Serotonin transporter

The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene.[5] SERT is a type of monoamine transporter protein that transports serotonin from the synaptic cleft back to the presynaptic neuron.[6]

This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is the target of many antidepressant medications of the SSRI and tricyclic antidepressant classes.[7] It is a member of the sodium:neurotransmitter symporter family. A repeat length polymorphism in the promoter of this gene has been shown to affect the rate of serotonin uptake and may play a role in sudden infant death syndrome, aggressive behavior in Alzheimer disease patients, post-traumatic stress disorder and depression-susceptibility in people experiencing emotional trauma.[8]

SLC6A4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSLC6A4, 5-HTT, 5HTT, HTT, OCD1, SERT, SERT1, hSERT, Solute Carrier Family 6 (neurotransmitter transporter), member 4, solute carrier family 6 member 4, 5-HTTLPR
External IDsOMIM: 182138 MGI: 96285 HomoloGene: 817 GeneCards: SLC6A4
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001045

NM_010484

RefSeq (protein)

NP_001036

NP_034614

Location (UCSC)Chr 17: 30.19 – 30.24 MbChr 11: 77 – 77.03 Mb
PubMed search[3][4]
Wikidata

Mechanism of action

Serotonin-reuptake transporters are dependent on both the concentration of potassium ion in the cytoplasm and the concentrations of sodium and chloride ions in the extracellular fluid. In order to function properly the serotonin transporter requires the membrane potential created by the sodium-potassium adenosine triphosphatase.

The serotonin transporter first binds a sodium ion, followed by the serotonin, and then a chloride ion, thus it is allowed, thanks to the membrane potential, to flip inside the cell freeing all the elements previously bound. Right after the release of the serotonin in the cytoplasm a potassium ion binds to the transporter which is now able to flip back out returning to its active state.[9]

Function

The serotonin transporter removes serotonin from the synaptic cleft back into the synaptic boutons. Thus, it terminates the effects of serotonin and simultaneously enables its reuse by the presynaptic neuron.[7]

Neurons communicate by using chemical messengers like serotonin between cells. The transporter protein, by recycling serotonin, regulates its concentration in a gap, or synapse, and thus its effects on a receiving neuron's receptors.

Medical studies have shown that changes in serotonin transporter metabolism appear to be associated with many different phenomena, including alcoholism, clinical depression, obsessive-compulsive disorder (OCD), romantic love,[10] hypertension and generalized social phobia.[11]

The serotonin transporter is also present in platelets; there, serotonin functions as a vasoconstrictive substance. It also serves as a signalling molecule to induce platelet aggregation.

Pharmacology

SERT spans the plasma membrane 12 times. It belongs to the NE, DA, SERT monoamine transporter family. Transporters are important sites for agents that treat psychiatric disorders. Drugs that reduce the binding of serotonin to transporters (serotonin reuptake inhibitors, or SRIs) are used to treat mental disorders. The selective serotonin reuptake inhibitor (SSRI) fluoxetine and the tricyclic antidepressant (TCA) clomipramine are examples of serotonin reuptake inhibitors (SRIs).

Following the elucidation of structures of the homologous bacterial transporter, LeuT, co-crystallized with tricyclic antidepressants in the vestibule leading from the extracellular space to the central substrate site it was inferred that this binding site did also represent the binding site relevant for antidepressant binding in SERT.[12] However, studies on SERT showed that tricyclic antidepressants and selective serotonin reuptake inhbitors bind to the central binding site overlapping the substrate binding site.[13][14][15] The Drosophila dopamine transporter, which displays a pharmacology similar to SERT, was crystallized with tricyclic antidepressants and confirmed the earlier finding that the substrate binding site is also the antidepressant binding site.[16]

Mattson 2005
12a
Tamagnan 2005
4b

Ligands

  • DASB
  • compound 4b: Ki = 17 pM; 710-fold and 11,100-fold selective over DAT and NET[17]
  • compound (+)-12a: Ki = 180 pM at hSERT; >1000-fold selective over hDAT, hNET, 5-HT1A, and 5-HT6.[18] Isosteres[19]
  • 3-cis-(3-Aminocyclopentyl)indole 8a: Ki = 220 pM[20]
  • allosteric modulator: 3′-Methoxy-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5′(4′H)-isoxazole} (compound 7a)[21]

