Two genes for de novo purine nucleotide synthesis on human chromosome 4 are closely linked and divergently transcribed.
A cDNA encoding human glutamine phosphoribosylpyrophosphate amidotransferase for step one in de novo purine nucleotide synthesis was cloned, sequenced, and expressed in Chinese hamster ovary cells to yield functional enzyme. Enzyme function was dependent upon removal of an 11-amino-acid propeptide. A mutant enzyme having three propeptide amino acid replacements was not processed and was not active. The human genes GPAT, encoding the amidotransferase, and AIRC, encoding a bifunctional enzyme for steps six and seven in the pathway, were cloned and characterized. GPAT and AIRC are closely linked and divergently transcribed from an intergenic region of approximately 625 base pairs. Expression of a luciferase reporter from the GPAT promoter was approximately 3-4-fold higher than from the AIRC promoter. The GPAT gene was mapped to the q12 region of chromosome 4.
Brayton
K A
KA
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907.
Chen
Z
Z
Zhou
G
G
Nagy
P L
PL
Gavalas
A
A
Trent
J M
JM
Deaven
L L
LL
Dixon
J E
JE
Zalkin
H
H
D000582:Amidophosphoribosyltransferase / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001412:Bacillus subtilis / Q000201:enzymology; D001483:Base Sequence; D015139:Blotting, Southern; D016466:CHO Cells; D002262:Carboxy-Lyases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002645:Chickens; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D004926:Escherichia coli / Q000201:enzymology; D005796:Genes; D008040:Genetic Linkage; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011544:Pseudogenes; D011685:Purine Nucleotides / Q000096:biosynthesis*; D051381:Rats; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
D011685:Purine Nucleotides; D004247:DNA; D000582:Amidophosphoribosyltransferase; D002262:Carboxy-Lyases; C022378:phosphoribosylaminoimidazole carboxylase