ID   XDH_CHICK               Reviewed;        1358 AA.
AC   P47990;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 146.
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:6953967, ECO:0000269|PubMed:7852355};
DE   Includes:
DE     RecName: Full=Xanthine oxidase;
DE              Short=XO;
DE              EC=1.17.3.2 {ECO:0000250|UniProtKB:P22985};
DE     AltName: Full=Xanthine oxidoreductase;
DE              Short=XOR;
GN   Name=XDH;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND CATALYTIC
RP   ACTIVITY.
RC   TISSUE=Liver;
RX   PubMed=7852355; DOI=10.1074/jbc.270.6.2818;
RA   Satoh A., Amaya Y., Noda K., Nishino T.;
RT   "The structure of chicken liver xanthine dehydrogenase. cDNA cloning and
RT   the domain structure.";
RL   J. Biol. Chem. 270:2818-2826(1995).
RN   [2]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX   PubMed=6953967; DOI=10.1042/bj2020555;
RA   Coolbear K.P., Herzberg G.R., Brosnan J.T.;
RT   "Subcellular localization of chicken liver xanthine dehydrogenase. A
RT   possible source of cytoplasmic reducing equivalents.";
RL   Biochem. J. 202:555-558(1982).
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.
CC       {ECO:0000250|UniProtKB:P47989}.
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; Evidence={ECO:0000269|PubMed:6953967,
CC         ECO:0000269|PubMed:7852355};
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; Evidence={ECO:0000269|PubMed:6953967,
CC         ECO:0000269|PubMed:7852355};
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:0000250|UniProtKB:P22985};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC   -!- COFACTOR:
CC       Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302; Evidence={ECO:0000250};
CC       Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC       {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC         Evidence={ECO:0000250|UniProtKB:P22985};
CC       Note=Binds 2 [2Fe-2S] clusters per subunit.
CC       {ECO:0000250|UniProtKB:P22985};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250}. Cytoplasm
CC       {ECO:0000269|PubMed:6953967}.
CC   -!- TISSUE SPECIFICITY: Detected in liver (at protein level).
CC       {ECO:0000269|PubMed:6953967}.
CC   -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; D13221; BAA02502.1; -; mRNA.
DR   PIR; A55711; XOCHDH.
DR   RefSeq; NP_990458.1; NM_205127.1.
DR   AlphaFoldDB; P47990; -.
DR   SMR; P47990; -.
DR   STRING; 9031.ENSGALP00000014144; -.
DR   PaxDb; 9031-ENSGALP00000014144; -.
DR   GeneID; 396025; -.
DR   KEGG; gga:396025; -.
DR   CTD; 7498; -.
DR   VEuPathDB; HostDB:geneid_396025; -.
DR   eggNOG; KOG0430; Eukaryota.
DR   InParanoid; P47990; -.
DR   PhylomeDB; P47990; -.
DR   Reactome; R-GGA-421178; Urate synthesis.
DR   PRO; PR:P47990; -.
DR   Proteomes; UP000000539; Unassembled WGS sequence.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR   GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISS:UniProtKB.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR   GO; GO:0070674; F:hypoxanthine dehydrogenase activity; TAS:Reactome.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0030151; F:molybdenum ion binding; IEA:InterPro.
DR   GO; GO:0043546; F:molybdopterin cofactor binding; ISS:UniProtKB.
DR   GO; GO:0004854; F:xanthine dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0004855; F:xanthine oxidase activity; ISS:UniProtKB.
DR   GO; GO:0034418; P:urate biosynthetic process; TAS:Reactome.
DR   GO; GO:0009115; P:xanthine catabolic process; ISS:UniProtKB.
DR   Gene3D; 3.10.20.30; -; 1.
DR   Gene3D; 3.30.465.10; -; 1.
DR   Gene3D; 1.10.150.120; [2Fe-2S]-binding domain; 1.
DR   Gene3D; 3.90.1170.50; Aldehyde oxidase/xanthine dehydrogenase, a/b hammerhead; 1.
DR   Gene3D; 3.30.365.10; Aldehyde oxidase/xanthine dehydrogenase, molybdopterin binding domain; 5.
DR   Gene3D; 3.30.390.50; CO dehydrogenase flavoprotein, C-terminal domain; 1.
DR   Gene3D; 3.30.43.10; Uridine Diphospho-n-acetylenolpyruvylglucosamine Reductase, domain 2; 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-like.
DR   InterPro; IPR008274; AldOxase/xan_DH_MoCoBD1.
DR   InterPro; IPR046867; AldOxase/xan_DH_MoCoBD2.
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; IPR014309; Xanthine_DH_Mopterin-bd_su.
DR   InterPro; IPR014307; Xanthine_DH_ssu.
DR   NCBIfam; TIGR02963; xanthine_xdhA; 1.
DR   NCBIfam; TIGR02965; xanthine_xdhB; 1.
DR   PANTHER; PTHR11908; XANTHINE DEHYDROGENASE; 1.
DR   PANTHER; PTHR11908:SF80; XANTHINE DEHYDROGENASE_OXIDASE; 1.
DR   Pfam; PF01315; Ald_Xan_dh_C; 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   Pfam; PF02738; MoCoBD_1; 1.
DR   Pfam; PF20256; MoCoBD_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; SSF54292; 2Fe-2S ferredoxin-like; 1.
DR   SUPFAM; SSF55447; CO dehydrogenase flavoprotein C-terminal domain-like; 1.
DR   SUPFAM; SSF47741; CO dehydrogenase ISP C-domain like; 1.
