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PR01203

Identifier
5HTTRANSPORT  [View Relations]  [View Alignment]  
Accession
PR01203
No. of Motifs
4
Creation Date
22-JUN-1999
Title
Serotonin (5-HT) neurotransmitter transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD017173
INTERPRO; IPR002437
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. RAMAMOORTHY, S., BAUMAN, A.L., MOORE, K.R., HAN, H., YANG-FENG, T.,
CHANG, A.S., GANAPATHY, V. AND BLAKELY, R.D.
Antidepressant- and cocaine-sensitive human serotonin transporter:
molecular cloning, expression, and chromosomal localization.
PROC.NATL.ACAD.SCI.U.S.A. 90 2542-2546 (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].
 
The 5-HT neurotransmitter transporter is known to be expressed in the brain
and also in the periphery: on platelet, placental and pulmonary cell
membranes. The brain 5-HT transporter is thought to be the principal site
of action of therapeutic anti-depressants (which inhibit this transporter),
and it may also mediate the behavioural effects of cocaine and amphetamines
[6].  The human form (630 amino acids) is 92% identical to the rat brain
5-HT transporter, and shares the same predicted topology and conserved sites
for post-translational modification.
 
5HTTRANSPORT is a 4-element fingerprint that provides a signature for the
5-HT neurotransmitter transporter. The fingerprint was derived from an
initial alignment of 4 sequences: the motifs were drawn from conserved
regions located within the N-terminal portion of the alignment, focusing on
those sections that characterise the 5-HT transporter but distinguish it
from others - motifs 1-4 all reside within the putative cytoplasmic
N-terminus. A single iteration on SPTR37_9f was required to reach
convergence, no further sequences being identified beyond the starting set.
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
NTSE_CAVPO    NTSE_HUMAN    NTSE_MOUSE    NTSE_RAT      
Sequence Titles
NTSE_CAVPO  SODIUM-DEPENDENT SEROTONIN TRANSPORTER (5HT TRANSPORTER) (5HTT) - CAVIA PORCELLUS (GUINEA PIG). 
NTSE_HUMAN SODIUM-DEPENDENT SEROTONIN TRANSPORTER (5HT TRANSPORTER) (5HTT) - HOMO SAPIENS (HUMAN).
NTSE_MOUSE SODIUM-DEPENDENT SEROTONIN TRANSPORTER (5HT TRANSPORTER) (5HTT) - MUS MUSCULUS (MOUSE).
NTSE_RAT SODIUM-DEPENDENT SEROTONIN TRANSPORTER (5HT TRANSPORTER) (5HTT) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  1  300  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
ENGVLQKGVP NTSE_RAT 23 23 -
ENGVLQKVVP NTSE_HUMAN 23 23 -
ENGVLQKGVP NTSE_MOUSE 23 23 -
ENSILQKSGP NTSE_CAVPO 23 23 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TTADRAEPSQI NTSE_RAT 33 0 -
TPGDKVESGQI NTSE_HUMAN 33 0 -
TPADKAEPGQI NTSE_MOUSE 33 0 -
TSAGGVESGQI NTSE_CAVPO 33 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
SNGYSAVPSTS NTSE_RAT 44 0 -
SNGYSAVPSPG NTSE_HUMAN 44 0 -
SNGYSAVPSTS NTSE_MOUSE 44 0 -
FNGYSSVPSTG NTSE_CAVPO 44 0 -

Motif 4 width=10
Element Seqn Id St Int Rpt
AGDEASHSIP NTSE_RAT 55 0 -
AGDDTRHSIP NTSE_HUMAN 55 0 -
AGDEAPHSTP NTSE_MOUSE 55 0 -
MGDDAEHSVP NTSE_CAVPO 55 0 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
ENGVLQKGVP NTSE_RAT 23 23 -
ENGVLQKVVP NTSE_HUMAN 23 23 -
ENGVLQKGVP NTSE_MOUSE 23 23 -
ENSILQKSGP NTSE_CAVPO 23 23 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TTADRAEPSQI NTSE_RAT 33 0 -
TPGDKVESGQI NTSE_HUMAN 33 0 -
TPADKAEPGQI NTSE_MOUSE 33 0 -
TSAGGVESGQI NTSE_CAVPO 33 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
SNGYSAVPSTS NTSE_RAT 44 0 -
SNGYSAVPSPG NTSE_HUMAN 44 0 -
SNGYSAVPSTS NTSE_MOUSE 44 0 -
FNGYSSVPSTG NTSE_CAVPO 44 0 -

Motif 4 width=10
Element Seqn Id St Int Rpt
AGDEASHSIP NTSE_RAT 55 0 -
AGDDTRHSIP NTSE_HUMAN 55 0 -
AGDEAPHSTP NTSE_MOUSE 55 0 -
MGDDAEHSVP NTSE_CAVPO 55 0 -