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Sodium-dependent serotonin transporter (SERT) (5HT transporter) (5HTT) (Solute carrier family 6 member 4)

 SC6A4_MOUSE             Reviewed;         630 AA.
Q60857; O35241; Q5NCR6;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
27-JUL-2011, sequence version 4.
25-OCT-2017, entry version 145.
RecName: Full=Sodium-dependent serotonin transporter;
Short=SERT {ECO:0000250|UniProtKB:P31652};
AltName: Full=5HT transporter;
Short=5HTT;
AltName: Full=Solute carrier family 6 member 4;
Name=Slc6a4; Synonyms=Htt, Sert;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=9037532; DOI=10.1016/S0169-328X(96)00172-6;
Chang A.S., Chang S.M., Starnes D.M., Schroeter S., Bauman A.L.,
Blakely R.D.;
"Cloning and expression of the mouse serotonin transporter.";
Brain Res. Mol. Brain Res. 43:185-192(1996).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=129;
PubMed=9073170; DOI=10.1016/S0169-328X(96)00234-3;
Bengel D., Heils A., Petri S., Seemann M., Glatz K., Andrews A.,
Murphy D.L., Lesch K.P.;
"Gene structure and 5'-flanking regulatory region of the murine
serotonin transporter.";
Brain Res. Mol. Brain Res. 44:286-292(1997).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
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., 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.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-114.
STRAIN=BALB/cJ;
Saito N., Sakai N., Kobayashi S., Fujimoto M., Morikawa O.,
Ikegaki N.;
Submitted (MAY-1995) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 69-630.
PubMed=8507984; DOI=10.1007/BF00417438;
Gregor P., Patel A., Shimada S., Lin C.L., Rochelle J.M., Kitayama S.,
Seldin M.F., Uhl G.R.;
"Murine serotonin transporter: sequence and localization to chromosome
11.";
Mamm. Genome 4:283-284(1993).
[6]
DISRUPTION PHENOTYPE.
PubMed=9547354;
Bengel D., Murphy D.L., Andrews A.M., Wichems C.H., Feltner D.,
Heils A., Mossner R., Westphal H., Lesch K.P.;
"Altered brain serotonin homeostasis and locomotor insensitivity to 3,
4-methylenedioxymethamphetamine ('Ecstasy') in serotonin transporter-
deficient mice.";
Mol. Pharmacol. 53:649-655(1998).
[7]
INTERACTION WITH TGFB1I1.
PubMed=16803896; DOI=10.1074/jbc.M603877200;
Carneiro A.M.D., Blakely R.D.;
"Serotonin-, protein kinase C-, and Hic-5-associated redistribution of
the platelet serotonin transporter.";
J. Biol. Chem. 281:24769-24780(2006).
[8]
INTERACTION WITH NOS1; SEC23A; SEC24C AND PATJ.
PubMed=17452640; DOI=10.1073/pnas.0610964104;
Chanrion B., Mannoury la Cour C., Bertaso F., Lerner-Natoli M.,
Freissmuth M., Millan M.J., Bockaert J., Marin P.;
"Physical interaction between the serotonin transporter and neuronal
nitric oxide synthase underlies reciprocal modulation of their
activity.";
Proc. Natl. Acad. Sci. U.S.A. 104:8119-8124(2007).
[9]
DEVELOPMENTAL STAGE.
PubMed=20676059; DOI=10.1038/emboj.2010.172;
Garcia-Frigola C., Herrera E.;
"Zic2 regulates the expression of Sert to modulate eye-specific
refinement at the visual targets.";
EMBO J. 29:3170-3183(2010).
[10]
INDUCTION.
PubMed=22572884; DOI=10.1124/mol.112.079079;
Ushijima K., Koyanagi S., Sato Y., Ogata T., Matsunaga N.,
Fujimura A., Ohdo S.;
"Role of activating transcription factor-4 in 24-hour rhythm of
serotonin transporter expression in the mouse midbrain.";
Mol. Pharmacol. 82:264-270(2012).
-!- 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. {ECO:0000269|PubMed:9037532}.
-!- SUBUNIT: 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. {ECO:0000250, ECO:0000269|PubMed:16803896,
ECO:0000269|PubMed:17452640}.
-!- INTERACTION:
Q9Z0J4:Nos1; NbExp=4; IntAct=EBI-15633326, EBI-397596;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9037532};
Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7K4Y6}.
Endomembrane system {ECO:0000250|UniProtKB:P31652}; Multi-pass
membrane protein {ECO:0000255}. Endosome membrane
{ECO:0000250|UniProtKB:P31652}; Multi-pass membrane protein
{ECO:0000255}. Note=Could be part of recycling endosomes. Density
of transporter molecules on the plasma membrane is itself
regulated by STX1A. Density of transporter molecules on the plasma
membrane is also regulated by serotonin (By similarity).
{ECO:0000250|UniProtKB:P31645, ECO:0000250|UniProtKB:P31652}.
-!- 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.
{ECO:0000269|PubMed:20676059}.
-!- INDUCTION: Expressed in a circadian manner in the midbrain with a
higher level expression seen during the dark phase (at protein
level). {ECO:0000269|PubMed:22572884}.
-!- PTM: Glycosylated; modification with sialylated N-glycans is a
requirement for transporters to associate with each other and to
function as homooligomeric forms. {ECO:0000250}.
-!- PTM: 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. {ECO:0000250}.
-!- DISRUPTION PHENOTYPE: Loss of serotonin uptake.
{ECO:0000269|PubMed:9547354}.
-!- MISCELLANEOUS: This protein is the target of psychomotor
stimulants such as amphetamines or cocaine.
-!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF)
(TC 2.A.22) family. SLC6A4 subfamily. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=X66119; Type=Frameshift; Positions=195; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; AF013604; AAB67172.1; -; mRNA.
EMBL; Y08870; CAA70092.1; -; Genomic_DNA.
EMBL; Y08871; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08872; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08873; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08874; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08875; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08876; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08877; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08878; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08879; CAA70092.1; JOINED; Genomic_DNA.
EMBL; Y08880; CAA70092.1; JOINED; Genomic_DNA.
EMBL; AL603842; CAI35067.1; -; Genomic_DNA.
EMBL; U26452; AAA84750.1; -; Genomic_DNA.
EMBL; X66119; -; NOT_ANNOTATED_CDS; mRNA.
CCDS; CCDS25074.1; -.
RefSeq; NP_034614.2; NM_010484.2.
RefSeq; XP_006532362.1; XM_006532299.2.
RefSeq; XP_006532363.1; XM_006532300.2.
RefSeq; XP_006532364.1; XM_006532301.3.
UniGene; Mm.300318; -.
ProteinModelPortal; Q60857; -.
SMR; Q60857; -.
BioGrid; 200481; 1.
DIP; DIP-60923N; -.
IntAct; Q60857; 5.
STRING; 10090.ENSMUSP00000021195; -.
BindingDB; Q60857; -.
ChEMBL; CHEMBL4642; -.
PhosphoSitePlus; Q60857; -.
MaxQB; Q60857; -.
PaxDb; Q60857; -.
PRIDE; Q60857; -.
Ensembl; ENSMUST00000021195; ENSMUSP00000021195; ENSMUSG00000020838.
Ensembl; ENSMUST00000108402; ENSMUSP00000104039; ENSMUSG00000020838.
GeneID; 15567; -.
KEGG; mmu:15567; -.
UCSC; uc007kgf.2; mouse.
CTD; 6532; -.
MGI; MGI:96285; Slc6a4.
eggNOG; KOG3659; Eukaryota.
eggNOG; COG0733; LUCA.
GeneTree; ENSGT00760000118857; -.
HOGENOM; HOG000116406; -.
HOVERGEN; HBG071421; -.
InParanoid; Q60857; -.
KO; K05037; -.
OMA; NMPAATF; -.
OrthoDB; EOG091G08PX; -.
TreeFam; TF343812; -.
Reactome; R-MMU-380615; Serotonin clearance from the synaptic cleft.
PRO; PR:Q60857; -.
Proteomes; UP000000589; Chromosome 11.
Bgee; ENSMUSG00000020838; -.
CleanEx; MM_HTT; -.
ExpressionAtlas; Q60857; baseline and differential.
Genevisible; Q60857; MM.
GO; GO:0005829; C:cytosol; ISO:MGI.
GO; GO:0012505; C:endomembrane system; ISS:UniProtKB.
GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0045121; C:membrane raft; ISO:MGI.
GO; GO:0043005; C:neuron projection; IBA:GO_Central.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0098793; C:presynapse; IEA:GOC.
GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
GO; GO:0019811; F:cocaine binding; IEA:Ensembl.
GO; GO:0005330; F:dopamine:sodium symporter activity; IBA:GO_Central.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0008504; F:monoamine transmembrane transporter activity; ISO:MGI.
