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Q60857

- SC6A4_MOUSE

UniProt

Q60857 - SC6A4_MOUSE

Protein

Sodium-dependent serotonin transporter

Gene

Slc6a4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 4 (27 Jul 2011)
      Previous versions | rss
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    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. protein binding Source: UniProtKB
    6. serotonin:sodium symporter activity Source: UniProtKB
    7. 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

    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

    GO - Cellular componenti

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

    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

    ArrayExpressiQ60857.
    BgeeiQ60857.
    CleanExiMM_HTT.
    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8787CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini181 – 25272ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini596 – 63035CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei88 – 10821Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei116 – 13520Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei160 – 18021Helical; Name=3Sequence 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

    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.
    GeneTreeiENSGT00740000115174.
    HOGENOMiHOG000116406.
    HOVERGENiHBG071421.
    InParanoidiQ5NCR6.
    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

    METTPLNSQK VLSECKDKED CQENGVLQKG VPTPADKAGP GQISNGYSAV    50
    PSTSAGDEAP HSTPAATTTL VAEIHQGERE TWGKKMDFLL SVIGYAVDLG 100
    NIWRFPYICY QNGGGAFLLP YTIMAIFGGI PLFYMELALG QYHRNGCISI 150
    WKKICPIFKG IGYAICIIAF YIASYYNTII AWALYYLISS FTDQLPWTSC 200
    KNSWNTGNCT NYFAQDNITW TLHSTSPAEE FYLRHVLQIH QSKGLQDLGT 250
    ISWQLALCIM LIFTIIYFSI WKGVKTSGKV VWVTATFPYI VLSVLLVRGA 300
    TLPGAWRGVV FYLKPNWQKL LETGVWVDAA AQIFFSLGPG FGVLLAFASY 350
    NKFNNNCYQD ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD 400
    AGPSLLFITY AEAIANMPAS TFFAIIFFLM LITLGLDSTF AGLEGVITAV 450
    LDEFPHIWAK RREWFVLIVV ITCILGSLLT LTSGGAYVVT LLEEYATGPA 500
    VLTVALIEAV VVSWFYGITQ FCSDVKEMLG FSPGWFWRIC WVAISPLFLL 550
    FIICSFLMSP PQLRLFQYNY PHWSIILGYC IGTSSVICIP IYIIYRLIST 600
    PGTLKERIIK SITPETPTEI PCGDIRMNAV 630
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ENSGT00740000115174.
    HOGENOMi HOG000116406.
    HOVERGENi HBG071421.
    InParanoidi Q5NCR6.
    KOi K05037.
    OMAi TSCKNSW.
    OrthoDBi EOG793B71.
    TreeFami TF343812.

    Miscellaneous databases

    NextBioi 288538.
    PROi Q60857.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q60857.
    Bgeei Q60857.
    CleanExi MM_HTT.
    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

    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 1, 2014
    This is version 120 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