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PR01204

Identifier
GLY1TRNSPORT  [View Relations]  [View Alignment]  
Accession
PR01204
No. of Motifs
4
Creation Date
21-JUN-1999
Title
Glycine neurotransmitter transporter type 1 (GLYT-1) signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD017177
INTERPRO; IPR003028
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. 296 425-436 (1998).
 
6. MALANDRO, M.S. AND KILBERG, M.S.
Molecular biology of mammalian amino acid transporters.
ANNU.REV.BIOCHEMISTRY 65 305-336 (1996).
 
7. LIU, Q.R., LOPEZ-CORCUERA, B., MANDIYAN, S., NELSON, H. AND NELSON, N.
Cloning and expression of a spinal cord- and brain-specific glycine
transporter with novel structural features.
J.BIOL.CHEM. 268 22802-22808 (1993).

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].
 
Glycine is known to serve two contrasting roles as a neurotransmitter in
the central nervous system. Firstly, it serves as an inhibitory neuro-
transmitter in the spinal cord, brainstem and retina, where it activates a
ligand-gated Cl- channel. Secondly, it is an obligatory co-agonist for
activation of the N-methyl-D-aspartate (NMDA) receptor - unless glycine
is also bound to the NMDA receptor, glutamate cannot activate this ion
channel. Not surprisingly, then, plasma membranes possess glycine
transporters in order to regulate its concentration. Two independent genes
have been identified that encode Na+ and Cl- -coupled glycine transporters.
Their products, referred to as GLYT-1 and GLYT-2, have differing
distribution patterns within the central nervous system, suggesting they
may subserve unique functions [6]. Indeed the distribution of the GLYT-1
transporter suggests it may play a role in regulating glycine
concentrations in brain regions containing glycine-dependent NMDA receptors
[7]. Three different mRNA isoforms for GLYT-1 have been detected. These
arise as a result of differential splicing, or the usage of multiple
promoter sites. They encode transporters of 633, 638 and 692 amino acid
residues, all three having 50-60% similarity to other transporters in the
Na+ and Cl- -coupled neurotransmitter transporter superfamily.
 
GLY1TRNSPORT is a 4-element fingerprint that provides a signature for the
glycine neurotransmitter transporter type 1 (GLYT-1). The fingerprint was
derived from an initial alignment of 3 sequences: the motifs were drawn
from conserved regions located within the first third of the alignment,
focusing on those sections that characterise the glycine transporter
but distinguish it from others - motifs 1-2 reside within the putative
cytoplasmic N-terminus; and motifs 3-4 encode portions of the large
extracellular loop located between TM domains 3 and 4. Two iterations on
SPTR37_9f were required to reach convergence, at which point a true set
comprising 4 sequences was identified.
Summary Information
4 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
44444
30000
20000
1234
True Positives
NTGL_BOVIN    NTGL_HUMAN    NTGL_MOUSE    NTGL_RAT      
Sequence Titles
NTGL_BOVIN  SODIUM- AND CHLORIDE-DEPENDENT GLYCINE TRANSPORTER 1 (GLYT-1) - BOS TAURUS (BOVINE). 
NTGL_HUMAN SODIUM- AND CHLORIDE-DEPENDENT GLYCINE TRANSPORTER 1 (GLYT-1) - HOMO SAPIENS (HUMAN).
NTGL_MOUSE SODIUM- AND CHLORIDE-DEPENDENT GLYCINE TRANSPORTER 1 (GLYT-1) - MUS MUSCULUS (MOUSE).
NTGL_RAT SODIUM- AND CHLORIDE-DEPENDENT GLYCINE TRANSPORTER 1 (GLYT-1) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  2  300  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
NGAVPSEATKKDQN NTGL_RAT 11 11 -
NGAVPSEATKRDQN NTGL_HUMAN 70 70 -
NGAVPSEATKKDQN NTGL_BOVIN 16 16 -

Motif 2 width=11
Element Seqn Id St Int Rpt
LTRGNWGNQIE NTGL_RAT 25 0 -
LKRGNWGNQIE NTGL_HUMAN 84 0 -
LKRGNWGNQIE NTGL_BOVIN 30 0 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VLDASNLTNGSRP NTGL_RAT 159 123 -
VLDASNLTNGSRP NTGL_HUMAN 218 123 -
VLDNPNITNGSQP NTGL_BOVIN 164 123 -

Motif 4 width=16
Element Seqn Id St Int Rpt
ALSGNLSHLFNYTLQR NTGL_RAT 173 1 -
ALPSNLSHLLNHSLQR NTGL_HUMAN 232 1 -
ALPGNVSQALNQTLKR NTGL_BOVIN 178 1 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
NGAVPSEATKKDQN NTGL_MOUSE 11 11 -
NGAVPSEATKKDQN NTGL_RAT 11 11 -
NGAVPSEATKRDQN NTGL_HUMAN 70 70 -
NGAVPSEATKKDQN NTGL_BOVIN 16 16 -

Motif 2 width=11
Element Seqn Id St Int Rpt
LTRGNWGNQIE NTGL_MOUSE 25 0 -
LTRGNWGNQIE NTGL_RAT 25 0 -
LKRGNWGNQIE NTGL_HUMAN 84 0 -
LKRGNWGNQIE NTGL_BOVIN 30 0 -

Motif 3 width=13
Element Seqn Id St Int Rpt
VLDASNLTNGSRP NTGL_MOUSE 159 123 -
VLDASNLTNGSRP NTGL_RAT 159 123 -
VLDASNLTNGSRP NTGL_HUMAN 218 123 -
VLDNPNITNGSQP NTGL_BOVIN 164 123 -

Motif 4 width=16
Element Seqn Id St Int Rpt
ALSGNLSHLFNYTLQR NTGL_MOUSE 173 1 -
ALSGNLSHLFNYTLQR NTGL_RAT 173 1 -
ALPSNLSHLLNHSLQR NTGL_HUMAN 232 1 -
ALPGNVSQALNQTLKR NTGL_BOVIN 178 1 -