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 24-JAN-2024, entry version 162. 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], FUNCTION, TRANSPORTER ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. 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: Mediates sodium- and chloride-dependent transport of CC norepinephrine (also known as noradrenaline) (PubMed:16269905). Can CC also mediate sodium- and chloride-dependent transport of dopamine (By CC similarity). {ECO:0000250|UniProtKB:P23975, CC ECO:0000269|PubMed:16269905}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-noradrenaline(out) + chloride(out) + Na(+)(out) = (R)- CC noradrenaline(in) + chloride(in) + Na(+)(in); Xref=Rhea:RHEA:70923, CC ChEBI:CHEBI:17996, ChEBI:CHEBI:29101, ChEBI:CHEBI:72587; CC Evidence={ECO:0000269|PubMed:16269905}; CC -!- CATALYTIC ACTIVITY: CC Reaction=chloride(out) + dopamine(out) + Na(+)(out) = chloride(in) + CC dopamine(in) + Na(+)(in); Xref=Rhea:RHEA:70919, ChEBI:CHEBI:17996, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:59905; CC Evidence={ECO:0000250|UniProtKB:P23975}; CC -!- CATALYTIC ACTIVITY: CC Reaction=chloride(out) + dopamine(out) + 2 Na(+)(out) = chloride(in) + CC dopamine(in) + 2 Na(+)(in); Xref=Rhea:RHEA:70931, ChEBI:CHEBI:17996, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:59905; CC Evidence={ECO:0000250|UniProtKB:P23975}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=98 nM for noradrenaline in inbred long-sleep mice CC {ECO:0000269|PubMed:16269905}; CC KM=89.1 nM for noradrenaline in inbred short-sleep mice CC {ECO:0000269|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:0000255}. 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) CC (TC 2.A.22) family. SLC6A2 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; O55192; 2 sites, No reported glycans. DR GlyGen; O55192; 2 sites. DR iPTMnet; O55192; -. DR PhosphoSitePlus; O55192; -. DR MaxQB; O55192; -. DR PaxDb; 10090-ENSMUSP00000072709; -. DR PeptideAtlas; O55192; -. DR ProteomicsDB; 255472; -. DR Antibodypedia; 1363; 151 antibodies from 28 providers. DR DNASU; 20538; -. DR Ensembl; ENSMUST00000072939.8; ENSMUSP00000072709.7; ENSMUSG00000055368.15. DR Ensembl; ENSMUST00000165470.9; ENSMUSP00000129869.2; ENSMUSG00000055368.15. DR GeneID; 20538; -. DR KEGG; mmu:20538; -. DR UCSC; uc009muh.2; mouse. DR AGR; MGI:1270850; -. 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; 3084493at2759; -. DR PhylomeDB; O55192; -. DR TreeFam; TF343812; -. DR Reactome; R-MMU-442660; Na+/Cl- dependent neurotransmitter transporters. DR BioGRID-ORCS; 20538; 3 hits in 78 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 cell types or tissues. DR GO; GO:0009986; C:cell surface; ISO:MGI. 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:0005886; C:plasma membrane; ISO:MGI. 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; ISO:MGI. DR GO; GO:0048487; F:beta-tubulin binding; ISO:MGI. DR GO; GO:0005330; F:dopamine:sodium symporter activity; ISO:MGI. 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; IDA:UniProtKB. 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; IDA:SynGO. DR GO; GO:0006836; P:neurotransmitter transport; IDA:MGI. DR GO; GO:0015874; P:norepinephrine transport; ISO:MGI. 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 NCBIfam; NF037979; Na_transp; 1. DR PANTHER; PTHR11616:SF307; SODIUM-DEPENDENT NORADRENALINE TRANSPORTER; 1. DR PANTHER; PTHR11616; SODIUM/CHLORIDE DEPENDENT TRANSPORTER; 1. DR Pfam; PF00209; SNF; 1. DR PRINTS; PR00176; NANEUSMPORT. DR PRINTS; PR01201; NORTRANSPORT. DR SUPFAM; SSF161070; SNF-like; 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. DR Genevisible; O55192; MM. PE 1: Evidence at protein 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 //