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PR00663

Identifier
GALANINR  [View Relations]  [View Alignment]  
Accession
PR00663
No. of Motifs
5
Creation Date
22-FEB-1997  (UPDATE 13-NOV-2000)
Title
Galanin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01418 GALANIN1R; PR01419 GALANIN2R; PR01420 GALANIN3R

INTERPRO; IPR000405
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].
 
GALANINR is a 5-element fingerprint that provides a signature for the
galanin receptors. The fingerprint was derived from an initial alignment of 
9 sequences: the motifs were drawn from conserved sections within either 
loop or TM regions, focusing on those areas of the alignment that 
characterise the galanin receptors but distinguish them from the rest of the
rhodopsin-like superfamily - motifs 1 and 2 span the first external loop;
motif 3 spans part of the second cytoplasmic loop, leading into TM domain 4;
motif 4 spans the C-terminal portion of the second external loop and part of
TM domain 5; and motif 5 spans the C-terminal portion of the third external
loop. Two iterations on SPTR39_14f were required to reach convergence, at
which point a true set comprising 10 sequences was identified. Two partial
matches were also found: Q62828 is a rat galanin receptor N-terminal
fragment that fails to match the 3 C-terminal motifs; and Q9U721 is a 
Drosophila allatostatin receptor, closely related to the galanin receptors, which 
which matches motifs 1 and 3.
Summary Information
  10 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
2 codes involving 2 elements
Composite Feature Index
51010101010
400000
300000
221100
12345
True Positives
GALR_HUMAN    GALR_MOUSE    GALR_RAT      GALS_RAT      
O43603 O60755 O88626 O88853
O88854 Q9QWZ2
True Positive Partials
Codes involving 2 elements
Q62828 Q9U721
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).
GALS_RAT GALANIN RECEPTOR TYPE 2 (GAL2-R) (GALR2) - Rattus norvegicus (Rat).
O43603 GALANIN RECEPTOR GALR2 - HOMO SAPIENS (HUMAN).
O60755 GALANIN 2 RECEPTOR HOMOLOG - HOMO SAPIENS (HUMAN).
O88626 GALANIN RECEPTOR TYPE 3 - RATTUS NORVEGICUS (RAT).
O88853 GALANIN RECEPTOR TYPE 3 - MUS MUSCULUS (MOUSE).
O88854 GALANIN RECEPTOR TYPE 2 - MUS MUSCULUS (MOUSE).
Q9QWZ2 GALANIN RECEPTOR GALR3 - Rattus norvegicus (Rat).

Q62828 GALANIN RECEPTOR - Rattus norvegicus (Rat).
Q9U721 ALLATOSTATIN RECEPTOR - Drosophila melanogaster (Fruit fly).
Scan History
SPTR39_14f 2  40   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
FILCCVPFQATIYTL O60755 71 71 -
FILCCVPFQAAIYTL O88853 71 71 -
FILCCVPFQAAIYTL O88626 71 71 -
FILCCVPFQATIYTL O88854 73 73 -
FILCCVPFQATIYTL GALS_RAT 74 74 -
FILCCVPFQATIYTL O43603 74 74 -
YLLFCIPFQATVYAL GALR_MOUSE 84 84 -
YLLFCIPFQATVYAL GALR_RAT 83 83 -
YLLFCIPFQATVYAL GALR_HUMAN 84 84 -

Motif 2 width=19
Element Seqn Id St Int Rpt
WLFGALVCKAVHLLIYLTM O60755 88 2 -
WLFGAFVCKTVHLLIYLTM O88853 88 2 -
WLFGAFVCKTVHLLIYLTM O88626 88 2 -
WVFGSLLCKAVHFLIFLTM O88854 90 2 -
WVFGSLLCKAVHFLIFLTM GALS_RAT 91 2 -
WVFGSLLCKAVHFLIFLTM O43603 91 2 -
WVLGAFICKFIHYFFTVSM GALR_MOUSE 101 2 -
WVLGAFICKFIHYFFTVSM GALR_RAT 100 2 -
WVLGAFICKFIHYFFTVSM GALR_HUMAN 101 2 -

Motif 3 width=17
Element Seqn Id St Int Rpt
SRALRTPRNARAAVGLV O60755 130 23 -
SRALRTPRNARAAVGLV O88853 130 23 -
SRALRTPRNARAAVGLV O88626 130 23 -
SRELRTPRNALAAIGLI O88854 132 23 -
SRELRTPRNALAAIGLI GALS_RAT 133 23 -
SRELRTPRNALAAIGLI O43603 133 23 -
SSSLRVSRNALLGVGFI GALR_MOUSE 143 23 -
SSSLRVSRNALLGVGFI GALR_RAT 142 23 -
SSSLRVSRNALLGVGCI GALR_HUMAN 143 23 -

Motif 4 width=16
Element Seqn Id St Int Rpt
RRRALDVATFAAGYLL O60755 180 33 -
RRRALDVATFAAGYLL O88853 180 33 -
RRRALDVATFAAGYLL O88626 180 33 -
RRRAMDLCTFVFSYLL O88854 182 33 -
RRRAMDLCTFVFSYLL GALS_RAT 183 33 -
RRRAMDICTFVFSYLL O43603 183 33 -
HKKAYVVCTFVFGYLL GALR_MOUSE 195 35 -
HKKAYVVCTFVFGYLL GALR_RAT 194 35 -
HKKAYVVCTFVFGYLL GALR_HUMAN 196 36 -

Motif 5 width=21
Element Seqn Id St Int Rpt
YGRFAFSPATYACRLASHCLA O60755 260 64 -
YGRFAFSPATYACRLASHCLA O88853 260 64 -
YGRFAFSPATYACRLASHCLA O88626 260 64 -
FGRFPLTRATYALRILSHLVS O88854 260 62 -
FGRFPLTRATYALRILSHLVS GALS_RAT 261 62 -
FGQFPLTRATYALRILSHLVS O43603 261 62 -
FGAFPLTPASFFFRITAHCLA GALR_MOUSE 271 60 -
FGAFPLTPASFFFRITAHCLA GALR_RAT 270 60 -
FGVFPLTPASFLFRITAHCLA GALR_HUMAN 272 60 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
FILCCVPFQATIYTL O60755 71 71 -
FILCCVPFQAAIYTL O88853 71 71 -
FILCCVPFQAAIYTL O88626 71 71 -
FILCCVPFQAAIYTL Q9QWZ2 71 71 -
FILCCVPFQATIYTL O88854 73 73 -
FILCCVPFQATIYTL GALS_RAT 74 74 -
FILCCVPFQATIYTL O43603 74 74 -
YLLFCIPFQATVYAL GALR_MOUSE 84 84 -
YLLFCIPFQATVYAL GALR_RAT 83 83 -
YLLFCIPFQATVYAL GALR_HUMAN 84 84 -

Motif 2 width=19
Element Seqn Id St Int Rpt
WLFGALVCKAVHLLIYLTM O60755 88 2 -
WLFGAFVCKTVHLLIYLTM O88853 88 2 -
WLFGAFVCKTVHLLIYLTM O88626 88 2 -
WLFGAFVCKTVHLLIYLTM Q9QWZ2 88 2 -
WVFGSLLCKAVHFLIFLTM O88854 90 2 -
WVFGSLLCKAVHFLIFLTM GALS_RAT 91 2 -
WVFGSLLCKAVHFLIFLTM O43603 91 2 -
WVLGAFICKFIHYFFTVSM GALR_MOUSE 101 2 -
WVLGAFICKFIHYFFTVSM GALR_RAT 100 2 -
WVLGAFICKFIHYFFTVSM GALR_HUMAN 101 2 -

Motif 3 width=17
Element Seqn Id St Int Rpt
SRALRTPRNARAAVGLV O60755 130 23 -
SRALRTPRNARAAVGLV O88853 130 23 -
SRALRTPRNARAAVGLV O88626 130 23 -
SRALRTPRNARAAVGLV Q9QWZ2 130 23 -
SRELRTPRNALAAIGLI O88854 132 23 -
SRELRTPRNALAAIGLI GALS_RAT 133 23 -
SRELRTPRNALAAIGLI O43603 133 23 -
SSSLRVSRNALLGVGFI GALR_MOUSE 143 23 -
SSSLRVSRNALLGVGFI GALR_RAT 142 23 -
SSSLRVSRNALLGVGCI GALR_HUMAN 143 23 -

Motif 4 width=16
Element Seqn Id St Int Rpt
RRRALDVATFAAGYLL O60755 180 33 -
RRRALDVATFAAGYLL O88853 180 33 -
RRRALDVATFAAGYLL O88626 180 33 -
RRRALDVATFAAGYLL Q9QWZ2 180 33 -
RRRAMDLCTFVFSYLL O88854 182 33 -
RRRAMDLCTFVFSYLL GALS_RAT 183 33 -
RRRAMDICTFVFSYLL O43603 183 33 -
HKKAYVVCTFVFGYLL GALR_MOUSE 195 35 -
HKKAYVVCTFVFGYLL GALR_RAT 194 35 -
HKKAYVVCTFVFGYLL GALR_HUMAN 196 36 -

Motif 5 width=21
Element Seqn Id St Int Rpt
YGRFAFSPATYACRLASHCLA O60755 260 64 -
YGRFAFSPATYACRLASHCLA O88853 260 64 -
YGRFAFSPATYACRLASHCLA O88626 260 64 -
YGRFAFSPATYACRLASHCLA Q9QWZ2 260 64 -
FGRFPLTRATYALRILSHLVS O88854 260 62 -
FGRFPLTRATYALRILSHLVS GALS_RAT 261 62 -
FGQFPLTRATYALRILSHLVS O43603 261 62 -
FGAFPLTPASFFFRITAHCLA GALR_MOUSE 271 60 -
FGAFPLTPASFFFRITAHCLA GALR_RAT 270 60 -
FGVFPLTPASFLFRITAHCLA GALR_HUMAN 272 60 -