| Post Translational Modifications | Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. |
| Function | 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. 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. Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes. 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. 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. 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. |
| Protein Name | Sodium-Dependent Serotonin TransporterSert5ht Transporter5httSolute Carrier Family 6 Member 4 |
| Database Links | Reactome: R-HSA-380615 |
| Cellular Localisation | Cell MembraneMulti-Pass Membrane ProteinEndomembrane SystemEndosome MembraneSynapseCell JunctionFocal AdhesionCell ProjectionNeuron ProjectionCould Be Part Of Recycling EndosomesDensity Of Transporter Molecules On The Plasma Membrane Is Itself Regulated By Stx1aDensity Of Transporter Molecules On The Plasma Membrane Is Also Regulated By SerotoninDensity Of Transporter Molecules Seems To Be Modulated By Itgav:itgb3 |
| Alternative Protein Names | Sodium-Dependent Serotonin Transporter proteinSert protein5ht Transporter protein5htt proteinSolute Carrier Family 6 Member 4 proteinSLC6A4 proteinHTT proteinSERT protein |
Information sourced from Uniprot.org
