Sodium:neurotransmitter symporter, orphan (IPR002438)
Short name: Na/ntran_symport_orphan
Overlapping homologous superfamilies
- Sodium:neurotransmitter symporter superfamily (IPR037272)
- Sodium:neurotransmitter symporter (IPR000175)
- Sodium:neurotransmitter symporter, orphan (IPR002438)
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 orphan transporters are an expanding group of putative transporters that have been cloned, but as yet have uncharacterised substrate(s) for transport. They include NTT4 and NTT73, which were cloned from rat brain tissues [PMID: 8093354], and a family of alternatively-spliced variants from kidney [PMID: 9932288]. Sequence analysis strongly suggests that these indeed are Na+ and Cl- -coupled cell membrane transporters, since they show significant identity, and similar predicted topology, to the functionally-characterised members of this superfamily.
- PR01206 (ORPHTRNSPORT)