Sodium:neurotransmitter symporter, noradrenaline (IPR002435)

Short name: Na/ntran_symport_noradrenaline

Overlapping homologous superfamilies

Family relationships


Neurotransmitter transport systems are integral to the release, re-uptake and recycling of neurotransmitters at synapses. High affinity transport proteins found in the plasma membrane of presynaptic nerve terminals and glial cells are responsible for the removal from the extracellular space of released-transmitters, thereby terminating their actions [PMID: 15336049]. Plasma membrane neurotransmitter transporters fall into two structurally and mechanistically distinct families. The majority of the transporters constitute an extensive family of homologous proteins that derive energy from the co-transport of Na+ and Cl-, in order to transport neurotransmitter molecules into the cell against their concentration gradient. The family has a common structure of 12 presumed transmembrane helices and includes carriers for gamma-aminobutyric acid (GABA), noradrenaline/adrenaline, dopamine, serotonin, proline, glycine, choline, betaine and taurine. They are structurally distinct from the second more-restricted family of plasma membrane transporters, which are responsible for excitatory amino acid transport. The latter couple glutamate and aspartate uptake to the cotransport of Na+ and the counter-transport of K+, with no apparent dependence on Cl- [PMID: 8811182]. In addition, both of these transporter families are distinct from the vesicular neurotransmitter transporters [PMID: 8103691, PMID: 7823024].

Sequence analysis of the Na+/Cl- neurotransmitter superfamily reveals that it can be divided into four subfamilies, these being transporters for monoamines, the amino acids proline and glycine, GABA, and a group of orphan transporters [PMID: 9779464].

The human noradrenaline transporter is the primary target for widely-used tricyclic antidepressant drugs, such as desipramine. Cloning studies have revealed a single noradrenaline transporter isoform. The cDNA sequence predicts a protein of ~617 amino acids, with 12-13 highly hydrophobic regions, as would be expected for a member of the Na+ and Cl- -coupled neurotransmitter superfamily [PMID: 2008212]. Related noradrenaline transporter species have been identified in both Drosophila and Rana catesbeiana (Bull frog). In mammalian species, mRNA for the transporter is localised to the brainstem and the adrenal glands. Chromosome mapping has placed the encoding gene to chromosome 16q12.2 in humans [PMID: 8478011]. Recently, a bovine noradrenaline transporter variant has been identified that shows altered targeting to the plasma membrane. This has implicated the cytoplasmic facing C terminus in the intracellular trafficking of this protein [PMID: 9480909].

GO terms

Biological Process

GO:0006836 neurotransmitter transport

Molecular Function

GO:0005328 neurotransmitter:sodium symporter activity

Cellular Component

GO:0005887 integral component of plasma membrane
GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.