GO; GO:0017022; F:myosin binding; IEA:Ensembl.
GO; GO:0050998; F:nitric-oxide synthase binding; IPI:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0017137; F:Rab GTPase binding; ISO:MGI.
GO; GO:0015222; F:serotonin transmembrane transporter activity; ISS:UniProtKB.
GO; GO:0005335; F:serotonin:sodium symporter activity; ISS:UniProtKB.
GO; GO:0017075; F:syntaxin-1 binding; IEA:Ensembl.
GO; GO:0048854; P:brain morphogenesis; IMP:BHF-UCL.
GO; GO:0071321; P:cellular response to cGMP; IEA:Ensembl.
GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl.
GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
GO; GO:0007613; P:memory; IEA:Ensembl.
GO; GO:0015844; P:monoamine transport; ISO:MGI.
GO; GO:0021941; P:negative regulation of cerebellar granule cell precursor proliferation; IEA:Ensembl.
GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
GO; GO:0046621; P:negative regulation of organ growth; IMP:BHF-UCL.
GO; GO:0032227; P:negative regulation of synaptic transmission, dopaminergic; IEA:Ensembl.
GO; GO:0045787; P:positive regulation of cell cycle; IMP:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
GO; GO:0014064; P:positive regulation of serotonin secretion; IEA:Ensembl.
GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
GO; GO:0051259; P:protein oligomerization; ISS:UniProtKB.
GO; GO:0042493; P:response to drug; IEA:Ensembl.
GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
GO; GO:0009636; P:response to toxic substance; ISO:MGI.
GO; GO:0006837; P:serotonin transport; IMP:UniProtKB.
GO; GO:0051610; P:serotonin uptake; IDA:UniProtKB.
GO; GO:0035176; P:social behavior; IGI:BHF-UCL.
GO; GO:0042713; P:sperm ejaculation; IEA:Ensembl.
GO; GO:0021794; P:thalamus development; ISO:MGI.
GO; GO:0042310; P:vasoconstriction; IEA:Ensembl.
InterPro; IPR000175; Na/ntran_symport.
InterPro; IPR013086; Na/ntran_symport_serotonin_N.
PANTHER; PTHR11616; PTHR11616; 1.
Pfam; PF03491; 5HT_transport_N; 1.
Pfam; PF00209; SNF; 1.
PRINTS; PR01203; 5HTTRANSPORT.
PRINTS; PR00176; NANEUSMPORT.
PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
1: Evidence at protein level;
Cell membrane; Complete proteome; Disulfide bond; Endosome;
Glycoprotein; Membrane; Metal-binding; Neurotransmitter transport;
Phosphoprotein; Reference proteome; Sodium; Symport; Transmembrane;
Transmembrane helix; Transport.
CHAIN 1 630 Sodium-dependent serotonin transporter.
/FTId=PRO_0000214759.
TOPO_DOM 1 87 Cytoplasmic. {ECO:0000305}.
TRANSMEM 88 112 Helical; Name=1.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 113 115 Extracellular. {ECO:0000305}.
TRANSMEM 116 135 Helical; Name=2.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 136 160 Cytoplasmic. {ECO:0000305}.
TRANSMEM 161 186 Helical; Name=3.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 187 252 Extracellular. {ECO:0000305}.
TRANSMEM 253 271 Helical; Name=4.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 272 277 Cytoplasmic. {ECO:0000305}.
TRANSMEM 278 297 Helical; Name=5.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 298 324 Extracellular. {ECO:0000305}.
TRANSMEM 325 347 Helical; Name=6.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 348 360 Cytoplasmic. {ECO:0000305}.
TRANSMEM 361 380 Helical; Name=7.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 381 421 Extracellular. {ECO:0000305}.
TRANSMEM 422 443 Helical; Name=8.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 444 463 Cytoplasmic. {ECO:0000305}.
TRANSMEM 464 483 Helical; Name=9.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 484 494 Extracellular. {ECO:0000305}.
TRANSMEM 495 516 Helical; Name=10.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 517 538 Cytoplasmic. {ECO:0000305}.
TRANSMEM 539 558 Helical; Name=11.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 559 574 Extracellular. {ECO:0000305}.
TRANSMEM 575 595 Helical; Name=12.
{ECO:0000250|UniProtKB:P31645}.
TOPO_DOM 596 630 Cytoplasmic. {ECO:0000305}.
REGION 611 630 Required for serotonin uptake activity.
{ECO:0000250|UniProtKB:P31645}.
