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SERT

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Target not currently curated in GtoImmuPdb

Target id: 928

Nomenclature: SERT

Systematic Nomenclature: SLC6A4

Family: Monoamine transporter subfamily

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 630 17q11.2 SLC6A4 solute carrier family 6 member 4
Mouse - 630 11 46.18 cM Slc6a4 solute carrier family 6 (neurotransmitter transporter, serotonin), member 4
Rat - 630 10q26 Slc6a4 solute carrier family 6 member 4
Previous and Unofficial Names Click here for help
5-HTT | SERT1 | HTT | 5HT transporter | 5HTT | serotonin transporter | sodium-dependent serotonin transporter | solute carrier family 6 (neurotransmitter transporter), member 4 | solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 | solute carrier family 6 (neurotransmitter transporter
Database Links Click here for help
Specialist databases
Bioparadigms SLC Tables SLC6A4 (Hs)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the ts3 human serotonin transporter complexed with s-citalopram at the central and allosteric sites
PDB Id:  5I73
Ligand:  escitalopram
Resolution:  3.24Å
Species:  Human
References:  7
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the ts3 human serotonin transporter complexed with paroxetine at the central site
PDB Id:  5I6X
Ligand:  paroxetine
Resolution:  3.14Å
Species:  Human
References:  7
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
5-hydroxytryptamine Substrate is endogenous in the given species Hs -
MDMA Hs -
p-chloroamphetamine Hs -
Stoichiometry Click here for help
1 5-HT:1 Na+:1 Cl- (in), + 1 K+ (out) [21]

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
paroxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 10.1 pKd 7
pKd 10.1 (Kd 8x10-11 M) [7]
[3H]paroxetine Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Inhibition 9.7 pKd
pKd 9.7 (Kd 2x10-10 M)
clomipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.6 pKd 22
pKd 9.6 (Kd 2.8x10-10 M) [22]
escitalopram Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.7 pKd 7
pKd 8.7 (Kd 2.1x10-9 M) [7]
fluvoxamine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.7 pKd 22
pKd 8.7 (Kd 2.2x10-9 M) [22]
[3H]citalopram Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Inhibition 8.3 pKd
pKd 8.3 (Kd 5x10-9 M)
atomoxetine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.1 pKd 6
pKd 8.1 (Kd 8.9x10-9 M) [6]
protriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pKd 22
pKd 7.7 (Kd 1.96x10-8 M) [22]
nefazodone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.7 pKd 6
pKd 6.7 (Kd 2x10-7 M) [6]
clomipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.7 pKi 22
pKi 9.7 (Ki 2.1x10-10 M) [22]
paroxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.6 pKi 22
pKi 9.6 (Ki 2.5x10-10 M) [22]
sertraline Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.1 pKi
pKi 9.1 (Ki 7.9x10-10 M)
vortioxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.8 pKi 4
pKi 8.8 (Ki 1.6x10-9 M) [4]
fluoxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.5 pKi 22
pKi 8.5 (Ki 3x10-9 M) [22]
citalopram Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.4 pKi 5
pKi 8.4 (Ki 4.38x10-9 M) [5]
Description: Displacement of [3H]citalopram from human SERT expressed in HEK293 cells.
H05 Small molecule or natural product Click here for species-specific activity table Rn Inhibition 8.3 pKi 25
pKi 8.3 (Ki 4.81x10-9 M) [25]
duloxetine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.3 pKi 10
pKi 8.3 (Ki 5x10-9 M) [10]
fluvoxamine Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Rn Inhibition 8.2 pKi 13
pKi 8.2 (Ki 6.5x10-9 M) [13]
Description: Inhibition of [3]5-HT uptake into rat astrocyte cultures.
nortriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKi 3
pKi 8.2 (Ki 6.98x10-9 M) [3]
dosulepin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pKi 22
pKi 8.1 (Ki 8.6x10-9 M) [22]
desvenlafaxine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.8 pKi 9
pKi 7.8 (Ki 1.5x10-8 M) [9]
amoxapine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pKi 3
pKi 7.7 (Ki 1.8x10-8 M) [3]
desipramine Small molecule or natural product Approved drug Ligand has a PDB structure Rn Inhibition 7.7 pKi 1
pKi 7.7 (Ki 2x10-8 M) [1]
imipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pKi 20
pKi 7.7 (Ki 2.03x10-8 M) [20]
Description: Displacement of [3H]citalopram from hSERT.
ziprasidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.3 pKi
pKi 7.3 (Ki 5.3x10-8 M)
lofepramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.2 pKi 22
pKi 7.2 (Ki 6x10-8 M) [22]
lumateperone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.2 pKi 14,19
pKi 7.2 (Ki 6.2x10-8 M) [14,19]
doxepin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.2 pKi 22
pKi 7.2 (Ki 6.8x10-8 M) [22]
amitriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKi 2
pKi 6.8 (Ki 1.41x10-7 M) [2]
trimipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.8 pKi 22
pKi 6.8 (Ki 1.49x10-7 M) [22]
desipramine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKi 15
pKi 6.8 (Ki 1.63x10-7 M) [15]
Description: Assay using HEK-293 cells transfected with hSERT
sibutramine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.0 pKi 3
pKi 6.0 (Ki 1.108x10-6 M) [3]
phenelzine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition <5.0 pKi 22
pKi <5.0 (Ki >1x10-5 M) [22]
vilazodone Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.8 – 9.3 pIC50 8,12
pIC50 8.8 – 9.3 (IC50 1.58x10-9 – 5x10-10 M) [8,12]
escitalopram Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 9.0 pIC50 16
pIC50 9.0 (IC50 1x10-9 M) [16]
dapoxetine Small molecule or natural product Approved drug Primary target of this compound Hs Inhibition 8.9 pIC50 11
pIC50 8.9 (IC50 1.12x10-9 M) [11]
Description: Inhibition of the reuptake of [3H]5-HT
venlafaxine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 17
pIC50 7.6 (IC50 2.7x10-8 M) [17]
milnacipran Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.3 pIC50 23
pIC50 7.3 (IC50 5.012x10-8 M) [23]
levomilnacipran Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.5 pIC50 24
pIC50 6.5 (IC50 3.2x10-7 M) [24]
norzotepine Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.2 pIC50 18
pIC50 5.2 (IC50 6.191x10-6 M) [18]
zotepine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.1 pIC50 18
pIC50 5.1 (IC50 7.27x10-6 M) [18]
View species-specific inhibitor tables
Inhibitor Comments
Although nefazodone is claimed to be an inhibitor of the serotonin and norepinephrine transporters, the dopamine transporter appears to have a similar dissociation constant to the norepinephrine transporter [6].

