SC6A4_BOVIN
ID SC6A4_BOVIN Reviewed; 630 AA.
AC Q9XT49;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Sodium-dependent serotonin transporter;
DE Short=SERT {ECO:0000250|UniProtKB:P31652};
DE AltName: Full=5HT transporter;
DE Short=5HTT;
DE AltName: Full=Solute carrier family 6 member 4;
GN Name=SLC6A4; Synonyms=SERT;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10407194; DOI=10.1016/s0169-328x(99)00178-3;
RA Mortensen O.V., Kristensen A.S., Rudnick G., Wiborg O.;
RT "Molecular cloning, expression and characterization of a bovine serotonin
RT transporter.";
RL Brain Res. Mol. Brain Res. 71:120-126(1999).
CC -!- FUNCTION: Serotonin transporter whose primary function in the central
CC nervous system involves the regulation of serotonergic signaling via
CC transport of serotonin molecules from the synaptic cleft back into the
CC pre-synaptic terminal for re-utilization. Plays a key role in mediating
CC regulation of the availability of serotonin to other receptors of
CC serotonergic systems. Terminates the action of serotonin and recycles
CC it in a sodium-dependent manner. {ECO:0000269|PubMed:10407194}.
CC -!- SUBUNIT: Monomer or homooligomer (By similarity). Interacts (via C-
CC terminus) with SCAMP2; the interaction is direct and retains
CC transporter molecules intracellularly. Interacts with filamentous actin
CC and STX1A (By similarity). Interacts with SEC23A, SEC24C and PATJ.
CC Interacts with NOS1; the interaction may diminish the cell surface
CC localization of SERT in the brain and, correspondingly, reduce
CC serotonin reuptake. Interacts with TGFB1I1 (By similarity). Interacts
CC with ITGAV:ITGB3 (By similarity). {ECO:0000250|UniProtKB:P31645,
CC ECO:0000250|UniProtKB:P31652, ECO:0000250|UniProtKB:Q60857}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q60857};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7K4Y6}.
CC Endomembrane system {ECO:0000250|UniProtKB:P31652}; Multi-pass membrane
CC protein {ECO:0000255}. Endosome membrane
CC {ECO:0000250|UniProtKB:P31652}; Multi-pass membrane protein
CC {ECO:0000255}. Synapse {ECO:0000250|UniProtKB:Q60857}. Cell junction,
CC focal adhesion {ECO:0000250|UniProtKB:Q60857}. Note=Could be part of
CC recycling endosomes. Density of transporter molecules on the plasma
CC membrane is itself regulated by STX1A. Density of transporter molecules
CC on the plasma membrane is also regulated by serotonin (By similarity).
CC Density of transporter molecules seems to be modulated by ITGAV:ITGB3
CC (By similarity). {ECO:0000250|UniProtKB:P31645,
CC ECO:0000250|UniProtKB:P31652, ECO:0000250|UniProtKB:Q60857}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta, brain stem, bone marrow,
CC kidney, lung, heart, adrenal gland, liver, parathyroid gland, thyroid
CC gland, small intestine and pancreas.
CC -!- PTM: Phosphorylation at Thr-276 increases 5-HT uptake and is required
CC for cGMP-mediated SERT regulation. {ECO:0000250|UniProtKB:P31645}.
CC -!- MISCELLANEOUS: This protein is the target of psychomotor stimulants
CC such as amphetamines or cocaine.
CC -!- SIMILARITY: Belongs to the sodium:neurotransmitter symporter (SNF) (TC
CC 2.A.22) family. SLC6A4 subfamily. {ECO:0000305}.
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DR EMBL; AF119122; AAD26262.1; -; mRNA.
DR RefSeq; NP_777034.1; NM_174609.2.
DR AlphaFoldDB; Q9XT49; -.
DR SMR; Q9XT49; -.
DR STRING; 9913.ENSBTAP00000025774; -.
DR PaxDb; Q9XT49; -.
DR PRIDE; Q9XT49; -.
DR Ensembl; ENSBTAT00000025774; ENSBTAP00000025774; ENSBTAG00000019349.
DR Ensembl; ENSBTAT00000082189; ENSBTAP00000067324; ENSBTAG00000019349.
DR GeneID; 282365; -.
DR KEGG; bta:282365; -.
DR CTD; 6532; -.
DR VEuPathDB; HostDB:ENSBTAG00000019349; -.
DR VGNC; VGNC:49971; SLC6A4.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000157855; -.
