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P31645

- SC6A4_HUMAN

UniProt

P31645 - SC6A4_HUMAN

Protein

Sodium-dependent serotonin transporter

Gene

SLC6A4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 147 (01 Oct 2014)
      Sequence version 1 (01 Jul 1993)
      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.3 Publications

    GO - Molecular functioni

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

    Keywords - Biological processi

    Neurotransmitter transport, Symport, Transport

    Protein family/group databases

    TCDBi2.A.22.1.1. the neurotransmitter:sodium symporter (nss) family.

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:11050. SLC6A4.

    Subcellular locationi

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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cell membrane, Endosome, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi611 – 6111S → A: Loss of 10 % of serotonin uptake activity. Loss of 5 % of serotonin uptake activity; when associated with A-613 and A-616. 1 Publication
    Mutagenesisi611 – 6111S → D: Loss of 61 % of serotonin uptake activity. Loss of 95 % of serotonin uptake activity and lack of association between VIM and the plasma membrane; when associated with D-613 and D-616. 1 Publication
    Mutagenesisi613 – 6131T → A: Loss of 26 % of serotonin uptake activity. Loss of 5 % of serotonin uptake activity; when associated with A-611 and A-616. 1 Publication
    Mutagenesisi613 – 6131T → D: Loss of 26 % of serotonin uptake activity. Loss of 95 % of serotonin uptake activity and lack of association between VIM and the plasma membrane; when associated with D-611 and D-616. 1 Publication
    Mutagenesisi616 – 6161T → A: No change. Loss of 5 % of serotonin uptake activity; when associated with A-611 and A-613. 1 Publication
    Mutagenesisi616 – 6161T → D: No change. Loss of 95 % of serotonin uptake activity and lack of association between VIM and the plasma membrane; when associated with D-611 and D-613. 1 Publication

    Organism-specific databases

    MIMi103780. phenotype.
    164230. phenotype.
    PharmGKBiPA312.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 630630Sodium-dependent serotonin transporterPRO_0000214757Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei47 – 471Phosphotyrosine1 Publication
    Modified residuei142 – 1421Phosphotyrosine1 Publication
    Glycosylationi208 – 2081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi217 – 2171N-linked (GlcNAc...)Sequence Analysis
    Modified residuei276 – 2761Phosphothreonine; by PKG1 Publication
    Modified residuei611 – 6111Phosphoserine1 Publication
    Modified residuei613 – 6131Phosphothreonine1 Publication
    Modified residuei616 – 6161Phosphothreonine1 Publication

    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 at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation. Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity.3 Publications

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiP31645.
    PRIDEiP31645.

    PTM databases

    PhosphoSiteiP31645.

    Expressioni

    Tissue specificityi

    Expressed in platelets (at protein level).1 Publication

    Inductioni

    Down-regulated when plasma serotonin is elevated.2 Publications

    Gene expression databases

    ArrayExpressiP31645.
    BgeeiP31645.
    CleanExiHS_HTT.
    HS_SLC6A4.
    GenevestigatoriP31645.

    Interactioni

    Subunit structurei

    Monomer or homooligomer By similarity. Interacts with TGFB1I1. Interacts (via sialylated form) with MYH9. 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 filamentous actin and STX1A 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 RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly.By similarity4 Publications

    Protein-protein interaction databases

    BioGridi112423. 5 interactions.
    IntActiP31645. 2 interactions.
    MINTiMINT-577123.
    STRINGi9606.ENSP00000261707.

    Structurei

    3D structure databases

    ProteinModelPortaliP31645.
    SMRiP31645. 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 activityAdd
    BLAST
    Regioni616 – 6249Interaction with RAB4A

