Primary Structure of the Human Platelet Serotonin Uptake Site: Identity with the Brain Serotonin Transporter

Abstract

Abstract: A cDNA encoding the human platelet serotonin (5‐HT) uptake site was isolated and sequenced using the PCR. The cDNA represents a ˜3.1‐kb mRNA transcript and contains an open reading frame encoding a hydrophobic polypeptide of 630 amino acids with 12 membrane‐spanning segments, a calculated molecular mass of 70,320 Da, and an estimated isoelectrical point of 5.84. The human platelet 5‐HT uptake site is identical with the human brain 5‐HT transporter and ˜92% homologous to the rat protein. Hydropathicity analysis indicates 12 membrane‐spanning segments with two putative glycosylation sites within the second extracellular loop. The human platelet 5‐HT uptake site contains two intraplasmatic consensus phosphorylation sites for cyclic AMP‐dependent protein kinase recognition located in the cytoplasmatic N‐terminal region and three potential protein kinase C phosphorylation sites. The identity of the human platelet 5‐HT uptake site and the brain 5‐HT transporter indicates that both proteins are encoded by the same single‐copy gene, which has been assigned to the human chromosome 17. Our findings are likely to facilitate molecular pharmacologic and genetic investigations of the 5‐HT transporter in psychiatric disorders.