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PR01418

Identifier
GALANIN1R  [View Relations]  [View Alignment]  
Accession
PR01418
No. of Motifs
6
Creation Date
13-NOV-2000
Title
Galanin 1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00663 GALANINR
GCRDB; GCR_2450; GCR_2589; GCR_1438; GCR_1861; GCR_1928; GCR_2004

GCRDB; GCR_2455
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ATTWOOD, T.K. AND FINDLAY, J.B.C. 
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
 
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
 
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
 
5. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
 
6. WATSON, S. AND ARKINSTALL, S.
Galanin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.124-125.
 
7. WANG, S., HASHEMI, T., FRIED, S., CLEMMONS, A.L. AND HAWES, B.E.
Differential intracellular signaling of the GalR1 and GalR2 galanin
receptor subtypes.
BIOCHEMISTRY 37 6711-6717 (1998).
 
8. BRANCHEK, T.A, SMITH, K.E., GERALD, C. AND WALKER, M.W.
Galanin receptor subtypes.
TRENDS PHARMACOL.SCI. 21(3) 109-117 (2000).

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine,
paracrine and endocrine processes). They show considerable diversity at the
sequence level, on the basis of which they can be separated into distinct
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,
but between which there is no statistically significant similarity in
sequence [1]. The currently known clan members include the rhodopsin-like
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family. 
 
The rhodopsin-like GPCRs themselves represent a widespread protein family
that includes hormone, neurotransmitter and light receptors, all of 
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary
widely in structure and character, the amino acid sequences of the 
receptors are very similar and are believed to adopt a common structural 
framework comprising 7 transmembrane (TM) helices [3-5]. 
 
Galanin is a neurotransmitter in the peripheral and central nervous systems
with a wide spectrum of activity [6]. In the periphery, galanin inhibits
glucose-induced insulin release and may be the sympathetic mediator of this
effect during stress. In the CNS, it inhibits firing of locus coeruleus
cells, is synergistic with opiates in inducing analgesia at the level of the
spinal cord, and stimulates feeding behaviour and release of growth hormone
[6]. Its ability to inhibit acetylcholine release in the hippocampus has led
to the suggestion that galanin antagonists may be of use in the treatment of
Alzheimer's disease. 
 
Galanin receptors are expressed abundantly in a wide range of CNS and
peripheral tissues, mirroring the distribution of galanin. Three receptor
subtypes have been identified, differing from one another in terms of their
expression patterns, affinity for various peptide analogues and G protein-
coupling specificity [7]. All are capable of activating K+ channels by
coupling to G proteins of the Gi/Go class [8].	
 
The galanin 1 receptor subtype is expressed at significant levels in regions
of the brain and spinal cord including the hypothalamus, amygdala,
hippocampus, thalamus and brainstem. It has also been detected throughout
the length of the human gastro-intestinal tract [8]. Activation of the
receptor by galanin leads to decreased cAMP levels, opening of inwardly
rectifying K+ channels and stimulation of MAP kinase activity, indicating
coupling to a Gi-protein. The receptor does not appear to couple to Go-, Gq-
or Gs-proteins [7].
 
GALANIN1R is a 6-element fingerprint that provides a signature for the
galanin 1 receptor. The fingerprint was derived from an initial alignment of
3 sequences: the motifs were drawn from conserved sections within N-, 
C-terminal or loop regions, focusing on those areas of the alignment that
characterise the galanin 1 receptors but distinguish them from the rest of 
the galanin receptor family - motifs 1 and 2 span the N-terminus; motifs 3
and 4 encompass the second external loop; motif 5 spans the third 
cytoplasmic loop; and motif 6 resides within the C-terminus. A single
iteration on SPTR39_14f was required to reach convergence, no further
sequences being identified beyond the starting set. A single partial match 
was found, Q62828, a rat galanin receptor N-terminal fragment that
matches only motifs 1 and 2.
Summary Information
   3 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6333333
5000000
4000000
3000000
2110000
123456
True Positives
GALR_HUMAN    GALR_MOUSE    GALR_RAT      
True Positive Partials
Codes involving 2 elements
Q62828
Sequence Titles
GALR_HUMAN  GALANIN RECEPTOR TYPE 1 (GAL1-R) (GALR1) - Homo sapiens (Human). 
GALR_MOUSE GALANIN RECEPTOR TYPE 1 (GAL1-R) (GALR1) - Mus musculus (Mouse).
GALR_RAT GALANIN RECEPTOR TYPE 1 (GAL1-R) (GALR1) - Rattus norvegicus (Rat).

