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PR01420

Identifier
GALANIN3R  [View Relations]  [View Alignment]  
Accession
PR01420
No. of Motifs
5
Creation Date
13-NOV-2000
Title
Galanin 3 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00663 GALANINR
GCRDB; GCR_2508
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. SMITH, K.E., WALKER, M.W., ARTYMYSHYN, R., BARD, J., BOROWSKY, B., 
TAMM J.A., YAO, W.-J., VAYSSE, P.J.-J., BRANCHEK, T.A., GERALD, C. AND 
JONES, K.A.
Galanin GALR3 receptors: cloning and functional expression of rat and
human receptors.
J.BIOL.CHEM. 273(36) 23321-23326 (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 3 receptor subtype is expressed abundantly in the periphery and
at lower levels in the CNS. In the brain, the highest levels have been found
in the hypothalamus and pituitary. Expression has also been detected in 
peripheral tissues, including the pancreas, liver, kidney, stomach, adrenal 
gland, lung and spleen [7]. Activation of the receptor by galanin leads to 
opening of inwardly rectifying K+ channels, indicating a coupling to Gi type
G proteins [8].
 
GALANIN3R is a 5-element fingerprint that provides a signature for the
galanin 3 receptor. The fingerprint was derived from an initial alignment of
3 sequences: the motifs were drawn from conserved sections within N-, 
C-terminal and loop regions, focusing on those areas of the alignment that
characterise the galanin 3 receptors but distinguish them from the rest of
the galanin receptor family - motif 1 resides within the N-terminus; motif 2
lies in the second external loop; motif 3 spans the third cytoplasmic loop;
and motifs 4 and 5 reside at the C-terminus. Two iterations on SPTR39_14f 
were required to reach convergence, at which point a true set comprising 4
sequences was identified.
Summary Information
4 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
544444
400000
300000
200000
12345
True Positives
O60755        O88626        O88853        Q9QWZ2        
Sequence Titles
O60755      GALANIN 2 RECEPTOR HOMOLOG - HOMO SAPIENS (HUMAN). 
O88626 GALANIN RECEPTOR TYPE 3 - RATTUS NORVEGICUS (RAT).
O88853 GALANIN RECEPTOR TYPE 3 - MUS MUSCULUS (MOUSE).
Q9QWZ2 GALANIN RECEPTOR GALR3 - Rattus norvegicus (Rat).
Scan History
SPTR39_14f 2  250  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MADIQNISLDSPGSVG O88626 1 1 -
MADIQNISLDSPGSVG O88853 1 1 -
MADAQNISLDSPGSVG O60755 1 1 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TVRYGALELCV O88626 163 146 -
TVRYGALELCV O88853 163 146 -
TVRYGALELCV O60755 163 146 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AAAEARRRATGRAGRAM O88626 221 47 -
AAAEARRRATGRAGRAM O88853 221 47 -
AAAEARRRATGRAGRAM O60755 221 47 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RLWPCGRRRHRH O88626 304 66 -
RLWPCGHRRHRH O88853 304 66 -
RLWPCGRRRRHR O60755 304 66 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GPAGYPGDARPRGWSM O88626 332 16 -
GPAGYPGDARPRGWSM O88853 333 17 -
GPPGCPGDARPSGRLL O60755 329 13 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
MADIQNISLDSPGSVG O88626 1 1 -
MADIQNISLDSPGSVG Q9QWZ2 1 1 -
MADIQNISLDSPGSVG O88853 1 1 -
MADAQNISLDSPGSVG O60755 1 1 -

Motif 2 width=11
Element Seqn Id St Int Rpt
TVRYGALELCV O88626 163 146 -
TVRYGALELCV Q9QWZ2 163 146 -
TVRYGALELCV O88853 163 146 -
TVRYGALELCV O60755 163 146 -

Motif 3 width=17
Element Seqn Id St Int Rpt
AAAEARRRATGRAGRAM O88626 221 47 -
AAAEARRRATGRAGRAM Q9QWZ2 221 47 -
AAAEARRRATGRAGRAM O88853 221 47 -
AAAEARRRATGRAGRAM O60755 221 47 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RLWPCGRRRHRH O88626 304 66 -
RLWPCGRRRHRH Q9QWZ2 304 66 -
RLWPCGHRRHRH O88853 304 66 -
RLWPCGRRRRHR O60755 304 66 -

Motif 5 width=16
Element Seqn Id St Int Rpt
GPAGYPGDARPRGWSM O88626 332 16 -
GPAGYPGDARPRGWSM Q9QWZ2 332 16 -
GPAGYPGDARPRGWSM O88853 333 17 -
GPPGCPGDARPSGRLL O60755 329 13 -