REGION 616 624 Interaction with RAB4A. {ECO:0000250}.
METAL 94 94 Sodium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 96 96 Sodium 2; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 97 97 Sodium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 101 101 Sodium 2. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 336 336 Sodium 2. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 368 368 Sodium 2. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 434 434 Sodium 1; via carbonyl oxygen.
{ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 437 437 Sodium 1. {ECO:0000250|UniProtKB:Q7K4Y6}.
METAL 438 438 Sodium 1. {ECO:0000250|UniProtKB:Q7K4Y6}.
MOD_RES 47 47 Phosphotyrosine.
{ECO:0000250|UniProtKB:P31645}.
MOD_RES 142 142 Phosphotyrosine.
{ECO:0000250|UniProtKB:P31645}.
MOD_RES 276 276 Phosphothreonine.
{ECO:0000250|UniProtKB:P31645}.
MOD_RES 611 611 Phosphoserine.
{ECO:0000250|UniProtKB:P31645,
ECO:0000255}.
MOD_RES 613 613 Phosphothreonine.
{ECO:0000250|UniProtKB:P31645,
ECO:0000255}.
MOD_RES 616 616 Phosphothreonine.
{ECO:0000250|UniProtKB:P31645,
ECO:0000255}.
CARBOHYD 208 208 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 217 217 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 200 209 {ECO:0000250|UniProtKB:P31645}.
CONFLICT 39 39 G -> E (in Ref. 1; AAB67172, 2; CAA70092
and 4; AAA84750). {ECO:0000305}.
CONFLICT 152 152 K -> R (in Ref. 1; AAB67172 and 2;
CAA70092). {ECO:0000305}.
CONFLICT 196 196 P -> Q (in Ref. 2; CAA70092).
{ECO:0000305}.
CONFLICT 415 415 A -> R (in Ref. 2; CAA70092).
{ECO:0000305}.
SEQUENCE 630 AA; 70048 MW; 2B6ABD26E3288CD0 CRC64;
METTPLNSQK VLSECKDKED CQENGVLQKG VPTPADKAGP GQISNGYSAV PSTSAGDEAP
HSTPAATTTL VAEIHQGERE TWGKKMDFLL SVIGYAVDLG NIWRFPYICY QNGGGAFLLP
YTIMAIFGGI PLFYMELALG QYHRNGCISI WKKICPIFKG IGYAICIIAF YIASYYNTII
AWALYYLISS FTDQLPWTSC KNSWNTGNCT NYFAQDNITW TLHSTSPAEE FYLRHVLQIH
QSKGLQDLGT ISWQLALCIM LIFTIIYFSI WKGVKTSGKV VWVTATFPYI VLSVLLVRGA
TLPGAWRGVV FYLKPNWQKL LETGVWVDAA AQIFFSLGPG FGVLLAFASY NKFNNNCYQD
ALVTSVVNCM TSFVSGFVIF TVLGYMAEMR NEDVSEVAKD AGPSLLFITY AEAIANMPAS
TFFAIIFFLM LITLGLDSTF AGLEGVITAV LDEFPHIWAK RREWFVLIVV ITCILGSLLT
LTSGGAYVVT LLEEYATGPA VLTVALIEAV VVSWFYGITQ FCSDVKEMLG FSPGWFWRIC
WVAISPLFLL FIICSFLMSP PQLRLFQYNY PHWSIILGYC IGTSSVICIP IYIIYRLIST
PGTLKERIIK SITPETPTEI PCGDIRMNAV


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EIAAB12295 Eaat1,Excitatory amino acid transporter 1,GLAST-1,Glial glutamate transporter,Rat,Rattus norvegicus,Slc1a3,Sodium-dependent glutamate_aspartate transporter 1,Solute carrier family 1 member 3
EIAAB12308 Eaat4,Excitatory amino acid transporter 4,High-affinity neuronal glutamate transporter,Rat,Rattus norvegicus,Slc1a6,Sodium-dependent glutamate_aspartate transporter,Solute carrier family 1 member 6
EIAAB12307 Eaat4,Excitatory amino acid transporter 4,High-affinity neuronal glutamate transporter,Mouse,Mus musculus,Slc1a6,Sodium-dependent glutamate_aspartate transporter,Solute carrier family 1 member 6
E1625r ELISA kit DA transporter,DAT,Rat,Rattus norvegicus,Slc6a3,Sodium-dependent dopamine transporter,Solute carrier family 6 member 3 96T


 

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