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Q60857 (SC6A4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium-dependent serotonin transporter
Alternative name(s):
5HT transporter
Short name=5HTT
Solute carrier family 6 member 4
Gene names
Name:Slc6a4
Synonyms:Htt, Sert
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length630 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner By similarity.

Subunit structure

Monomer or homooligomer By similarity. Interacts (via C-terminus) with VIM. Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with GTP-bound RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly. Interacts (via sialylated form) with MYH9. Interacts with filamentous actin and STX1A By similarity. Interacts with SEC23A, SEC24C and INADL. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake. Interacts with TGFB1I1. Ref.7 Ref.8

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Endomembrane system By similarity; Multi-pass membrane protein. Endosome membrane By similarity. Note: Translocates from intracellular locations to the plasma membrane. Density of transporter molecules on the plasma membrane is itself regulated by serotonin By similarity.

Developmental stage

Expressed in the uncrossed ipsilateral retinal ganglion cells (iRGCs) of the peripheral ventrotemporal (VT) region segment in the retina at 16.5 dpc. Ref.9

Post-translational modification

Glycosylated; modification with sialylated N-glycans is a requirement for transporters to associate with each other and to function as homooligomeric forms By similarity.

Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity By similarity. Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation By similarity.

Disruption phenotype

Loss of serotonin uptake. Ref.6

Miscellaneous

This protein is the target of psychomotor stimulants such as amphetamines or cocaine.

Sequence similarities

Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily. [View classification]

Sequence caution

The sequence X66119 differs from that shown. Reason: Frameshift at position 195.

Ontologies

Keywords
   Biological processNeurotransmitter transport
Symport
Transport
   Cellular componentCell membrane
Endosome
Membrane
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain morphogenesis

Inferred from mutant phenotype PubMed 19208814. Source: BHF-UCL

cellular response to cGMP

Inferred from electronic annotation. Source: Ensembl

cellular response to organic substance

Inferred from direct assay PubMed 18794345. Source: MGI

cellular response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

circadian rhythm

Inferred from electronic annotation. Source: Ensembl

memory

Inferred from electronic annotation. Source: Ensembl

monoamine transport

Inferred from sequence orthology PubMed 16024787. Source: MGI

negative regulation of cerebellar granule cell precursor proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of organ growth

Inferred from mutant phenotype PubMed 19208814. Source: BHF-UCL

negative regulation of synaptic transmission, dopaminergic

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell cycle

Inferred from mutant phenotype PubMed 19308295. Source: UniProtKB

positive regulation of gene expression

Inferred from mutant phenotype PubMed 19308295. Source: UniProtKB

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

protein oligomerization

Inferred from sequence or structural similarity. Source: UniProtKB

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

serotonin transport

Inferred from mutant phenotype PubMed 19308295. Source: UniProtKB

serotonin uptake

Inferred from direct assay Ref.8. Source: UniProtKB

social behavior

Inferred from genetic interaction PubMed 19208814. Source: BHF-UCL

sperm ejaculation

Inferred from electronic annotation. Source: Ensembl

thalamus development

Inferred from electronic annotation. Source: Ensembl

vasoconstriction

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from electronic annotation. Source: Ensembl

endomembrane system

Inferred from sequence or structural similarity. Source: UniProtKB

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from electronic annotation. Source: InterPro

membrane raft

Inferred from electronic annotation. Source: Ensembl

neuron projection

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionactin filament binding

Inferred from sequence or structural similarity. Source: UniProtKB

cocaine binding

Inferred from electronic annotation. Source: Ensembl

monoamine transmembrane transporter activity

Inferred from sequence orthology PubMed 16024787. Source: MGI

nitric-oxide synthase binding

Inferred from physical interaction Ref.8. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

serotonin transmembrane transporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

serotonin:sodium symporter activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 630630Sodium-dependent serotonin transporter
PRO_0000214759