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0733.
    HOGENOMiHOG000116406.
    HOVERGENiHBG071421.
    InParanoidiP31645.
    KOiK05037.
    OMAiTSCKNSW.
    OrthoDBiEOG793B71.
    PhylomeDBiP31645.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P31645-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    METTPLNSQK QLSACEDGED CQENGVLQKV VPTPGDKVES GQISNGYSAV    50
    PSPGAGDDTR HSIPATTTTL VAELHQGERE TWGKKVDFLL SVIGYAVDLG 100
    NVWRFPYICY QNGGGAFLLP YTIMAIFGGI PLFYMELALG QYHRNGCISI 150
    WRKICPIFKG IGYAICIIAF YIASYYNTIM AWALYYLISS FTDQLPWTSC 200
    KNSWNTGNCT NYFSEDNITW TLHSTSPAEE FYTRHVLQIH RSKGLQDLGG 250
    ISWQLALCIM LIFTVIYFSI WKGVKTSGKV VWVTATFPYI ILSVLLVRGA 300
    TLPGAWRGVL FYLKPNWQKL LETGVWIDAA AQIFFSLGPG FGVLLAFASY 350
    NKFNNNCYQD ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD 400
    AGPSLLFITY AEAIANMPAS TFFAIIFFLM LITLGLDSTF AGLEGVITAV 450
    LDEFPHVWAK RRERFVLAVV ITCFFGSLVT LTFGGAYVVK LLEEYATGPA 500
    VLTVALIEAV AVSWFYGITQ FCRDVKEMLG FSPGWFWRIC WVAISPLFLL 550
    FIICSFLMSP PQLRLFQYNY PYWSIILGYC IGTSSFICIP TYIAYRLIIT 600
    PGTFKERIIK SITPETPTEI PCGDIRLNAV 630
    Length:630
    Mass (Da):70,325
    Last modified:July 1, 1993 - v1
    Checksum:i0EB535B0A579BDA2
    GO
    Isoform 2 (identifier: P31645-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MSQSRRVNPDDRELGGDLQIQAPRDQLGSLADGHQCHLLTSRM

    Show »
    Length:672
    Mass (Da):74,979
    Checksum:i142F04437BA1DE39
    GO

    Polymorphismi

    A polymorphism in the promoter region (5-HTT gene-linked polymorphic region, 5-HTTLPR) is located approximately 1 kb upstream of the transcription initiation site and is composed of 16 repeat elements. The polymorphism consists of a 44-bp insertion or deletion involving repeat elements 6 to 8. The short allele is associated with lower transcriptional efficiency of the promoter compared with the long allele. Over half of the Caucasian population has a short allele. Individuals with one or two copies of the short allele exhibit more depressive symptoms, diagnosable depression and suicidality in relation to stressful life events than individuals homozygous for the long allele.
    The polymorphism Val-425 seems to be linked to a susceptibility to obsessive-compulsive disorder (OCD) [MIMi:164230].
    Genetic variations in SLC6A4 determine the genetic susceptibility to alcoholism [MIMi:103780].

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti56 – 561G → A.1 Publication
    Corresponds to variant rs6355 [ dbSNP | Ensembl ].
    VAR_014181
    Natural varianti201 – 2011K → N.
    Corresponds to variant rs2228673 [ dbSNP | Ensembl ].
    VAR_029158
    Natural varianti425 – 4251I → L.
    Corresponds to variant rs28914832 [ dbSNP | Ensembl ].
    VAR_036788
    Natural varianti425 – 4251I → V Polymorphism linked with susceptibility to obsessive-compulsive disorder; increased serotonin transport capacity. 2 Publications
    VAR_026751
    Natural varianti465 – 4651F → L.
    Corresponds to variant rs28914833 [ dbSNP | Ensembl ].
    VAR_036789
    Natural varianti550 – 5501L → V.
    Corresponds to variant rs28914834 [ dbSNP | Ensembl ].
    VAR_036790
    Natural varianti605 – 6051K → N.1 Publication
    Corresponds to variant rs6352 [ dbSNP | Ensembl ].
    VAR_014182

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MSQSRRVNPDDRELGGDLQI QAPRDQLGSLADGHQCHLLT SRM in isoform 2. 1 PublicationVSP_046553

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X70697 mRNA. Translation: CAA50029.1.
    L05568 mRNA. Translation: AAA35492.1.
    AY902473 mRNA. Translation: AAW80933.1.
    EU099989 Genomic DNA. Translation: ABV02581.1.
    BC069484 mRNA. Translation: AAH69484.1.
    U79746 Genomic DNA. Translation: AAB93475.1.
    AK308014 mRNA. No translation available.
    CCDSiCCDS11256.1. [P31645-1]
    PIRiA47398.
    RefSeqiNP_001036.1. NM_001045.5. [P31645-1]
    UniGeneiHs.134662.
    Hs.29792.

