SLC6A4

Protein identityUniProt · HPA

UniProt accession

P31645

Gene

SLC6A4

Ensembl

ENSG00000108576

Chromosome

17

Canonical length

630 aa

Protein class

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

Subcellular location

Golgi apparatus,Vesicles

Quaternary structure

Homooligomer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

630 residues, UniProt reviewed canonical sequence.

>P31645|SLC6A4
     1  METTPLNSQK QLSACEDGED CQENGVLQKV VPTPGDKVES GQISNGYSAV PSPGAGDDTR
    61  HSIPATTTTL VAELHQGERE TWGKKVDFLL SVIGYAVDLG NVWRFPYICY QNGGGAFLLP
   121  YTIMAIFGGI PLFYMELALG QYHRNGCISI WRKICPIFKG IGYAICIIAF YIASYYNTIM
   181  AWALYYLISS FTDQLPWTSC KNSWNTGNCT NYFSEDNITW TLHSTSPAEE FYTRHVLQIH
   241  RSKGLQDLGG ISWQLALCIM LIFTVIYFSI WKGVKTSGKV VWVTATFPYI ILSVLLVRGA
   301  TLPGAWRGVL FYLKPNWQKL LETGVWIDAA AQIFFSLGPG FGVLLAFASY NKFNNNCYQD
   361  ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD AGPSLLFITY AEAIANMPAS
   421  TFFAIIFFLM LITLGLDSTF AGLEGVITAV LDEFPHVWAK RRERFVLAVV ITCFFGSLVT
   481  LTFGGAYVVK LLEEYATGPA VLTVALIEAV AVSWFYGITQ FCRDVKEMLG FSPGWFWRIC
   541  WVAISPLFLL FIICSFLMSP PQLRLFQYNY PYWSIILGYC IGTSSFICIP TYIAYRLIIT
   601  PGTFKERIIK SITPETPTEI PCGDIRLNAV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SLC6A4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

12

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

38 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SLC6A4.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 148 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Obsessive-compulsive disorder

Disease | ImmuneIEDB

Conditions an epitope on SLC6A4 was assayed in.

• influenza T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.43

gnomAD pLI

0.25

gnomAD missense Z

1.93

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amino acid transport
• behavioral response to cocaine
• brain morphogenesis
• cellular response to cGMP
• cellular response to retinoic acid
• circadian rhythm
• conditioned place preference
• enteric nervous system development
• male mating behavior
• membrane depolarization
• memory
• monoamine transport
• negative regulation of cerebellar granule cell precursor proliferation
• negative regulation of neuron differentiation
• negative regulation of organ growth
• negative regulation of synaptic transmission, dopaminergic
• neurotransmitter transport
• platelet aggregation
• positive regulation of cell cycle
• positive regulation of gene expression
• response to estradiol
• response to hypoxia
• response to nutrient
• response to toxic substance
• response to xenobiotic stimulus
• serotonin uptake
• sodium ion transmembrane transport
• vasoconstriction
• positive regulation of serotonin secretion
• regulation of thalamus size

Molecular functions

• actin filament binding
• antiporter activity
• identical protein binding
• integrin binding
• monoamine transmembrane transporter activity
• monoatomic cation channel activity
• neurotransmitter transmembrane transporter activity
• nitric-oxide synthase binding
• serotonin binding
• serotonin:sodium:chloride symporter activity
• sodium ion binding
• syntaxin-1 binding
• cocaine binding

Cellular components

• endomembrane system
• endosome membrane
• focal adhesion
• membrane raft
• neuron projection
• plasma membrane
• postsynaptic membrane
• presynaptic membrane
• serotonergic synapse
• synapse

Protein domainsUniProt · Pfam · InterPro

• Sodium:neurotransmitter symporter
• Sodium:neurotransmitter symporter superfamily
• Sodium:neurotransmitter symporter family
• Sodium:neurotransmitter symporter, serotonin, N-terminal
• Serotonin (5-HT) neurotransmitter transporter, N-terminus

KeywordsUniProt

• Antiport
• Cell junction
• Cell membrane
• Cell projection
• Disulfide bond
• Endosome
• Glycoprotein
• Membrane
• Metal-binding
• Neurotransmitter transport
• Phosphoprotein
• Sodium
• Synapse
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of SLC6A4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NOS1
• PATJ
• SEC23A
• SEC24C
• STX1A
• TGFB1I1
• SCAMP2
• ITGB3