Skip Header

Contribute Send feedback
Read comments (?) or add your own

P80457 (XDH_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Xanthine dehydrogenase/oxidase

Including the following 2 domains:

  1. Xanthine dehydrogenase
    Short name=XD
    EC=1.17.1.4
  2. Xanthine oxidase
    Short name=XO
    EC=1.17.3.2
    Alternative name(s):
    Xanthine oxidoreductase
    Short name=XOR
Gene names
Name:XDH
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length1332 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species.

Catalytic activity

Xanthine + NAD+ + H2O = urate + NADH. Ref.4 Ref.6 Ref.7 Ref.8

Hypoxanthine + NAD+ + H2O = xanthine + NADH. Ref.4 Ref.6 Ref.7 Ref.8

Xanthine + H2O + O2 = urate + H2O2. Ref.4 Ref.6 Ref.7 Ref.8

Cofactor

Binds 2 2Fe-2S clusters. Ref.6 Ref.7 Ref.8 Ref.9

FAD. Ref.6 Ref.7 Ref.8 Ref.9

Binds 1 molybdenum ion (molybdopterin) per subunit. Ref.6 Ref.7 Ref.8 Ref.9

Enzyme regulation

Can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups. Ref.4 Ref.5 Ref.6

Subunit structure

Homodimer. Interacts with BTN1A1 By similarity. Ref.6 Ref.9

Subcellular location

Cytoplasm By similarity. Peroxisome. Secreted Ref.6 Ref.7 Ref.8.

Tissue specificity

Detected in milk (at protein level). Ref.6 Ref.7 Ref.8

Post-translational modification

Subject to partial proteolysis; this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O).

Contains sulfhydryl groups that are easily oxidized (in vitro); this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O).

Sequence similarities

Belongs to the xanthine dehydrogenase family.

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

Contains 1 FAD-binding PCMH-type domain.

Biophysicochemical properties

Kinetic parameters:

KM=111 µM for molecular oxygen in dehydrogenase form Ref.4 Ref.5

KM=37.7 µM for molecular oxygen in oxygenase form

KM=20.8 µM for NAD

KM=5 µM for xanthine

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 13321331Xanthine dehydrogenase/oxidase
PRO_0000166082

Regions

Domain4 – 91882Fe-2S ferredoxin-type
Domain229 – 414186FAD-binding PCMH-type
Nucleotide binding257 – 2648FAD
Nucleotide binding347 – 3515FAD

Sites

Active site12611Proton acceptor Ref.8
Metal binding431Iron-sulfur 1
Metal binding481Iron-sulfur 1
Metal binding511Iron-sulfur 1
Metal binding731Iron-sulfur 1
Metal binding1131Iron-sulfur 2
Metal binding1161Iron-sulfur 2
Metal binding1481Iron-sulfur 2
Metal binding1501Iron-sulfur 2
Metal binding7671Molybdenum
Metal binding7981Molybdenum; via carbonyl oxygen
Metal binding9121Molybdenum; via amide nitrogen
Metal binding10791Molybdenum; via amide nitrogen
Binding site3371FAD
Binding site3601FAD
Binding site4041FAD; via amide nitrogen and carbonyl oxygen
Binding site4221FAD
Binding site8021Substrate
Binding site8801Substrate
Binding site9141Substrate
Binding site10101Substrate; via amide nitrogen

Amino acid modifications

Glycosylation10731N-linked (GlcNAc...) Potential
Disulfide bond535 ↔ 992In oxidase form By similarity

Experimental info

Mutagenesis3351R → A: Promotes conversion to the oxidase form that utilizes molecular oxygen as electron acceptor. Interferes with normal conversion to the dehydrogenase form by reducing agents. Ref.5
Mutagenesis3361W → A: Promotes conversion to the oxidase form that utilizes molecular oxygen as electron acceptor. Interferes with normal conversion to the dehydrogenase form by reducing agents. Ref.5
Mutagenesis4271R → Q: Promotes conversion to the oxidase form that utilizes molecular oxygen as electron acceptor. Interferes with normal conversion to the dehydrogenase form by reducing agents. Ref.5
Sequence conflict1881T → TQ in CAA67117. Ref.2
Sequence conflict1991E → K in CAA67117. Ref.2
Sequence conflict3661M → V in CAA67117. Ref.2
Sequence conflict5521D → H in CAA58497. Ref.1
Sequence conflict9581R → K in CAA67117. Ref.2
Sequence conflict9761Q → E in CAA67117. Ref.2
Sequence conflict1039 – 10402GQ → E in CAA67117. Ref.2
Sequence conflict12441L → V in CAA67117. Ref.2
Sequence conflict12681A → P in CAA67117. Ref.2
Sequence conflict1279 – 12813RAA → ARG in CAA67117. Ref.2

