XDH_DROPS
ID XDH_DROPS Reviewed; 1343 AA.
AC P22811; Q299Q9; Q56RA2;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Xanthine dehydrogenase;
DE Short=XD;
DE EC=1.17.1.4;
DE AltName: Full=Protein rosy locus;
GN Name=ry; Synonyms=XDH; ORFNames=GA20500;
OS Drosophila pseudoobscura pseudoobscura (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=46245;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2493563; DOI=10.1093/oxfordjournals.molbev.a040529;
RA Riley M.A.;
RT "Nucleotide sequence of the Xdh region in Drosophila pseudoobscura and an
RT analysis of the evolution of synonymous codons.";
RL Mol. Biol. Evol. 6:33-52(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MV2-25 / Tucson 14011-0121.94;
RX PubMed=15632085; DOI=10.1101/gr.3059305;
RA Richards S., Liu Y., Bettencourt B.R., Hradecky P., Letovsky S.,
RA Nielsen R., Thornton K., Hubisz M.J., Chen R., Meisel R.P., Couronne O.,
RA Hua S., Smith M.A., Zhang P., Liu J., Bussemaker H.J., van Batenburg M.F.,
RA Howells S.L., Scherer S.E., Sodergren E., Matthews B.B., Crosby M.A.,
RA Schroeder A.J., Ortiz-Barrientos D., Rives C.M., Metzker M.L., Muzny D.M.,
RA Scott G., Steffen D., Wheeler D.A., Worley K.C., Havlak P., Durbin K.J.,
RA Egan A., Gill R., Hume J., Morgan M.B., Miner G., Hamilton C., Huang Y.,
RA Waldron L., Verduzco D., Clerc-Blankenburg K.P., Dubchak I., Noor M.A.F.,
RA Anderson W., White K.P., Clark A.G., Schaeffer S.W., Gelbart W.M.,
RA Weinstock G.M., Gibbs R.A.;
RT "Comparative genome sequencing of Drosophila pseudoobscura: chromosomal,
RT gene, and cis-element evolution.";
RL Genome Res. 15:1-18(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 298-1062.
RX PubMed=15545653; DOI=10.1534/genetics.104.033068;
RA Bartolome C., Maside X., Yi S., Grant A.L., Charlesworth B.;
RT "Patterns of selection on synonymous and nonsynonymous variants in
RT Drosophila miranda.";
RL Genetics 169:1495-1507(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; M33977; AAA29022.1; -; Genomic_DNA.
DR EMBL; CM000070; EAL27642.2; -; Genomic_DNA.
DR EMBL; AY754605; AAX13180.1; -; Genomic_DNA.
DR PIR; A31946; A31946.
DR RefSeq; XP_001358503.2; XM_001358466.3.
DR AlphaFoldDB; P22811; -.
DR SMR; P22811; -.
DR STRING; 7237.FBpp0282224; -.
DR EnsemblMetazoa; FBtr0283786; FBpp0282224; FBgn0012736.
DR GeneID; 4801405; -.
DR KEGG; dpo:Dpse_GA20500; -.
DR eggNOG; KOG0430; Eukaryota.
DR HOGENOM; CLU_001681_1_2_1; -.
DR InParanoid; P22811; -.
DR OMA; DIGYVWG; -.
DR Proteomes; UP000001819; Chromosome 2.
DR Bgee; FBgn0012736; Expressed in insect adult head and 2 other tissues.
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:0004854; F:xanthine dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0004855; F:xanthine oxidase activity; IEA:InterPro.
DR GO; GO:0006525; P:arginine metabolic process; IEA:EnsemblMetazoa.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:EnsemblMetazoa.
DR GO; GO:0006650; P:glycerophospholipid metabolic process; IEA:EnsemblMetazoa.
DR GO; GO:0006206; P:pyrimidine nucleobase metabolic process; IEA:EnsemblMetazoa.
DR GO; GO:0006568; P:tryptophan metabolic process; IEA:EnsemblMetazoa.
DR GO; GO:0009115; P:xanthine catabolic process; ISS:UniProtKB.
DR CDD; cd00207; fer2; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.43.10; -; 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 3: Inferred from homology;
KW 2Fe-2S; FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Molybdenum;
KW NAD; Oxidoreductase; Peroxisome; Reference proteome.
