XDH

Protein identityUniProt · HPA

UniProt accession

P47989

Gene

XDH

Ensembl

ENSG00000158125

Chromosome

2

Canonical length

1333 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nucleoli

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism. [provided by RefSeq, Jan 2014]

Canonical amino-acid sequenceUniProt

1333 residues, UniProt reviewed canonical sequence.

>P47989|XDH
     1  MTADKLVFFV NGRKVVEKNA DPETTLLAYL RRKLGLSGTK LGCGEGGCGA CTVMLSKYDR
    61  LQNKIVHFSA NACLAPICSL HHVAVTTVEG IGSTKTRLHP VQERIAKSHG SQCGFCTPGI
   121  VMSMYTLLRN QPEPTMEEIE NAFQGNLCRC TGYRPILQGF RTFARDGGCC GGDGNNPNCC
   181  MNQKKDHSVS LSPSLFKPEE FTPLDPTQEP IFPPELLRLK DTPRKQLRFE GERVTWIQAS
   241  TLKELLDLKA QHPDAKLVVG NTEIGIEMKF KNMLFPMIVC PAWIPELNSV EHGPDGISFG
   301  AACPLSIVEK TLVDAVAKLP AQKTEVFRGV LEQLRWFAGK QVKSVASVGG NIITASPISD
   361  LNPVFMASGA KLTLVSRGTR RTVQMDHTFF PGYRKTLLSP EEILLSIEIP YSREGEYFSA
   421  FKQASRREDD IAKVTSGMRV LFKPGTTEVQ ELALCYGGMA NRTISALKTT QRQLSKLWKE
   481  ELLQDVCAGL AEELHLPPDA PGGMVDFRCT LTLSFFFKFY LTVLQKLGQE NLEDKCGKLD
   541  PTFASATLLF QKDPPADVQL FQEVPKGQSE EDMVGRPLPH LAADMQASGE AVYCDDIPRY
   601  ENELSLRLVT STRAHAKIKS IDTSEAKKVP GFVCFISADD VPGSNITGIC NDETVFAKDK
   661  VTCVGHIIGA VVADTPEHTQ RAAQGVKITY EELPAIITIE DAIKNNSFYG PELKIEKGDL
   721  KKGFSEADNV VSGEIYIGGQ EHFYLETHCT IAVPKGEAGE MELFVSTQNT MKTQSFVAKM
   781  LGVPANRIVV RVKRMGGGFG GKETRSTVVS TAVALAAYKT GRPVRCMLDR DEDMLITGGR
   841  HPFLARYKVG FMKTGTVVAL EVDHFSNVGN TQDLSQSIME RALFHMDNCY KIPNIRGTGR
   901  LCKTNLPSNT AFRGFGGPQG MLIAECWMSE VAVTCGMPAE EVRRKNLYKE GDLTHFNQKL
   961  EGFTLPRCWE ECLASSQYHA RKSEVDKFNK ENCWKKRGLC IIPTKFGISF TVPFLNQAGA
  1021  LLHVYTDGSV LLTHGGTEMG QGLHTKMVQV ASRALKIPTS KIYISETSTN TVPNTSPTAA
  1081  SVSADLNGQA VYAACQTILK RLEPYKKKNP SGSWEDWVTA AYMDTVSLSA TGFYRTPNLG
  1141  YSFETNSGNP FHYFSYGVAC SEVEIDCLTG DHKNLRTDIV MDVGSSLNPA IDIGQVEGAF
  1201  VQGLGLFTLE ELHYSPEGSL HTRGPSTYKI PAFGSIPIEF RVSLLRDCPN KKAIYASKAV
  1261  GEPPLFLAAS IFFAIKDAIR AARAQHTGNN VKELFRLDSP ATPEKIRNAC VDKFTTLCVT
  1321  GVPENCKPWS VRV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against XDH can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.19

Highest tissue expression

64 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about XDH.

Disease | AllUniProt

Conditions XDH is implicated in, by any mechanism.

• Xanthinuria 1 (XAN1) MIM:278300

Disease | GeneticClinVar

52 pathogenic / likely-pathogenic of 1,042 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary xanthinuria type 1
• Xanthinuria type II

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.86

gnomAD pLI

0

gnomAD missense Z

-1.45

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenosine catabolic process
• allantoin metabolic process
• amide catabolic process
• AMP catabolic process
• dAMP catabolic process
• deoxyadenosine catabolic process
• deoxyguanosine catabolic process
• deoxyinosine catabolic process
• dGMP catabolic process
• GMP catabolic process
• guanine catabolic process
• IMP catabolic process
• inosine catabolic process
• iron-sulfur cluster assembly
• lactation
• regulation of epithelial cell differentiation
• hypoxanthine catabolic process
• xanthine catabolic process

Molecular functions

• 2 iron, 2 sulfur cluster binding
• FAD binding
• flavin adenine dinucleotide binding
• iron ion binding
• molybdopterin cofactor binding
• protein homodimerization activity
• hypoxanthine dehydrogenase activity
• hypoxanthine oxidase activity
• xanthine dehydrogenase activity
• xanthine oxidase activity

Cellular components

• cytosol
• extracellular space
• peroxisome
• sarcoplasmic reticulum

Protein domainsUniProt · Pfam · InterPro

• Aldehyde oxidase/xanthine dehydrogenase, a/b hammerhead
• 2Fe-2S ferredoxin-type iron-sulfur binding domain
• Molybdopterin dehydrogenase, FAD-binding
• [2Fe-2S]-binding
• CO dehydrogenase flavoprotein, C-terminal
• 2Fe-2S ferredoxin, iron-sulphur binding site
• Aldehyde oxidase/xanthine dehydrogenase, first molybdopterin binding domain
• Beta-grasp domain superfamily
• FAD-binding domain, PCMH-type
• FAD-binding, type PCMH, subdomain 1
• FAD-binding, type PCMH, subdomain 2
• Aldehyde oxidase/xanthine dehydrogenase-like
• Oxidoreductase, molybdopterin binding site
• 2Fe-2S ferredoxin-like superfamily
• FAD-binding, type PCMH-like superfamily
• CO dehydrogenase flavoprotein, C-terminal domain superfamily
• Aldehyde oxidase/xanthine dehydrogenase, a/b hammerhead superfamily
• [2Fe-2S]-binding domain superfamily
• Aldehyde oxidase/xanthine dehydrogenase, molybdopterin binding domain superfamily
• Aldehyde oxidase/xanthine dehydrogenase, second molybdopterin binding domain
• 2Fe-2S iron-sulfur cluster binding domain
• FAD binding domain in molybdopterin dehydrogenase
• Aldehyde oxidase and xanthine dehydrogenase, a/b hammerhead domain
• [2Fe-2S] binding domain
• Molybdopterin cofactor-binding domain
• CO dehydrogenase flavoprotein C-terminal domain
• Molybdopterin cofactor-binding domain
• Xanthine dehydrogenase, small subunit

KeywordsUniProt

• 2Fe-2S
• Cytoplasm
• Disulfide bond
• FAD
• Flavoprotein
• Iron
• Iron-sulfur
• Metal-binding
• Molybdenum
• NAD
• Oxidoreductase
• Peroxisome
• Secreted

InteractionsUniProt · HPA

Protein binding partners of XDH in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• BTN1A1