A cluster of novel serotonin receptor 3-like genes on human chromosome 3.
The ligand-gated ion channel family includes receptors for serotonin (5-hydroxytryptamine, 5-HT), acetylcholine, GABA, and glutamate. Drugs targeting subtypes of these receptors have proven useful for the treatment of various neuropsychiatric and neurological disorders. To identify new ligand-gated ion channels as potential therapeutic targets, drafts of human genome sequence were interrogated. Portions of four novel genes homologous to 5-HT(3A) and 5-HT(3B) receptors were identified within human sequence databases. We named the genes 5-HT(3C1)-5-HT(3C4). Radiation hybrid (RH) mapping localized these genes to chromosome 3q27-28. All four genes shared similar intron-exon organizations and predicted protein secondary structure with 5-HT(3A) and 5-HT(3B). Orthologous genes were detected by Southern blotting in several species including dog, cow, and chicken, but not in rodents, suggesting that these novel genes are not present in rodents or are very poorly conserved. Two of the novel genes are predicted to be pseudogenes, but two other genes are transcribed and spliced to form appropriate open reading frames. The 5-HT(3C1) transcript is expressed almost exclusively in small intestine and colon, suggesting a possible role in the serotonin-responsiveness of the gut.
Department of Bioinformatics, Pharmacia Corporation, Kalamazoo, MI 49007, USA.
Alla M
AM
Karnovsky
Lisa F
LF
Gotow
Denise D
DD
McKinley
Julie L
JL
Piechan
Cara L
CL
Ruble
Cynthia J
CJ
Mills
Kathleen A B
KA
Schellin
Jerry L
JL
Slightom
Laura R
LR
Fitzgerald
Christopher W
CW
Benjamin
Steven L
SL
Roberds
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003001:Cloning, Molecular; D005091:Exons; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D021101:Radiation Hybrid Mapping; D044406:Receptors, Serotonin, 5-HT3 / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D044406:Receptors, Serotonin, 5-HT3