PRIMARY STRUCTURE OF THE HUMAN PLATELET SEROTONIN UPTAKE SITE - IDENTITY WITH THE BRAIN-SEROTONIN TRANSPORTER

A cDNA encoding the human platelet serotonin (5-HT) uptake site was is olated and sequenced using the PCR. The cDNA represents a approximatel y 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 id entical with the human brain 5-HT transporter and approximately 92% ho mologous to the rat protein. Hydropathicity analysis indicates 12 memb rane-spanning segments with two putative glycosylation sites within th e second extracellular loop. The human platelet 5-HT uptake site conta ins two intraplasmatic consensus phosphorylation sites for cyclic AMP- dependent protein kinase recognition located in the cytoplasmatic N-te rminal region and three potential protein kinase C phosphorylation sit es. 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 gene tic investigations of the 5-HT transporter in psychiatric disorders.