DR   SUPFAM; SSF54665; CO dehydrogenase molybdoprotein N-domain-like; 1.
DR   SUPFAM; SSF56176; FAD-binding/transporter-associated domain-like; 1.
DR   SUPFAM; SSF56003; Molybdenum cofactor-binding domain; 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; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; Iron;
KW   Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase; Peroxisome;
KW   Reference proteome.
FT   CHAIN           1..1358
FT                   /note="Xanthine dehydrogenase/oxidase"
FT                   /id="PRO_0000166083"
FT   DOMAIN          8..95
FT                   /note="2Fe-2S ferredoxin-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT   DOMAIN          255..440
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT   ACT_SITE        1290
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         47
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         52
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         55
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         77
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         117
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         120
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         152
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         154
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         283..290
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         363
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         373..377
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         386
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         430
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         448
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         796
FT                   /ligand="Mo-molybdopterin"
FT                   /ligand_id="ChEBI:CHEBI:71302"
FT                   /ligand_part="Mo"
FT                   /ligand_part_id="ChEBI:CHEBI:28685"
FT                   /evidence="ECO:0000250"
FT   BINDING         827
FT                   /ligand="Mo-molybdopterin"
FT                   /ligand_id="ChEBI:CHEBI:71302"
FT                   /ligand_part="Mo"
FT                   /ligand_part_id="ChEBI:CHEBI:28685"
FT                   /evidence="ECO:0000250"
FT   BINDING         831
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         909
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         941
FT                   /ligand="Mo-molybdopterin"
FT                   /ligand_id="ChEBI:CHEBI:71302"
FT                   /ligand_part="Mo"
FT                   /ligand_part_id="ChEBI:CHEBI:28685"
FT                   /evidence="ECO:0000250"
FT   BINDING         943
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1039
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1108
FT                   /ligand="Mo-molybdopterin"
FT                   /ligand_id="ChEBI:CHEBI:71302"
FT                   /ligand_part="Mo"
FT                   /ligand_part_id="ChEBI:CHEBI:28685"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   1358 AA;  149614 MW;  53B049B38704995F CRC64;
     MAPPETGDEL VFFVNGKKVV EKDVDPETTL LTYLRRKLGL CGTKLGCGEG GCGACTVMIS
     KYDPFQKKIL HHTANACLFP ICALHHVAVT TVEGIGNTKS RLHPAQERIA KSHGSQCGFC
     TPGIVMSMYT LLRNKPKPKM EDIEDAFQGN LCRCTGYRPI LEGYRTFAVD SNCCGKAANG
     TGCCHSKGEN SMNGGCCGGK ANGPGCCMNE KENVTMMSSS LFDSSEFQPL DPTQEPIFPP
     ELMTQRNKEQ KQVCFKGERV MWIQPTTLQE LVALKSQYPN AKLVVGNTEV GIEMRLKNML
     YPVILAPAWI PEMNAVQQTE TGITFGAACT LSSVEEVLRK AVAELPSYKT EIFQAALEQL
     RWFAGPQIRN VAALGGNIMT ASPISDLNPV LMASGSKLTL ISMEGKRTVM MDEKFFTGYR
     KTIVKPEEVL LSVEIPYSKE GEYFSAFKQA YRREDDIAIV TCGMRVLFQH GTSRVQEVKL
     SYGGMAPTTI LALKTCRELA GRDWNEKLLQ DACRLLAGEM DLSPSAPGGM VEFRRTLTLS
     FFFKFYLTVL QKLSKDQNGP NNLCEPVPPN YISATELFHK DPIASTQLFQ EVPRGQLVED
     TVGRPLVHLS AAKQACGEAV YCDDIPHYEN ELYLTLVTST QAHAKILSID ASEAQSVPGF
     VCFVSAKDVP GSNITGIAND ETVFAEDVVT CVGHIIGAVI ADTQEHSRRA AKAVKIKYEE
     LKPIVTIQEA IEQQSFIKPI KRIKKGDVNK GFEESDHILE GEMHIGGQEH FYLETHCTLA
     VPKGEDGEME LFVSTQNLMK TQEFTASALG VPSNRIVVRV KRMGGGFGGK ETRNTILTTV
     VAVAAFKTGR PVRCMLDRDE DMLISGGRHP FLGRYKVGFM KNGKIKSLEV SYYSNGGNSA
     DLSHGVMDRA LLHLDNSYNI PNVSIMGFIC KTNLSSNTAF RGFGGPQGMM IAECWMSDLA
     RKCGLPPEEV RKINLYHEGD LTHFNQKLEG FTLRRCWDEC LSSSNYHARK KLIEEFNKQN
     RWKKRGMCII PTKFGISFTV PFLNQAGALV HVYTDGSVLL THGGTEMGQG LHTKMIQVAS
     RSLGIPTSKI YISETSTNTV PNTSPTAASV SADINGMAVH NACQTILKRL EPIKQSNLKG
     SWEDWIKTAY ENCISLSATG FYRIPDVGYN FETNKGKPFH YFSYGVACSE VEIDCLTGDH
     KNIRTDIVMD VGTSLNPAID IGQIEGAFVQ GIGLFTMEEL RYSPEGNLYT RGPGMYKIPA
     FGDIPTEFYV SLLRDCPNSK AIYSSKAVGE PPLFLSASVF YAIKDAIYSA REDSGVTEPF
     RLDSPATPER IRNACVDTFT KMCPSAEPGT FKPWSVRA
//