cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase.
We isolated cDNAs encoding xanthine dehydrogenase (XD; xanthine:NAD+ oxidoreductase, EC 1.1.1.204) from a human liver cDNA library. The complete nucleotide sequence of human XD was determined; the deduced amino acid sequence encoded a protein of 1336 amino acid residues of M(r) 147,782. Human XD possessed many of the signature sequences typical of XDs from flies and rodents, including an unusual cysteine distribution, a potential 2Fe/2S binding site, and a putative molybdopterin cofactor binding domain. Analysis of potential NAD binding sites suggested a simple hypothesis for the conversion of human XD into the oxygen metabolite forming xanthine oxidase (XO; xanthine:oxygen oxidoreductase, EC 1.1.3.22). Using a human XD complementary RNA hybridization probe, we found a 5100-base RNA in human liver by RNA blot-hybridization analysis. This RNA exhibited tissue-specific distribution that may be pertinent to XD- and XO-mediated oxygen radical injury in ischemia/reperfusion and inflammation. A second 4500-base RNA was detected in some tissues and may arise through differential transcription termination.
Wright
R M
RM
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262-0059.
Vaitaitis
G M
GM
Wilson
C M
CM
Repine
T B
TB
Terada
L S
LS
Repine
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004175:Diptera / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014968:Xanthine Dehydrogenase / Q000235:genetics*; D014969:Xanthine Oxidase / Q000235:genetics*
D018076:DNA, Complementary; D012333:RNA, Messenger; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase