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MGP002868

UniProt Annotations

Entry Information
Gene Namesolute carrier family 6 (neurotransmitter transporter), member 4
Protein EntrySC6A4_HUMAN
UniProt IDP31645
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P31645-1; Sequence=Displayed; Name=2; IsoId=P31645-2; Sequence=VSP_046553;
FunctionSerotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner. {ECO:0000269|PubMed:17506858, ECO:0000269|PubMed:18227069, ECO:0000269|PubMed:19270731}.
InductionDown-regulated when plasma serotonin is elevated. {ECO:0000269|PubMed:18227069, ECO:0000269|PubMed:19270731}.
MiscellaneousThis protein is the target of psychomotor stimulants such as amphetamines or cocaine.
PolymorphismA polymorphism in the promoter region (5-HTT gene- linked polymorphic region, 5-HTTLPR) is located approximately 1 kb upstream of the transcription initiation site and is composed of 16 repeat elements. The polymorphism consists of a 44-bp insertion or deletion involving repeat elements 6 to 8. The short allele is associated with lower transcriptional efficiency of the promoter compared with the long allele. Over half of the Caucasian population has a short allele. Individuals with one or two copies of the short allele exhibit more depressive symptoms, diagnosable depression and suicidality in relation to stressful life events than individuals homozygous for the long allele.
PolymorphismGenetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIM:103780].
PolymorphismThe polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder (OCD) [MIM:164230].
PtmGlycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each other and to function as homooligomeric forms. {ECO:0000250}.
PtmPhosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity. {ECO:0000269|PubMed:17913921, ECO:0000269|PubMed:19270731, ECO:0000269|PubMed:21992875}.
SimilarityBelongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily. {ECO:0000305}.
Subcellular LocationCell membrane; Multi-pass membrane protein. Endomembrane system; Multi-pass membrane protein. Endosome membrane; Multi-pass membrane protein. Note=Translocates from intracellular locations to the plasma membrane. Density of transporter molecules on the plasma membrane is itself regulated by serotonin.
SubunitMonomer or homooligomer (By similarity). Interacts with TGFB1I1. Interacts (via sialylated form) with MYH9. Interacts with SEC23A, SEC24C and INADL. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake. Interacts with filamentous actin and STX1A (By similarity). Interacts (via C- terminus) with VIM. Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly. {ECO:0000250, ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:16870614, ECO:0000269|PubMed:18227069, ECO:0000269|PubMed:19270731}.
Tissue SpecificityExpressed in platelets (at protein level). {ECO:0000269|PubMed:17506858}.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/slc6a4/";
Web ResourceName=Protein Spotlight; Note=Love, love, love... -Issue 123 of November 2010; URL="http://web.expasy.org/spotlight/back_issues/123";
Web ResourceName=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=SLC6A4";
Web ResourceName=Wikipedia; Note=Serotonin transporter entry; URL="http://en.wikipedia.org/wiki/Serotonin_transporter";
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