Genetics

Slc6a4, ISH, mouse, dorsal raphe
Slc6a4 is expressed in median and dorsal raphe in the midbrain of the postnatal day 56 mouse.[22] Allen Brain Atlases

The gene that encodes the serotonin transporter is called solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4, see Solute carrier family). In humans the gene is found on chromosome 17 on location 17q11.1–q12.[23]

Mutations associated with the gene may result in changes in serotonin transporter function, and experiments with mice have identified more than 50 different phenotypic changes as a result of genetic variation. These phenotypic changes may, e.g., be increased anxiety and gut dysfunction.[24] Some of the human genetic variations associated with the gene are:[24]

Length variation in 5-HTTLPR

The promotor region of the SLC6A4 gene contains a polymorphism with "short" and "long" repeats in a region: 5-HTT-linked polymorphic region (5-HTTLPR or SERTPR).[25] The short variation has 14 repeats of a sequence while the long variation has 16 repeats.[23] The short variation leads to less transcription for SLC6A4, and it has been found that it can partly account for anxiety-related personality traits.[26] This polymorphism has been extensively investigated in over 300 scientific studies (as of 2006).[27] The 5-HTTLPR polymorphism may be subdivided further: One study published in 2000 found 14 allelic variants (14-A, 14-B, 14-C, 14-D, 15, 16-A, 16-B, 16-C, 16-D, 16-E, 16-F, 19, 20 and 22) in a group of around 200 Japanese and Caucasian people.[23]

In addition to altering the expression of SERT protein and concentrations of extracellular serotonin in the brain, the 5-HTTLPR variation is associated with changes in brain structure. One study found less grey matter in perigenual anterior cingulate cortex and amygdala for short allele carriers of the 5-HTTLPR polymorphism compared to subjects with the long/long genotype.[28]

In contrast, a 2008 meta-analysis found no significant overall association between the 5-HTTLPR polymorphism and autism.[29] A hypothesized gene-environment interaction between the short/short allele of the 5-HTTLPR and life stress as predictor for major depression has suffered a similar fate: after an influential[30] initial report[31] there were mixed results in replication,[32] and a 2009 meta-analysis was negative.[33] See 5-HTTLPR for more information.

rs25532

rs25532 is a SNP (C>T) close to the site of 5-HTTLPR. It has been examined in connection with obsessive compulsive disorder (OCD).[34]

I425V

I425V is a rare mutation on the ninth exon. Researchers have found this genetic variation in unrelated families with OCD, and have found that it leads to faulty transporter function and regulation. A second variant in the same gene of some patients with this mutation suggests a genetic "double hit", resulting in greater biochemical effects and more severe symptoms.[35][36][37]

VNTR in STin2

Another noncoding polymorphism is a VNTR in the second intron (STin2). It is found with three alleles: 9, 10 and 12 repeats. A meta-analysis has found that the 12 repeat allele of the STin2 VNTR polymorphism had some minor (with odds ratio 1.24), but statistically significant, association with schizophrenia.[38] A 2008 meta-analysis found no significant overall association between the STin2 VNTR polymorphism and autism.[29] Furthermore, a 2003 meta-analysis of affective disorders, major depressive disorder and bipolar disorder, found a minor association to the intron 2 VNTR polymorphism, but the results of the meta-analysis were dependent upon a large effect from one individual study.[39]

The polymorphism has also been related to personality traits with a 2008 Russian study finding individuals with the STin2.10 allele having lower neuroticism scores as measured with the Eysenck Personality Inventory.[40]

Neuroimaging

The distribution of the serotonin transporter in the brain may be imaged with positron emission tomography using radioligands called DASB and DAPP; the first such studies on the human brain were reported in 2000.[41] DASB and DAPP are not the only radioligands for the serotonin transporter. There are numerous others, with the most popular probably being the β-CIT radioligand with an iodine-123 isotope that is used for brain scanning with single photon emission computed tomography (SPECT).[42] The radioligands have been used to examine whether variables such as age, gender or genotype are associated with differential serotonin transporter binding.[43] Healthy subjects that have a high score of neuroticism — a personality trait in the Revised NEO Personality Inventory — have been found to have more serotonin transporter binding in the thalamus.[44]

