Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system.
In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes.
Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied.
The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672).
Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)
Monomer or homooligomer (By similarity). Interacts with TGFB1I1 (PubMed:16803896). Interacts with SEC23A, SEC24C and PATJ.
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 the N-terminus) with STX1A (via the H3 domain); this interaction regulates SLC4A6 channel conductance (By similarity).
Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly (PubMed:16870614). Interacts with ITGAV:ITGB3 (PubMed:18317590). Interacts (via C-terminus) with ITGB3; this interaction regulates SLC6A4 trafficking (PubMed:18317590)
Expressed in platelets (at protein level)
No mutation information available.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to HTT, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 60
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT07057011 | Premature Ejaculation | Therapeutic Outcomes of Selective Serotonin Reuptake Inhibitors and Phosphodiesterase-5 Inhibitors Combination Therapy Versus Monotherapy | NA | NOT_YET_RECRUITING |
| NCT01710202 | Major Depressive Disorder, Anxiety Disorders | Sensitivity of Short and Long Allele Carriers of the 5-HTTLPR to Environmental Threat Post Hydrocortisone Administration | N/A | COMPLETED |
| NCT04540029 | Prenatal Stress | Measuring Outcomes of Maternal COVID-19-related Prenatal Exposure | N/A | COMPLETED |
| NCT00920946 | Huntington Disease | A Safety and Efficacy Study of Dimebon in Patients With Huntington Disease | PHASE3 | COMPLETED |
| NCT04120493 | Huntington's Disease | Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington's Disease | PHASE1, PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT01936051 | OCD | Modeling Between Plasma Concentration and Serotonin Transporter Occupancy Induced by Escitalopram in Obsessive-compulsive Disorder(OCD) Patients | N/A | COMPLETED |
| NCT07378644 | Huntington Disease | Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 in Participants With Huntington's Disease | PHASE2, PHASE3 | RECRUITING |
| NCT00456430 | Depression | Serotonin Transporter Genetic Variation and Amygdalar Activation Correlates of Antidepressant Response | PHASE4 | COMPLETED |
| NCT02132286 | Major Depressive Disorder | Serotonin Transporter Genetic Variation and Amygdala Responses to Antidepressant Medications in Major Depression | PHASE4 | COMPLETED |
| NCT06082713 | Huntington Disease | Extracellular Vesicles for HD | N/A | RECRUITING |