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Protein

Sodium-dependent serotonin transporter

Gene

Slc6a4

Organism
Rattus norvegicus (Rat)
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.5 Publications

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

  • actin filament binding Source: UniProtKB
  • cocaine binding Source: RGD
  • metal ion binding Source: UniProtKB-KW
  • myosin binding Source: UniProtKB
  • protein homodimerization activity Source: RGD
  • serotonin:sodium symporter activity Source: UniProtKB
  • serotonin transmembrane transporter activity Source: UniProtKB
  • syntaxin-1 binding Source: UniProtKB

GO - Biological processi

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

Keywords - Biological processi

Neurotransmitter transport, Symport, Transport

Keywords - Ligandi

Metal-binding, Sodium

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium-dependent serotonin transporter
Short name:
SERT1 Publication
Alternative name(s):
5HT transporter
Short name:
5HTT
Solute carrier family 6 member 4
Gene namesi
Name:Slc6a4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3714. 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

  • cytosol Source: Ensembl
  • endomembrane system Source: UniProtKB
  • endosome membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: GO_Central
  • membrane raft Source: RGD
  • neuron projection Source: RGD
  • plasma membrane Source: UniProtKB
  • presynapse Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi109C → A: Cocaine is effective at blocking transport. 1 Publication1
Mutagenesisi172I → C: Cocaine is effective at blocking transport. 1 Publication1
Mutagenesisi208N → Q: No change in transport function. Important decrease of transport function and serotonin uptake function; when associated with Q-217. 1 Publication1
Mutagenesisi217N → Q: No change in transport function. Important decrease of transport function and serotonin uptake function; when associated with Q-208. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL313.
GuidetoPHARMACOLOGYi928.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002147601 – 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...)1 Publication1
Glycosylationi217N-linked (GlcNAc...)1 Publication1
Modified residuei276Phosphothreonine1 Publication1
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.1 Publication
Phosphorylation upon PKC stimulation modifies the SERT distribution and density in the membrane, and diminishes the uptake capacity (By similarity). Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation.By similarity1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP31652.

PTM databases

iPTMnetiP31652.
SwissPalmiP31652.

Expressioni

Gene expression databases

BgeeiENSRNOG00000003476.
GenevisibleiP31652. RN.

Interactioni

Subunit structurei

Monomer or homooligomer. Interacts with TGFB1I1. Interacts (via C-terminus) with VIM. Interacts with RAB4 (GTP-bound form); the interaction retains transporter molecules intracellularly. 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 (By similarity). Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with filamentous actin and STX1A. Interacts (via sialylated form) with MYH9.By similarity5 Publications

GO - Molecular functioni

  • actin filament binding Source: UniProtKB
  • myosin binding Source: UniProtKB
  • protein homodimerization activity Source: RGD
  • syntaxin-1 binding Source: UniProtKB

Protein-protein interaction databases

IntActiP31652. 1 interactor.
STRINGi10116.ENSRNOP00000004717.

Chemistry databases

BindingDBiP31652.

Structurei

3D structure databases

ProteinModelPortaliP31652.
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.
InParanoidiP31652.
KOiK05037.
OMAiCRDVKEM.
OrthoDBiEOG091G08PX.
PhylomeDBiP31652.
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.

P31652-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METTPLNSQK VLSECKDRED CQENGVLQKG VPTTADRAEP SQISNGYSAV
60 70 80 90 100
PSTSAGDEAS HSIPAATTTL VAEIRQGERE TWGKKMDFLL SVIGYAVDLG
110 120 130 140 150
NIWRFPYICY QNGGGAFLLP YTIMAIFGGI PLFYMELALG QYHRNGCISI
160 170 180 190 200
WRKICPIFKG IGYAICIIAF YIASYYNTII AWALYYLISS LTDRLPWTSC
210 220 230 240 250
TNSWNTGNCT NYFAQDNITW TLHSTSPAEE FYLRHVLQIH QSKGLQDLGT
260 270 280 290 300
ISWQLTLCIV LIFTVIYFSI 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 ITCVLGSLLT LTSGGAYVVT LLEEYATGPA
510 520 530 540 550
VLTVALIEAV AVSWFYGITQ FCSDVKEMLG FSPGWFWRIC WVAISPLFLL
560 570 580 590 600
FIICSFLMSP PQLRLFQYNY PHWSIVLGYC IGMSSVICIP TYIIYRLIST
610 620 630
PGTLKERIIK SITPETPTEI PCGDIRMNAV
Length:630
Mass (Da):70,172
Last modified:July 1, 1993 - v1
Checksum:i44DA7C5888C403EE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti415A → G in AAA42186 (PubMed:1948036).Curated1
Sequence conflicti533 – 536PGWF → GMV in AAA42186 (PubMed:1948036).Curated4
Sequence conflicti621 – 630PCGDIRMNAV → RVGHPHECCVTHPGRGHLFP ATSLSSEKPTGLLL in AAA42186 (PubMed:1948036).Curated10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63995 mRNA. Translation: CAA45401.1.
X63253 mRNA. Translation: CAA44913.1.
M79450 mRNA. Translation: AAA42186.1.
Y11024 mRNA. Translation: CAA71909.1.
PIRiS19585.
S30604.
RefSeqiNP_037166.2. NM_013034.4.
XP_008766172.1. XM_008767950.2.
XP_017452530.1. XM_017597041.1.
XP_017452531.1. XM_017597042.1.
XP_017452532.1. XM_017597043.1.
UniGeneiRn.1663.

Genome annotation databases

EnsembliENSRNOT00000004717; ENSRNOP00000004717; ENSRNOG00000003476.
GeneIDi25553.
KEGGirno:25553.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63995 mRNA. Translation: CAA45401.1.
X63253 mRNA. Translation: CAA44913.1.
M79450 mRNA. Translation: AAA42186.1.
Y11024 mRNA. Translation: CAA71909.1.
PIRiS19585.
S30604.
RefSeqiNP_037166.2. NM_013034.4.
XP_008766172.1. XM_008767950.2.
XP_017452530.1. XM_017597041.1.
XP_017452531.1. XM_017597042.1.
XP_017452532.1. XM_017597043.1.
UniGeneiRn.1663.

3D structure databases

ProteinModelPortaliP31652.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP31652. 1 interactor.
STRINGi10116.ENSRNOP00000004717.

Chemistry databases

BindingDBiP31652.
ChEMBLiCHEMBL313.
GuidetoPHARMACOLOGYi928.

PTM databases

iPTMnetiP31652.
SwissPalmiP31652.

Proteomic databases

PaxDbiP31652.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000004717; ENSRNOP00000004717; ENSRNOG00000003476.
GeneIDi25553.
KEGGirno:25553.

Organism-specific databases

CTDi6532.
RGDi3714. Slc6a4.

Phylogenomic databases

eggNOGiKOG3659. Eukaryota.
COG0733. LUCA.
GeneTreeiENSGT00760000118857.
HOGENOMiHOG000116406.
HOVERGENiHBG071421.
InParanoidiP31652.
KOiK05037.
OMAiCRDVKEM.
OrthoDBiEOG091G08PX.
PhylomeDBiP31652.
TreeFamiTF343812.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP31652.

Gene expression databases

BgeeiENSRNOG00000003476.
GenevisibleiP31652. RN.

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_RAT
AccessioniPrimary (citable) accession number: P31652
Secondary accession number(s): P23976
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: November 30, 2016
This is version 138 of the entry and version 1 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. 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.