Secondary structure

1 ....................................................................................................................................................................................................................... 1332
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P80457 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 744BA523471948B7

FASTA1,332146,790
        10         20         30         40         50         60 
MTADELVFFV NGKKVVEKNA DPETTLLAYL RRKLGLRGTK LGCGEGGCGA CTVMLSKYDR 

        70         80         90        100        110        120 
LQDKIIHFSA NACLAPICTL HHVAVTTVEG IGSTKTRLHP VQERIAKSHG SQCGFCTPGI 

       130        140        150        160        170        180 
VMSMYTLLRN QPEPTVEEIE DAFQGNLCRC TGYRPILQGF RTFAKNGGCC GGNGNNPNCC 

       190        200        210        220        230        240 
MNQKKDHTVT LSPSLFNPEE FMPLDPTQEP IFPPELLRLK DVPPKQLRFE GERVTWIQAS 

       250        260        270        280        290        300 
TLKELLDLKA QHPEAKLVVG NTEIGIEMKF KNQLFPMIIC PAWIPELNAV EHGPEGISFG 

       310        320        330        340        350        360 
AACALSSVEK TLLEAVAKLP TQKTEVFRGV LEQLRWFAGK QVKSVASLGG NIITASPISD 

       370        380        390        400        410        420 
LNPVFMASGT KLTIVSRGTR RTVPMDHTFF PSYRKTLLGP EEILLSIEIP YSREDEFFSA 

       430        440        450        460        470        480 
FKQASRREDD IAKVTCGMRV LFQPGSMQVK ELALCYGGMA DRTISALKTT QKQLSKFWNE 

       490        500        510        520        530        540 
KLLQDVCAGL AEELSLSPDA PGGMIEFRRT LTLSFFFKFY LTVLKKLGKD SKDKCGKLDP 

       550        560        570        580        590        600 
TYTSATLLFQ KDPPANIQLF QEVPNGQSKE DTVGRPLPHL AAAMQASGEA VYCDDIPRYE 

       610        620        630        640        650        660 
NELFLRLVTS TRAHAKIKSI DVSEAQKVPG FVCFLSADDI PGSNETGLFN DETVFAKDTV 

       670        680        690        700        710        720 
TCVGHIIGAV VADTPEHAER AAHVVKVTYE DLPAIITIED AIKNNSFYGS ELKIEKGDLK 

       730        740        750        760        770        780 
KGFSEADNVV SGELYIGGQD HFYLETHCTI AIPKGEEGEM ELFVSTQNAM KTQSFVAKML 

       790        800        810        820        830        840 
GVPVNRILVR VKRMGGGFGG KETRSTLVSV AVALAAYKTG HPVRCMLDRN EDMLITGGRH 

       850        860        870        880        890        900 
PFLARYKVGF MKTGTIVALE VDHYSNAGNS RDLSHSIMER ALFHMDNCYK IPNIRGTGRL 

       910        920        930        940        950        960 
CKTNLSSNTA FRGFGGPQAL FIAENWMSEV AVTCGLPAEE VRWKNMYKEG DLTHFNQRLE 

       970        980        990       1000       1010       1020 
GFSVPRCWDE CLKSSQYYAR KSEVDKFNKE NCWKKRGLCI IPTKFGISFT VPFLNQAGAL 

      1030       1040       1050       1060       1070       1080 
IHVYTDGSVL VSHGGTEMGQ GLHTKMVQVA SKALKIPISK IYISETSTNT VPNSSPTAAS 

      1090       1100       1110       1120       1130       1140 
VSTDIYGQAV YEACQTILKR LEPFKKKNPD GSWEDWVMAA YQDRVSLSTT GFYRTPNLGY 

