Sodium-dependent noradrenaline transporter
Also known as: NAT1, NET1, SLC6A2, SLC6A5
Function
Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system. Is responsible for norepinephrine re-uptake and clearance from the synaptic cleft, thus playing a crucial role in norepinephrine inactivation and homeostasis (By similarity). Can also mediate sodium- and chloride-dependent transport of dopamine.
Classification
- Family (Pfam)
- PF00209 SNF
- InterPro
- Na/ntran_symport, Na/ntran_symport_noradrenaline, SNS_sf
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 35
- 8HFE EM 2.50A
- 8HFF EM 2.86A
- 8HFG EM 3.00A
- 8HFI EM 2.50A
- 8HFL EM 3.00A
- 8I3V EM 2.85A
- 8WGR EM 2.75A
- 8WGX EM 3.47A
- 8WTU EM 2.70A
- 8WTV EM 2.70A
- 8WTW EM 2.80A
- 8WTX EM 2.90A
- … and 23 more
A predicted model is available from AlphaFold.
Gene Ontology · 26
- GO:0030424 axon
- GO:0009986 cell surface
- GO:0016020 membrane
- GO:0032809 neuronal cell body membrane
- GO:0005886 plasma membrane
- GO:0042734 presynaptic membrane
- GO:0030672 synaptic vesicle membrane
- GO:0003779 actin binding
- GO:0043014 alpha-tubulin binding
- GO:0048487 beta-tubulin binding
- GO:0005330 dopamine:sodium symporter activity
- GO:0046872 metal ion binding
- GO:0008504 monoamine transmembrane transporter activity
- GO:0005326 neurotransmitter transmembrane transporter activity
- GO:0005328 neurotransmitter:sodium symporter activity
- GO:0005334 norepinephrine:sodium symporter activity
- GO:0006865 amino acid transport
- GO:0007268 chemical synaptic transmission
- GO:0051583 dopamine uptake involved in synaptic transmission
- GO:0015844 monoamine transport
- GO:0070050 neuron cellular homeostasis
- GO:0006836 neurotransmitter transport
- GO:0015874 norepinephrine transport
- GO:0051620 norepinephrine uptake
- GO:0009410 response to xenobiotic stimulus
- GO:0035725 sodium ion transmembrane transport
Disease associations
- postural orthostatic tachycardia syndrome MONDO:0011479
Drugs targeting this protein · 75
- BRETYLIUM TOSYLATE substrate
- AMOXAPINE inhibitor
- DESVENLAFAXINE inhibitor
- DULOXETINE HYDROCHLORIDE inhibitor
- PROTRIPTYLINE HYDROCHLORIDE inhibitor
- AMPHETAMINE ASPARTATE releasing agent
- AMPHETAMINE ADIPATE releasing agent
- ORPHENADRINE CITRATE inhibitor
- PHENMETRAZINE HYDROCHLORIDE inhibitor
- NEFAZODONE HYDROCHLORIDE inhibitor
- PHENYLPROPANOLAMINE HYDROCHLORIDE releasing agent
- PSEUDOEPHEDRINE HYDROCHLORIDE releasing agent
- DEXTROAMPHETAMINE ADIPATE releasing agent
- PHENTERMINE HYDROCHLORIDE releasing agent
- TRIMIPRAMINE MALEATE inhibitor
- METHAMPHETAMINE HYDROCHLORIDE inhibitor
- AMITRIPTYLINE HYDROCHLORIDE inhibitor
- ORPHENADRINE HYDROCHLORIDE inhibitor
- VENLAFAXINE HYDROCHLORIDE inhibitor
- NORTRIPTYLINE HYDROCHLORIDE inhibitor
- LISDEXAMFETAMINE DIMESYLATE releasing agent
- DESVENLAFAXINE SUCCINATE inhibitor
- BUPROPION HYDROBROMIDE inhibitor
- TAPENTADOL HYDROCHLORIDE inhibitor
- MAPROTILINE HYDROCHLORIDE inhibitor
- NOMIFENSINE MALEATE inhibitor
- GUANETHIDINE MONOSULFATE substrate
- REBOXETINE inhibitor
- DIBENZEPIN inhibitor
- DOTHIEPIN inhibitor
- PHENTERMINE releasing agent
- IOBENGUANE I 131 substrate
- DOXEPIN HYDROCHLORIDE inhibitor
- IMIPRAMINE HYDROCHLORIDE inhibitor
- DIETHYLPROPION HYDROCHLORIDE inhibitor
- DESIPRAMINE HYDROCHLORIDE inhibitor
- BUPROPION HYDROCHLORIDE inhibitor
- DEBRISOQUIN inhibitor
- ATOMOXETINE HYDROCHLORIDE inhibitor
- METHYLPHENIDATE HYDROCHLORIDE inhibitor
