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 isolated and sequenced using the PCR. The cDNA represents a approximately 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 approximately 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.
Lesch
K P
KP
Department of Psychiatry, University of Würzburg, F.R.G.
Wolozin
B L
BL
Murphy
D L
DL
Reiderer
P
P
D000328:Adult; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D017433:Protein Structure, Secondary; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011903:Raphe Nuclei / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000097:blood* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009838:Oligodeoxyribonucleotides; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D012313:RNA