Neuroimaging and genetics

Studies on the serotonin transporter have combined neuroimaging and genetics methods, e.g., a voxel-based morphometry study found less grey matter in perigenual anterior cingulate cortex and amygdala for short allele carriers of the 5-HTTLPR polymorphism compared to subjects with the long/long genotype.[28]

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1-Aminomethyl-5-methoxyindane

1-Aminomethyl-5-methoxyindane (AMMI), is a drug developed by a team led by David E. Nichols at Purdue University, which acts as a selective serotonin releasing agent (SSRA) and binds to the serotonin transporter with similar affinity to DFMDA.

2-Propanoyl-3-(4-isopropylphenyl)-tropane

2-Propanoyl-3-(4-isopropylphenyl)-tropane (WF-31, PIT) is a cocaine analogue which acts as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). Research shows WF-31 to be approximately ten times more potent than cocaine at binding to the serotonin transporter and at inhibiting its reuptake.

3,4-Dichloroamphetamine

3,4-Dichloroamphetamine (DCA), is an amphetamine derived drug invented by Eli Lilly in the 1960s, which has a number of pharmacological actions. It acts as a highly potent and selective serotonin releasing agent (SSRA) and binds to the serotonin transporter with high affinity, but also acts as a selective serotonergic neurotoxin in a similar manner to the related para-chloroamphetamine, though with slightly lower potency. It is also a monoamine oxidase inhibitor (MAOI), as well as a very potent inhibitor of the enzyme phenylethanolamine N-methyl transferase which normally functions to transform noradrenaline into adrenaline in the body.

3-MeO-PCP

3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. (also known as "Pixie Dust") It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ1 receptor and the serotonin transporter. The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor.

5-HTTLPR

5-HTTLPR (serotonin-transporter-linked polymorphic region) is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.

Since the polymorphism was identified in the middle of the 1990s,

it has been extensively investigated, e.g., in connection with neuropsychiatric disorders.

A 2006 scientific article stated that "over 300 behavioral, psychiatric, pharmacogenetic and other medical genetics papers" had analyzed the polymorphism. While often discussed as an example of gene-environment interaction, this contention is contested.

Amiflamine

Amiflamine (FLA-336) is a reversible inhibitor of monoamine oxidase A (MAO-A), thereby being a RIMA, and, to a lesser extent, semicarbazide-sensitive amine oxidase (SSAO), as well as a serotonin releasing agent (SRA). It is a derivative of the phenethylamine and amphetamine chemical classes. The (+)-enantiomer is the active stereoisomer.Amiflamine shows preference for inhibiting MAO-A in serotonergic relative to noradrenergic and dopaminergic neurons. In other words, at low doses, it can be used to selectively inhibit MAO-A enzymes in serotonin cells, whereas at higher doses it loses its selectivity. This property is attributed to amiflamine's higher affinity for the serotonin transporter over the norepinephrine and dopamine transporters, as transporter-mediated carriage is required for amiflamine to enter monoaminergic neurons. Other RIMAs such as Esfand, etryptamine & moclobemide would also be expected to behave similarly.

Boophone

Boophone is a small genus of herbaceous, perennial and bulbous plants in the Amaryllis family (Amaryllidaceae, subfamily Amaryllidoideae.) It consists of two confirmed species distributed across South Africa to Kenya and Uganda. It is closely related to Crossyne, a genus whose species have prostrate leaves. They are drought tolerant but not cold-hardy, and are very poisonous to livestock.

DASB

DASB, also known as 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, is a compound that binds to the serotonin transporter.

Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography (PET) since around year 2000.

In this context it is regarded as one of the superior radioligands for PET study of the serotonin transporter in the brain,

since it has high selectivity for the serotonin transporter.The DASB image from a human PET scan shows high binding in the midbrain, thalamus and striatum, moderate binding in the medial temporal lobe and anterior cingulate, and low binding in neocortex.

