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PR01201

Identifier
NORTRANSPORT  [View Relations]  [View Alignment]  
Accession
PR01201
No. of Motifs
3
Creation Date
21-JUN-1999
Title
Noradrenaline neurotransmitter transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD017172; PD013669
INTERPRO; IPR002435
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. PACHOLCZYK, T., BLAKELY, R.D. AND AMARA, S.G.
Expression cloning of a cocaine- and antidepressant-sensitive human
noradrenaline transporter.
NATURE 350 350-354 (1991).
 
7. BRUSS, M., KUNZ, J., LINGEN, B. AND BONISCH, H.
Chromosomal mapping of the human gene for the tricyclic antidepressant-
sensitive noradrenaline transporter.
HUM.GENET. 91 278-280 (1993).
 
8. BURTON, L.D., KIPPENBERGER, A.G., LINGEN, B., BONISCH, H. AND 
CHRISTIE, D.L.
A variant of the bovine noradrenaline transporter reveals the importance of
the C-terminal region for correct targeting to the membrane and functional
expression.
BIOCHEM.J. 330 909-914 (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 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 human noradrenaline transporter is the primary target for widely-
used tricyclic antidepressant drugs, such as desipramine. Cloning studies
have revealed a single noradrenaline transporter isoform. The cDNA sequence
predicts a protein of ~617 amino acids, with 12-13 highly hydrophobic
regions, as would be expected for a member of the Na+ and Cl- -coupled
neurotransmitter superfamily [6]. Related noradrenaline transporter species
have been identified in both Drosophila and bullfrog. In mammalian species,
mRNA for the transporter is localised to the brainstem and the adrenal
glands. Chromosome mapping has placed the encoding gene to chromosome 
16q12.2 in humans [7]. Recently, a bovine noradrenaline transporter variant
has been identified that shows altered targeting to the plasma membrane.
This has implicated the cytoplasmic facing C-terminus in the intracellular
trafficking of this protein [8].
 
NORTRANSPORT is a 3-element fingerprint that provides a signature for
noradrenaline neurotransmitter transporters. 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 noradrenaline transporter but
distinguish it from others - motifs 1-2 reside within the large putative
extracellular loop located between putative TM domains 3 and 4; and motif 3
lies at the start of the extracellular loop between TM domains 11 and 12.
Two iterations on SPTR37_9f were required to reach convergence, at which
point a true set comprising 5 sequences was identified.
Summary Information
5 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3555
2000
123
True Positives
NTNO_BOVIN    NTNO_HUMAN    NTNO_MOUSE    O42482        
Q63380
Sequence Titles
NTNO_BOVIN  SODIUM-DEPENDENT NORADRENALINE TRANSPORTER (NOREPINEPHRINE TRANSPORTER) (NET) - BOS TAURUS (BOVINE). 
NTNO_HUMAN SODIUM-DEPENDENT NORADRENALINE TRANSPORTER (NOREPINEPHRINE TRANSPORTER) (NET) - HOMO SAPIENS (HUMAN).
NTNO_MOUSE SODIUM-DEPENDENT NORADRENALINE TRANSPORTER (NOREPINEPHRINE TRANSPORTER) (NET) - MUS MUSCULUS (MOUSE).
O42482 L-EPINEPHRINE TRANSPORTER - RANA CATESBEIANA (BULL FROG).
Q63380 NOREPINEPHRINE TRANSPORTER (NACL-DEPENDENT NOREPINEPHRINE TRANSPORTER) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_9f  2  125  NSINGLE    
Initial Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
TDPKLLNAS NTNO_MOUSE 186 186 -
TDPKLLNSS NTNO_BOVIN 184 184 -
TDPKLLNGS NTNO_HUMAN 186 186 -

Motif 2 width=10
Element Seqn Id St Int Rpt
GDHTKYSKYK NTNO_MOUSE 197 2 -
GNHTKYSKYK NTNO_BOVIN 195 2 -
GNHTKYSKYK NTNO_HUMAN 197 2 -

Motif 3 width=10
Element Seqn Id St Int Rpt
INFKPLTYDD NTNO_MOUSE 538 331 -
INFKPLTYDD NTNO_BOVIN 536 331 -
INFKPLTYDD NTNO_HUMAN 538 331 -
Final Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
TDPKLLNAS NTNO_MOUSE 186 186 -
TDPKLLNAS Q63380 186 186 -
TDPKLLNSS NTNO_BOVIN 184 184 -
TDPKLLNGS NTNO_HUMAN 186 186 -
TDPTLLNAS O42482 199 199 -

Motif 2 width=10
Element Seqn Id St Int Rpt
GDHTKYSKYK NTNO_MOUSE 197 2 -
GDHTKYSKYK Q63380 197 2 -
GNHTKYSKYK NTNO_BOVIN 195 2 -
GNHTKYSKYK NTNO_HUMAN 197 2 -
GNGTKYSKYK O42482 210 2 -

Motif 3 width=10
Element Seqn Id St Int Rpt
INFKPLTYDD NTNO_MOUSE 538 331 -
INFKPLTYDD Q63380 538 331 -
INFKPLTYDD NTNO_BOVIN 536 331 -
INFKPLTYDD NTNO_HUMAN 538 331 -
VTHSPLSYDD O42482 551 331 -