Regions

Topological domain1 – 8787Cytoplasmic Potential
Transmembrane88 – 10821Helical; Name=1; Potential
Transmembrane116 – 13520Helical; Name=2; Potential
Transmembrane160 – 18021Helical; Name=3; Potential
Topological domain181 – 25272Extracellular Potential
Transmembrane253 – 27119Helical; Name=4; Potential
Transmembrane280 – 29718Helical; Name=5; Potential
Transmembrane333 – 35018Helical; Name=6; Potential
Transmembrane362 – 38322Helical; Name=7; Potential
Transmembrane417 – 43620Helical; Name=8; Potential
Transmembrane464 – 48219Helical; Name=9; Potential
Transmembrane498 – 51821Helical; Name=10; Potential
Transmembrane539 – 55820Helical; Name=11; Potential
Transmembrane577 – 59519Helical; Name=12; Potential
Topological domain596 – 63035Cytoplasmic Potential
Region611 – 63020Required for serotonin uptake activity By similarity
Region616 – 6249Interaction with RAB4A By similarity

Amino acid modifications

Modified residue471Phosphotyrosine By similarity
Modified residue1421Phosphotyrosine By similarity
Modified residue2761Phosphothreonine By similarity
Modified residue6111Phosphoserine Potential
Modified residue6131Phosphothreonine Potential
Modified residue6161Phosphothreonine Potential
Glycosylation2081N-linked (GlcNAc...) Potential
Glycosylation2171N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict391G → E in AAB67172. Ref.1
Sequence conflict391G → E in CAA70092. Ref.2
Sequence conflict391G → E in AAA84750. Ref.4
Sequence conflict1521K → R in AAB67172. Ref.1
Sequence conflict1521K → R in CAA70092. Ref.2
Sequence conflict1961P → Q in CAA70092. Ref.2
Sequence conflict4151A → R in CAA70092. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q60857 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: 2B6ABD26E3288CD0

FASTA63070,048
        10         20         30         40         50         60 
METTPLNSQK VLSECKDKED CQENGVLQKG VPTPADKAGP GQISNGYSAV PSTSAGDEAP 

        70         80         90        100        110        120 
HSTPAATTTL VAEIHQGERE TWGKKMDFLL SVIGYAVDLG NIWRFPYICY QNGGGAFLLP 

       130        140        150        160        170        180 
YTIMAIFGGI PLFYMELALG QYHRNGCISI WKKICPIFKG IGYAICIIAF YIASYYNTII 

       190        200        210        220        230        240 
AWALYYLISS FTDQLPWTSC KNSWNTGNCT NYFAQDNITW TLHSTSPAEE FYLRHVLQIH 

       250        260        270        280        290        300 
QSKGLQDLGT ISWQLALCIM LIFTIIYFSI WKGVKTSGKV VWVTATFPYI VLSVLLVRGA 

       310        320        330        340        350        360 
TLPGAWRGVV FYLKPNWQKL LETGVWVDAA AQIFFSLGPG FGVLLAFASY NKFNNNCYQD 

       370        380        390        400        410        420 
ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD AGPSLLFITY AEAIANMPAS 

       430        440        450        460        470        480 
TFFAIIFFLM LITLGLDSTF AGLEGVITAV LDEFPHIWAK RREWFVLIVV ITCILGSLLT 

       490        500        510        520        530        540 
LTSGGAYVVT LLEEYATGPA VLTVALIEAV VVSWFYGITQ FCSDVKEMLG FSPGWFWRIC 

       550        560        570        580        590        600 
WVAISPLFLL FIICSFLMSP PQLRLFQYNY PHWSIILGYC IGTSSVICIP IYIIYRLIST 