The cerebellum is often regarded as a region with no specific serotonin transporter binding and the brain region is used as a reference in some studies.Since the serotonin transporter is the target of SSRIs used in the treatment of major depression it has been natural to examine DASB binding in depressed patients.

Several such research studies have been performed.There are a number of alternative PET radioligands for imaging the serotonin transporter: [11C]ADAM, [11C]MADAM, [11C]AFM, [11C]DAPA, [11C]McN5652, and [11C]-NS 4194.

A related molecule to DASB, that can be labeled with fluorine-18, has also been suggested as a PET radioligand.

With single-photon emission computed tomography (SPECT) using the radioisotope iodine-123 there are further radioligands available: [123I]ODAM, [123I]IDAM, [123I]ADAM, and [123I]β-CIT.

A few studies have examined the difference in binding between the radioligands in nonhuman primates,

as well as in pigs.Other compounds that can be labeled to work as PET radioligands for the study of the serotonin system are, e.g., altanserin and WAY-100635.

Dapoxetine

Dapoxetine, marketed as Priligy and Westoxetin among others, is a medication used for the treatment of premature ejaculation (PE) in men 18–64 years old. Dapoxetine works by inhibiting the serotonin transporter, increasing serotonin's action at the post synaptic cleft, and as a consequence promoting ejaculatory delay. As a member of the selective serotonin reuptake inhibitor (SSRI) family, dapoxetine was initially created as an antidepressant. However, unlike other SSRIs, dapoxetine is absorbed and eliminated rapidly in the body. Its fast acting property makes it suitable for the treatment of PE but not as an antidepressant.Originally created by Eli Lilly pharmaceutical company, dapoxetine was sold to Johnson & Johnson in 2003 and submitted as a New Drug Application to the Food and Drug Administration (FDA) for the treatment of PE in 2004. Dapoxetine is sold in several European and Asian countries, and in Mexico. In the US, dapoxetine has been in phase III development since 2003. However, it is expected to be marketed soon. In 2012, Menarini acquired the rights to commercialise Dapoxetine in Europe, most of Asia, Africa, Latin America and the Middle East.

Harm avoidance

Harm avoidance (HA) is a personality trait characterized by excessive worrying; pessimism; shyness; and being fearful, doubtful, and easily fatigued. In MRI studies HA was correlated with reduced grey matter volume in the orbito-frontal, occipital and parietal regions.Harm avoidance is a temperament assessed in the Temperament and Character Inventory (TCI), its revised version (TCI-R) and the Tridimensional Personality Questionnaire (TPQ) and is positively related to the trait neuroticism and inversely to extraversion in the Revised NEO Personality Inventory and the Eysenck Personality Questionnaire. Researchers have contended that harm avoidance represents a composite personality dimension with neurotic introversion at one end of the spectrum and stable extraversion at the other end. Harm avoidance has also been found to have moderate inverse relationships with conscientiousness and openness to experience in the five factor model.The HA of TPQ and TCI-R has four subscales:

Anticipatory worry (HA1)

Fear of uncertainty (HA2)

Shyness/Shyness with strangers (HA3)

Fatigability/Fatigability and asthenia (weakness) (HA4)It has been suggested that HA is related to high serotonergic activity,

and much research has gone into investigating the link between HA and components of the serotonin system, e.g. genetic variation in 5-HTTLPR in the serotonin transporter gene.

Klaus-Peter Lesch

Klaus-Peter Lesch is a clinical psychiatrist who has been investigating the neurobiological foundation of personality traits.

His 1996 paper

on the association between the 5-HTTLPR polymorphism in the serotonin transporter gene and the personality trait neuroticism has been highly cited and was one of the first papers in personality genetics.

He is professor at the University of Würzburg.

Among his coauthors has been Peter Riederer.

McN5652

McN5652 is a molecule that can be radiolabeled and then used as a radioligand in positron emission tomography (PET) studies. The [11C]-(+)-McN5652 enantiomer binds to the serotonin transporter. The radioligand is used for molecular neuroimaging and for imaging of the lungs.It was developed by Johnson & Johnson's McNeil Laboratories. According to McNeil, McN5652 was among the strongest SRI ever reported at the time of its discovery (sub nM Ki). However, it is not completely 5-HT selective: the racemate has 5-HT=0.68, NA=2.9, and D=36.8nM, whereas (+)-enantiomer has 5-HT=0.39, NA=1.8, and D=23.5 nM. Paroxetine was listed as 5-HT=0.44 nM, NA=20, and DA=460nM in the same paper by the same authors.

