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PR01199

Identifier
CRTTRANSPORT  [View Relations]  [View Alignment]  
Accession
PR01199
No. of Motifs
3
Creation Date
22-JUN-1999
Title
Creatine transporter signature
Database References
PRINTS; PR00176 NANEUSMPORT
PRODOM; PD017171
INTERPRO; IPR002984
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. HAPPE, H.K. AND MURRIN, L.C.
In situ hybridization analysis of CHOT1, a creatine transporter, in the rat
central nervous system.
J.COMP.NEUROL. 351 94-103 (1995).
 
7. SCHLOSS, P., MAYSER, W. AND BETZ, H.
The putative rat choline transporter CHOT1 transports creatine and is
highly expressed in neural and muscle-rich tissues.
BIOCHEM.BIOPHYS.RES.COMMUN. 198 637-645 (1994).
 
8. NASH, S.R., GIROS, B., KINGSMORE, S.F., ROCHELLE, J.M., SUTERM S.T.,
GREGOR, P., SELDIN, M.F. AND CARON. M.G.
Cloning, pharmacological characterization, and genomic localization of the
human creatine transporter.
RECEPTORS CHANNELS 2 165-174 (1994).

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]. 
 
A Na+ and Cl- -coupled creatine transporter has been cloned from human and
rodent tissues. Initially it was mistaken for a choline transporter [6,7].
The creatine transporter species homologues are near identical (98% identity
human vs. rat and rabbit) and they are most closely related to the trans-
porters reported for taurine, GABA and betaine. Northern blot analysis of
creatine transporter distribution reveals that the highest levels of mRNA
expression are in: skeletal muscle, kidney and heart, with lower levels in
brain and other tissues. Within the brain, the highest levels were detected
in the cerebellum and hippocampus. This expression pattern correlates well
with those tissues known to possess a high creatine uptake capacity [8].
 
CRTTRANSPORT is a 3-element fingerprint that provides a signature for the
creatine transporter. The fingerprint was derived from an initial alignment
of 3 sequences: the motifs were drawn from conserved regions spanning the
first third of the alignment, focusing on those sections that characterise 
the creatine transporter but distinguish it from others - motif 1 resides
within the putative cytoplasmic N-terminus; and motifs 2-3 encode portions
of the large extracellular loop located between putative 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  3 elements
0 codes involving 2 elements
Composite Feature Index
3444
2000
123
True Positives
NTCH_RAT      NTCR_BOVIN    NTCR_HUMAN    NTCR_RABIT    
Sequence Titles
NTCH_RAT    SODIUM-DEPENDENT CHOLINE TRANSPORTER (CHOT1) - RATTUS NORVEGICUS (RAT). 
NTCR_BOVIN SODIUM- AND CHLORIDE-DEPENDENT CREATINE TRANSPORTER 1 (CT1) - BOS TAURUS (BOVINE).
NTCR_HUMAN SODIUM- AND CHLORIDE-DEPENDENT CREATINE TRANSPORTER 1 (CT1) - HOMO SAPIENS (HUMAN).
NTCR_RABIT SODIUM- AND CHLORIDE-DEPENDENT CREATINE TRANSPORTER 1 (CT1) - ORYCTOLAGUS CUNICULUS (RABBIT).
Scan History
SPTR37_9f  2  200  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MAKKSAENGIYSVS NTCR_HUMAN 1 1 -
MAKKSAENGIYSVS NTCR_RABIT 1 1 -
MANKSTENGIYSVS NTCR_BOVIN 1 1 -

Motif 2 width=12
Element Seqn Id St Int Rpt
CVEIFRHEDCAN NTCR_HUMAN 181 166 -
CVEIFRHEDCAN NTCR_RABIT 181 166 -
CVEIFRHEDCAN NTCR_BOVIN 181 166 -

Motif 3 width=14
Element Seqn Id St Int Rpt
SLANLTCDQLADRR NTCR_HUMAN 194 1 -
SLANLTCDQLAERR NTCR_RABIT 194 1 -
TMANLTCDQLADRR NTCR_BOVIN 194 1 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MAKKSAENGIYSVS NTCH_RAT 1 1 -
MAKKSAENGIYSVS NTCR_HUMAN 1 1 -
MAKKSAENGIYSVS NTCR_RABIT 1 1 -
MANKSTENGIYSVS NTCR_BOVIN 1 1 -

Motif 2 width=12
Element Seqn Id St Int Rpt
CVEIFRHEDCAN NTCH_RAT 181 166 -
CVEIFRHEDCAN NTCR_HUMAN 181 166 -
CVEIFRHEDCAN NTCR_RABIT 181 166 -
CVEIFRHEDCAN NTCR_BOVIN 181 166 -

Motif 3 width=14
Element Seqn Id St Int Rpt
SLANLTCDQLADRR NTCH_RAT 194 1 -
SLANLTCDQLADRR NTCR_HUMAN 194 1 -
SLANLTCDQLAERR NTCR_RABIT 194 1 -
TMANLTCDQLADRR NTCR_BOVIN 194 1 -