      1150       1160       1170       1180       1190       1200 
SFETNSGNAF HYFTYGVACS EVEIDCLTGD HKNLRTDIVM DVGSSLNPAI DIGQVEGAFV 

      1210       1220       1230       1240       1250       1260 
QGLGLFTLEE LHYSPEGSLH TRGPSTYKIP AFGSIPTEFR VSLLRDCPNK KAIYASKAVG 

      1270       1280       1290       1300       1310       1320 
EPPLFLGASV FFAIKDAIRA ARAQHTNNNT KELFRLDSPA TPEKIRNACV DKFTTLCVTG 

      1330 
APGNCKPWSL RV

« Hide

References

[1]"Purification of the bovine xanthine oxidoreductase from milk fat globule membranes and cloning of complementary deoxyribonucleic acid."
Berglund L., Rasmussen J.T., Andersen M.D., Rasmussen M.S., Petersen T.E.
J. Dairy Sci. 79:198-204(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Mammary gland.
[2]"The xanthine oxidoreductase gene: structure and regulation."
Terao M., Kurosaki M., Zanotta S., Garattini E.
Biochem. Soc. Trans. 25:791-796(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Properties of rabbit liver aldehyde oxidase and the relationship of the enzyme to xanthine oxidase and dehydrogenase."
Turner N.A., Doyle W.A., Ventom A.M., Bray R.C.
Eur. J. Biochem. 232:646-657(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-23; 186-205 AND 552-562.
Tissue: Milk.
[4]"Milk xanthine oxidase type D (dehydrogenase) and type O (oxidase). Purification, interconversion and some properties."
Battelli M.G., Lorenzoni E., Stripe F.
Biochem. J. 131:191-198(1973) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, CONVERSION BY PARTIAL PROTEOLYSIS AND BY REDUCING AGENTS.
[5]"Unique amino acids cluster for switching from the dehydrogenase to oxidase form of xanthine oxidoreductase."
Kuwabara Y., Nishino T., Okamoto K., Matsumura T., Eger B.T., Pai E.F., Nishino T.
Proc. Natl. Acad. Sci. U.S.A. 100:8170-8175(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-335; TRP-336 AND ARG-427.
[6]"Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion."
Enroth C., Eger B.T., Okamoto K., Nishino T., Nishino T., Pai E.F.
Proc. Natl. Acad. Sci. U.S.A. 97:10723-10728(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEXES WITH FAD; IRON-SULFUR CENTERS; SALICYLATE, SUBUNIT, COFACTOR, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"An extremely potent inhibitor of xanthine oxidoreductase. Crystal structure of the enzyme-inhibitor complex and mechanism of inhibition."
Okamoto K., Eger B.T., Nishino T., Kondo S., Pai E.F., Nishino T.
J. Biol. Chem. 278:1848-1855(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH FAD; MOLYBDOPTERIN; IRON-SULFUR CENTERS AND SYNTHETIC INHIBITOR TEI-6720, COFACTOR, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[8]"The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition."
Okamoto K., Matsumoto K., Hille R., Eger B.T., Pai E.F., Nishino T.
Proc. Natl. Acad. Sci. U.S.A. 101:7931-7936(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) IN COMPLEX WITH FAD; MOLYBDOPTERIN; IRON-SULFUR CENTERS AND INHIBITOR FYX-051, ACTIVE SITE, COFACTOR, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]"Substrate orientation and catalysis at the molybdenum site in xanthine oxidase: crystal structures in complex with xanthine and lumazine."
Pauff J.M., Cao H., Hille R.
J. Biol. Chem. 284:8760-8767(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH FAD; MOLYBDOPTERIN; IRON-SULFUR CENTERS; CALCIUM IONS; XANTHINE AND LUMAZINE, COFACTOR, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X83508 mRNA. Translation: CAA58497.1.
X98491 mRNA. Translation: CAA67117.1.
IPIIPI00695367.
PIRS65135.
RefSeqNP_776397.1. NM_173972.2.
UniGeneBt.5403.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FIQX-ray2.50A1-219[»]
B220-569[»]
C570-1332[»]
1FO4X-ray2.10A/B1-1332[»]
1N5XX-ray2.80A/B2-1331[»]
1V97X-ray1.94A/B1-1332[»]
1VDVX-ray1.98A/B2-1331[»]
3AM9X-ray2.17A/B1-1332[»]
3AMZX-ray2.10A/B1-1332[»]
3AX7X-ray2.34A/B1-1332[»]
3AX9X-ray2.30A/B1-1332[»]
3B9JX-ray2.30A/I1-219[»]
B/J220-569[»]
C/K570-1332[»]
3BDJX-ray2.00A/B1-1332[»]
3ETRX-ray2.20A/L2-165[»]
B/M224-528[»]
C/N571-1325[»]
3EUBX-ray2.602/A/J/S1-165[»]
3/B/K/T224-528[»]
4/C/L/U571-1332[»]
3NRZX-ray1.80A/J2-165[»]
B/K224-528[»]
C/L571-1326[»]
3NS1X-ray2.60A/J2-165[»]
B/K224-528[»]
C/L571-1325[»]
3NVVX-ray1.82A/J2-165[»]
B/K195-528[»]
C/L571-1325[»]
3NVWX-ray1.60A/J2-165[»]
B/K195-528[»]
C/L571-1326[»]
3NVYX-ray2.00A/J2-165[»]
B/K195-528[»]
C/L571-1326[»]
3NVZX-ray1.60A/J2-165[»]
B/K224-528[»]
C/L571-1325[»]
3SR6X-ray2.10A/J2-165[»]
B/K224-528[»]
C/L571-1315[»]
3UNAX-ray1.90A/B1-1332[»]
3UNCX-ray1.65A/B1-1332[»]
3UNIX-ray2.20A/B1-1332[»]
DisProtDP00450.
DP00451.
ProteinModelPortalP80457.
SMRP80457. Positions 2-165, 224-528, 571-1328.
ModBaseSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000032520.