Mesembrenone

Mesembrenone is an alkaloid constituent of Sceletium tortuosum (Kanna). Similar to modern synthetic antidepressants, it is a potent (IC50 < 1 μM) selective inhibitor of the serotonin transporter (SERT) (that is, a selective serotonin reuptake inhibitor; Ki = 27 nM) and also a phosphodiesterase 4 (PDE4) inhibitor (Ki = 470 nM).

Monoamine reuptake inhibitor

A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.

Reuptake

Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmitting a neural impulse.

Reuptake is necessary for normal synaptic physiology because it allows for the recycling of neurotransmitters and regulates the level of neurotransmitter present in the synapse, thereby controlling how long a signal resulting from neurotransmitter release lasts. Because neurotransmitters are too large and hydrophilic to diffuse through the membrane, specific transport proteins are necessary for the reabsorption of neurotransmitters. Much research, both biochemical and structural, has been performed to obtain clues about the mechanism of reuptake.

Reuptake enhancer

A reuptake enhancer (RE), also sometimes referred to as a reuptake activator, is a type of reuptake modulator which enhances the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to a decrease in the extracellular concentrations of the neurotransmitter and therefore a decrease in neurotransmission.

The antidepressant tianeptine was once claimed to be a (selective) serotonin reuptake enhancer (SRE or SSRE), but the role of serotonin reuptake in its mechanism is doubtful. Tianeptine has no affinity for the serotonin transporter, neither increases nor decreases extracellular levels of serotonin in cortico-limbic structures of conscious rats, and it didn't show any other long-term effect on the serotonin pathway. Thus, tianeptine's role as an SSRE may have been the coincidence of a yet unknown mechanism of action.

Coluracetam is a choline-reuptake enhancer. The flavone luteoline as well as some of its derivatives enhance the reuptake at the dopamine transporter, extracts of Caulis Sinomenii activate DA/NE transporters.

Reuptake inhibitor

A reuptake inhibitor (RI) is a type of drug known as a reuptake modulator that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.Most known reuptake inhibitors affect the monoamine neurotransmitters serotonin, norepinephrine (and epinephrine), and dopamine. However, there are also a number of pharmaceuticals and research chemicals that act as reuptake inhibitors for other neurotransmitters such as glutamate, γ-aminobutyric acid (GABA), glycine, adenosine, choline (the precursor of acetylcholine), and the endocannabinoids, among others.

Salicylmethylecgonine

Salicylmethylecgonine, (2′-Hydroxycocaine) is a tropane derivative drug which is both a synthetic analogue and a possible active metabolite of cocaine. Its potency in vitro is around 10x that of cocaine, although it is only around three times more potent than cocaine when administered to mice (likely owing to it having a higher LogP: 2.89 than that of cocaine: 2.62) Note however that the compound 2′-Acetoxycocaine would act as a prodrug to Salicylmethylecgonine in humans, and has a more efficient partition coefficient which would act as a delivery system and would circumvent this reason for a loss in potency. Salicylmethylecgonine also shows increased behavioral stimulation compared to cocaine similar to the phenyltropanes. The hydroxy branch renders the molecule a QSAR of a 10-fold increase over cocaine in its binding potency for the dopamine transporter & a 52-fold enhanced affinity for the norepinephrine transporter. It also has a reduced selectivity for the serotonin transporter though only due to its greater increase at NET binding; its SERT affinity being 4-fold increased compared to cocaine. However, in overall binding affinity (not uptake inhibition) it displaces ligands better across the board than cocaine in all monoamine categories.

Study of molecular modeling inferred that, in addition to intramolecular hydrogen bonding between the adjacent 3β-carbonyl and the 2′-OH ortho group of 185d (i.e. salicylmethylecgonine), that intermolecular hydrogen bonding between its hydroxy ortho substituent and the dopamine transporter was also possible; and was rationalized to be due to its nearness of where the nitrogen and oxygen atoms reside in the para-hydroxy of dopamine itself and its own intrinsic relation to DAT whereby that mutual hydroxyl functionality is mediated in both salicylmethylecgonine and dopamine in a similar manner. That is, at serine residue 359 on DAT, as the distance of the hydroxy to the bridge-nitrogen on salicylmethylecgonine is 7.96 Å (close to that of the distance between the p-OH & the NH2 atoms of dopamine, their distance apart being 7.83 Å). Which may play a role in this analogs increased behavioral stimulation over its parent compound cocaine. The meta-hydroxy group of dopamine, by contrast, has a distance of 6.38 Å from its nitrogen and is believed to engage with the 356 residue on DAT.

Serotonin reuptake inhibitor

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine (5-HT)) by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

SRIs are not synonymous with selective serotonin reuptake inhibitors (SSRIs), as the latter term is usually used to describe the class of antidepressants of the same name, and because SRIs, unlike SSRIs, can either be selective or non-selective in their action. For example, cocaine, which non-selectively inhibits the reuptake of serotonin, norepinephrine, and dopamine, is an SRI but not an SSRI.

SRIs are used predominantly as antidepressants (e.g., SSRIs, SNRIs, and TCAs), though they are also commonly used in the treatment of other psychological conditions such as anxiety disorders and eating disorders. Less often, SRIs are also used to treat a variety of other medical conditions including neuropathic pain and fibromyalgia (e.g., duloxetine, milnacipran), and premature ejaculation (e.g., dapoxetine) as well as for dieting (e.g., sibutramine). Additionally, some clinically used drugs such as chlorpheniramine, dextromethorphan, and methadone possess SRI properties secondarily to their primary mechanism of action(s) and this contributes to their side effect and drug interaction profiles.

A closely related type of drug is a serotonin releasing agent (SRA), an example of which is fenfluramine.

List of PDB id codes

5I6X, 5I73, 5I75, 5I6Z, 5I71, 5I74

Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for SLC6A4
Genomic location for SLC6A4
Band17q11.2Start30,194,319 bp[1]
End30,236,002 bp[1]
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)[2]
Chromosome 11 (mouse)
Genomic location for SLC6A4
Genomic location for SLC6A4
Band11 B5|11 46.18 cMStart76,998,603 bp[2]
End77,032,340 bp[2]
RNA expression pattern
PBB GE SLC6A4 207519 at fs
More reference expression data
Gene ontology
Molecular function cocaine binding
nitric-oxide synthase binding
protein homodimerization activity
myosin binding
syntaxin-1 binding
metal ion binding
neurotransmitter:sodium symporter activity
actin filament binding
monoamine transmembrane transporter activity
Rab GTPase binding
protein binding
serotonin transmembrane transporter activity
symporter activity
serotonin:sodium symporter activity
dopamine:sodium symporter activity
serotonin binding
Cellular component integral component of membrane
cytosol
endosome
membrane
integral component of plasma membrane
membrane raft
neuron projection
endosome membrane
endomembrane system
presynapse
plasma membrane
integral component of postsynaptic membrane
integral component of presynaptic membrane
serotonergic synapse
Biological process cellular response to organic substance
cellular response to retinoic acid
response to estradiol
cellular response to cGMP
response to hypoxia
negative regulation of neuron differentiation
sperm ejaculation
response to nutrient
GO:0042310 vasoconstriction
negative regulation of cerebellar granule cell precursor proliferation
memory
monoamine transport
response to organic substance
brain development
positive regulation of gene expression
positive regulation of cell cycle
serotonin transport
protein oligomerization
circadian rhythm
transmembrane transport
social organism behavior
serotonin uptake
neurotransmitter transport
negative regulation of organ growth
protein homooligomerization
response to toxic substance
negative regulation of synaptic transmission, dopaminergic
response to drug
brain morphogenesis
positive regulation of serotonin secretion
neurotransmitter biosynthetic process
dopamine uptake involved in synaptic transmission
regulation of thalamus size
Sources:Amigo / QuickGO
Vesicular
Other
DAT
(DRIs)
NET
(NRIs)
SERT
(SRIs)
VMATs
Others
DRAs
NRAs
SRAs
Others

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