVHFSA NACLAPICSL HHVAVTTVEG IGSTKTRLHP VQERIAKSHG SQCGFCTPGI
VMSMYTLLRN QPEPTMEEIE NAFQGNLCRC TGYRPILQGF RTFARDGGCC GGDGNNPNCC
MNQKKDHSVS LSPSLFKPEE FTPLDPTQEP IFPPELLRLK DTPRKQLRFE GERVTWIQAS
TLKELLDLKA QHPDAKLVVG NTEIGIEMKF KNMLFPMIVC PAWIPELNSV EHGPDGISFG
AACPLSIVEK TLVDAVAKLP AQKTEVFRGV LEQLRWFAGK QVKSVASVGG NIITASPISD
LNPVFMASGA KLTLVSRGTR RTVQMDHTFF PGYRKTLLSP EEILLSIEIP YSREGEYFSA
FKQASRREDD IAKVTSGMRV LFKPGTTEVQ ELALCYGGMA NRTISALKTT QRQLSKLWKE
ELLQDVCAGL AEELHLPPDA PGGMVDFRCT LTLSFFFKFY LTVLQKLGQE NLEDKCGKLD
PTFASATLLF QKDPPADVQL FQEVPKGQSE EDMVGRPLPH LAADMQASGE AVYCDDIPRY
ENELSLRLVT STRAHAKIKS IDTSEAKKVP GFVCFISADD VPGSNITGIC NDETVFAKDK
VTCVGHIIGA VVADTPEHTQ RAAQGVKITY EELPAIITIE DAIKNNSFYG PELKIEKGDL
KKGFSEADNV VSGEIYIGGQ EHFYLETHCT IAVPKGEAGE MELFVSTQNT MKTQSFVAKM
LGVPANRIVV RVKRMGGGFG GKETRSTVVS TAVALAAYKT GRPVRCMLDR DEDMLITGGR
HPFLARYKVG FMKTGTVVAL EVDHFSNVGN TQDLSQSIME RALFHMDNCY KIPNIRGTGR
LCKTNLPSNT AFRGFGGPQG MLIAECWMSE VAVTCGMPAE EVRRKNLYKE GDLTHFNQKL
EGFTLPRCWE ECLASSQYHA RKSEVDKFNK ENCWKKRGLC IIPTKFGISF TVPFLNQAGA
LLHVYTDGSV LLTHGGTEMG QGLHTKMVQV ASRALKIPTS KIYISETSTN TVPNTSPTAA
SVSADLNGQA VYAACQTILK RLEPYKKKNP SGSWEDWVTA AYMDTVSLSA TGFYRTPNLG
YSFETNSGNP FHYFSYGVAC SEVEIDCLTG DHKNLRTDIV MDVGSSLNPA IDIGQVEGAF
VQGLGLFTLE ELHYSPEGSL HTRGPSTYKI PAFGSIPIEF RVSLLRDCPN KKAIYASKAV
GEPPLFLAAS IFFAIKDAIR AARAQHTGNN VKELFRLDSP ATPEKIRNAC VDKFTTLCVT
GVPENCKPWS VRV
