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2.A.22.1.2
Noradrenaline (norepinephrine):Na+ symporter (NET1, NAT1, SLC6?A2) (also transports 1-methyl-4-tetrahydropyridinium and amphetamines; it is a target of cocaine and amphetamines as well as of therapetics for depression, obsessive-compulsive disorders, and post-traumatic stress disorder. This homooligomeric transporter binds one substrate molecule per transporter subunit (Schwartz et al., 2005; Schlessinger et al., 2011; Andersen et al., 2011). Extracellular loop 3 contributes to substrate and inhibitor selectivity (Lynagh et al. 2013). The highly conserved MELAL and GQXXRXG motifs, located in the second transmembrane domain and the first intracellular loop of hNET, respectively, are determinants of NET cell surface expression, and substrate and inhibitor binding (Sucic and Bryan-Lluka 2007). Based on modeling, the high affinity substrate binding site (S1) of the human norepinephrine transporter has been predicted and then verified by mutational studies (Jha et al. 2020).  

Accession Number:P23975
Protein Name:NTNO aka NET aka SLC6A2 aka NAT1 aka NET1
Length:617
Molecular Weight:69332.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Noradrenaline, Na+, 1-methyl-4-tetrahydropyridinium, amphetamines

Cross database links:

RefSeq: NP_001034.1    NP_001165972.1   
Entrez Gene ID: 6530   
Pfam: PF00209   
OMIM: 163970  gene
604715  phenotype
KEGG: hsa:6530    hsa:6530   

Gene Ontology

GO:0005887 C:integral to plasma membrane
GO:0005624 C:membrane fraction
GO:0005334 F:norephinephrine:sodium symporter activity
GO:0005515 F:protein binding
GO:0015844 P:monoamine transport
GO:0006836 P:neurotransmitter transport
GO:0007268 P:synaptic transmission
GO:0005334 F:norepinephrine:sodium symporter activity

References (10)

[1] “Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.”  Pacholczyk T.et.al.   2008212
[2] “Molecular cloning and organization of the coding region of the human norepinephrine transporter gene.”  Poerzgen P.et.al.   7488042
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.”  Torres G.E.et.al.   11343649
[5] “Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency.”  Shannon J.R.et.al.   10684912
[6] “Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter.”  Pacholczyk T.et.al.   2008212
[7] “Molecular cloning and organization of the coding region of the human norepinephrine transporter gene.”  Poerzgen P.et.al.   7488042
[8] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[9] “Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1.”  Torres G.E.et.al.   11343649
[10] “Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency.”  Shannon J.R.et.al.   10684912

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MLLARMNPQV QPENNGADTG PEQPLRARKT AELLVVKERN GVQCLLAPRD GDAQPRETWG 
61:	KKIDFLLSVV GFAVDLANVW RFPYLCYKNG GGAFLIPYTL FLIIAGMPLF YMELALGQYN 
121:	REGAATVWKI CPFFKGVGYA VILIALYVGF YYNVIIAWSL YYLFSSFTLN LPWTDCGHTW 
181:	NSPNCTDPKL LNGSVLGNHT KYSKYKFTPA AEFYERGVLH LHESSGIHDI GLPQWQLLLC 
241:	LMVVVIVLYF SLWKGVKTSG KVVWITATLP YFVLFVLLVH GVTLPGASNG INAYLHIDFY 
301:	RLKEATVWID AATQIFFSLG AGFGVLIAFA SYNKFDNNCY RDALLTSSIN CITSFVSGFA 
361:	IFSILGYMAH EHKVNIEDVA TEGAGLVFIL YPEAISTLSG STFWAVVFFV MLLALGLDSS 
421:	MGGMEAVITG LADDFQVLKR HRKLFTFGVT FSTFLLALFC ITKGGIYVLT LLDTFAAGTS 
481:	ILFAVLMEAI GVSWFYGVDR FSNDIQQMMG FRPGLYWRLC WKFVSPAFLL FVVVVSIINF 
541:	KPLTYDDYIF PPWANWVGWG IALSSMVLVP IYVIYKFLST QGSLWERLAY GITPENEHHL 
601:	VAQRDIRQFQ LQHWLAI