| Literature References | 1. ATTELL, D. AND MOBBS, P.
Neurotransmitter transporters.
CURR.OPIN.NEUROBIOL. 4 353-359 (1994).
2. MALANDRO, M.S. AND KILBERG, M.S.
Molecular biology of mammalian amino acid transporters.
ANNU.REV.BIOCHEMISTRY 65 305-336 (1996).
3. AMARA, S.G. AND ARRIZA, J.L.
Neurotransmitter transporters: three distinct gene families.
CURR.OPIN.NEUROBIOL. 3 337-344 (1993).
4. UHL, G.R. AND JOHNSON, P.S.
Neurotransmitter transporters: Three important gene families for neuronal
function.
J.EXP.BIOL. 196 229-236 (1994).
5. LILL, H. AND NELSON, N.
Homologies and family relationships among Na+/Cl- neurotransmitter
transporters.
METHODS ENZYMOL. 306 425-436 (1998).
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| Documentation | Neurotransmitter transport systems are integral to the release, re-uptake
and recycling of neurotransmitters at synapses. High affinity tranport
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 [1]. 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
tranport. The latter couple glutamate and aspartate uptake to the co-
transport of Na+ and the counter-transport of K+, with no apparent
dependence on Cl- [2]. In addition, both of these transporter families
are distinct from the vesicular neurotransmitter transporters [3,4].
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 [5].
NANEUSMPORT is an 8-element fingerprint that provides a signature for the
Na+/Cl- -coupled neurotransmitter transporter superfamily. The fingerprint
was derived from an initial alignment of 9 sequences: the motifs were drawn
from TM regions 1-3, 5, 7-8 and 10-11 respectively (the other TM regions
were not sufficiently well-conserved to be included in the fingerprint).
Two iterations on OWL22.1 were required to reach convergence, at which
point a true set comprising 33 sequences was identified. A single partial
match was also found, S28306, a hypothetical protein fragment from
C.elegans that is similar to 6 of the 8 motifs.
An update on SPTR37_9f identified a true set of 61 sequences, and 19
partial matches.
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