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Protein

Sodium-dependent serotonin transporter

Gene

Slc6a4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi94Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi96Sodium 2; via carbonyl oxygenBy similarity1
Metal bindingi97Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi101Sodium 2By similarity1
Metal bindingi336Sodium 2By similarity1
Metal bindingi368Sodium 2By similarity1
Metal bindingi434Sodium 1; via carbonyl oxygenBy similarity1
Metal bindingi437Sodium 1By similarity1
Metal bindingi438Sodium 1By similarity1

GO - Molecular functioni

GO - Biological processi

  • brain morphogenesis Source: BHF-UCL
  • cellular response to cGMP Source: Ensembl
  • cellular response to organic substance Source: MGI
  • cellular response to retinoic acid Source: Ensembl
  • chemical synaptic transmission Source: GO_Central
  • circadian rhythm Source: Ensembl
  • memory Source: Ensembl
  • monoamine transport Source: MGI
  • negative regulation of cerebellar granule cell precursor proliferation Source: Ensembl
  • negative regulation of neuron differentiation Source: Ensembl
  • negative regulation of organ growth Source: BHF-UCL
  • negative regulation of synaptic transmission, dopaminergic Source: Ensembl
  • positive regulation of cell cycle Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • protein homooligomerization Source: Ensembl
  • protein oligomerization Source: UniProtKB
  • response to drug Source: Ensembl
  • response to estradiol Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to nutrient Source: Ensembl
  • response to toxic substance Source: MGI
  • serotonin transport Source: UniProtKB
  • serotonin uptake Source: UniProtKB
  • social behavior Source: BHF-UCL
  • sperm ejaculation Source: Ensembl
  • thalamus development Source: MGI
  • vasoconstriction Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Keywords - Ligandi

Metal-binding, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-380615. Serotonin clearance from the synaptic cleft.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent serotonin transporter
Short name:
SERTBy similarity
Alternative name(s):
5HT transporter
Short name:
5HTT
Solute carrier family 6 member 4
Gene namesi
Name:Slc6a4
Synonyms:Htt, Sert
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:96285. Slc6a4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 87CytoplasmicCuratedAdd BLAST87
Transmembranei88 – 112Helical; Name=1By similarityAdd BLAST25
Topological domaini113 – 115ExtracellularCurated3
Transmembranei116 – 135Helical; Name=2By similarityAdd BLAST20
Topological domaini136 – 160CytoplasmicCuratedAdd BLAST25
Transmembranei161 – 186Helical; Name=3By similarityAdd BLAST26
Topological domaini187 – 252ExtracellularCuratedAdd BLAST66
Transmembranei253 – 271Helical; Name=4By similarityAdd BLAST19
Topological domaini272 – 277CytoplasmicCurated6
Transmembranei278 – 297Helical; Name=5By similarityAdd BLAST20
Topological domaini298 – 324ExtracellularCuratedAdd BLAST27
Transmembranei325 – 347Helical; Name=6By similarityAdd BLAST23
Topological domaini348 – 360CytoplasmicCuratedAdd BLAST13
Transmembranei361 – 380Helical; Name=7By similarityAdd BLAST20
Topological domaini381 – 421ExtracellularCuratedAdd BLAST41
Transmembranei422 – 443Helical; Name=8By similarityAdd BLAST22
Topological domaini444 – 463CytoplasmicCuratedAdd BLAST20
Transmembranei464 – 483Helical; Name=9By similarityAdd BLAST20
Topological domaini484 – 494ExtracellularCuratedAdd BLAST11
Transmembranei495 – 516Helical; Name=10By similarityAdd BLAST22
Topological domaini517 – 538CytoplasmicCuratedAdd BLAST22
Transmembranei539 – 558Helical; Name=11By similarityAdd BLAST20
Topological domaini559 – 574ExtracellularCuratedAdd BLAST16
Transmembranei575 – 595Helical; Name=12By similarityAdd BLAST21
Topological domaini596 – 630CytoplasmicCuratedAdd BLAST35

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Loss of serotonin uptake.1 Publication

Chemistry databases

ChEMBLiCHEMBL4642.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002147591 – 630Sodium-dependent serotonin transporterAdd BLAST630

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47PhosphotyrosineBy similarity1
Modified residuei142PhosphotyrosineBy similarity1
Disulfide bondi200 ↔ 209By similarity
Glycosylationi208N-linked (GlcNAc...)Sequence analysis1
Glycosylationi217N-linked (GlcNAc...)Sequence analysis1
Modified residuei276PhosphothreonineBy similarity1
Modified residuei611PhosphoserineSequence analysisBy similarity1
Modified residuei613PhosphothreonineSequence analysisBy similarity1
Modified residuei616PhosphothreonineSequence analysisBy similarity1

Post-translational modificationi

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. Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ60857.
PaxDbiQ60857.
PRIDEiQ60857.

PTM databases

PhosphoSitePlusiQ60857.

Expressioni

Developmental stagei

Expressed in the uncrossed ipsilateral retinal ganglion cells (iRGCs) of the peripheral ventrotemporal (VT) region segment in the retina at 16.5 dpc.1 Publication

Inductioni

Expressed in a circadian manner in the midbrain with a higher level expression seen during the dark phase (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000020838.
CleanExiMM_HTT.
ExpressionAtlasiQ60857. baseline and differential.
GenevisibleiQ60857. MM.

Interactioni

Subunit structurei

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 PATJ. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake. Interacts with TGFB1I1.By similarity2 Publications

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • nitric-oxide synthase binding Source: UniProtKB
  • Rab GTPase binding Source: MGI

Protein-protein interaction databases

BioGridi200481. 1 interactor.
DIPiDIP-60923N.
STRINGi10090.ENSMUSP00000021195.

Chemistry databases

BindingDBiQ60857.

Structurei

3D structure databases

ProteinModelPortaliQ60857.
SMRiQ60857.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni611 – 630Required for serotonin uptake activityBy similarityAdd BLAST20
Regioni616 – 624Interaction with RAB4ABy similarity9

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiQ60857.
KOiK05037.
OMAiCRDVKEM.
OrthoDBiEOG091G08PX.
TreeFamiTF343812.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 2 hits.
PfamiPF03491. 5HT_transport_N. 1 hit.
PF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01203. 5HTTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q60857-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METTPLNSQK VLSECKDKED CQENGVLQKG VPTPADKAGP GQISNGYSAV
60 70 80 90 100
PSTSAGDEAP HSTPAATTTL VAEIHQGERE TWGKKMDFLL SVIGYAVDLG
110 120 130 140 150
NIWRFPYICY QNGGGAFLLP YTIMAIFGGI PLFYMELALG QYHRNGCISI
160 170 180 190 200
WKKICPIFKG IGYAICIIAF YIASYYNTII AWALYYLISS FTDQLPWTSC
210 220 230 240 250
KNSWNTGNCT NYFAQDNITW TLHSTSPAEE FYLRHVLQIH QSKGLQDLGT
260 270 280 290 300
ISWQLALCIM LIFTIIYFSI WKGVKTSGKV VWVTATFPYI VLSVLLVRGA
310 320 330 340 350
TLPGAWRGVV FYLKPNWQKL LETGVWVDAA AQIFFSLGPG FGVLLAFASY
360 370 380 390 400
NKFNNNCYQD ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD
410 420 430 440 450
AGPSLLFITY AEAIANMPAS TFFAIIFFLM LITLGLDSTF AGLEGVITAV
460 470 480 490 500
LDEFPHIWAK RREWFVLIVV ITCILGSLLT LTSGGAYVVT LLEEYATGPA
510 520 530 540 550
VLTVALIEAV VVSWFYGITQ FCSDVKEMLG FSPGWFWRIC WVAISPLFLL
560 570 580 590 600
FIICSFLMSP PQLRLFQYNY PHWSIILGYC IGTSSVICIP IYIIYRLIST
610 620 630
PGTLKERIIK SITPETPTEI PCGDIRMNAV
Length:630
Mass (Da):70,048
Last modified:July 27, 2011 - v4
Checksum:i2B6ABD26E3288CD0
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39G → E in AAB67172 (PubMed:9037532).Curated1
Sequence conflicti39G → E in CAA70092 (PubMed:9073170).Curated1
Sequence conflicti39G → E in AAA84750 (Ref. 4) Curated1
Sequence conflicti152K → R in AAB67172 (PubMed:9037532).Curated1
Sequence conflicti152K → R in CAA70092 (PubMed:9073170).Curated1
Sequence conflicti196P → Q in CAA70092 (PubMed:9073170).Curated1
Sequence conflicti415A → R in CAA70092 (PubMed:9073170).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013604 mRNA. Translation: AAB67172.1.
Y08870
, 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.
CCDSiCCDS25074.1.
RefSeqiNP_034614.2. NM_010484.2.
XP_006532362.1. XM_006532299.2.
XP_006532363.1. XM_006532300.2.
XP_006532364.1. XM_006532301.3.
UniGeneiMm.300318.

Genome annotation databases

EnsembliENSMUST00000021195; ENSMUSP00000021195; ENSMUSG00000020838.
ENSMUST00000108402; ENSMUSP00000104039; ENSMUSG00000020838.
GeneIDi15567.
KEGGimmu:15567.
UCSCiuc007kgf.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013604 mRNA. Translation: AAB67172.1.
Y08870
, 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.
CCDSiCCDS25074.1.
RefSeqiNP_034614.2. NM_010484.2.
XP_006532362.1. XM_006532299.2.
XP_006532363.1. XM_006532300.2.
XP_006532364.1. XM_006532301.3.
UniGeneiMm.300318.

3D structure databases

ProteinModelPortaliQ60857.
SMRiQ60857.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200481. 1 interactor.
DIPiDIP-60923N.
STRINGi10090.ENSMUSP00000021195.

Chemistry databases

BindingDBiQ60857.
ChEMBLiCHEMBL4642.

PTM databases

PhosphoSitePlusiQ60857.

Proteomic databases

MaxQBiQ60857.
PaxDbiQ60857.
PRIDEiQ60857.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021195; ENSMUSP00000021195; ENSMUSG00000020838.
ENSMUST00000108402; ENSMUSP00000104039; ENSMUSG00000020838.
GeneIDi15567.
KEGGimmu:15567.
UCSCiuc007kgf.2. mouse.

Organism-specific databases

CTDi6532.
MGIiMGI:96285. Slc6a4.

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiQ60857.
KOiK05037.
OMAiCRDVKEM.
OrthoDBiEOG091G08PX.
TreeFamiTF343812.

Enzyme and pathway databases

ReactomeiR-MMU-380615. Serotonin clearance from the synaptic cleft.

Miscellaneous databases

PROiQ60857.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020838.
CleanExiMM_HTT.
ExpressionAtlasiQ60857. baseline and differential.
GenevisibleiQ60857. MM.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 2 hits.
PfamiPF03491. 5HT_transport_N. 1 hit.
PF00209. SNF. 1 hit.
[Graphical view]
PRINTSiPR01203. 5HTTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEiPS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSC6A4_MOUSE
AccessioniPrimary (citable) accession number: Q60857
Secondary accession number(s): O35241, Q5NCR6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 140 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.