5HT4R, is an ~45kD multipass serotonin receptor that is expressed in the brain, gastrointestinal tract, bladder, vascular endothelial cells, atrium, kidney, and adrenal gland. It is involved in the regulation of learning, memory, anxiety, smooth muscle contraction, and adrenal corticosteroid secretion. Alternate splicing of human 5HT4R generates multiple isoforms with either a 14aa insertion in the second extracellular loop or a deletion or various substitutions in the C-terminal cytoplasmic region. Different isoforms show tissue specific expression patterns or increased activity in the absence of ligand. Human 5HT4R shares 94-88aa sequence identity with mouse and rat 5HT4R, respectively.
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