Details of the Target
General Information of Target
Target ID | LDTP03605 | |||||
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Target Name | Sodium-dependent serotonin transporter (SLC6A4) | |||||
Gene Name | SLC6A4 | |||||
Gene ID | 6532 | |||||
Synonyms |
HTT; SERT; Sodium-dependent serotonin transporter; SERT; 5HT transporter; 5HTT; Solute carrier family 6 member 4 |
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3D Structure | ||||||
Sequence |
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT PGTFKERIIKSITPETPTEIPCGDIRLNAV |
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Target Type |
Successful
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Target Bioclass |
Transporter and channel
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Family |
Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family, SLC6A4 subfamily
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Subcellular location |
Cell membrane
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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.
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TTD ID | ||||||
Uniprot ID | ||||||
DrugMap ID | ||||||
Ensemble ID | ||||||
HGNC ID | ||||||
ChEMBL ID |
Target Site Mutations in Different Cell Lines
Cell line | Mutation details | Probe for labeling this protein in this cell | |||
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HT115 | SNV: p.A401T | DBIA Probe Info | |||
KMS11 | SNV: p.S532R | DBIA Probe Info | |||
MCC13 | SNV: p.L292F | DBIA Probe Info | |||
NCIH446 | SNV: p.G342R | . | |||
NCIH661 | SNV: p.G517V | . | |||
OVCAR4 | SNV: p.S48L | DBIA Probe Info | |||
SHP77 | SNV: p.V281M | DBIA Probe Info |
Probe(s) Labeling This Target
ABPP Probe
Probe name | Structure | Binding Site(Ratio) | Interaction ID | Ref | |
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DBIA Probe Info |
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C2971(3.49); C636(2.36) | LDD3311 | [1] | |
NAIA_5 Probe Info |
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C664(0.00); C1524(0.00); C431(0.00); C278(0.00) | LDD2224 | [2] |
Competitor(s) Related to This Target
References