Protein / target
Sodium-dependent serotonin transporter
Protein at a glance
Biological role
Neurotransmitter transmembrane transporter activity
Primary system
Nervous system
Strongest disease association
obsessive-compulsive disorder
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
53 approved · 11 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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 (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)
Subcellular location
Domains and Gene Ontology detail (54)Hide
Gene Ontology
- Cendomembrane system
- Cendosome membrane
- Cfocal adhesion
- CGolgi apparatus
- Cmembrane raft
- Cneuron projection
- Cplasma membrane
- Cpostsynaptic membrane
- Cpresynaptic membrane
- Cserotonergic synapse
- Csynapse
- Factin filament binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Synaptic signalling
- ·Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one…
- ·Synapse
- ·postsynaptic membrane
- ·presynaptic membrane
Haemostasis
- ·Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one…
- ·platelet aggregation
Ion channel gating
- ·monoatomic cation channel activity
- ·sodium ion transmembrane transport
Excitatory neurotransmission
- ·Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one…
Cell adhesion
- ·Cell junction, focal adhesion
Transcriptional regulation
- ·positive regulation of gene expression
View underlying pathways (2)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Serotonin transporter inhibitor
Appears in clinical studies involving major depressive disorder, fibromyalgia, muscular disease, neuropathic pain
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,176 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 67 total
major depressive disorder · generalized anxiety disorder · depressive disorder
major depressive disorder
attention deficit-hyperactivity disorder · Pain · obsessive-compulsive disorder
major depressive disorder · cocaine abuse · cocaine use disorder
major depressive disorder · major depressive episode · fibromyalgia
obsessive-compulsive disorder · anxiety disorder · panic disorder
major depressive disorder · schizophrenia · pulmonary hypertension
depressive disorder · major depressive disorder · Agitation
major depressive disorder
major depressive disorder · melancholia · depressive disorder
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- Product recall
Recall (Class II): DULOXETINE HYDROCHLORIDE
- Product recall
Recall (Class II): DULOXETINE HYDROCHLORIDE
- Product recall
Recall (Class II): DULOXETINE HYDROCHLORIDE
- Product recall
Recall (Class II): DULOXETINE HYDROCHLORIDE
- New publicationPrevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.
- New publicationDuloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China.
- New publicationEfficacy and safety of duloxetine 60 mg and 120 mg daily in patients hospitalized for severe depression: a double-blind randomized trial.
- Regulatory approval
Approval: Yentreve (EMA)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.