SC6A2_HUMAN
ID SC6A2_HUMAN Reviewed; 617 AA.
AC P23975; B2R707; B4DX48; Q96KH8;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-1992, sequence version 1.
DT 03-AUG-2022, entry version 204.
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; Synonyms=NAT1, NET1, SLC6A5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2008212; DOI=10.1038/350350a0;
RA Pacholczyk T., Blakely R.D., Amara S.G.;
RT "Expression cloning of a cocaine- and antidepressant-sensitive human
RT noradrenaline transporter.";
RL Nature 350:350-354(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RX PubMed=7488042; DOI=10.1006/bbrc.1995.2582;
RA Poerzgen P., Boenisch H., Bruss M.;
RT "Molecular cloning and organization of the coding region of the human
RT norepinephrine transporter gene.";
RL Biochem. Biophys. Res. Commun. 215:1145-1150(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Lung;
RX PubMed=9655936; DOI=10.1016/s0167-4781(98)00072-4;
RA Porzgen P., Bonisch H., Hammermann R., Bruss M.;
RT "The human noradrenaline transporter gene contains multiple polyadenylation
RT sites and two alternatively spliced C-terminal exons.";
RL Biochim. Biophys. Acta 1398:365-370(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INTERACTION WITH PRKCABP.
RX PubMed=11343649; DOI=10.1016/s0896-6273(01)00267-7;
RA Torres G.E., Yao W.-D., Mohn A.R., Quan H., Kim K.-M., Levey A.I.,
RA Staudinger J., Caron M.G.;
RT "Functional interaction between monoamine plasma membrane transporters and
RT the synaptic PDZ domain-containing protein PICK1.";
RL Neuron 30:121-134(2001).
RN [8]
RP VARIANT OI PRO-457.
RX PubMed=10684912; DOI=10.1056/nejm200002243420803;
RA Shannon J.R., Flattem N.L., Jordan J., Jacob G., Black B.K., Biaggioni I.,
RA Blakely R.D., Robertson D.;
RT "Orthostatic intolerance and tachycardia associated with norepinephrine-
RT transporter deficiency.";
RL N. Engl. J. Med. 342:541-549(2000).
CC -!- FUNCTION: Amine transporter. Terminates the action of noradrenaline by
CC its high affinity sodium-dependent reuptake into presynaptic terminals.
CC {ECO:0000269|PubMed:2008212}.
CC -!- SUBUNIT: Interacts with PRKCABP. {ECO:0000269|PubMed:11343649}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:2008212};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7K4Y6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P23975-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23975-2; Sequence=VSP_044479;
CC Name=3;
CC IsoId=P23975-3; Sequence=VSP_054119;
CC -!- DISEASE: Orthostatic intolerance (OI) [MIM:604715]: Syndrome
CC characterized by lightheadedness, fatigue, altered mentation and
CC syncope. It is associated with postural tachycardia. Plasma
CC norepinephrine concentration is abnormally high.
CC {ECO:0000269|PubMed:10684912}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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; M65105; AAA59943.1; -; mRNA.
DR EMBL; X91117; CAA62566.1; -; Genomic_DNA.
DR EMBL; X91120; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91121; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91122; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91123; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91124; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91125; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91126; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91127; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91118; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91119; CAA62566.1; JOINED; Genomic_DNA.
DR EMBL; X91117; CAC39181.1; -; Genomic_DNA.
DR EMBL; X91118; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91119; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91120; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91121; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91122; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91123; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91124; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91125; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91126; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; X91127; CAC39181.1; JOINED; Genomic_DNA.
DR EMBL; AK301811; BAG63260.1; -; mRNA.
DR EMBL; AK312793; BAG35654.1; -; mRNA.
DR EMBL; AC136621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW82831.1; -; Genomic_DNA.
DR EMBL; CH471092; EAW82833.1; -; Genomic_DNA.
DR EMBL; CH471092; EAW82835.1; -; Genomic_DNA.
DR CCDS; CCDS10754.1; -. [P23975-1]
DR CCDS; CCDS54011.1; -. [P23975-2]
DR CCDS; CCDS58463.1; -. [P23975-3]
DR PIR; S14278; S14278.
DR RefSeq; NP_001034.1; NM_001043.3. [P23975-1]
DR RefSeq; NP_001165972.1; NM_001172501.1. [P23975-1]
DR RefSeq; NP_001165973.1; NM_001172502.1. [P23975-3]
DR RefSeq; NP_001165975.1; NM_001172504.1. [P23975-2]
DR RefSeq; XP_006721326.1; XM_006721263.2. [P23975-2]
DR RefSeq; XP_011521597.1; XM_011523295.1. [P23975-2]
DR AlphaFoldDB; P23975; -.
DR SMR; P23975; -.
DR BioGRID; 112421; 3.
DR MINT; P23975; -.
DR STRING; 9606.ENSP00000219833; -.
DR BindingDB; P23975; -.
DR ChEMBL; CHEMBL222; -.
DR DrugBank; DB04836; Amineptine.
DR DrugBank; DB05964; Amitifadine.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB00289; Atomoxetine.
DR DrugBank; DB00245; Benzatropine.
DR DrugBank; DB04889; Bicifadine.
DR DrugBank; DB01156; Bupropion.
DR DrugBank; DB01114; Chlorpheniramine.
DR DrugBank; DB01242; Clomipramine.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB05688; CRx-119.
DR DrugBank; DB00924; Cyclobenzaprine.
DR DrugBank; DB12305; Dasotraline.
DR DrugBank; DB05642; DDP-225.
DR DrugBank; DB04840; Debrisoquine.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB06700; Desvenlafaxine.
DR DrugBank; DB06701; Dexmethylphenidate.
DR DrugBank; DB01576; Dextroamphetamine.
DR DrugBank; DB00514; Dextromethorphan.
DR DrugBank; DB00937; Diethylpropion.
DR DrugBank; DB00988; Dopamine.
DR DrugBank; DB09167; Dosulepin.
DR DrugBank; DB01142; Doxepin.
DR DrugBank; DB06262; Droxidopa.
DR DrugBank; DB00476; Duloxetine.
DR DrugBank; DB01363; Ephedra sinica root.
DR DrugBank; DB01364; Ephedrine.
DR DrugBank; DB01175; Escitalopram.
DR DrugBank; DB09194; Etoperidone.
DR DrugBank; DB01381; Ginkgo biloba.
DR DrugBank; DB00226; Guanadrel.
DR DrugBank; DB01170; Guanethidine.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB06704; Iobenguane.
DR DrugBank; DB09546; Iobenguane sulfate I-123.
DR DrugBank; DB01221; Ketamine.
DR DrugBank; DB08918; Levomilnacipran.
DR DrugBank; DB00408; Loxapine.
DR DrugBank; DB00934; Maprotiline.
DR DrugBank; DB00579; Mazindol.
DR DrugBank; DB00454; Meperidine.
DR DrugBank; DB01577; Metamfetamine.
DR DrugBank; DB00422; Methylphenidate.
DR DrugBank; DB06148; Mianserin.
DR DrugBank; DB01454; Midomafetamine.
DR DrugBank; DB04896; Milnacipran.
DR DrugBank; DB01442; MMDA.
DR DrugBank; DB01149; Nefazodone.
DR DrugBank; DB13931; Netarsudil.
DR DrugBank; DB04821; Nomifensine.
DR DrugBank; DB00368; Norepinephrine.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB01173; Orphenadrine.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB01579; Phendimetrazine.
DR DrugBank; DB00830; Phenmetrazine.
DR DrugBank; DB00191; Phentermine.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB00344; Protriptyline.
DR DrugBank; DB00852; Pseudoephedrine.
DR DrugBank; DB09363; Rauwolfia serpentina root.
DR DrugBank; DB00234; Reboxetine.
DR DrugBank; DB16629; Serdexmethylphenidate.
DR DrugBank; DB01104; Sertraline.
DR DrugBank; DB01105; Sibutramine.
DR DrugBank; DB14754; Solriamfetol.
DR DrugBank; DB06204; Tapentadol.
DR DrugBank; DB06156; Tesofensine.
DR DrugBank; DB00193; Tramadol.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB06333; Trodusquemine.
DR DrugBank; DB00285; Venlafaxine.
DR DrugBank; DB09185; Viloxazine.
DR DrugBank; DB09068; Vortioxetine.
DR DrugBank; DB05012; XEN-2174.
DR DrugBank; DB09225; Zotepine.
DR DrugCentral; P23975; -.
DR GuidetoPHARMACOLOGY; 926; -.
DR TCDB; 2.A.22.1.2; the neurotransmitter:sodium symporter (nss) family.
DR GlyGen; P23975; 3 sites.
DR iPTMnet; P23975; -.
DR PhosphoSitePlus; P23975; -.
DR BioMuta; SLC6A2; -.
DR DMDM; 128616; -.
DR MassIVE; P23975; -.
DR MaxQB; P23975; -.
DR PaxDb; P23975; -.
DR PeptideAtlas; P23975; -.
DR PRIDE; P23975; -.
DR ProteomicsDB; 5409; -.
DR ProteomicsDB; 54172; -. [P23975-1]
DR ProteomicsDB; 77077; -.
DR Antibodypedia; 1363; 141 antibodies from 28 providers.
DR DNASU; 6530; -.
DR Ensembl; ENST00000219833.13; ENSP00000219833.8; ENSG00000103546.19. [P23975-2]
DR Ensembl; ENST00000379906.6; ENSP00000369237.2; ENSG00000103546.19. [P23975-1]
DR Ensembl; ENST00000567238.1; ENSP00000457375.1; ENSG00000103546.19. [P23975-3]
DR Ensembl; ENST00000568943.6; ENSP00000457473.1; ENSG00000103546.19. [P23975-1]
DR GeneID; 6530; -.
DR KEGG; hsa:6530; -.
DR MANE-Select; ENST00000568943.6; ENSP00000457473.1; NM_001172501.3; NP_001165972.1.
DR UCSC; uc002eif.4; human. [P23975-1]
DR CTD; 6530; -.
DR DisGeNET; 6530; -.
DR GeneCards; SLC6A2; -.
DR HGNC; HGNC:11048; SLC6A2.
DR HPA; ENSG00000103546; Tissue enhanced (adrenal gland, brain).
DR MalaCards; SLC6A2; -.
DR MIM; 163970; gene.
DR MIM; 604715; phenotype.
DR neXtProt; NX_P23975; -.
DR OpenTargets; ENSG00000103546; -.
DR Orphanet; 443236; Postural orthostatic tachycardia syndrome due to NET deficiency.
DR PharmGKB; PA310; -.
DR VEuPathDB; HostDB:ENSG00000103546; -.
DR eggNOG; KOG3659; Eukaryota.
DR GeneTree; ENSGT00940000158960; -.
DR HOGENOM; CLU_006855_9_5_1; -.
DR InParanoid; P23975; -.
DR OMA; NLWGFAY; -.
DR OrthoDB; 250396at2759; -.
DR PhylomeDB; P23975; -.
DR TreeFam; TF343812; -.
DR PathwayCommons; P23975; -.
DR Reactome; R-HSA-442660; Na+/Cl- dependent neurotransmitter transporters.
DR Reactome; R-HSA-5619109; Defective SLC6A2 causes orthostatic intolerance (OI).
DR SignaLink; P23975; -.
DR SIGNOR; P23975; -.
DR BioGRID-ORCS; 6530; 12 hits in 1066 CRISPR screens.
DR ChiTaRS; SLC6A2; human.
DR GeneWiki; Norepinephrine_transporter; -.
DR GenomeRNAi; 6530; -.
DR Pharos; P23975; Tclin.
DR PRO; PR:P23975; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P23975; protein.
DR Bgee; ENSG00000103546; Expressed in placenta and 97 other tissues.
DR ExpressionAtlas; P23975; baseline and differential.
DR Genevisible; P23975; HS.
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:0016020; C:membrane; TAS:ProtInc.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0042734; C:presynaptic membrane; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; IPI:ARUK-UCL.
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; IDA:MGI.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; ISS: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:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IBA:GO_Central.
DR GO; GO:0015844; P:monoamine transport; IDA:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; TAS:ARUK-UCL.
DR GO; GO:0006836; P:neurotransmitter transport; ISS:ARUK-UCL.
DR GO; GO:0015874; P:norepinephrine transport; IBA:GO_Central.
DR GO; GO:0051620; P:norepinephrine uptake; ISS:ARUK-UCL.
DR GO; GO:0048265; P:response to pain; IEA:Ensembl.
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 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Membrane; Metal-binding; Neurotransmitter transport;
KW Reference proteome; Sodium; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..617
FT /note="Sodium-dependent noradrenaline transporter"
FT /id="PRO_0000214748"
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..23
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 CARBOHYD 198
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 176..185
FT /evidence="ECO:0000250|UniProtKB:Q7K4Y6"
FT VAR_SEQ 1..135
FT /note="MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGD
FT AQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFY
FT MELALGQYNREGAATVWKICPFFK -> MGVQWWSHTQGEVAVGLGLGDSYLTPCPCP
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054119"
FT VAR_SEQ 611..617
FT /note="LQHWLAI -> MKTRQGRRRATNSCQISC (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044479"
FT VARIANT 7
FT /note="N -> K (in dbSNP:rs11568323)"
FT /id="VAR_029157"
FT VARIANT 69
FT /note="V -> I (in dbSNP:rs1805064)"
FT /id="VAR_011756"
FT VARIANT 99
FT /note="T -> I (in dbSNP:rs1805065)"
FT /id="VAR_011757"
FT VARIANT 245
FT /note="V -> I (in dbSNP:rs1805066)"
FT /id="VAR_011758"
FT VARIANT 283
FT /note="T -> R (in dbSNP:rs45564432)"
FT /id="VAR_020048"
FT VARIANT 292
FT /note="N -> T (in dbSNP:rs5563)"
FT /id="VAR_011759"
FT VARIANT 356
FT /note="V -> L (in dbSNP:rs5565)"
FT /id="VAR_011760"
FT VARIANT 369
FT /note="A -> P (in dbSNP:rs5566)"
FT /id="VAR_011761"
FT VARIANT 375
FT /note="N -> S (in dbSNP:rs5567)"
FT /id="VAR_011762"
FT VARIANT 449
FT /note="V -> I (in dbSNP:rs2234910)"
FT /id="VAR_014800"
FT VARIANT 457
FT /note="A -> P (in OI; loss of function; dbSNP:rs121918126)"
FT /evidence="ECO:0000269|PubMed:10684912"
FT /id="VAR_010022"
FT VARIANT 463
FT /note="K -> R (in dbSNP:rs5570)"
FT /id="VAR_011763"
FT VARIANT 478
FT /note="G -> S (in dbSNP:rs1805067)"
FT /id="VAR_011764"
FT VARIANT 528
FT /note="F -> C (in dbSNP:rs5558)"
FT /id="VAR_011765"
FT VARIANT 548
FT /note="Y -> H (in dbSNP:rs5559)"
FT /id="VAR_011766"
FT VARIANT 549
FT /note="I -> T (in dbSNP:rs3743788)"
FT /id="VAR_021861"
SQ SEQUENCE 617 AA; 69332 MW; BDC6DF31316907BB CRC64;
MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD GDAQPRETWG
KKIDFLLSVV GFAVDLANVW RFPYLCYKNG GGAFLIPYTL FLIIAGMPLF YMELALGQYN
REGAATVWKI CPFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW
NSPNCTDPKL LNGSVLGNHT KYSKYKFTPA AEFYERGVLH LHESSGIHDI GLPQWQLLLC
LMVVVIVLYF SLWKGVKTSG KVVWITATLP YFVLFVLLVH GVTLPGASNG INAYLHIDFY
RLKEATVWID AATQIFFSLG AGFGVLIAFA SYNKFDNNCY RDALLTSSIN CITSFVSGFA
IFSILGYMAH EHKVNIEDVA TEGAGLVFIL YPEAISTLSG STFWAVVFFV MLLALGLDSS
MGGMEAVITG LADDFQVLKR HRKLFTFGVT FSTFLLALFC ITKGGIYVLT LLDTFAAGTS
ILFAVLMEAI GVSWFYGVDR FSNDIQQMMG FRPGLYWRLC WKFVSPAFLL FVVVVSIINF
KPLTYDDYIF PPWANWVGWG IALSSMVLVP IYVIYKFLST QGSLWERLAY GITPENEHHL
VAQRDIRQFQ LQHWLAI
