Cloning and expression of the human N-acetylglutamate synthase gene.
N-acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme catalyzing the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthase I (CPSI), the first enzyme of the urea cycle. Patients with NAGS deficiency develop hyperammonemia because CPSI is inactive without NAG. The human NAGS cDNA was isolated from a liver library based on its similarity to mouse NAGS. The deduced amino acid sequence contains an N-terminal putative mitochondrial targeting signal of 49 amino acids (63% identity with mouse NAGS) followed by a "variable domain" of 45 amino acids (35% identity) and a "conserved domain" of 440 amino acids (92% identity). A cDNA sequence containing the "conserved domain" complements an NAGS-deficient Escherichia coli strain and the recombinant protein has arginine-responsive NAGS catalytic activity. The NAGS gene is expressed in the liver and small intestine; the intestinal transcript is smaller in size than liver transcript.
Caldovic
Ljubica
L
Children's Research Institute, Children's National Medical Center, The George Washington University, 111 Michigan Ave NW, Washington, DC 20010, USA.
Morizono
Hiroki
H
Gracia Panglao
Maria
M
Gallegos
Rene
R
Yu
Xiaolin
X
Shi
Dashuang
D
Malamy
Michael H
MH
Allewell
Norma M
NM
Tuchman
Mendel
M
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D051046:Amino-Acid N-Acetyltransferase; D000818:Animals; D003001:Cloning, Molecular; D015723:Gene Library; D005816:Genetic Complementation Test; D006801:Humans; D008099:Liver / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution
D011994:Recombinant Proteins; D000123:Acetyltransferases; D051046:Amino-Acid N-Acetyltransferase; C494874:NAGS protein, human; C494877:Nags protein, mouse