SC6A2_MOUSE
ID SC6A2_MOUSE Reviewed; 617 AA.
AC O55192; Q6QU62;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Sodium-dependent noradrenaline transporter;
DE AltName: Full=Norepinephrine transporter;
DE Short=NET;
DE AltName: Full=Solute carrier family 6 member 2;
GN Name=Slc6a2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=9603188; DOI=10.1046/j.1471-4159.1998.70062241.x;
RA Fritz J.D., Jayanthi L.D., Thoreson M.A., Blakely R.D.;
RT "Cloning and chromosomal mapping of the murine norepinephrine
RT transporter.";
RL J. Neurochem. 70:2241-2251(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=16269905; DOI=10.1097/01.alc.0000183009.57805.a6;
RA Haughey H.M., Kaiser A.L., Johnson T.E., Bennett B., Sikela J.M.,
RA Zahniser N.R.;
RT "Norepinephrine transporter: a candidate gene for initial ethanol
RT sensitivity in inbred long-sleep and short-sleep mice.";
RL Alcohol. Clin. Exp. Res. 29:1759-1768(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Amine transporter. Terminates the action of noradrenaline by
CC its high affinity sodium-dependent reuptake into presynaptic terminals.
CC {ECO:0000305|PubMed:16269905}.
CC -!- SUBUNIT: Interacts with PRKCABP. {ECO:0000250|UniProtKB:P23975}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P23975};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7K4Y6}.
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. SLC6A2 subfamily. {ECO:0000305}.
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DR EMBL; U76306; AAB94302.1; -; mRNA.
DR EMBL; AY525777; AAS17725.1; -; mRNA.
DR EMBL; AY525778; AAS17726.1; -; mRNA.
DR EMBL; CH466525; EDL11093.1; -; Genomic_DNA.
DR CCDS; CCDS22525.1; -.
DR RefSeq; NP_033235.3; NM_009209.3.
DR RefSeq; XP_006530856.1; XM_006530793.3.
DR RefSeq; XP_006530857.1; XM_006530794.3.
DR AlphaFoldDB; O55192; -.
DR SMR; O55192; -.
DR MINT; O55192; -.
DR STRING; 10090.ENSMUSP00000072709; -.
DR BindingDB; O55192; -.
DR ChEMBL; CHEMBL2370; -.
DR DrugCentral; O55192; -.
DR GlyGen; O55192; 2 sites.
DR iPTMnet; O55192; -.
DR PhosphoSitePlus; O55192; -.
DR MaxQB; O55192; -.
DR PaxDb; O55192; -.
DR PeptideAtlas; O55192; -.
DR PRIDE; O55192; -.
DR ProteomicsDB; 255472; -.
DR Antibodypedia; 1363; 141 antibodies from 28 providers.
DR DNASU; 20538; -.
DR Ensembl; ENSMUST00000072939; ENSMUSP00000072709; ENSMUSG00000055368.
DR Ensembl; ENSMUST00000165470; ENSMUSP00000129869; ENSMUSG00000055368.
DR GeneID; 20538; -.
DR KEGG; mmu:20538; -.
DR UCSC; uc009muh.2; mouse.
DR CTD; 6530; -.
DR MGI; MGI:1270850; Slc6a2.
DR VEuPathDB; HostDB:ENSMUSG00000055368; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000158960; -.
DR HOGENOM; CLU_006855_9_0_1; -.
DR InParanoid; O55192; -.
DR OMA; NLWGFAY; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; O55192; -.
DR TreeFam; TF343812; -.
DR Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters.
DR BioGRID-ORCS; 20538; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Slc6a2; mouse.
DR PRO; PR:O55192; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; O55192; protein.
DR Bgee; ENSMUSG00000055368; Expressed in carotid body and 149 other tissues.
DR Genevisible; O55192; MM.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0032809; C:neuronal cell body membrane; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0043014; F:alpha-tubulin binding; IEA:Ensembl.
