PMID:7681602

Citation	Ramamoorthy, S, Bauman, AL, Moore, KR, Han, H, Yang-Feng, T, Chang, AS, Ganapathy, V and Blakely, RD (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc. Natl. Acad. Sci. U.S.A. 90:2542-6
Abstract	A Na(+)- and Cl(-)-coupled serotonin (5-hydroxytryptamine, 5HT) transporter is expressed on human neuronal, platelet, placental, and pulmonary membranes. The brain 5HT transporter appears to be a principal site of action of therapeutic antidepressants and may mediate behavioral and/or toxic effects of cocaine and amphetamines. Oligonucleotides derived from consensus transporter sequences were used to identify human placental cDNAs highly related to the rat brain 5HT carrier. Transfection of one of these cDNAs into HeLa cells yields a high-affinity (Km = 463 nM), Na(+)- and Cl(-)-dependent 5HT transport activity which can be blocked by selective 5HT transport inhibitors, including paroxetine, fluoxetine, and imipramine, and which is antagonized by cocaine and amphetamine. Sequence analysis reveals a 630-amino acid open reading frame bearing 92% identity to the cloned rat brain 5HT transporter, with identical predicted topological features and conserved sites for posttranslational modifications. Unlike the rodent, where a single mRNA appears to encode 5HT transporters, multiple hybridizing RNAs are observed in human placenta and lung. Somatic cell hybrid and in situ hybridization studies are consistent, however, with a single gene encoding the human 5HT transporter, localized to chromosome 17q11.1-17q12.
Links	PubMed PMC46124
Keywords	Amino Acid Sequence; Antidepressive Agents/pharmacology; Base Sequence; Binding, Competitive; Blood Platelets/metabolism; Carrier Proteins/drug effects; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Cocaine/pharmacology; Female; HeLa Cells; Humans; Kinetics; Lung/metabolism; Membrane Glycoproteins/drug effects; Membrane Glycoproteins/genetics; Membrane Glycoproteins/metabolism; Membrane Transport Proteins; Molecular Sequence Data; Nerve Tissue Proteins; Neurons/metabolism; Oligodeoxyribonucleotides; Placenta/physiology; Poly A/genetics; Poly A/isolation & purification; Polymerase Chain Reaction/methods; Pregnancy; RNA/genetics; RNA/isolation & purification; RNA, Messenger; Serotonin/metabolism; Serotonin Plasma Membrane Transport Proteins; Sodium/pharmacology; Transfection; Trophoblasts/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:SC6A4	involved_in	GO:0051610: serotonin uptake	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:SC6A4		GO:0051610: serotonin uptake	ECO:0000315:		P		Figure 2 shows the antagonism of cocaine in uptake assays.	complete CACAO 9340

References

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