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Q60857

- SC6A4_MOUSE

UniProt

Q60857 - SC6A4_MOUSE

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Protein

Sodium-dependent serotonin transporter

Gene

Slc6a4

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 (By similarity).By similarity

GO - Molecular functioni

  1. actin filament binding Source: UniProtKB
  2. cocaine binding Source: Ensembl
  3. monoamine transmembrane transporter activity Source: MGI
  4. nitric-oxide synthase binding Source: UniProtKB
  5. serotonin:sodium symporter activity Source: UniProtKB
  6. serotonin transmembrane transporter activity Source: UniProtKB

GO - Biological processi

  1. brain morphogenesis Source: BHF-UCL
  2. cellular response to cGMP Source: Ensembl
  3. cellular response to organic substance Source: MGI
  4. cellular response to retinoic acid Source: Ensembl
  5. circadian rhythm Source: Ensembl
  6. memory Source: Ensembl
  7. monoamine transport Source: MGI
  8. negative regulation of cerebellar granule cell precursor proliferation Source: Ensembl
  9. negative regulation of neuron differentiation Source: Ensembl
  10. negative regulation of organ growth Source: BHF-UCL
  11. negative regulation of synaptic transmission, dopaminergic Source: Ensembl
  12. positive regulation of cell cycle Source: UniProtKB
  13. positive regulation of gene expression Source: UniProtKB
  14. protein homooligomerization Source: Ensembl
  15. protein oligomerization Source: UniProtKB
  16. response to drug Source: Ensembl
  17. response to estradiol Source: Ensembl
  18. response to hypoxia Source: Ensembl
  19. response to nutrient Source: Ensembl
  20. response to toxic substance Source: Ensembl
  21. serotonin transport Source: UniProtKB
  22. serotonin uptake Source: UniProtKB
  23. social behavior Source: BHF-UCL
  24. sperm ejaculation Source: Ensembl
  25. thalamus development Source: Ensembl
  26. vasoconstriction Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent serotonin transporter
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
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:96285. Slc6a4.

Subcellular locationi

Cell membrane By similarity; 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).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8787CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei88 – 10821Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei116 – 13520Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei160 – 18021Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini181 – 25272ExtracellularSequence AnalysisAdd
BLAST
Transmembranei253 – 27119Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei280 – 29718Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei333 – 35018Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei362 – 38322Helical; Name=7Sequence AnalysisAdd
BLAST
Transmembranei417 – 43620Helical; Name=8Sequence AnalysisAdd
BLAST
Transmembranei464 – 48219Helical; Name=9Sequence AnalysisAdd
BLAST
Transmembranei498 – 51821Helical; Name=10Sequence AnalysisAdd
BLAST
Transmembranei539 – 55820Helical; Name=11Sequence AnalysisAdd
BLAST
Transmembranei577 – 59519Helical; Name=12Sequence AnalysisAdd
BLAST
Topological domaini596 – 63035CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytosol Source: Ensembl
  2. endomembrane system Source: UniProtKB
  3. endosome Source: UniProtKB-KW
  4. integral component of plasma membrane Source: InterPro
  5. membrane raft Source: Ensembl
  6. neuron projection Source: Ensembl
  7. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Loss of serotonin uptake.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 630630Sodium-dependent serotonin transporterPRO_0000214759Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei47 – 471PhosphotyrosineBy similarity
Modified residuei142 – 1421PhosphotyrosineBy similarity
Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence Analysis
Glycosylationi217 – 2171N-linked (GlcNAc...)Sequence Analysis
Modified residuei276 – 2761PhosphothreonineBy similarity
Modified residuei611 – 6111PhosphoserineSequence Analysis
Modified residuei613 – 6131PhosphothreonineSequence Analysis
Modified residuei616 – 6161PhosphothreonineSequence Analysis

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

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ60857.
PRIDEiQ60857.

PTM databases

PhosphoSiteiQ60857.

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

BgeeiQ60857.
CleanExiMM_HTT.
ExpressionAtlasiQ60857. baseline and differential.
GenevestigatoriQ60857.

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 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.By similarity2 Publications

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ60857.
SMRiQ60857. Positions 78-614.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni611 – 63020Required for serotonin uptake activityBy similarityAdd
BLAST
Regioni616 – 6249Interaction with RAB4ABy similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0733.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiQ60857.
KOiK05037.
OMAiTSCKNSW.
OrthoDBiEOG793B71.
TreeFamiTF343812.

Family and domain databases

InterProiIPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view]
PANTHERiPTHR11616. PTHR11616. 1 hit.
PfamiPF03491. 5HT_transporter. 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti39 – 391G → E in AAB67172. (PubMed:9037532)Curated
Sequence conflicti39 – 391G → E in CAA70092. (PubMed:9073170)Curated
Sequence conflicti39 – 391G → E in AAA84750. 1 PublicationCurated
Sequence conflicti152 – 1521K → R in AAB67172. (PubMed:9037532)Curated
Sequence conflicti152 – 1521K → R in CAA70092. (PubMed:9073170)Curated
Sequence conflicti196 – 1961P → Q in CAA70092. (PubMed:9073170)Curated
Sequence conflicti415 – 4151A → R in CAA70092. (PubMed:9073170)Curated

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_006532299.1.
XP_006532363.1. XM_006532300.1.
XP_006532364.1. XM_006532301.1.
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.
CCDSi CCDS25074.1.
RefSeqi NP_034614.2. NM_010484.2.
XP_006532362.1. XM_006532299.1.
XP_006532363.1. XM_006532300.1.
XP_006532364.1. XM_006532301.1.
UniGenei Mm.300318.

3D structure databases

ProteinModelPortali Q60857.
SMRi Q60857. Positions 78-614.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200481. 1 interaction.
DIPi DIP-60923N.
STRINGi 10090.ENSMUSP00000021195.

Chemistry

BindingDBi Q60857.
ChEMBLi CHEMBL4642.

PTM databases

PhosphoSitei Q60857.

Proteomic databases

PaxDbi Q60857.
PRIDEi Q60857.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000021195 ; ENSMUSP00000021195 ; ENSMUSG00000020838 .
ENSMUST00000108402 ; ENSMUSP00000104039 ; ENSMUSG00000020838 .
GeneIDi 15567.
KEGGi mmu:15567.
UCSCi uc007kgf.2. mouse.

Organism-specific databases

CTDi 6532.
MGIi MGI:96285. Slc6a4.

Phylogenomic databases

eggNOGi COG0733.
GeneTreei ENSGT00760000118857.
HOGENOMi HOG000116406.
HOVERGENi HBG071421.
InParanoidi Q60857.
KOi K05037.
OMAi TSCKNSW.
OrthoDBi EOG793B71.
TreeFami TF343812.

Miscellaneous databases

NextBioi 288538.
PROi Q60857.
SOURCEi Search...

Gene expression databases

Bgeei Q60857.
CleanExi MM_HTT.
ExpressionAtlasi Q60857. baseline and differential.
Genevestigatori Q60857.

Family and domain databases

InterProi IPR000175. Na/ntran_symport.
IPR013086. Na/ntran_symport_serotonin_N.
[Graphical view ]
PANTHERi PTHR11616. PTHR11616. 1 hit.
Pfami PF03491. 5HT_transporter. 1 hit.
PF00209. SNF. 1 hit.
[Graphical view ]
PRINTSi PR01203. 5HTTRANSPORT.
PR00176. NANEUSMPORT.
PROSITEi PS00610. NA_NEUROTRAN_SYMP_1. 1 hit.
PS00754. NA_NEUROTRAN_SYMP_2. 1 hit.
PS50267. NA_NEUROTRAN_SYMP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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.
  10. "Role of activating transcription factor-4 in 24-hour rhythm of serotonin transporter expression in the mouse midbrain."
    Ushijima K., Koyanagi S., Sato Y., Ogata T., Matsunaga N., Fujimura A., Ohdo S.
    Mol. Pharmacol. 82:264-270(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.

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: October 29, 2014
This is version 121 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

External Data

Dasty 3