Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P22985 (XDH_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. 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·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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1331 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. Ref.5

Catalytic activity

Xanthine + NAD+ + H2O = urate + NADH. Ref.4 Ref.5

Hypoxanthine + NAD+ + H2O = xanthine + NADH. Ref.4 Ref.5

Xanthine + H2O + O2 = urate + H2O2. Ref.4 Ref.5

Cofactor

Binds 2 2Fe-2S clusters. Ref.4 Ref.5

FAD. Ref.4 Ref.5

Binds 1 molybdenum-molybdopterin (Mo-MPT) cofactor per subunit By similarity. Ref.4 Ref.5

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.1 Ref.4

Subunit structure

Homodimer. Interacts with BTN1A1 By similarity. Ref.1

Subcellular location

Peroxisome. Cytoplasm. Secreted By similarity Ref.3.

Induction

By interferon. Ref.1 Ref.4

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.

Ontologies

Keywords
   Cellular componentCytoplasm
Peroxisome
Secreted
   Ligand2Fe-2S
FAD
Flavoprotein
Iron
Iron-sulfur
Metal-binding
Molybdenum
NAD
   Molecular functionOxidoreductase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbone resorption

Inferred from mutant phenotype PubMed 12653206. Source: RGD

response to aluminum ion

Inferred from direct assay PubMed 11787993. Source: RGD

xanthine catabolic process

Inferred from direct assay Ref.4. Source: UniProtKB

   Cellular_componentcytosol

Inferred from direct assay PubMed 11913970. Source: RGD

extracellular space

Inferred from direct assay PubMed 14728722. Source: RGD

peroxisome

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_function2 iron, 2 sulfur cluster binding

Inferred from direct assay Ref.4. Source: UniProtKB

UDP-N-acetylmuramate dehydrogenase activity

Inferred from electronic annotation. Source: InterPro

electron carrier activity

Inferred from electronic annotation. Source: InterPro

flavin adenine dinucleotide binding

Inferred from direct assay Ref.4. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

molybdopterin cofactor binding

Inferred from direct assay Ref.4. Source: UniProtKB

xanthine dehydrogenase activity

Inferred from direct assay Ref.4. Source: UniProtKB

xanthine oxidase activity

Inferred from direct assay Ref.4. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 13311330Xanthine dehydrogenase/oxidase
PRO_0000166086

Regions

Domain4 – 91882Fe-2S ferredoxin-type
Domain228 – 413186FAD-binding PCMH-type
Nucleotide binding256 – 2638FAD
Nucleotide binding346 – 3505FAD

Sites

Active site12611Proton acceptor
Metal binding431Iron-sulfur 1
Metal binding481Iron-sulfur 1
Metal binding511Iron-sulfur 1
Metal binding731Iron-sulfur 1
Metal binding1121Iron-sulfur 2
Metal binding1151Iron-sulfur 2
Metal binding1471Iron-sulfur 2
Metal binding1491Iron-sulfur 2
Metal binding7671Molybdenum By similarity
Metal binding7981Molybdenum; via carbonyl oxygen By similarity
Metal binding9121Molybdenum; via amide nitrogen By similarity
Metal binding10791Molybdenum; via amide nitrogen By similarity
Binding site3361FAD By similarity
Binding site3591FAD
Binding site4031FAD; via amide nitrogen and carbonyl oxygen
Binding site4211FAD By similarity
Binding site8021Substrate
Binding site8801Substrate
Binding site9141Substrate By similarity
Binding site10101Substrate; via amide nitrogen

Amino acid modifications

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

Experimental info

Mutagenesis335 – 3362WF → AL: Converts the enzyme to the oxidase form that utilizes molecular oxygen as electron acceptor. Interferes with normal conversion to the dehydrogenase form by reducing agents. Ref.5
Mutagenesis5351C → A: Slows the conversion from the dehydrogenase form to the oxidase form; when associated with R-992. Abolishes conversion from the dehydrogenase form to the oxidase form; when associated with R-992 and S-1316. Ref.4 Ref.5
Mutagenesis9921C → R: Slows the conversion from the dehydrogenase form to the oxidase form; when associated with A-535. Abolishes conversion from the dehydrogenase form to the oxidase form; when associated with A-535 and S-1316. Ref.4 Ref.5
Mutagenesis13161C → S: Abolishes conversion from the dehydrogenase form to the oxidase form; when associated with A-535 and R-992. Ref.4 Ref.5

