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PR01197

Identifier
GAT3TRNSPORT  [View Relations]  [View Alignment]  
Accession
PR01197
No. of Motifs
3
Creation Date
21-JUN-1999
Title
GAT-3 GABA neurotransmitter transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD023332; PD023335
INTERPRO; IPR002982
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).
 
6. DURKIN, M.M., SMITH, K.E., BORDEN, L.A., WEINSHANK, R.L., BRANCHEK, T.A.
AND GUSTAFSON, E.L.
Localization of messenger RNAs encoding three GABA transporters in rat
brain: an in situ hybridization study.
BRAIN RES.MOL.BRAIN RES. 33 7-21 (1995).
 
7. MINELLI, A., DEBIASI, S., BRECHA, N.C., ZUCCARELLO, L.V. AND CONTI, F.
GAT-3, a high-affinity GABA plasma membrane transporter, is localized to
astrocytic processes, and it is not confined to the vicinity of GABAergic
synapses in the cerebral cortex.
J.NEUROSCIENCE 16 6255-6264 (1996).

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].
 
GABA is the major inhibitory transmitter in the mammalian brain, and is
widely distributed throughout the nervous system. Molecular cloning
studies have resulted in the cloning of three Na+ and Cl- -coupled GABA
transporters (known as GAT-1, GAT-2, GAT-3) and a betaine/GABA transporter
(BGT-1). Each transporter shows varying affinities for GABA, different
substrate and blocker pharmacologies, and different tissue localisation [6].
 
Brain regions containing GAT-3 mRNA transcripts include the retina,
olfactory bulb, subfornical organ, hypothalamus, midline thalamus and
brainstem. GAT-3 mRNA was found to be absent from the neocortex and 
cerebellar cortex, and very weak in the hippocampus [6]. Furthermore,
immunocytological studies have demonstrated that this transporter may be
localised solely to glial (non-neuronal) cells, suggesting that glial GABA
uptake may function to limit the spread of GABA from the synapse, as well
as to regulate overall GABA levels.
 
GAT3TRNSPORT is a 3-element fingerprint that provides a signature for the
GAT-3 GABA neurotransmitter transporter. The fingerprint was derived from
an initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise the GAT-3 GABA transporter but distinguish it
from others - motif 1 resides within the putative cytoplasmic N-terminus;
motif 2 encodes a portion of the large putative cytoplasmic loop; and motif
3 lies on the putative cytoplasmic C-terminus. A single iteration on
SPTR37_9f was required to reach convergence, no further sequences being
identified beyond the starting set.
Summary Information
3 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3333
2000
123
True Positives
NTG3_HUMAN    NTG3_MOUSE    NTG3_RAT      
Sequence Titles
NTG3_HUMAN  SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 3 - HOMO SAPIENS (HUMAN). 
NTG3_MOUSE SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 3 (GAT4) - MUS MUSCULUS (MOUSE).
NTG3_RAT SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 3 - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  1  300  NSINGLE    
Initial Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
ARDKAVHER NTG3_MOUSE 37 37 -
ARDKAVHER NTG3_RAT 37 37 -
KRDKAVHER NTG3_HUMAN 42 42 -

Motif 2 width=10
Element Seqn Id St Int Rpt
SNYSHVSLQN NTG3_MOUSE 184 138 -
SNYSHVSLQN NTG3_RAT 184 138 -
SNYSHVSLQN NTG3_HUMAN 189 138 -

Motif 3 width=13
Element Seqn Id St Int Rpt
DLKMRGKLGASPR NTG3_MOUSE 588 394 -
DLKMRGKLGASPR NTG3_RAT 588 394 -
DLKMRGKLGVSPR NTG3_HUMAN 593 394 -
Final Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
ARDKAVHER NTG3_MOUSE 37 37 -
ARDKAVHER NTG3_RAT 37 37 -
KRDKAVHER NTG3_HUMAN 42 42 -

Motif 2 width=10
Element Seqn Id St Int Rpt
SNYSHVSLQN NTG3_MOUSE 184 138 -
SNYSHVSLQN NTG3_RAT 184 138 -
SNYSHVSLQN NTG3_HUMAN 189 138 -

Motif 3 width=13
Element Seqn Id St Int Rpt
DLKMRGKLGASPR NTG3_MOUSE 588 394 -
DLKMRGKLGASPR NTG3_RAT 588 394 -
DLKMRGKLGVSPR NTG3_HUMAN 593 394 -