SERT

Target id: 928

Nomenclature: SERT

Systematic Nomenclature: SLC6A4

Family: Monoamine transporter subfamily

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for SERT in GtoImmuPdb

Gene and Protein Information
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
5-HTT | SERT1 | HTT | 5HT transporter | 5HTT | serotonin transporter | sodium-dependent serotonin transporter | solute carrier family 6 (neurotransmitter transporter), member 4
Database Links
Specialist databases
Bioparadigms SLC Tables SLC6A4 (Hs)
Other databases
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
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
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
5-hydroxytryptamine Hs -
MDMA Hs -
p-chloroamphetamine Hs -
Stoichiometry
1 5-HT:1 Na+:1 Cl- (in), + 1 K+ (out) [21]

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
paroxetine Hs Inhibition 10.1 pKd 7
pKd 10.1 (Kd 8x10-11 M) [7]
[3H]paroxetine Hs Inhibition 9.7 pKd
pKd 9.7 (Kd 2x10-10 M)
clomipramine Hs Inhibition 9.6 pKd 22
pKd 9.6 (Kd 2.8x10-10 M) [22]
escitalopram Hs Inhibition 8.7 pKd 7
pKd 8.7 (Kd 2.1x10-9 M) [7]
fluvoxamine Hs Inhibition 8.7 pKd 22
pKd 8.7 (Kd 2.2x10-9 M) [22]
[3H]citalopram Hs Inhibition 8.3 pKd
pKd 8.3 (Kd 5x10-9 M)
atomoxetine Hs Inhibition 8.1 pKd 6
pKd 8.1 (Kd 8.9x10-9 M) [6]
protriptyline Hs Inhibition 7.7 pKd 22
pKd 7.7 (Kd 1.96x10-8 M) [22]
nefazodone Hs Inhibition 6.7 pKd 6
pKd 6.7 (Kd 2x10-7 M) [6]
clomipramine Hs Inhibition 9.7 pKi 22
pKi 9.7 (Ki 2.1x10-10 M) [22]
paroxetine Hs Inhibition 9.6 pKi 22
pKi 9.6 (Ki 2.5x10-10 M) [22]
sertraline Hs Inhibition 9.1 pKi
pKi 9.1 (Ki 7.9x10-10 M)
vortioxetine Hs Inhibition 8.8 pKi 4
pKi 8.8 (Ki 1.6x10-9 M) [4]
fluoxetine Hs Inhibition 8.5 pKi 22
pKi 8.5 (Ki 3x10-9 M) [22]
citalopram 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.
duloxetine Hs Inhibition 8.3 pKi 10
pKi 8.3 (Ki 5x10-9 M) [10]
fluvoxamine 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 Hs Inhibition 8.2 pKi 3
pKi 8.2 (Ki 6.98x10-9 M) [3]
dosulepin Hs Inhibition 8.1 pKi 22
pKi 8.1 (Ki 8.6x10-9 M) [22]
desvenlafaxine Hs Inhibition 7.8 pKi 9
pKi 7.8 (Ki 1.5x10-8 M) [9]
amoxapine Hs Inhibition 7.7 pKi 3
pKi 7.7 (Ki 1.8x10-8 M) [3]
desipramine Rn Inhibition 7.7 pKi 1
pKi 7.7 (Ki 2x10-8 M) [1]
imipramine Hs Inhibition 7.7 pKi 20
pKi 7.7 (Ki 2.03x10-8 M) [20]
Description: Displacement of [3H]citalopram from hSERT.
ziprasidone Hs Inhibition 7.3 pKi
pKi 7.3 (Ki 5.3x10-8 M)
lofepramine Hs Inhibition 7.2 pKi 22
pKi 7.2 (Ki 6x10-8 M) [22]
lumateperone Hs Inhibition 7.2 pKi 14,19
pKi 7.2 (Ki 6.2x10-8 M) [14,19]
doxepin Hs Inhibition 7.2 pKi 22
pKi 7.2 (Ki 6.8x10-8 M) [22]
amitriptyline Hs Inhibition 6.8 pKi 2
pKi 6.8 (Ki 1.41x10-7 M) [2]
trimipramine Hs Inhibition 6.8 pKi 22
pKi 6.8 (Ki 1.49x10-7 M) [22]
desipramine 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 Hs Inhibition 6.0 pKi 3
pKi 6.0 (Ki 1.108x10-6 M) [3]
phenelzine Hs Inhibition <5.0 pKi 22
pKi <5.0 (Ki >1x10-5 M) [22]
vilazodone Hs Inhibition 8.8 – 9.3 pIC50 8,12
pIC50 8.8 – 9.3 (IC50 1.58x10-9 – 5x10-10 M) [8,12]
escitalopram Hs Inhibition 9.0 pIC50 16
pIC50 9.0 (IC50 1x10-9 M) [16]
dapoxetine 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 Hs Inhibition 7.6 pIC50 17
pIC50 7.6 (IC50 2.7x10-8 M) [17]
milnacipran Hs Inhibition 7.3 pIC50 23
pIC50 7.3 (IC50 5.012x10-8 M) [23]
levomilnacipran Hs Inhibition 6.5 pIC50 24
pIC50 6.5 (IC50 3.2x10-7 M) [24]
norzotepine Hs Inhibition 5.2 pIC50 18
pIC50 5.2 (IC50 6.191x10-6 M) [18]
zotepine 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 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
Disease:  Anxiety
OMIM: 607834
Disease:  Obsessive-compulsive disorder; OCD
Disease Ontology: DOID:10933
OMIM: 164230

References

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Contributors

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How to cite this page

Stefan Bröer.
Monoamine transporter subfamily: SERT. Last modified on 02/05/2016. Accessed on 22/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=928.