Proteomic databases

PaxDbP80457.
PRIDEP80457.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID280960.
KEGGbta:280960.

Organism-specific databases

CTD7498.

Phylogenomic databases

eggNOGCOG4630.
HOGENOMHOG000191197.
HOVERGENHBG004182.
InParanoidP80457.
KOK00106.
OrthoDBEOG45X7V8.

Enzyme and pathway databases

SABIO-RKP80457.

Family and domain databases

Gene3D1.10.150.120. 1 hit.
3.10.20.30. 1 hit.
3.30.365.10. 6 hits.
3.30.43.10. 1 hit.
3.30.465.10. 1 hit.
3.90.1170.50. 1 hit.
InterProIPR002888. 2Fe-2S-bd.
IPR001041. 2Fe-2S_ferredoxin-type.
IPR006058. 2Fe2S_fd_BS.
IPR000674. Ald_Oxase/Xan_DH_a/b.
IPR016208. Ald_Oxase/xanthine_DH.
IPR008274. AldOxase/xan_DH_Mopterin-bd.
IPR012675. Beta-grasp_dom.
IPR005107. CO_DH_flav_C.
IPR016169. CO_DH_flavot_FAD-bd_sub2.
IPR016166. FAD-bd_2.
IPR016167. FAD-bd_2_sub1.
IPR002346. Mopterin_DH_FAD-bd.
IPR022407. OxRdtase_Mopterin_BS.
IPR014307. Xanthine_DH_ssu.
[Graphical view]
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.
SMARTSM01008. Ald_Xan_dh_C. 1 hit.
SM01092. CO_deh_flav_C. 1 hit.
[Graphical view]
SUPFAMSSF47741. 2Fe-2S_bind. 1 hit.
SSF56003. Ald_xan_DH_mo_bd. 1 hit.
SSF54665. Aldxan_dh_hamm. 1 hit.
SSF55447. CO_deh_flav_C. 1 hit.
SSF56176. FAD-binding_2. 1 hit.
SSF54292. Ferredoxin. 1 hit.
TIGRFAMsTIGR02963. xanthine_xdhA. 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

BindingDBP80457.
ChEMBLCHEMBL3649.
EvolutionaryTraceP80457.
NextBio20805070.

Entry information

Entry nameXDH_BOVIN
AccessionPrimary (citable) accession number: P80457
Secondary accession number(s): Q95325
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: April 3, 2013
This is version 123 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents