Human Gene SLC6A4 (ENST00000261707.7) Description and Page Index
Description: Serotonin 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. (from UniProt P31645) RefSeq Summary (NM_001045): This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]. Sequence Note: The RefSeq transcript and protein were derived from transcript and genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments. There is an upstream in-frame AUG at nt 451-453 with a weak Kozak signal. This was not annotated as the translation start because it has a weak Kozak signal, while the downstream AUG at nt 577-579 has a strong Kozak signal, and is not conserved in-frame in other vertebrates except chimp. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AK313166.1, AK308014.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1968189 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## CDS uses downstream in-frame AUG :: upstream AUG and CDS extension is not conserved MANE Ensembl match :: ENST00000650711.1/ ENSP00000498537.1 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END## Gencode Transcript: ENST00000261707.7 Gencode Gene: ENSG00000108576.10 Transcript (Including UTRs) Position: hg38 chr17:30,194,321-30,235,968 Size: 41,648 Total Exon Count: 15 Strand: - Coding Region Position: hg38 chr17:30,198,456-30,221,958 Size: 23,503 Coding Exon Count: 13
ID:SC6A4_HUMAN DESCRIPTION: RecName: Full=Sodium-dependent serotonin transporter; AltName: Full=5HT transporter; Short=5HTT; AltName: Full=Solute carrier family 6 member 4; FUNCTION: Serotonin 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. SUBUNIT: Monomer 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. SUBCELLULAR LOCATION: Cell 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. TISSUE SPECIFICITY: Expressed in platelets (at protein level). INDUCTION: Down-regulated when plasma serotonin is elevated. PTM: Glycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each other and to function as homooligomeric forms (By similarity). PTM: Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation (By similarity). Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity. POLYMORPHISM: A 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. POLYMORPHISM: The polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder (OCD) [MIM:164230]. POLYMORPHISM: Genetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIM:103780]. MISCELLANEOUS: This protein is the target of psychomotor stimulants such as amphetamines or cocaine. SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SLC6A4"; WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=SLC6A4"; WEB RESOURCE: Name=Wikipedia; Note=Serotonin transporter entry; URL="http://en.wikipedia.org/wiki/Serotonin_transporter"; WEB RESOURCE: Name=Protein Spotlight; Note=Love, love, love...- Issue 123 of November 2010; URL="http://web.expasy.org/spotlight/back_issues/sptlt123.shtml"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/slc6a4/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P31645
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.