THE HUMAN 5-HT2 RECEPTOR IS ENCODED BY A MULTIPLE INTRON EXON GENE

Serotonin (5-hydroxytryptamine; 5-HT) mediates many central and peripheral nervous system functions by its interaction with specific neuronal receptors. Here we report the genomic structure of the human 5-HT2 receptor. The SacI-EcoRI restriction fragment of rat 5-HT2 receptor cDNA was used as a probe to identify and isolate two positive clones of 8.5 and 7.0 kb from an EcoRI restriction digest of a chromosome 13 specific EcoRI fragment lambda-phage human genomic library. Subcloning and sequencing of these fragments showed the 8.5 kb fragment (designated lambda-SE-5) contained the first two exons of the 5-HT2 receptor gene. The 7.0 kb insert (lambda-SE-2) contained an incomplete third exon. A HindIII-EcoRI fragment of this insert was used as a probe to isolate a 9.0 kb clone (lambda-SH-2), which contained the entire third exon, from a chromosome 13 specific HindIII-fragment lambda-phage human genomic library. The isolation of these three clones (lambda-SE-5, lambda-SE-2 and lambda-SH-2) shows that the human 5-HT2 receptor gene consists of three exons separated by two introns and spans over 20 kb. The deduced amino acid sequence of the human. mouse and rat 5-HT2 receptors are highly conserved and all three share a 90% sequence similarity.