Occupancy of the allosteric site by escitalopram sterically hinders ligand unbinding from the central site. This allows the drug to negatively regulate (inhibit) SERT activity [7].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Htr2atm1Grch|Htr2atm2Grch|Slc6a4+|Slc6a4tm1(cre)Grch Htr2atm1Grch/Htr2atm2Grch,Slc6a4tm1(cre)Grch/Slc6a4+
involves: 129S6/SvEvTac
MGI:109521  MGI:96285  MP:0001362 abnormal anxiety-related response PMID: 16873667 
Htr1atm2Rhn|Slc6a4+|Slc6a4tm1(tTA)Cogr Htr1atm2Rhn/Htr1atm2Rhn,Slc6a4tm1(tTA)Cogr/Slc6a4+
involves: 129S1/Sv * BALB/cJ * C57BL/6 * CBA
MGI:96273  MGI:96285  MP:0006276 abnormal autonomic nervous system physiology PMID: 18599790 
Htr1btm1Rhn|Slc6a4tm1Kpl Htr1btm1Rhn/Htr1btm1Rhn,Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
MGI:96274  MGI:96285  MP:0000285 abnormal heart valve morphology PMID: 16380550 
Htr1atm2Rhn|Slc6a4+|Slc6a4tm1(tTA)Cogr Htr1atm2Rhn/Htr1atm2Rhn,Slc6a4tm1(tTA)Cogr/Slc6a4+
involves: 129S1/Sv * BALB/cJ * C57BL/6 * CBA
MGI:96273  MGI:96285  MP:0004811 abnormal neuron physiology PMID: 18599790 
Htr1btm1Rhn|Slc6a4tm1Kpl Htr1btm1Rhn/Htr1btm1Rhn,Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
MGI:96274  MGI:96285  MP:0003141 cardiac fibrosis PMID: 16380550 
Htr1atm2Rhn|Slc6a4+|Slc6a4tm1(tTA)Cogr Htr1atm2Rhn/Htr1atm2Rhn,Slc6a4tm1(tTA)Cogr/Slc6a4+
involves: 129S1/Sv * BALB/cJ * C57BL/6 * CBA
MGI:96273  MGI:96285  MP:0005534 decreased body temperature PMID: 18599790 
Htr1btm1Rhn|Slc6a4tm1Kpl Htr1btm1Rhn/Htr1btm1Rhn,Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
MGI:96274  MGI:96285  MP:0005140 decreased cardiac muscle contractility PMID: 16380550 
Htr1atm2Rhn|Slc6a4+|Slc6a4tm1(tTA)Cogr Htr1atm2Rhn/Htr1atm2Rhn,Slc6a4tm1(tTA)Cogr/Slc6a4+
involves: 129S1/Sv * BALB/cJ * C57BL/6 * CBA
MGI:96273  MGI:96285  MP:0005333 decreased heart rate PMID: 18599790 
Htr1atm2Rhn|Slc6a4+|Slc6a4tm1(tTA)Cogr Htr1atm2Rhn/Htr1atm2Rhn,Slc6a4tm1(tTA)Cogr/Slc6a4+
involves: 129S1/Sv * BALB/cJ * C57BL/6 * CBA
MGI:96273  MGI:96285  MP:0008770 decreased survivor rate PMID: 18599790 
Htr1btm1Rhn|Slc6a4tm1Kpl Htr1btm1Rhn/Htr1btm1Rhn,Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
MGI:96274  MGI:96285  MP:0002795 dilated cardiomyopathy PMID: 16380550 
Htr1btm1Rhn|Slc6a4tm1Kpl Htr1btm1Rhn/Htr1btm1Rhn,Slc6a4tm1Kpl/Slc6a4tm1Kpl
involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
MGI:96274  MGI:96285  MP:0003958 heart valve hyperplasia PMID: 16380550 
Htr1atm2Rhn|Slc6a4+|Slc6a4tm1(tTA)Cogr Htr1atm2Rhn/Htr1atm2Rhn,Slc6a4tm1(tTA)Cogr/Slc6a4+
involves: 129S1/Sv * BALB/cJ * C57BL/6 * CBA
MGI:96273  MGI:96285  MP:0002083 premature death PMID: 18599790 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Anxiety
OMIM: 607834
Disease:  Obsessive-compulsive disorder; OCD
Disease Ontology: DOID:10933
OMIM: 164230

References

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