       610        620        630 
PGTLKERIIK SITPETPTEI PCGDIRMNAV 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and expression of the mouse serotonin transporter."
Chang A.S., Chang S.M., Starnes D.M., Schroeter S., Bauman A.L., Blakely R.D.
Brain Res. Mol. Brain Res. 43:185-192(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Gene structure and 5'-flanking regulatory region of the murine serotonin transporter."
Bengel D., Heils A., Petri S., Seemann M., Glatz K., Andrews A., Murphy D.L., Lesch K.P.
Brain Res. Mol. Brain Res. 44:286-292(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Saito N., Sakai N., Kobayashi S., Fujimoto M., Morikawa O., Ikegaki N.
Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
Strain: BALB/c.
[5]"Murine serotonin transporter: sequence and localization to chromosome 11."
Gregor P., Patel A., Shimada S., Lin C.L., Rochelle J.M., Kitayama S., Seldin M.F., Uhl G.R.
Mamm. Genome 4:283-284(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 69-630.
[6]"Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ('Ecstasy') in serotonin transporter-deficient mice."
Bengel D., Murphy D.L., Andrews A.M., Wichems C.H., Feltner D., Heils A., Mossner R., Westphal H., Lesch K.P.
Mol. Pharmacol. 53:649-655(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[7]"Serotonin-, protein kinase C-, and Hic-5-associated redistribution of the platelet serotonin transporter."
Carneiro A.M.D., Blakely R.D.
J. Biol. Chem. 281:24769-24780(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TGFB1I1.
[8]"Physical interaction between the serotonin transporter and neuronal nitric oxide synthase underlies reciprocal modulation of their activity."
Chanrion B., Mannoury la Cour C., Bertaso F., Lerner-Natoli M., Freissmuth M., Millan M.J., Bockaert J., Marin P.
Proc. Natl. Acad. Sci. U.S.A. 104:8119-8124(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOS1; SEC23A; SEC24C AND INADL.
[9]"Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets."
Garcia-Frigola C., Herrera E.
EMBO J. 29:3170-3183(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF013604 mRNA. Translation: AAB67172.1.
Y08870 expand/collapse EMBL AC list , Y08871, Y08872, Y08873, Y08874, Y08875, Y08876, Y08877, Y08878, Y08879, Y08880 Genomic DNA. Translation: CAA70092.1.
AL603842 Genomic DNA. Translation: CAI35067.1.
U26452 Genomic DNA. Translation: AAA84750.1.
X66119 mRNA. No translation available.
CCDSCCDS25074.1.
RefSeqNP_034614.2. NM_010484.2.
XP_006532362.1. XM_006532299.1.
XP_006532363.1. XM_006532300.1.
XP_006532364.1. XM_006532301.1.
UniGeneMm.300318.

3D structure databases

ProteinModelPortalQ60857.
SMRQ60857. Positions 78-614.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200481. 1 interaction.
STRING10090.ENSMUSP00000021195.

Chemistry

BindingDBQ60857.
ChEMBLCHEMBL4642.

PTM databases

PhosphoSiteQ60857.

Proteomic databases

PaxDbQ60857.
PRIDEQ60857.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021195; ENSMUSP00000021195; ENSMUSG00000020838.
ENSMUST00000108402; ENSMUSP00000104039; ENSMUSG00000020838.
GeneID15567.
KEGGmmu:15567.
UCSCuc007kgf.2. mouse.

Organism-specific databases

CTD6532.
MGIMGI:96285. Slc6a4.

Phylogenomic databases

eggNOGCOG0733.
GeneTreeENSGT00740000115174.
HOGENOMHOG000116406.
HOVERGENHBG071421.
InParanoidQ5NCR6.
KOK05037.
OMATSCKNSW.
OrthoDBEOG793B71.
TreeFamTF343812.

Gene expression databases

ArrayExpressQ60857.
BgeeQ60857.
CleanExMM_HTT.
GenevestigatorQ60857.

Family and domain databases

InterProIPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view]
PANTHERPTHR11616. PTHR11616. 1 hit.
PfamPF03491. 5HT_transporter. 1 hit.
PF00209. SNF. 1 hit.
[Graphical view]
PRINTSPR01203. 5HTTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio288538.
PROQ60857.
SOURCESearch...

Entry information

Entry nameSC6A4_MOUSE
AccessionPrimary (citable) accession number: Q60857
Secondary accession number(s): O35241, Q5NCR6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 119 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot