Sodium-dependent noradrenaline transporter

Details

Name
Sodium-dependent noradrenaline transporter
Kind
protein
Synonyms
  • NAT1
  • NET
  • NET1
  • Norepinephrine transporter
  • SLC6A5
  • Solute carrier family 6 member 2
Gene Name
SLC6A2
UniProtKB Entry
P23975Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000970|Sodium-dependent noradrenaline transporter
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Number of residues
617
Molecular Weight
69331.42
Theoretical pI
7.53
GO Classification
Functions
actin binding / alpha-tubulin binding / beta-tubulin binding / dopamine / metal ion binding / neurotransmitter / neurotransmitter transmembrane transporter activity
Processes
amino acid transport / chemical synaptic transmission / dopamine uptake involved in synaptic transmission / neuron cellular homeostasis / neurotransmitter transport / norepinephrine uptake / response to xenobiotic stimulus / sodium ion transmembrane transport
Components
axon / cell surface / neuronal cell body membrane / presynaptic membrane
General Function
Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921)
Specific Function
actin binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
63-88 93-116 136-166 234-254 258-282 307-332 339-362 403-428 444-464 466-492 523-545 549-569
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010343|Sodium-dependent noradrenaline transporter (SLC6A2)
ATGCTTCTGGCGCGGATGAACCCGCAGGTGCAGCCCGAGAACAACGGGGCGGACACGGGT
CCAGAGCAGCCCCTTCGGGCGCGCAAAACTGCGGAGCTGCTGGTGGTGAAGGAGCGCAAC
GGCGTCCAGTGCCTGCTGGCGCCCCGCGACGGCGACGCGCAGCCCCGGGAGACCTGGGGC
AAGAAGATCGACTTCCTGCTGTCCGTAGTCGGCTTCGCAGTGGACCTGGCCAACGTGTGG
CGCTTCCCCTACCTCTGCTACAAGAACGGCGGCGGTGCCTTCTTGATCCCGTACACACTG
TTCCTTATCATCGCGGGGATGCCCCTGTTCTACATGGAGCTGGCTCTGGGACAGTACAAC
CGGGAGGGGGCTGCCACCGTTTGGAAAATCTGCCCATTCTTCAAAGGCGTTGGCTATGCT
GTCATCCTGATCGCCCTGTACGTTGGCTTCTACTACAACGTCATCATCGCCTGGTCACTC
TACTACCTCTTCTCCTCCTTCACCCTCAACCTGCCCTGGACCGACTGTGGCCACACCTGG
AACAGCCCCAACTGTACCGACCCCAAGCTCCTCAATGGCTCCGTGCTTGGCAACCACACC
AAGTACTCCAAGTACAAGTTCACGCCGGCAGCCGAGTTTTATGAGCGTGGTGTCCTGCAC
CTTCACGAGAGCAGCGGGATTCATGACATCGGCCTGCCCCAGTGGCAGCTCTTGCTCTGT
CTGATGGTCGTCGTCATCGTCTTGTATTTTAGCCTCTGGAAAGGGGTGAAGACATCAGGA
AAGGTGGTGTGGATCACAGCCACGCTGCCTTACTTCGTGCTGTTCGTGCTCCTGGTCCAT
GGCGTCACGCTGCCCGGAGCCTCCAATGGCATCAATGCCTACCTGCACATCGACTTCTAC
CGCTTGAAAGAGGCCACGGTATGGATTGATGCCGCAACTCAGATATTTTTTTCCTTGGGG
GCTGGATTTGGAGTATTGATTGCATTTGCCAGTTACAACAAATTTGACAACAACTGTTAC
AGGGATGCCCTGCTGACCAGCAGCATCAACTGTATCACCAGCTTCGTCTCTGGGTTCGCC
ATCTTCTCCATCCTTGGTTACATGGCCCATGAACACAAGGTCAACATTGAGGATGTGGCC
ACAGAAGGAGCTGGCCTAGTGTTCATCCTGTATCCAGAGGCCATTTCTACCCTGTCTGGA
TCTACATTCTGGGCTGTTGTGTTTTTCGTCATGCTCCTGGCGCTGGGCCTTGACAGCTCA
ATGGGAGGCATGGAGGCTGTCATCACGGGCCTGGCAGATGACTTCCAGGTCCTGAAGCGA
CACCGGAAACTCTTCACATTTGGCGTCACCTTCAGCACTTTCCTTCTCGCCCTGTTCTGC
ATAACCAAGGGTGGAATTTACGTCTTGACCCTCCTGGACACCTTTGCTGCGGGCACCTCC
ATCCTTTTTGCTGTCCTCATGGAAGCCATCGGAGTTTCCTGGTTTTATGGAGTGGACAGG
TTCAGCAACGACATCCAGCAGATGATGGGGTTCAGGCCGGGTCTATACTGGAGACTGTGC
TGGAAGTTCGTCAGTCCTGCCTTCCTCCTGTTCGTGGTTGTGGTCAGCATCATCAACTTC
AAGCCACTCACCTACGACGACTACATCTTCCCGCCCTGGGCCAACTGGGTGGGGTGGGGC
ATCGCCCTGTCCTCCATGGTCCTGGTGCCCATCTACGTCATCTATAAGTTCCTCAGCACG
CAGGGCTCTCTTTGGGAGAGACTGGCCTATGGCATCACGCCAGAGAACGAGCACCACCTG
GTGGCTCAGAGGGACATCAGACAGTTCCAGTTGCAACACTGGCTGGCCATCTGA
Chromosome Location
16
Locus
16q12.2
External Identifiers
ResourceLink
UniProtKB IDP23975
UniProtKB Entry NameSC6A2_HUMAN
GenBank Protein ID189258
GenBank Gene IDM65105
GeneCard IDSLC6A2
GenAtlas IDSLC6A2
HGNC IDHGNC:11048
PDB ID(s)8HFE, 8HFF, 8HFG, 8HFI, 8HFL, 8Y8Z, 8Y90, 8Y91, 8Y92, 8Y93, 8Y94, 8Y95, 8YR2
KEGG IDhsa:6530
IUPHAR/Guide To Pharmacology ID926
NCBI Gene ID6530
General References
  1. Pacholczyk T, Blakely RD, Amara SG: Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350-4. [Article]
  2. Porzgen P, Bonisch H, Bruss M: Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem Biophys Res Commun. 1995 Oct 24;215(3):1145-50. [Article]
  3. Porzgen P, Bonisch H, Hammermann R, Bruss M: The human noradrenaline transporter gene contains multiple polyadenylation sites and two alternatively spliced C-terminal exons. Biochim Biophys Acta. 1998 Jul 9;1398(3):365-70. [Article]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  5. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [Article]
  6. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [Article]
  7. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D: Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med. 2000 Feb 24;342(8):541-9. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Phentermineapproved, illicityestargetinhibitorDetails
Reboxetineapproved, experimentalyestargetinhibitorDetails
AtomoxetineapprovedyestargetinhibitorDetails
ProtriptylineapprovedyestargetinhibitorDetails
ImipramineapprovedyestargetinhibitorDetails
Mazindolapproved, investigationalyestargetinhibitorDetails
Phenmetrazineapproved, illicityestargetinhibitorDetails
Diethylpropionapproved, illicityestargetinhibitorDetails
Tramadolapproved, investigationalyestargetinhibitorDetails
Guanadrelapprovedyestargetpartial agonistDetails
VenlafaxineapprovedyestargetinhibitorDetails
AmitriptylineapprovedyestargetinhibitorDetails
Methylphenidateapproved, investigationalunknowntargetinhibitorDetails
DuloxetineapprovedyestargetinhibitorDetails
NortriptylineapprovedyestargetinhibitorDetails
AmoxapineapprovedyestargetinhibitorDetails
TrimipramineapprovedyestargetinhibitorDetails
Cocaineapproved, illicityestargetinhibitorDetails
Maprotilineapproved, investigationalyestargetinhibitorDetails
Sibutramineapproved, illicit, investigational, withdrawnyestargetinhibitorDetails
Doxepinapproved, investigationalyestargetinhibitorDetails
Nefazodoneapproved, withdrawnyestargetinhibitorDetails
Desipramineapproved, investigationalyestargetinhibitorDetails
BupropionapprovedyestargetinhibitorDetails
GuanethidineapprovedyestargetinducerDetails
Clomipramineapproved, investigational, vet_approvedunknowntargetinhibitorDetails
Paroxetineapproved, investigationalunknowntargetinhibitorDetails
Amineptineillicit, withdrawnunknowntargetDetails
Debrisoquineapproved, investigationalyestargetinducerDetails
BicifadineinvestigationalyestargetmodulatorDetails
Milnacipranapproved, investigationalyestargetinhibitorDetails
XEN-2174investigationalunknowntargetDetails
CRx-119investigationalunknowntargetDetails
DasotralineinvestigationalyestargetinhibitorDetails
TesofensineinvestigationalunknowntargetDetails
AmitifadineinvestigationalyestargetinhibitorDetails
DDP-225investigationalunknowntargetDetails
TapentadolapprovedyestargetinhibitorDetails
TrodusquemineinvestigationalunknowntargetDetails
Nomifensineapproved, withdrawnunknowntargetDetails
EscitalopramapprovedunknowntargetinhibitorDetails
ChlorpheniramineapprovedunknowntargetinhibitorDetails
Ginkgo bilobaapproved, investigational, nutraceuticalunknowntargetinhibitorDetails
OrphenadrineapprovedyestargetinhibitorDetails
Desvenlafaxineapproved, investigationalyestargetinhibitorDetails
Mianserinapproved, investigationalunknowntargetinhibitorDetails
Dexmethylphenidateapproved, investigationalyestargetinhibitorDetails
PseudoephedrineapprovedyestargetinhibitorDetails
Dextroamphetamineapproved, illicityestargetnegative modulatorDetails
Phendimetrazineapproved, illicityestargetnegative modulatorDetails
Ephedra sinica rootnutraceuticalyestargetnegative modulatorDetails
MMDAexperimental, illicityestargetnegative modulatorDetails
Metamfetamineapproved, illicit, withdrawnyestargetnegative modulatorDetails
Midomafetamineexperimental, illicit, investigationalyestargetnegative modulatorDetails
Ephedrineapprovedunknowntargetinverse agonistDetails
NorepinephrineapprovedunknowntransportersubstrateDetails
Droxidopaapproved, investigationalunknowntransportersubstrateDetails
Midomafetamineexperimental, illicit, investigationalunknowntransporterDetails
Iobenguaneapproved, investigationalnotransportersubstrateDetails
Levomilnacipranapproved, investigationalyestargetinhibitorDetails
LoxapineapprovedunknowntargetbinderDetails
Amphetamineapproved, illicit, investigationalunknowntargetagonistsubstrateDetails
DextromethorphanapprovedunknowntargetinhibitorDetails
DopamineapprovedunknowntargetinhibitorDetails
MeperidineapprovedunknowntargetinhibitorDetails
Ketamineapproved, vet_approvedunknowntargetinhibitorDetails
Vortioxetineapproved, investigationalunknowntargetblockerDetails
Iobenguane sulfate I-123approved, investigationalnotransportersubstrateDetails
DosulepinapprovedyestargetinhibitorDetails
Viloxazineapproved, investigational, withdrawnyestargetinhibitorDetails
EtoperidonewithdrawnnotransporterinhibitorDetails
NetarsudilapprovedyestargetinhibitorDetails
Zotepineapproved, investigational, withdrawnyestargetantagonistDetails
Rauwolfia serpentina rootinvestigationalunknowntransporterinhibitorDetails
BenzatropineapprovednotargetinhibitorDetails
SolriamfetolapprovedunknowntargetDetails
CyclobenzaprineapprovedunknowntargetinhibitorDetails
SertralineapprovedunknowntargetinhibitordownregulatorDetails
PseudoephedrineapprovedunknowntransporterinhibitorDetails
NortriptylineapprovedunknowntransportersubstrateinhibitorDetails
Procaineapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
SerdexmethylphenidateapprovedyestargetinhibitorDetails
Tenamfetamineexperimental, illicityestargetinhibitorDetails
NisoxetineexperimentalyestargetinhibitorDetails
SeproxetineinvestigationalyestargetinhibitorDetails
RadafaxineinvestigationalyestargetinhibitorDetails
EsreboxetineinvestigationalyestargetblockerDetails
NS-2359investigationalyestargetinhibitorDetails
Iobenguaneapproved, investigationalyestargetmodulatorDetails
AmpreloxetineinvestigationalyestargetmodulatorDetails
AcetaminophenapprovedyestargetinhibitorDetails