ID   XDH_DICDI               Reviewed;        1358 AA.
AC   Q54FB7;
DT   08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2005, sequence version 1.
DT   27-MAR-2024, entry version 130.
DE   RecName: Full=Xanthine dehydrogenase;
DE            Short=XD;
DE            EC=1.17.1.4;
GN   Name=xdh; ORFNames=DDB_G0291047;
OS   Dictyostelium discoideum (Social amoeba).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
CC   -!- FUNCTION: Key enzyme in purine degradation. Catalyzes the oxidation of
CC       hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric
CC       acid (By similarity). {ECO:0000250}.
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   -!- 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   -!- 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}.
CC   -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC       {ECO:0000305}.
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DR   EMBL; AAFI02000174; EAL61954.1; -; Genomic_DNA.
DR   RefSeq; XP_635420.1; XM_630328.1.
DR   AlphaFoldDB; Q54FB7; -.
DR   SMR; Q54FB7; -.
DR   STRING; 44689.Q54FB7; -.
DR   PaxDb; 44689-DDB0230176; -.
DR   EnsemblProtists; EAL61954; EAL61954; DDB_G0291047.
DR   GeneID; 8627921; -.
DR   KEGG; ddi:DDB_G0291047; -.
DR   dictyBase; DDB_G0291047; xdh.
DR   eggNOG; KOG0430; Eukaryota.
DR   HOGENOM; CLU_001681_1_2_1; -.
DR   InParanoid; Q54FB7; -.
DR   OMA; PHPTQER; -.
DR   PhylomeDB; Q54FB7; -.
DR   Reactome; R-DDI-74259; Purine catabolism.
DR   Reactome; R-DDI-964975; Vitamin B6 activation to pyridoxal phosphate.
DR   Reactome; R-DDI-9748787; Azathioprine ADME.
DR   PRO; PR:Q54FB7; -.
DR   Proteomes; UP000002195; Chromosome 5.
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:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0043546; F:molybdopterin cofactor binding; ISS:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0004854; F:xanthine dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0009115; P:xanthine catabolic process; ISS:UniProtKB.
DR   CDD; cd00207; fer2; 1.
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; 4.
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   PANTHER; PTHR11908; XANTHINE DEHYDROGENASE; 1.
DR   PANTHER; PTHR11908:SF100; XANTHINE DEHYDROGENASE; 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.
PE   3: Inferred from homology;
KW   2Fe-2S; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum;
KW   NAD; Oxidoreductase; Peroxisome; Reference proteome.
FT   CHAIN           1..1358
FT                   /note="Xanthine dehydrogenase"
FT                   /id="PRO_0000327650"
FT   DOMAIN          18..107
FT                   /note="2Fe-2S ferredoxin-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT   DOMAIN          253..447
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT   ACT_SITE        1302
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         56
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         61
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         64
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         89
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         129
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         132
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         164
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         166
FT                   /ligand="[2Fe-2S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:190135"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:P22985"
FT   BINDING         281..288
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         366
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         376..380
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         389
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         437
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         455
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250"
FT   BINDING         805
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         836
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         840
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         918
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         950
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         952
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1048
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         1117
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;  149928 MW;  AF9AEE1059FE076F CRC64;
     MIDDENLNGK EPFLKKENQL LFFLNGEKVL INEPNPELST LDYIRSIGLT GLKRGCSEGA
     CGSCTFMLSN VVKDDNDTFR IVHRAVNGCL YPLCALDGMA VTTIEGLGNI DKGLHSIQER
     ISENSGSQCG FCTPGIIMAL YAFLRSNPNS TQKDIEQNFD GNLCRCTGYR PILDAAKSFA
     NQPSDEQLVE LPLPPMATID DKKDDTQMIC PGTGKPCNCK TKTSHIPNKP MELNSEPIFP
     PFLMEYKKES LKFTGSRVTW YTPTTLEELL KIKKEKTNAK IVVGNTEIGI ETRFRSIVYP
     TIICPTRVEE LIQIQKEDNG VRVGASVTLT EMKSYLNGII KSSENDEIAN KKNGTFKAII
     SQLKWFAGNQ VRNAASIGGN LCTASPISDL NPVLLAAGAV LTMVSLDDNG AKVRRQVPIN
     QFFLRYRVVD IKPEEILESV FIPYTRPLEF IQAYKQSRRR EDDIAIVSCC FRVLLEPIAE
     SASNTVDSNF KIKDCVLAYG GMNVKAVTCE KTEKQLIGSV WSRELLNDAC LNLESDLPLA
     AGAPGGMIEY RRSLTTGFFF KYFLTVSKQL YQISNGNPLY LVSDKEKSAT DAYSRPLSFG
     EQNYQTQPDK HPITQPIKHQ SADKQVTGEA LYVDDVKMKS LYAVMVPSLK AHANIKSVDA
     SKALKAPGVK AFFSAKDIPG INDCGPVIHD EEVFVTKTAL FHGAPIGCIV AETHIQALEA
     SKLVAIEYEE LPAITSIEDA ISKQSFFPFT HLLKDGDMEK GWSESDHIID GEFKVGAQEH
     FYLEPNGTLV IPGEGKELTV ISSTQNPTKT QAIVASVLGI GQNQVVCKLK RLGGGFGGKE
     TRSIFSSCVA AIASYHMKEP VRIILDRDTD MSTTGTRHPF IARYRVGFTK EGLIKALDLE
     LYADAGFSYD ISVGVLDRAI FHSENSYKIP NVNILGRLCK TNLPSNTAFR GYGGPQAMII
     CENWVEKISK TLGMDSYKIR ELNFYKEAEV TAYRQSVVNN MMKRVWDELM VKSNYHQRLI
     AVEKFNKENR YKKRGISIIP TKFGMSFTVK TLNQAGALVH VYTDGTILVT HGGTEMGQGL
     NTKMIQIAAR AFNVPVSDVF ISETSTDKVP NTAPTAASVS SDLNGMAVLD ACQQILLRME
     PIREKNPNVP FKQLCTLCFV ERVNLSANGF YATPNVGYMF KDSGVGEGTP FNYFNFGAAC
     SEVEIDTLTG DHTTLRSDVI LDVGDSLNPT IDIGQVEGAF VQGMGWSTLE EVVTFPSGYM
     FTRGPSTYKI PGFNDVPIEF NVSLLGDAPN PKAIHSSKGV GEPPLFLGSS VYFAIRQAIT
     AARLENNLTN WFDLQSPATC ERIRTSCLDN FVLQFRKQ
//