General Information of the Protein
Protein ID
PT00891
Protein Name
Sodium-dependent serotonin transporter
Secondarily
Protein Name
5HT transporter
Solute carrier family 6 member 4
Gene Name
SLC6A4
Sequence
METTPLNSQKVLSECKDREDCQENGVLQKGVPTTADRAEPSQISNGYSAVPSTSAGDEASHSIPAATTTLVAEIRQGERETWGKKMDFLLSVIGYAVDLGNIWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIIAWALYYLISSLTDRLPWTSCTNSWNTGNCTNYFAQDNITWTLHSTSPAEEFYLRHVLQIHQSKGLQDLGTISWQLTLCIVLIFTVIYFSIWKGVKTSGKVVWVTATFPYIVLSVLLVRGATLPGAWRGVVFYLKPNWQKLLETGVWVDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHIWAKRREWFVLIVVITCVLGSLLTLTSGGAYVVTLLEEYATGPAVLTVALIEAVAVSWFYGITQFCSDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPHWSIVLGYCIGMSSVICIPTYIIYRLISTPGTLKERIIKSITPETPTEIPCGDIRMNAV
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Organism
Rattus norvegicus, Rat
Protein Classification
Transporter
>
Electrochemical transporter
>
SLC superfamily of solute carriers
>
SLC06 neurotransmitter transporter family
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:1944572, PubMed:1948036, PubMed:8601815, PubMed:10407194, PubMed:10716733, PubMed:21730057, PubMed:15627510) (By similarity). 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 (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 (By similarity). 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:1944572, PubMed:1948036, PubMed:8601815, PubMed:10407194, PubMed:10716733, PubMed:21730057, PubMed:15627510) (By similarity). 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 (PubMed:8968583, PubMed:14642278).
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Uniprot ID
Primary ID:
P31652

Secondarily ID:
P23976
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Ensembl ID
ENSG00000108576
Subcellular Location
Cell membrane
Endomembrane system
Endosome membrane
Synapse
Cell junction
Focal adhesion
Cell projection
Neuron projection
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000011 , CHO
Compound ID Compound Name Compound Formula
CP0035807
Cocaine
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C17H21NO4
 1
1
IC50 = 400 nM
   TI
   LI
   LO
   TS
CP0933737
bip-tyr-thr-ala-pro-phe
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C45H52N6O10
 1
1
IC50 = 32000 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0035807
Cocaine
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C17H21NO4
 11
1 IC50 = 304 nM
2 IC50 = 1045 nM
3 IC50 = 1050 nM
4 IC50 = 1059 nM
5 Ki = 45 nM
6 Ki = 95 nM
7 Ki = 96 nM
8 Ki = 112.11 nM
9 Ki = 155 nM
10 Ki = 160 nM
11 Ki = 172 nM
CP0105706
10-methoxyibogamine
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C20H26N2O
 1
1 IC50 = 590 nM
CP0358061
2-(2-((dimethylamino)methyl)phenylthio)-5-iodoaniline
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C15H17IN2S
 1
1 Ki = 0.013 nM
Similar Protein(s) and Bioactivity Statistics
90% Identity
Protein ID Protein Name Protein Organism
PT01609 Sodium-dependent serotonin transporter Mus musculus, Mouse
50% Identity
Protein ID Protein Name Protein Organism
PT00871 Sodium-dependent serotonin transporter Homo sapiens, Human