- ESREBOXETINE inhibitor
- PHENDIMETRAZINE TARTRATE inhibitor
- FAXELADOL inhibitor
- EDIVOXETINE inhibitor
- PYROVALERONE HYDROCHLORIDE inhibitor
- TEDATIOXETINE inhibitor
- LEVOMILNACIPRAN HYDROCHLORIDE inhibitor
- VILOXAZINE HYDROCHLORIDE inhibitor
- BETHANIDINE SULFATE substrate
- LIAFENSINE inhibitor
- GUANADREL SULFATE substrate
- DASOTRALINE inhibitor
- CENTANAFADINE inhibitor
- BENZPHETAMINE HYDROCHLORIDE releasing agent
- DEXTROAMPHETAMINE SULFATE releasing agent
- TESOFENSINE inhibitor
- SIBUTRAMINE HYDROCHLORIDE inhibitor
- DEXTROAMPHETAMINE SACCHARATE releasing agent
- IMIPRAMINE PAMOATE inhibitor
- PSEUDOEPHEDRINE SULFATE releasing agent
- DESVENLAFAXINE FUMARATE inhibitor
- AMPHETAMINE releasing agent
- MILNACIPRAN HYDROCHLORIDE inhibitor
- NS-2359 inhibitor
- AMPRELOXETINE inhibitor
- SERDEXMETHYLPHENIDATE CHLORIDE inhibitor
- SERDEXMETHYLPHENIDATE inhibitor
- MIDOMAFETAMINE releasing agent
- AMPHETAMINE SULFATE releasing agent
- BICIFADINE inhibitor
- AMITIFADINE inhibitor
- DEXTROAMPHETAMINE releasing agent
- MAZINDOL inhibitor
- METHYLPHENIDATE inhibitor
- DEXMETHYLPHENIDATE HYDROCHLORIDE inhibitor
Related proteins · sequence + function similarity
- Sodium-dependent noradrenaline transporter 1.00
- Sodium-dependent noradrenaline transporter 0.99
- Sodium-dependent dopamine transporter 0.97
- Sodium-dependent dopamine transporter 0.97
- Sodium-dependent dopamine transporter 0.97
- Sodium- and chloride-dependent GABA transporter 2 0.96
- Sodium-dependent dopamine transporter 0.96
- Sodium- and chloride-dependent GABA transporter 2 0.96
- Sodium-dependent serotonin transporter 0.96
- Sodium- and chloride-dependent GABA transporter 2 0.96
- Sodium-dependent serotonin transporter 0.96
- Sodium- and chloride-dependent taurine transporter 0.96
Co-cited proteins · studied together in the literature
- Sodium-dependent dopamine transporter 1 shared papers
- Sodium-dependent dopamine transporter 2 shared papers
- PRKCA-binding protein 1 shared papers
Literature · 13 cited papers
- Palmitoylation regulates norepinephrine transporter uptake, surface localization, and total expression with pathogenic implications in postural orthostatic tachycardia syndrome. J. Neurochem. · 2025
- Molecular basis of human noradrenaline transporter reuptake and inhibition. Nature · 2024
- Dimerization and antidepressant recognition at noradrenaline transporter. Nature · 2024
- The sequence and analysis of duplication-rich human chromosome 16. Nature · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Pharmacological properties of the naturally occurring Ala(457)Pro variant of the human norepinephrine transporter. Pharmacogenetics · 2002
- Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron · 2001
- Structural domains of chimeric dopamine-noradrenaline human transporters involved in the Na(+)- and Cl(-)-dependence of dopamine transport. Mol. Pharmacol. · 2000
- Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N. Engl. J. Med. · 2000
- The human noradrenaline transporter gene contains multiple polyadenylation sites and two alternatively spliced C-terminal exons. Biochim. Biophys. Acta · 1998
- Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence. J. Biol. Chem. · 1994
- Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem. Biophys. Res. Commun. · 1995
- … and 1 more in the literature graph
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