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PR01206

Identifier
ORPHTRNSPORT  [View Relations]  [View Alignment]  
Accession
PR01206
No. of Motifs
3
Creation Date
22-JUN-1999
Title
Orphan neurotransmitter transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
INTERPRO; IPR002438
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. LIU, G-R., MANDIYAN, S., LOPEZ-CORCUERA, B., NELSON, H. AND NELSON, N.
A rat brain cDNA encoding the neurotransmitter transporter with an unusual
structure.
FEBS LETT. 315 114-118 (1993).
 
7. NASH, S.R., GIROS, B., KINGSMORE, S.F. AND KIM, K.M.
Cloning, gene structure and genomic localization of an orphan transporter 
from mouse kidney with six alternatively-spliced isoforms.
RECEPTORS CHANNELS 6 113-128 (1998).

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]. The latter is 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 [6], and a family of alternatively-spliced variants
from kidney [7]. 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.
 
ORPHTRNSPORT is a 3-element fingerprint that provides a signature for
orphan neurotransmitter transporters. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions from the central portion of the alignment, focusing on those
sections that characterise orphan neurotransmitter transporters but
distinguish them from others - motifs 1-2 lie within the large putative
extracellular loop located between TM domains 3 and 4; and motif 3 resides
within the putative extracellular loop between TM domains 7 and 8. Two
iterations on SPTR37_9f were required to reach convergence, at which point
a true set comprising 10 sequences was identifed. Amonst these matches is
a renal organic solute transporter from rat.
Summary Information
11 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3111111
2000
123
True Positives
NTT4_RAT      NTT7_RAT      O88575        O88576        
O88577 O88578 O88579 O88580
O88581 Q62687 Q64093
Sequence Titles
NTT4_RAT    SODIUM- AND CHLORIDE-DEPENDENT TRANSPORTER NTT4 - RATTUS NORVEGICUS (RAT). 
NTT7_RAT SODIUM- AND CHLORIDE-DEPENDENT TRANSPORTER NTT73 - RATTUS NORVEGICUS (RAT).
O88575 ORPHAN TRANSPORTER - MUS MUSCULUS (MOUSE).
O88576 ORPHAN TRANSPORTER ISOFORM A12 - MUS MUSCULUS (MOUSE).
O88577 ORPHAN TRANSPORTER ISOFORM A11 - MUS MUSCULUS (MOUSE).
O88578 ORPHAN TRANSPORTER ISOFORM B11 - MUS MUSCULUS (MOUSE).
O88579 ORPHAN TRANSPORTER ISOFORM A10 - MUS MUSCULUS (MOUSE).
O88580 ORPHAN TRANSPORTER ISOFORM B9 - MUS MUSCULUS (MOUSE).
O88581 ORPHAN TRANSPORTER ISOFORM A8 - MUS MUSCULUS (MOUSE).
Q62687 RENAL OSMOTIC STRESS-INDUCED NA-CL ORGANIC SOLUTE COTRANSPORTER - RATTUS NORVEGICUS (RAT).
Q64093 NEUROTRANSMITTER TRANSPORTER RB21A - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  2  250  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ECQSSGTVSYFWY O88576 150 150 -
ECQSSGTVSYFWY O88579 150 150 -
ECEKSSATTYFWY NTT4_RAT 195 195 -
ECEKSSATTYYWY NTT7_RAT 196 196 -

Motif 2 width=12
Element Seqn Id St Int Rpt
RQTLNITSDISN O88576 163 0 -
RQTLNITSDISN O88579 163 0 -
REALDISNSISE NTT4_RAT 208 0 -
REALAISSSISE NTT7_RAT 209 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
FKASNDYGRCL O88576 312 137 -
FKASNDYGRCL O88579 312 137 -
FKANIMNEKCV NTT4_RAT 357 137 -
FKANIVNEKCI NTT7_RAT 358 137 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
ECQSSGTVSYFWY O88576 150 150 -
ECQSSGTVSYFWY Q62687 150 150 -
ECQSSGTVSYFWY O88581 150 150 -
ECQSSGTVSYFWY O88580 150 150 -
ECQSSGTVSYFWY O88579 150 150 -
ECQSSGTVSYFWY O88578 150 150 -
ECQSSGTVSYFWY O88577 150 150 -
ECEKASSTQYFWY O88575 181 181 -
ECEKASSTQYFWY Q64093 162 162 -
ECEKSSATTYFWY NTT4_RAT 195 195 -
ECEKSSATTYYWY NTT7_RAT 196 196 -

Motif 2 width=12
Element Seqn Id St Int Rpt
RQTLNITSDISN O88576 163 0 -
RQTLNITSDISN Q62687 163 0 -
RQTLNITSDISN O88581 163 0 -
RQTLNITSDISN O88580 163 0 -
RQTLNITSDISN O88579 163 0 -
RQTLNITSDISN O88578 163 0 -
RQTLNITSDISN O88577 163 0 -
RKTLNISPSIQE O88575 194 0 -
RKTLNISPSIQE Q64093 175 0 -
REALDISNSISE NTT4_RAT 208 0 -
REALAISSSISE NTT7_RAT 209 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
FKASNDYGRCL O88576 312 137 -
FKASNDYGRCL Q62687 312 137 -
FKASNDYGRCL O88581 312 137 -
FKASNDYGRCL O88580 312 137 -
FKASNDYGRCL O88579 312 137 -
FKASNDYGRCL O88578 312 137 -
FKASNDYGRCL O88577 312 137 -
FKATFNYENCL O88575 343 137 -
FKATFNYENCL Q64093 324 137 -
FKANIMNEKCV NTT4_RAT 357 137 -
FKANIVNEKCI NTT7_RAT 358 137 -