Secondary structure

............................................................................................................................................................................................................................... 1331
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P22985 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: BF2586A9C63A0B2C

FASTA1,331146,243
        10         20         30         40         50         60 
MTADELVFFV NGKKVVEKNA DPETTLLVYL RRKLGLCGTK LGCGEGGCGA CTVMISKYDR 

        70         80         90        100        110        120 
LQNKIVHFSV NACLAPICSL HHVAVTTVEG IGNTQKLHPV QERIARSHGS QCGFCTPGIV 

       130        140        150        160        170        180 
MSMYTLLRNQ PEPTVEEIEN AFQGNLCRCT GYRPILQGFR TFAKDGGCCG GSGNNPNCCM 

       190        200        210        220        230        240 
NQTKDQTVSL SPSLFNPEDF KPLDPTQEPI FPPELLRLKD TPQKKLRFEG ERVTWIQAST 

       250        260        270        280        290        300 
MEELLDLKAQ HPDAKLVVGN TEIGIEMKFK NMLFPLIVCP AWIPELNSVV HGPEGISFGA 

       310        320        330        340        350        360 
SCPLSLVESV LAEEIAKLPE QKTEVFRGVM EQLRWFAGKQ VKSVASIGGN IITASPISDL 

       370        380        390        400        410        420 
NPVFMASGAK LTLVSRGTRR TVRMDHTFFP GYRKTLLRPE EILLSIEIPY SKEGEFFSAF 

       430        440        450        460        470        480 
KQASRREDDI AKVTSGMRVL FKPGTIEVQE LSLCFGGMAD RTISALKTTP KQLSKSWNEE 

       490        500        510        520        530        540 
LLQSVCAGLA EELQLAPDAP GGMVEFRRTL TLSFFFKFYL TVLQKLGRAD LEDMCGKLDP 

       550        560        570        580        590        600 
TFASATLLFQ KDPPANVQLF QEVPKDQSEE DMVGRPLPHL AANMQASGEA VYCDDIPRYE 

       610        620        630        640        650        660 
NELSLRLVTS TRAHAKITSI DTSEAKKVPG FVCFLTAEDV PNSNATGLFN DETVFAKDEV 

       670        680        690        700        710        720 
TCVGHIIGAV VADTPEHAQR AARGVKITYE DLPAIITIQD AINNNSFYGS EIKIEKGDLK 

       730        740        750        760        770        780 
KGFSEADNVV SGELYIGGQE HFYLETNCTI AVPKGEAGEM ELFVSTQNTM KTQSFVAKML 

       790        800        810        820        830        840 
GVPDNRIVVR VKRMGGGFGG KETRSTVVST ALALAAHKTG RPVRCMLDRD EDMLITGGRH 

       850        860        870        880        890        900 
PFLAKYKVGF MKTGTVVALE VAHFSNGGNT EDLSRSIMER ALFHMDNAYK IPNIRGTGRI 

       910        920        930        940        950        960 
CKTNLPSNTA FRGFGGPQGM LIAEYWMSEV AITCGLPAEE VRRKNMYKEG DLTHFNQKLE 

       970        980        990       1000       1010       1020 
GFTLPRCWDE CIASSQYLAR KREVEKFNRE NCWKKRGLCI IPTKFGISFT LPFLNQGGAL 

      1030       1040       1050       1060       1070       1080 
VHVYTDGSVL LTHGGTEMGQ GLHTKMVQVA SRALKIPTSK IHISETSTNT VPNTSPTAAS 

      1090       1100       1110       1120       1130       1140 
ASADLNGQGV YEACQTILKR LEPFKKKKPT GPWEAWVMDA YTSAVSLSAT GFYKTPNLGY 

      1150       1160       1170       1180       1190       1200 
SFETNSGNPF HYFSYGVACS EVEIDCLTGD HKNLRTDIVM DVGSSLNPAI DIGQVEGAFV 

