Organization, structure, chromosomal assignment, and expression of the gene encoding the human endothelin-A receptor.
We have isolated and characterized the gene for the human endothelin-A receptor. Southern blot analyses demonstrated a single copy gene for the receptor. The gene spans more than 40 kilobases and contains eight exons and seven introns. Intron 1 exists in the 5'-noncoding region, and introns 2-7 occur in the coding region. The locations of introns 2-7 exist before or after the regions encoding the membrane-spanning domains. The transcription start site, determined by primer extension experiments, is 502 base pairs upstream of the methionine initiation codon. The 5'-flanking region lacks a typical TATA box but contains a potential SP-1-binding site 27 base pairs upstream of the transcription start site. Using human-rodent somatic hybrid cell DNA, the gene was assigned to human chromosome 4. Northern blot analyses revealed a 4.3-kilobase mRNA in a wide variety of human tissues, at the highest level in the aorta and at a substantial level in the cultured human mesangial cells. This is the first report of cloning of a gene for a member of the endothelin receptor family. The present study should give a clue to the discovery of possible disorders of the endothelin-A receptor, as well as facilitate the elucidation of the mechanisms by which the gene expression is regulated.
Hosoda
K
K
Department of Medicine, Kyoto University School of Medicine, Japan.
Nakao
K
K
Tamura
N
N
Arai
H
H
Ogawa
Y
Y
Suga
S
S
Nakanishi
S
S
Imura
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D006224:Cricetinae; D005091:Exons; D015870:Gene Expression; D006801:Humans; D006822:Hybrid Cells; D007438:Introns; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D017466:Receptors, Endothelin; D015183:Restriction Mapping; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D016329:Sp1 Transcription Factor