DR GO; GO:0048487; F:beta-tubulin binding; IEA:Ensembl.
DR GO; GO:0005330; F:dopamine:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008504; F:monoamine transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IMP:ARUK-UCL.
DR GO; GO:0005328; F:neurotransmitter:sodium symporter activity; IEA:InterPro.
DR GO; GO:0005334; F:norepinephrine:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
DR GO; GO:0015844; P:monoamine transport; ISO:MGI.
DR GO; GO:0098810; P:neurotransmitter reuptake; IMP:SynGO.
DR GO; GO:0006836; P:neurotransmitter transport; IDA:MGI.
DR GO; GO:0015874; P:norepinephrine transport; IBA:GO_Central.
DR GO; GO:0051620; P:norepinephrine uptake; IMP:ARUK-UCL.
DR GO; GO:0048265; P:response to pain; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR InterPro; IPR000175; Na/ntran_symport.
DR InterPro; IPR002435; Na/ntran_symport_noradrenaline.
DR InterPro; IPR037272; SNS_sf.
DR PANTHER; PTHR11616; PTHR11616; 1.
DR Pfam; PF00209; SNF; 1.
DR PRINTS; PR00176; NANEUSMPORT.
DR PRINTS; PR01201; NORTRANSPORT.
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 membrane; Disulfide bond; Glycoprotein; Membrane; Metal-binding;
KW Neurotransmitter transport; Reference proteome; Sodium; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..617
FT /note="Sodium-dependent noradrenaline transporter"
FT /id="PRO_0000214749"
FT TOPO_DOM 1..62
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 63..88
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 89..92
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 93..116
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 117..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 136..166
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 167..233
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 234..254
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 255..257
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 258..282
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 283..306
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 307..332
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 333..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 339..362
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 363..402
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 403..428
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 429..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 444..464
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 465
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 466..492
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 493..522
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 523..545
FT /note="Helical; Name=11"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 546..548
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TRANSMEM 549..569
FT /note="Helical; Name=12"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT TOPO_DOM 570..617
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 71
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 73
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 74
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 78
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 318
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 350
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 415
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 418
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT BINDING 419
FT /ligand="Na(+)"
FT /ligand_id="ChEBI:CHEBI:29101"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 176..185
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT CONFLICT 609..612
FT /note="FQLR -> LPLQ (in Ref. 1; AAB94302)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 617 AA; 69255 MW; 591641246B8DA59C CRC64;
MLLARMNPQV QPELGGADPL PEQPLRPCKT ADLLVVKERN GVQCLLASQD SDAQPRETWG
KKIDFLLSVV GFAVDLANVW RFPYLCYKNG GGAFLIPYTL FLIIAGMPLF YMELALGQYN
REGAATVWKI CPFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFASFTLN LPWTNCGHSW
NSPNCTDPKL LNASVLGDHT KYSKYKFTPA AEFYERGVLH LHESSGIHDI GLPQWQLLLC
LMVVIVVLYF SLWKGVKTSG KVVWITATLP YFVLFVLLVH GVTLPGASNG INAYLHIDFY
RLKEATVWID AATQIFFSLG AGFGVLIAFA SYNKFDNNCY RDALLTSTIN CVTSFISGFA
IFSILGYMAH EHKVNIEDVA TEGAGLVFIL YPEAISTLSG STFWAVLFFL MLLALGLDSS
MGGMEAVITG LADDFQVLKR HRKLFTCVVT ISTFLLALFC ITKGGIYVLT LLDTFAAGTS
ILFAVLMEAI GVSWFYGVDR FSNDIQQMMG FKPGLYWRLC WKFVSPAFLL FVVVVSIINF
KPLTYDDYTY PPWANWVGWG IALSSMILVP AYVIYKFLSI RGSLWERVAY GITPENEHHL
VAQRDVRQFQ LRHWLAI