    Genome annotation databases

    EnsembliENST00000261707; ENSP00000261707; ENSG00000108576. [P31645-1]
    ENST00000401766; ENSP00000385822; ENSG00000108576. [P31645-1]
    GeneIDi6532.
    KEGGihsa:6532.
    UCSCiuc002hey.5. human. [P31645-1]

    Polymorphism databases

    DMDMi400630.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    SHMPD

    The Singapore human mutation and polymorphism database

    Wikipedia

    Serotonin transporter entry

    Protein Spotlight

    Love, love, love... -Issue 123 of November 2010

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X70697 mRNA. Translation: CAA50029.1 .
    L05568 mRNA. Translation: AAA35492.1 .
    AY902473 mRNA. Translation: AAW80933.1 .
    EU099989 Genomic DNA. Translation: ABV02581.1 .
    BC069484 mRNA. Translation: AAH69484.1 .
    U79746 Genomic DNA. Translation: AAB93475.1 .
    AK308014 mRNA. No translation available.
    CCDSi CCDS11256.1. [P31645-1 ]
    PIRi A47398.
    RefSeqi NP_001036.1. NM_001045.5. [P31645-1 ]
    UniGenei Hs.134662.
    Hs.29792.

    3D structure databases

    ProteinModelPortali P31645.
    SMRi P31645. Positions 78-614.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112423. 5 interactions.
    IntActi P31645. 2 interactions.
    MINTi MINT-577123.
    STRINGi 9606.ENSP00000261707.

    Chemistry

    BindingDBi P31645.
    ChEMBLi CHEMBL2111346.
    DrugBanki DB04836. Amineptine.
    DB00321. Amitriptyline.
    DB00543. Amoxapine.
    DB00215. Citalopram.
    DB01242. Clomipramine.
    DB00907. Cocaine.
    DB01151. Desipramine.
    DB01191. Dexfenfluramine.
    DB00514. Dextromethorphan.
    DB01142. Doxepin.
    DB00476. Duloxetine.
    DB01175. Escitalopram.
    DB00472. Fluoxetine.
    DB00176. Fluvoxamine.
    DB00458. Imipramine.
    DB00422. Methylphenidate.
    DB04896. Milnacipran.
    DB00805. Minaprine.
    DB01149. Nefazodone.
    DB00540. Nortriptyline.
    DB00715. Paroxetine.
    DB00191. Phentermine.
    DB00344. Protriptyline.
    DB01104. Sertraline.
    DB01105. Sibutramine.
    DB01079. Tegaserod.
    DB00193. Tramadol.
    DB00656. Trazodone.
    DB00726. Trimipramine.
    DB00285. Venlafaxine.
    DB04832. Zimelidine.
    GuidetoPHARMACOLOGYi 928.

    Protein family/group databases

    TCDBi 2.A.22.1.1. the neurotransmitter:sodium symporter (nss) family.

    PTM databases

    PhosphoSitei P31645.

    Polymorphism databases

    DMDMi 400630.

    Proteomic databases

    PaxDbi P31645.
    PRIDEi P31645.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000261707 ; ENSP00000261707 ; ENSG00000108576 . [P31645-1 ]
    ENST00000401766 ; ENSP00000385822 ; ENSG00000108576 . [P31645-1 ]
    GeneIDi 6532.
    KEGGi hsa:6532.
    UCSCi uc002hey.5. human. [P31645-1 ]

    Organism-specific databases

    CTDi 6532.
    GeneCardsi GC17M028521.
    HGNCi HGNC:11050. SLC6A4.
    MIMi 103780. phenotype.
    164230. phenotype.
    182138. gene.
    neXtProti NX_P31645.
    PharmGKBi PA312.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0733.
    HOGENOMi HOG000116406.
    HOVERGENi HBG071421.
    InParanoidi P31645.
    KOi K05037.
    OMAi TSCKNSW.
    OrthoDBi EOG793B71.
    PhylomeDBi P31645.
    TreeFami TF343812.

    Miscellaneous databases

    GeneWikii Serotonin_transporter.
    GenomeRNAii 6532.
    NextBioi 25415.
    PROi P31645.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P31645.
    Bgeei P31645.
    CleanExi HS_HTT.
    HS_SLC6A4.
    Genevestigatori P31645.

