The primary structure of the rat guanylyl cyclase A/atrial natriuretic peptide receptor gene.
We have isolated and characterized three genomic clones and a genomic fragment amplified by the polymerase chain reaction that contain the rat guanylyl cyclase-A (GC-A)/atrial natriuretic peptide receptor gene. The gene spans about 17.5 kilobases and includes 22 exons and 21 introns. All of the exon-intron junction sequences coincide with the GT/AG consensus. GC-A consists of at least the following four distinguishable domains: extracellular ligand binding, transmembrane, kinase-like, and cyclase catalytic. Exon 7 encodes the putative transmembrane domain. The kinase-like and catalytic domains are encoded by exons 8-15 and 16-22, respectively. The 5' end of the transcript, estimated by primer extension and S1 mapping, is 370 nucleotides upstream of the methionine initiation codon. The initiator sequence (-3 to +5) of CACACTCC has two mismatches when compared with a consensus initiator sequence of CTCANTCT. The 5'-flanking region contains three potential Sp1-binding sites and an inverted CCAAT box, but no apparent TATA box. Three different and short interspersed, repetitive sequences are found within intervening sequences and within the 5'- and 3'-flanking regions of the gene (five rat identifier, two rat type 2 Alu equivalent, and seven Alu-like sequences). They fall between the four major domains suggestive that these may be sites for frequent recombination events. This first reported structure of a gene for a member of this new enzyme/receptor family should facilitate the search for new family members, as well as allow studies to progress on the mechanisms by which the gene is regulated.
Yamaguchi
M
M
Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Rutledge
L J
LJ
Garbers
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D005091:Exons; D005796:Genes; D006162:Guanylate Cyclase / Q000235:genetics*; D007438:Introns; D007527:Isoenzymes / Q000235:genetics*; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000235:genetics*; D015183:Restriction Mapping; D016385:TATA Box; D014158:Transcription, Genetic
D007527:Isoenzymes; D015345:Oligonucleotide Probes; D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor