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SLC6A4
HPA
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  • SLC6A4
PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
GENERAL INFORMATIONi

General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.

Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

SLC6A4
Synonyms 5-HTT, HTT, OCD1, SERT1
Gene descriptioni

Full gene name according to HGNC.

Solute carrier family 6 member 4
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

FDA approved drug targets
Human disease related genes
Metabolic proteins
Transporters
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

Membrane
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi

Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.

Chromosome 17
Cytoband q11.2
Chromosome location (bp) 30194319 - 30236002
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

4
Ensembl ENSG00000108576 (version 109)
Entrez gene 6532
HGNC HGNC:11050
UniProt P31645 (UniProt - Evidence at protein level)
neXtProt NX_P31645
GeneCards SLC6A4
Antibodypedia SLC6A4 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

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 1, 2, 3, 4, 5, 6. 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 (By similarity). 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 7, 8. 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 9, 10, 11, 12, 13, 14. 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 (By similarity).... show less
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Antiport, Neurotransmitter transport, Transport
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

Metal-binding, Sodium
Gene summary (Entrez)i

Useful information about the gene from Entrez

This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and 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. There have been conflicting results in the literature about the possible effect, if any, that this polymorphism may play in behavior and depression. [provided by RefSeq, May 2019]... show less
PROTEIN INFORMATIONi

The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.

The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.

The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.

The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)
Transmembrane regions
(predicted)
SLC6A4-201
ENSP00000261707
ENST00000261707
P31645
[Direct mapping] Sodium-dependent serotonin transporter
Show all
Metabolic proteins
Transporters
   Electrochemical Potential-driven transporters
Predicted membrane proteins
   Prediction method-based
   Membrane proteins predicted by MDM
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
   # TM segments-based
   >9TM proteins predicted by MDM
FDA approved drug targets
   Small molecule drugs
Human disease related genes
   Other diseases
   Mental and behavioural disorders
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Ezkurdia et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0005326 [neurotransmitter transmembrane transporter activity]
GO:0005335 [serotonin:sodium symporter activity]
GO:0005515 [protein binding]
GO:0005768 [endosome]
GO:0005886 [plasma membrane]
GO:0005887 [integral component of plasma membrane]
GO:0005925 [focal adhesion]
GO:0006836 [neurotransmitter transport]
GO:0008504 [monoamine transmembrane transporter activity]
GO:0009636 [response to toxic substance]
GO:0010008 [endosome membrane]
GO:0012505 [endomembrane system]
GO:0015293 [symporter activity]
GO:0015844 [monoamine transport]
GO:0016020 [membrane]
GO:0016021 [integral component of membrane]
GO:0022857 [transmembrane transporter activity]
GO:0035176 [social behavior]
GO:0035725 [sodium ion transmembrane transport]
GO:0042802 [identical protein binding]
GO:0043005 [neuron projection]
GO:0045121 [membrane raft]
GO:0045202 [synapse]
GO:0046621 [negative regulation of organ growth]
GO:0046872 [metal ion binding]
GO:0048854 [brain morphogenesis]
GO:0051015 [actin filament binding]
GO:0051378 [serotonin binding]
GO:0051610 [serotonin uptake]
GO:0070161 [anchoring junction]
GO:0071702 [organic substance transport]
GO:0071705 [nitrogen compound transport]
GO:0090067 [regulation of thalamus size]
Show all
630 aa
70.3 kDa
No >9
SLC6A4-202
ENSP00000378298
ENST00000394821
J3KPR9
[Direct mapping] Transporter
Show all
Metabolic proteins
Predicted membrane proteins
   Prediction method-based
   Membrane proteins predicted by MDM
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
   # TM segments-based
   >9TM proteins predicted by MDM
Human disease related genes
   Other diseases
   Mental and behavioural disorders
Protein evidence (Ezkurdia et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0005335 [serotonin:sodium symporter activity]
GO:0005768 [endosome]
GO:0005886 [plasma membrane]
GO:0005887 [integral component of plasma membrane]
GO:0005925 [focal adhesion]
GO:0006836 [neurotransmitter transport]
GO:0010008 [endosome membrane]
GO:0012505 [endomembrane system]
GO:0015293 [symporter activity]
GO:0016020 [membrane]
GO:0016021 [integral component of membrane]
GO:0022857 [transmembrane transporter activity]
GO:0045202 [synapse]
GO:0046872 [metal ion binding]
GO:0051610 [serotonin uptake]
GO:0055085 [transmembrane transport]
GO:0070161 [anchoring junction]
GO:0071702 [organic substance transport]
GO:0071705 [nitrogen compound transport]
GO:0098793 [presynapse]
Show all
618 aa
69 kDa
No >9
SLC6A4-203
ENSP00000385822
ENST00000401766
P31645
[Direct mapping] Sodium-dependent serotonin transporter
Show all
Metabolic proteins
Transporters
   Electrochemical Potential-driven transporters
Predicted membrane proteins
   Prediction method-based
   Membrane proteins predicted by MDM
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
   # TM segments-based
   >9TM proteins predicted by MDM
FDA approved drug targets
   Small molecule drugs
Human disease related genes
   Other diseases
   Mental and behavioural disorders
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Ezkurdia et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0005326 [neurotransmitter transmembrane transporter activity]
GO:0005335 [serotonin:sodium symporter activity]
GO:0005515 [protein binding]
GO:0005768 [endosome]
GO:0005886 [plasma membrane]
GO:0005887 [integral component of plasma membrane]
GO:0005925 [focal adhesion]
GO:0006836 [neurotransmitter transport]
GO:0008504 [monoamine transmembrane transporter activity]
GO:0009636 [response to toxic substance]
GO:0010008 [endosome membrane]
GO:0012505 [endomembrane system]
GO:0015293 [symporter activity]
GO:0015844 [monoamine transport]
GO:0016020 [membrane]
GO:0016021 [integral component of membrane]
GO:0022857 [transmembrane transporter activity]
GO:0035176 [social behavior]
GO:0035725 [sodium ion transmembrane transport]
GO:0042802 [identical protein binding]
GO:0043005 [neuron projection]
GO:0045121 [membrane raft]
GO:0045202 [synapse]
GO:0046621 [negative regulation of organ growth]
GO:0046872 [metal ion binding]
GO:0048854 [brain morphogenesis]
GO:0051015 [actin filament binding]
GO:0051378 [serotonin binding]
GO:0051610 [serotonin uptake]
GO:0070161 [anchoring junction]
GO:0071702 [organic substance transport]
GO:0071705 [nitrogen compound transport]
GO:0090067 [regulation of thalamus size]
Show all
630 aa
70.3 kDa
No >9
SLC6A4-206
ENSP00000498537
ENST00000650711
P31645
[Direct mapping] Sodium-dependent serotonin transporter
Show all
Metabolic proteins
Transporters
   Electrochemical Potential-driven transporters
Predicted membrane proteins
   Prediction method-based
   Membrane proteins predicted by MDM
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
   # TM segments-based
   >9TM proteins predicted by MDM
FDA approved drug targets
   Small molecule drugs
Human disease related genes
   Other diseases
   Mental and behavioural disorders
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0001666 [response to hypoxia]
GO:0005326 [neurotransmitter transmembrane transporter activity]
GO:0005335 [serotonin:sodium symporter activity]
GO:0005515 [protein binding]
GO:0005768 [endosome]
GO:0005886 [plasma membrane]
GO:0005887 [integral component of plasma membrane]
GO:0005925 [focal adhesion]
GO:0006836 [neurotransmitter transport]
GO:0006837 [serotonin transport]
GO:0007420 [brain development]
GO:0007584 [response to nutrient]
GO:0007613 [memory]
GO:0007623 [circadian rhythm]
GO:0008504 [monoamine transmembrane transporter activity]
GO:0009410 [response to xenobiotic stimulus]
GO:0009636 [response to toxic substance]
GO:0010008 [endosome membrane]
GO:0010033 [response to organic substance]
GO:0010628 [positive regulation of gene expression]
GO:0012505 [endomembrane system]
GO:0014064 [positive regulation of serotonin secretion]
GO:0015293 [symporter activity]
GO:0015844 [monoamine transport]
GO:0016020 [membrane]
GO:0016021 [integral component of membrane]
GO:0017075 [syntaxin-1 binding]
GO:0019811 [cocaine binding]
GO:0021941 [negative regulation of cerebellar granule cell precursor proliferation]
GO:0022857 [transmembrane transporter activity]
GO:0032227 [negative regulation of synaptic transmission, dopaminergic]
GO:0032355 [response to estradiol]
GO:0035176 [social behavior]
GO:0035725 [sodium ion transmembrane transport]
GO:0042310 [vasoconstriction]
GO:0042713 [sperm ejaculation]
GO:0042734 [presynaptic membrane]
GO:0042802 [identical protein binding]
GO:0043005 [neuron projection]
GO:0045121 [membrane raft]
GO:0045202 [synapse]
GO:0045211 [postsynaptic membrane]
GO:0045665 [negative regulation of neuron differentiation]
GO:0045787 [positive regulation of cell cycle]
GO:0046621 [negative regulation of organ growth]
GO:0046872 [metal ion binding]
GO:0048854 [brain morphogenesis]
GO:0050998 [nitric-oxide synthase binding]
GO:0051015 [actin filament binding]
GO:0051378 [serotonin binding]
GO:0051610 [serotonin uptake]
GO:0070161 [anchoring junction]
GO:0071300 [cellular response to retinoic acid]
GO:0071310 [cellular response to organic substance]
GO:0071321 [cellular response to cGMP]
GO:0071702 [organic substance transport]
GO:0071705 [nitrogen compound transport]
GO:0090067 [regulation of thalamus size]
GO:0098810 [neurotransmitter reuptake]
GO:0099154 [serotonergic synapse]
Show all
630 aa
70.3 kDa
No >9

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