    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. "Isolation of a cDNA encoding the human brain serotonin transporter."
      Lesch K.P., Wolozin B.L., Estler H.C., Murphy D.L., Riederer P.
      J. Neural Transm. 91:67-73(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Brain.
    2. "Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization."
      Ramamoorthy S., Bauman A.L., Moore K.R., Han H., Yang-Feng T., Chang A.S., Ganapathy V., Blakely R.D.
      Proc. Natl. Acad. Sci. U.S.A. 90:2542-2546(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter."
      Lesch K.P., Wolozin B.L., Murphy D.L., Reiderer P.
      J. Neurochem. 60:2319-2322(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Platelet.
    4. "Molecular characterization and intracellular regulation of the human serotonin transporter in Caco-2 cells."
      Iceta R., Mesonero J.E., Aramayona J.J., Alcalde A.I.
      J. Physiol. Pharmacol. 57:119-130(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. NIEHS SNPs program
      Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    7. Bradley C.C., Blakely R.D.
      Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
      Tissue: Placenta.
    8. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-317 (ISOFORM 2).
      Tissue: Lung.
    9. "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.
    10. "Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2."
      Mueller H.K., Wiborg O., Haase J.
      J. Biol. Chem. 281:28901-28909(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SCAMP2, SUBCELLULAR LOCATION.
    11. "Plasma serotonin levels and the platelet serotonin transporter."
      Brenner B., Harney J.T., Ahmed B.A., Jeffus B.C., Unal R., Mehta J.L., Kilic F.
      J. Neurochem. 102:206-215(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    12. "Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder."
      Zhang Y.W., Gesmonde J., Ramamoorthy S., Rudnick G.
      J. Neurosci. 27:10878-10886(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-276, VARIANT VAL-425.
    13. "Serotonin transamidates Rab4 and facilitates its binding to the C terminus of serotonin transporter."
      Ahmed B.A., Jeffus B.C., Bukhari S.I., Harney J.T., Unal R., Lupashin V.V., van der Sluijs P., Kilic F.
      J. Biol. Chem. 283:9388-9398(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RAB4, SUBCELLULAR LOCATION, INDUCTION BY SEROTONIN.
    14. "The cellular distribution of serotonin transporter is impeded on serotonin-altered vimentin network."
      Ahmed B.A., Bukhari I.A., Jeffus B.C., Harney J.T., Thyparambil S., Ziu E., Fraer M., Rusch N.J., Zimniak P., Lupashin V., Tang D., Kilic F.
      PLoS ONE 4:E4730-E4730(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH VIM, SUBCELLULAR LOCATION, INDUCTION BY SEROTONIN, MUTAGENESIS OF SER-611; THR-613 AND THR-616, PHOSPHORYLATION AT SER-611; THR-613 AND THR-616.
    15. "Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function."
      Annamalai B., Mannangatti P., Arapulisamy O., Shippenberg T.S., Jayanthi L.D., Ramamoorthy S.
      Mol. Pharmacol. 81:73-85(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-47 AND TYR-142.
    16. Cited for: VARIANTS ALA-56 AND ASN-605.
    17. "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype."
      Ozaki N., Goldman D., Kaye W.H., Plotnicov K., Greenberg B.D., Lappalainen J., Rudnick G., Murphy D.L.
      Mol. Psychiatry 8:933-936(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT VAL-425.
    18. "A human serotonin transporter mutation causes constitutive activation of transport activity."
      Kilic F., Murphy D.L., Rudnick G.
      Mol. Pharmacol. 64:440-446(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT VAL-425.
    19. "Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene."
      Caspi A., Sugden K., Moffitt T.E., Taylor A., Craig I.W., Harrington H., McClay J., Mill J., Martin J., Braithwaite A., Poulton R.
      Science 301:386-389(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: POLYMORPHISM IN THE PROMOTER REGION.
    20. "Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence."
      Feinn R., Nellissery M., Kranzler H.R.
      Am. J. Med. Genet. B Neuropsychiatr. Genet. 133:79-84(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM.

    Entry informationi

    Entry nameiSC6A4_HUMAN
    AccessioniPrimary (citable) accession number: P31645
    Secondary accession number(s): Q5EE02
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: July 1, 1993
    Last modified: October 1, 2014
    This is version 147 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3