DR InParanoid; Q9XT49; -.
DR OMA; SFICIPA; -.
DR OrthoDB; 250396at2759; -.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000019349; Expressed in rumen epithelium and 99 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:AgBase.
DR GO; GO:0012505; C:endomembrane system; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0050998; F:nitric-oxide synthase binding; IEA:Ensembl.
DR GO; GO:0051378; F:serotonin binding; IMP:AgBase.
DR GO; GO:0005335; F:serotonin:sodium symporter activity; ISS:UniProtKB.
DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl.
DR GO; GO:0071310; P:cellular response to organic substance; IEA:Ensembl.
DR GO; GO:0015844; P:monoamine transport; ISS:UniProtKB.
DR GO; GO:0046621; P:negative regulation of organ growth; IEA:Ensembl.
DR GO; GO:0045787; P:positive regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0090067; P:regulation of thalamus size; ISS:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; ISS:UniProtKB.
DR GO; GO:0006837; P:serotonin transport; ISS:UniProtKB.
DR GO; GO:0051610; P:serotonin uptake; ISS:UniProtKB.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR013086; Na/ntran_symport_serotonin_N.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF03491; 5HT_transport_N; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR01203; 5HTTRANSPORT.
DR PRINTS; PR00176; NANEUSMPORT.
DR SUPFAM; SSF161070; SSF161070; 1.
DR PROSITE; PS00610; NA_NEUROTRAN_SYMP_1; 1.
DR PROSITE; PS00754; NA_NEUROTRAN_SYMP_2; 1.
DR PROSITE; PS50267; NA_NEUROTRAN_SYMP_3; 1.
PE 2: Evidence at transcript level;
KW Cell junction; Cell membrane; Disulfide bond; Endosome; Glycoprotein;
KW Membrane; Metal-binding; Neurotransmitter transport; Phosphoprotein;
KW Reference proteome; Sodium; Symport; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..630
FT /note="Sodium-dependent serotonin transporter"
FT /id="PRO_0000214755"
FT TOPO_DOM 1..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 88..112
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 113..115
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 116..135
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 136..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 161..186
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 187..252
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 253..271
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 272..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 278..297
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 298..324
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 325..347
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 348..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 361..380
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 381..421
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 422..443
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 444..463
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 464..483
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 484..494
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 495..516
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 517..538
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 539..558
FT /note="Helical; Name=11"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 559..574
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 575..595
FT /note="Helical; Name=12"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT TOPO_DOM 596..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 616..624
FT /note="Interaction with RAB4A"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 96
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 97
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 101
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 336
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 368
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 434
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 437
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 438
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT MOD_RES 47
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT MOD_RES 142
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT MOD_RES 276
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P31645"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 200..209
FT /evidence="ECO:0000250|UniProtKB:P31645"
SQ SEQUENCE 630 AA; 70036 MW; C23E80EB3B80C9E8 CRC64;
METTPLNSQK ELSAYKDGED CQENGVLQKG VPAPGDKAES GQISNGYSAV PNPGAGDDTQ
HSIPAATTAL VAEVHPAERE TWAKKVDFLL SVIGYAVDLG NVWRFPYICY QNGGGAFLLP
YTIMAIFGGI PLFYMELALG QYHRNGCISI WTKICPIFKG IGCAICLIAF YIASYYNTII
AWALYYLISS FTEQLPWTSC ENSWNTGNCT NYFSEDNITW TLHSTSPAEE FYTRHVLQIH
RSKGLQDLGG LSWQLVLCIM FIFTVIYFSI WKGVKTSGKV VWVTATFPYI ILLILLVRGA
TLPGAWRGVL FYLKPNWQKL LETGVWVDAA AQIFFSLGPG FGVLLAFASY NKFHNNCYQD
ALVTSAVNCM TSFVSGFVIF TVLGYMAEMR KEDVSEVAKD AGPSLLFITY AEAIANMPAS
TFFAIVFFLM LITLGLDSTF AGLEGVITAV LDEFPHVWAK RREWFVLGVV ITCFFGSLVT
LTFGGAYVVK LLEEFATGPA VLTVALIEAV AVFWFYGINQ FCSDVKEMLG FSPGWFWKIC
WVAISPLFLL FIICSFLMSP PQLRLFQYDY PRWSIILGYC IGTSSFICIP TYITYRLIVT
PGTLKERIIK GITPETPTAI PCGDIRLNAV
