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PR01202

Identifier
DOPTRANSPORT  [View Relations]  [View Alignment]  
Accession
PR01202
No. of Motifs
4
Creation Date
21-JUN-1999
Title
Dopamine neurotransmitter transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD023333; PD037826
INTERPRO; IPR002436
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. GIROS, B., EL MESTIKAWY, S., GODINOT, N., ZHENG, K., HAN, H.,
YANG-FENG, T. AND CARON, M.G.
Cloning, pharmacological characterization, and chromosome assignment of the
human dopamine transporter.
MOL.PHARMACOL. 3 383-390 (1992).
 
7. GAINETDINOV, R.R., JONES, S.R. AND CARON, M.G.
Functional hyperdopaminergia in dopamine transporter knock-out mice.
BIOL.PSYCHIATRY 46 303-311 (1999).

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].
 
In the mammalian brain, the dopamine system is thought to be involved in 
the control of locomotion, cognition and endocrine function. The dopamine
transporter is critical for the removal of dopamine from the extracellular
space, following its release, and is the principal site of action for
psycho-stimulant drugs, such as cocaine and amphetamines, which inhibit
the transporter's activity. A single form of dopamine transporter
(containing ~620 amino acids) has been isolated from humans and other
mammals. Studies of its brain distribution show transcripts to be present
in areas previously established to possess dopaminergic systems, such as
the substantia nigra and ventral tegmental area, which regions are known
to contain dopaminergic cell bodies [6]. Targeted gene disruption of the
dopamine transporter has confirmed its importance in maintaining low
extracellular dopamine levels. Mice lacking the transporter show profound
alterations in the homeostasis of the nigrostriatal dopamine system of the
brain. Extracellular levels of dopamine are elevated and removal of
released dopamine is ~300 times slower then in control mice. Additionally,
the rather stereotyped behavioural responses observed in response to
administration of cocaine or amphetamine are greatly attenuated [7].
 
DOPTRANSPORT is a 4-element fingerprint that provides a signature for the
dopamine neurotransmitter transporter. The fingerprint was derived from
an initial alignment of 3 sequences: the motifs were drawn from conserved
regsions spanning virtually the full alignment length, focusing on those
sections that characterise the dopamine transporter but distinguish it from
others - motifs 1-3 reside within the putative cytoplasmic N-terminus; and 
motif 4 lies within the putative extracellular loop between TM domains 11
and 12. 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  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
NTDO_BOVIN    NTDO_HUMAN    NTDO_RAT      
Sequence Titles
NTDO_BOVIN  SODIUM-DEPENDENT DOPAMINE TRANSPORTER (DA TRANSPORTER) (DAT) - BOS TAURUS (BOVINE). 
NTDO_HUMAN SODIUM-DEPENDENT DOPAMINE TRANSPORTER (DA TRANSPORTER) (DAT) - HOMO SAPIENS (HUMAN).
NTDO_RAT SODIUM-DEPENDENT DOPAMINE TRANSPORTER (DA TRANSPORTER) (DAT) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  1  100  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MSKSKCSVGLMSSVVA NTDO_HUMAN 1 1 -
MSKSKCSVGPMSSVVA NTDO_RAT 1 1 -
MSEGRCSVAHMSSVVA NTDO_BOVIN 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
PAKEPNAVGPKEVE NTDO_HUMAN 17 0 -
PAKESNAVGPREVE NTDO_RAT 17 0 -
PAKEANAMGPKAVE NTDO_BOVIN 17 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
LTSSTLTNPRQSPVEAQD NTDO_HUMAN 42 11 -
LTNSTLINPPQTPVEAQE NTDO_RAT 42 11 -
LTNSTLLNPPQSPTEAQD NTDO_BOVIN 42 11 -

Motif 4 width=11
Element Seqn Id St Int Rpt
IVTFRPPHYGA NTDO_HUMAN 540 480 -
IVTFRPPHYGA NTDO_RAT 539 479 -
IATFRPPHYGA NTDO_BOVIN 537 477 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MSKSKCSVGLMSSVVA NTDO_HUMAN 1 1 -
MSKSKCSVGPMSSVVA NTDO_RAT 1 1 -
MSEGRCSVAHMSSVVA NTDO_BOVIN 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
PAKEPNAVGPKEVE NTDO_HUMAN 17 0 -
PAKESNAVGPREVE NTDO_RAT 17 0 -
PAKEANAMGPKAVE NTDO_BOVIN 17 0 -

Motif 3 width=18
Element Seqn Id St Int Rpt
LTSSTLTNPRQSPVEAQD NTDO_HUMAN 42 11 -
LTNSTLINPPQTPVEAQE NTDO_RAT 42 11 -
LTNSTLLNPPQSPTEAQD NTDO_BOVIN 42 11 -

Motif 4 width=11
Element Seqn Id St Int Rpt
IVTFRPPHYGA NTDO_HUMAN 540 480 -
IVTFRPPHYGA NTDO_RAT 539 479 -
IATFRPPHYGA NTDO_BOVIN 537 477 -