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PR01195

Identifier
GAT1TRNSPORT  [View Relations]  [View Alignment]  
Accession
PR01195
No. of Motifs
4
Creation Date
21-JUN-1999
Title
GAT-1 GABA neurotransmitter transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD011366; PD023334
INTERPRO; IPR002980
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., BRECHA, N.C., KARSCHIN, C., DEBIASI, S. AND CONTI, F.
GAT-1, a high-affinity GABA plasma membrane transporter, is localized to
neurons and astroglia in the cerebral cortex.
J.NEUROSCIENCE 15 7734-7746 (1995).

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 (TM) 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].
 
GAT-1 (~599 amino acids) has been found to be widely expressed in the
rodent brain, mRNA transcripts being observed in: the retina, olfactory
bulb, neocortex, ventral pallidum, hippocampus and cerebellum. The overall
distribution parallels that observed for GABA [6]. Further studies have
suggested that it is found in both neuronal and glial cell types [7].
 
GAT1TRNSPORT is a 4-element fingerprint that provides a signature for the
GAT-1 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-1 GABA transporter but distinguish it
from others - motif 1 resides within the putative cytoplasmic N-terminus;
motif 2 encodes a portion of the putative extracellular loop located
between putative TM domains 3 and 4; motif 3 lies at the start of the
fourth putative extracellular loop located between TM domains 7 and 8; and
motif 4 is located within the putative cytoplasmic C-terminus. Two
iterations on SPTR37_9f were required to reach convergence, at which point
a true set comprising 6 sequences was identified.
Summary Information
6 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
46666
30000
20000
1234
True Positives
NTG1_HUMAN    NTG1_MOUSE    NTG1_MUSCO    NTG1_RAT      
O73771 Q91494
Sequence Titles
NTG1_HUMAN  SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 1 - HOMO SAPIENS (HUMAN). 
NTG1_MOUSE SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 1 - MUS MUSCULUS (MOUSE).
NTG1_MUSCO SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 1 - MUS COOKII.
NTG1_RAT SODIUM- AND CHLORIDE-DEPENDENT GABA TRANSPORTER 1 - RATTUS NORVEGICUS (RAT).
O73771 GABA TRANSPORTER - RAJA SP.
Q91494 GAT-1 GABA TRANSPORTER - TORPEDO CALIFORNICA (PACIFIC ELECTRIC RAY).
Scan History
SPTR37_9f  2  200  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
SEAPVANDKPKTLVV NTG1_HUMAN 18 18 -
SEAPVASDKPKTLVV NTG1_RAT 18 18 -
SEAPVASDKPKTLVV NTG1_MOUSE 18 18 -

Motif 2 width=18
Element Seqn Id St Int Rpt
ERNMHQMTDGLDKPGQIR NTG1_HUMAN 194 161 -
ERNMHQMTDGLDKPGQIR NTG1_MOUSE 194 161 -
ERNMHQMTDGLDKPGQIR NTG1_RAT 194 161 -

Motif 3 width=10
Element Seqn Id St Int Rpt
HVTKRSIADV NTG1_MOUSE 346 134 -
HVTKRSIADV NTG1_RAT 347 135 -
HVTKRSIADV NTG1_HUMAN 347 135 -

Motif 4 width=18
Element Seqn Id St Int Rpt
NGPEQPQAGSSASKEAYI NTG1_MOUSE 581 225 -
NGPEQPQAGSSASKEAYI NTG1_RAT 582 225 -
NGPEHAQAGSSTSKEAYI NTG1_HUMAN 582 225 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
HDAPTSNDKPKTLVV O73771 18 18 -
SEAPVASDKPKTLVV NTG1_RAT 18 18 -
SEAPVASDKPKTLVV NTG1_MUSCO 18 18 -
SEAPVASDKPKTLVV NTG1_MOUSE 18 18 -
SEAPVANDKPKTLVV NTG1_HUMAN 18 18 -
HDAPVSNDKPKTLVV Q91494 18 18 -

Motif 2 width=18
Element Seqn Id St Int Rpt
ERNMHQLSDGLDQPGQIR O73771 193 160 -
ERNMHQMTDGLDKPGQIR NTG1_MOUSE 194 161 -
ERNMHQMTDGLDKPGQIR NTG1_RAT 194 161 -
ERNMHQMTDGLDKPGQIR NTG1_MUSCO 194 161 -
ERNMHQMTDGLDKPGQIR NTG1_HUMAN 194 161 -
ERNMHQLTDGLDQPGQIR Q91494 193 160 -

Motif 3 width=10
Element Seqn Id St Int Rpt
HVTKRSIADV NTG1_MOUSE 346 134 -
HVTKRSIADV NTG1_RAT 347 135 -
HVTKRSIADV NTG1_MUSCO 346 134 -
HVTKRSIADV NTG1_HUMAN 347 135 -
HVTNRPIADV Q91494 346 135 -
HVTNRPIADV O73771 346 135 -

Motif 4 width=18
Element Seqn Id St Int Rpt
NGPEQPQAGSSASKEAYI NTG1_MOUSE 581 225 -
NGPEQPQAGSSASKEAYI NTG1_RAT 582 225 -
NGPEQPQAGSSASKEAYI NTG1_MUSCO 581 225 -
NGPEHAQAGSSTSKEAYI NTG1_HUMAN 582 225 -
NGPEQTECGNTPSDEAYM Q91494 581 225 -
NGPEQPEHGITPSDEAYM O73771 581 225 -