Organization and nucleotide sequence of the 3' end of the human CAD gene.
Aspartate transcarbamylase (ATCase) is found as a monofunctional protein in prokaryotes and as a part of a multifunctional protein in fungi and animals. In mammals, this enzyme along with carbamyl phosphate synthetase II and dihydroorotase (DHOase) is encoded by a single gene called CAD. To determine the relationship between gene structure and the enzymatic domains of human CAD, we have isolated genomic clones of the human gene and sequenced the region corresponding to the 3' end of the gene. This includes exons encoding the end of the domain for DHOase, the complete domain for ATCase, and the bridge region connecting the two enzymatic domains. Three findings emerged. First, in comparing the human coding sequence to that obtained for other species that have a CAD gene, the length of the bridge region is conserved but its sequence is not. This is in contrast to the strong degree of positional identity observed for the segments of CAD encoding the DHOase and ATCase domains. Second, sets of exons appear to correspond to specific domains and subdomains of the encoded protein. Third, while overall there is a strong conservation of protein sequence among the ATCases of all species, reflecting conservation in catalytic function, two particular regions of the enzyme are more highly conserved among species where ATCase is a domain of a multifunctional protein as opposed to species where it is a monofunctional protein. Such findings may indicate regions of the ATCase domain that provide important structural contacts or functional channels when part of a multifunctional protein.
Davidson
J N
JN
University of Kentucky, Lexington 40536-0084.
Rao
G N
GN
Niswander
L
L
Andreano
C
C
Tamer
C
C
Chen
K C
KC
D000595:Amino Acid Sequence; D001221:Aspartate Carbamoyltransferase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004080:Dihydroorotase / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D009097:Multienzyme Complexes; C019820:carbamoyl phosphate synthase-aspartatecarbamoyl transferase complex; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)