Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus.
Agmatinase, which hydrolyzes agmatine to putrescine and urea, not only represents a potentially important mechanism for regulating the biological effects of agmatine in mammalian cells but also represents an alternative to ornithine decarboxylase for polyamine biosynthesis. We have isolated a full-length cDNA encoding human agmatinase whose function was confirmed by complementation in yeast. The single-copy human agmatinase gene located on chromosome 1 encodes a 352-residue protein with a putative mitochondrial targeting sequence at the NH(3)-terminus. Human agmatinase has about 30% identity to bacterial agmatinases and <20% identity to mammalian arginases. Residues required for binding of Mn(2+) at the active site in bacterial agmatinase and other members of the arginase superfamily are fully conserved in human agmatinase. Agmatinase mRNA is most abundant in human liver and kidney but also is expressed in several other tissues, including skeletal muscle and brain. Its expression in human liver is induced during hepatitis B virus infection, suggesting that agmatinase may play a role in the pathophysiology of this disease.
Mistry
Sanjay K
SK
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Burwell
Tim J
TJ
Chambers
Rebecca M
RM
Rudolph-Owen
Laura
L
Spaltmann
Frank
F
Cook
W Jim
WJ
Morris
Sidney M
SM
D001921:Brain / Q000201:enzymology; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D006509:Hepatitis B / Q000378:metabolism*; D006515:Hepatitis B virus; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D014512:Ureohydrolases / Q000235:genetics* / Q000378:metabolism*
D011073:Polyamines; D012333:RNA, Messenger; D014512:Ureohydrolases; C498226:AGMAT protein, human; C019625:agmatinase; D011700:Putrescine