Q62828 GALANIN RECEPTOR - Rattus norvegicus (Rat).
Scan History
SPTR39_14f 1  180  NSINGLE    
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
MELAMVNLSEGNGSDPEPPAPE GALR_MOUSE 1 1 -
MELAPVNLSEGNGSDPEPPAEP GALR_RAT 1 1 -
MELAVGNLSEGNASCPEPPAPE GALR_HUMAN 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
RPLFGIGVENFITL GALR_MOUSE 24 1 -
RPLFGIGVENFITL GALR_RAT 23 0 -
GPLFGIGVENFVTL GALR_HUMAN 24 1 -

Motif 3 width=14
Element Seqn Id St Int Rpt
AMASPVAYHQRLFH GALR_MOUSE 165 127 -
AMASPVAYYQRLFH GALR_RAT 164 127 -
AMASPVAYHQGLFH GALR_HUMAN 165 127 -

Motif 4 width=18
Element Seqn Id St Int Rpt
DSNQTFCWEQWPNKLHKK GALR_MOUSE 180 1 -
DSNQTFCWEHWPNQLHKK GALR_RAT 179 1 -
ASNQTFCWEQWPDPRHKK GALR_HUMAN 181 2 -

Motif 5 width=17
Element Seqn Id St Int Rpt
NHLHKKLKNMSKKSEAS GALR_MOUSE 224 26 -
NHLHKKLKNMSKKSEAS GALR_RAT 223 26 -
NHLHKKLKNMSKKSEAS GALR_HUMAN 225 26 -

Motif 6 width=13
Element Seqn Id St Int Rpt
RMDTPPSTNCTHV GALR_MOUSE 336 95 -
RIDTPPSTNCTHV GALR_RAT 334 94 -
RIDTPPSTNCTHV GALR_HUMAN 337 95 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
MELAMVNLSEGNGSDPEPPAPE GALR_MOUSE 1 1 -
MELAPVNLSEGNGSDPEPPAEP GALR_RAT 1 1 -
MELAVGNLSEGNASCPEPPAPE GALR_HUMAN 1 1 -

Motif 2 width=14
Element Seqn Id St Int Rpt
RPLFGIGVENFITL GALR_MOUSE 24 1 -
RPLFGIGVENFITL GALR_RAT 23 0 -
GPLFGIGVENFVTL GALR_HUMAN 24 1 -

Motif 3 width=14
Element Seqn Id St Int Rpt
AMASPVAYHQRLFH GALR_MOUSE 165 127 -
AMASPVAYYQRLFH GALR_RAT 164 127 -
AMASPVAYHQGLFH GALR_HUMAN 165 127 -

Motif 4 width=18
Element Seqn Id St Int Rpt
DSNQTFCWEQWPNKLHKK GALR_MOUSE 180 1 -
DSNQTFCWEHWPNQLHKK GALR_RAT 179 1 -
ASNQTFCWEQWPDPRHKK GALR_HUMAN 181 2 -

Motif 5 width=17
Element Seqn Id St Int Rpt
NHLHKKLKNMSKKSEAS GALR_MOUSE 224 26 -
NHLHKKLKNMSKKSEAS GALR_RAT 223 26 -
NHLHKKLKNMSKKSEAS GALR_HUMAN 225 26 -

Motif 6 width=13
Element Seqn Id St Int Rpt
RMDTPPSTNCTHV GALR_MOUSE 336 95 -
RIDTPPSTNCTHV GALR_RAT 334 94 -
RIDTPPSTNCTHV GALR_HUMAN 337 95 -