FT CHAIN 1..1343
FT /note="Xanthine dehydrogenase"
FT /id="PRO_0000166080"
FT DOMAIN 8..95
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 235..424
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1275
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 263..270
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 343
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 353..357
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 414
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 432
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 780
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 811
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 815
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 893
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 925
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 927
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 1092
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 CONFLICT 58
FT /note="V -> M (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="T -> A (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="V -> I (in Ref. 1; AAA29022 and 3; AAX13180)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="G -> E (in Ref. 1; AAA29022 and 3; AAX13180)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="L -> V (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
FT CONFLICT 734
FT /note="E -> D (in Ref. 3; AAX13180)"
FT /evidence="ECO:0000305"
FT CONFLICT 747
FT /note="S -> N (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
FT CONFLICT 762
FT /note="A -> G (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
FT CONFLICT 986
FT /note="A -> V (in Ref. 3; AAX13180)"
FT /evidence="ECO:0000305"
FT CONFLICT 1245
FT /note="Missing (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
FT CONFLICT 1320
FT /note="C -> F (in Ref. 1; AAA29022)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1343 AA; 147349 MW; A58C142336E14BC9 CRC64;
MSGQQKTSEL VFFVNGKKVT DTNPDPECTL LTYLRDKLRL CGTKLGCAEG GCGACTVVIS
RMDRGQNKIR HLAVNACLTP VCAMHGCAVT TVEGIGSTRT RLHPVQERLA KAHGSQCGFC
TPGIVMSMYA LLRSAEQPSM RDLEVAFQGN LCRCTGYRPI LEGYKTFTKE FACGMGDKCC
KVNGKGCGGG DDTQSVTDDT LFERSQFQPL DPSQEPIFPP ELQLTPTYDS ESLIFSSERV
TWYRPTTLQE LLQLKSDHPS AKLVVGNTEV GVEVKFKHFL YPHLINPTQV PELLEVRESE
ESIYFGAAVS LMEIDALLRQ RIEELPEAQT RLFQCAVDML HYFAGKQIRN VACLGGNIMT
GSPISDMNPV LTAAGARLEV ASLVGGKTSH RTVHMGTGFF TGYRRNVIEP HEVLLGIHFQ
KTTPDQHVVA FKQARRRDDD IAIVNAAVNV RFEPRTNVVA GISMAFGGMA PTTVLAPRTS
QLMVKQPLDH HLVERVAESL CGELPLAASA PGGMIAYRRA LVVSLIFKAY LSISRKLSEA
GIISTDAIPA EERSGAELFH TPVLRSAQLF ERVCSEQPVC DPIGRPEVHA AALKQATGEA
IYTDDIPRMD GELYLGLVLS TKPRAKITKL DASEALALEG VHAFFSHKDL TEHENEVGPV
FHDEHVFAAA EVHCYGQIVG AVAADNKALA QRAARLVRVE YEELAPVIVT IEQAIEHGSY
FPDYPRYVNK GNVEEAFAAA EHTYEGSCRM GGQEHFYLET HAAVAVPRDS DELELFCSTQ
HPSEVQKLVA HVTTLPAHRV VCRAKRLGGG FGGKESRGIS VALPVALAAY RLRRPVRCML
DRDEDMLITG TRHPFLFKYK VAFASDGLIT ACDIECYNNA GWSMDLSFSV LERAMYHFEN
CYRIPNVRVG GWVCKTNLPS NTAFRGFGGP QGMFAGEHII RDVARIVGRD VLDVMRLNFY
KTGDITHYNQ KLEHFPIERC LDDCLAQSRY HEKRTEIAKF NRENRWRKRG MAVIPTKYGI
AFGVMHLNQA GALINVYGDG SVLLSHGGVE IGQGLNTKMI QCAARALGIP IELIHISETA
TDKVPNTSPT AASVGSDLNG MAVLDACEKL NKRLAPIKEA LPQGTWQEWI NKAYFDRVSL
SATGFYAMPG IGYHPETNPN ARTYSYYTNG VGISVVEIDC LTGDHQVLST DIVMDIGSSI
NPAIDIGQIE GAFMQGYGLF TLEELMYSPQ GMLYSRGPGM YKLPGFADIP GEFNVSLLTG
APNPRAVYSS KAVGEPPLFI GSSAFFAIKE AIAAARQEQG LTGDFPLEAP STSARIRMAC
QDKFTNLLEI PEEGSFTPWN IVP