      1210       1220       1230       1240       1250       1260 
QGLGLFTMEE LHYSPEGSLH TRGPSTYKIP AFGSIPIEFR VSLLRDCPNK RAIYASKAVG 

      1270       1280       1290       1300       1310       1320 
EPPLFLASSI FFAIKDAIRA ARAQHGDNAK QLFQLDSPAT PEKIRNACVD QFTTLCVTGV 

      1330 
PENCKSWSVR I 

« Hide

References

[1]"Proteolytic conversion of xanthine dehydrogenase from the NAD-dependent type to the O2-dependent type. Amino acid sequence of rat liver xanthine dehydrogenase and identification of the cleavage sites of the enzyme protein during irreversible conversion by trypsin."
Amaya Y., Yamazaki K., Sato M., Noda K., Nishino T., Nishino T.
J. Biol. Chem. 265:14170-14175(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, ENZYME REGULATION, PROTEOLYTIC CONVERSION, SUBUNIT.
Tissue: Liver.
[2]"Identification of the rat xanthine dehydrogenase/oxidase promoter."
Chow C.W., Clark M., Rinaldo J., Chalkley R.
Nucleic Acids Res. 22:1846-1854(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 1-55.
Strain: Sprague-Dawley.
[3]"Ultrastructural localization of xanthine oxidoreductase activity in isolated rat liver cells."
Frederiks W.M., Vreeling-Sindelarova H.
Acta Histochem. 104:29-37(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[4]"Mechanism of the conversion of xanthine dehydrogenase to xanthine oxidase: identification of the two cysteine disulfide bonds and crystal structure of a non-convertible rat liver xanthine dehydrogenase mutant."
Nishino T., Okamoto K., Kawaguchi Y., Hori H., Matsumura T., Eger B.T., Pai E.F., Nishino T.
J. Biol. Chem. 280:24888-24894(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF MUTANT ALA-535/ARG-992/SER-1324 IN COMPLEX WITH FAD; URIC ACID AND IRON-SULFUR CENTERS, CATALYTIC ACTIVITY, DISULFIDE BOND, ENZYME REGULATION, MUTAGENESIS OF CYS-535; CYS-992 AND CYS-1316, COFACTOR.
[5]"Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase."
Asai R., Nishino T., Matsumura T., Okamoto K., Igarashi K., Pai E.F., Nishino T.
J. Biochem. 141:525-534(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF MUTANT ALA-335/LEU-336 IN COMPLEX WITH FAD AND IRON-SULFUR CENTER, MUTAGENESIS OF 335-TRP-PHE-336, CATALYTIC ACTIVITY, FUNCTION, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05579 mRNA. Translation: AAA42349.1.
AH000836 Unassigned DNA. Translation: AAA18869.1.
RefSeqNP_058850.1. NM_017154.1.
UniGeneRn.202951.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WYGX-ray2.60A2-1330[»]
2E3TX-ray2.28A/B1-1331[»]
3AN1X-ray1.73A/B1-1331[»]
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP22985.
ChEMBLCHEMBL1075246.

Proteomic databases

PaxDbP22985.
PRIDEP22985.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID497811.
KEGGrno:497811.
UCSCRGD:62043. rat.

Organism-specific databases

CTD7498.
RGD62043. Xdh.

Phylogenomic databases

eggNOGCOG4630.
HOGENOMHOG000191197.
HOVERGENHBG004182.
InParanoidP22985.
KOK00106.
PhylomeDBP22985.

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-15163.

Gene expression databases

GenevestigatorP22985.

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. SSF47741. 1 hit.
SSF54292. SSF54292. 1 hit.
SSF54665. SSF54665. 1 hit.
SSF55447. SSF55447. 1 hit.
SSF56003. SSF56003. 1 hit.
SSF56176. SSF56176. 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

EvolutionaryTraceP22985.
NextBio697781.
PROP22985.

Entry information

Entry nameXDH_RAT
AccessionPrimary (citable) accession number: P22985
Secondary accession number(s): Q63157
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references