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PR00542

Identifier
MUSCRINICM5R  [View Relations]  [View Alignment]  
Accession
PR00542
No. of Motifs
8
Creation Date
01-JUN-1996  (UPDATE 07-JUN-1999)
Title
Muscarinic M5 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00243 MUSCARINICR
INTERPRO; IPR000502
GCRDB; GCR_0235
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. KERLAVAGE, A.R., FRASER, C.M., CHUNG, F-Z. AND VENTER, J.C.
Molecular structure and evolution of adrenergic and cholinergic receptors.
PROTEINS 1 287-301 (1986).
 
7. WATSON, S. AND ARKINSTALL, S.
Acetylcholine.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.7-18.

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that 
encompasses a wide range of functions (including various autocrine, para-
crine 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]. 
 
The muscarinic acetylcholine receptors, present in the central nervous
system, spinal cord motoneurons and autonomic preganglia, modulate a
variety of physiological functions, including airway, eye and intestinal
smooth muscle contractions; heart rate; and glandular secretions. The
receptors mediate adenylate cyclase attenuation, calcium and potassium
channel activation, and phosphatidyl inositol turnover [6]. This diversity
may result from the occurrence of multiple receptor subtypes (of which 5
are currently known, designated M1 to M5), which have been classified
based on observed differences in ligand binding to receptors in membranes
from several tissues.
 
M5 mRNA has been found in the CNS, but a translation product has not been
identified [7]. It is thought that this receptor subtype may be important
during development, or may serve a unique function relative to the other
receptor subtypes [7]. No selective agonist has been described [7].
 
MUSCRINICM5R is an 8-element fingerprint that provides a signature for the
muscarinic M5 receptors. The fingerprint was derived from an initial
alignment of 2 sequences: the motifs were drawn from conserved sections
within either loop or N- and C-terminal regions, focusing on those areas
of the alignment that characterise the M5 receptors but distinguish them
from the rest of the muscarinic receptor family - motif 1 lies at the N-
terminus; motifs 2-7 span the third cytoplasmic loop; and motif 8 lies
at the C-terminus. A single iteration on OWL28.0 was required to reach
convergence, no further sequences being identified beyond the starting set.
 
An update on SPTR37_9f identified a true set of 3 sequences.
Summary Information
3 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
833333333
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
ACM5_HUMAN    ACM5_MACMU    ACM5_RAT      
Sequence Titles
ACM5_HUMAN  Muscarinic acetylcholine receptor M5 - Homo sapiens (Human). 
ACM5_MACMU Muscarinic acetylcholine receptor M5 - Macaca mulatta (Rhesus macaque).
ACM5_RAT Muscarinic acetylcholine receptor M5 - Rattus norvegicus (Rat).
Scan History
OWL28_0    1  50   NSINGLE    
SPTR37_9f 2 4 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
TVNGTPVNHQPLERHRL ACM5_HUMAN 11 11 -
TVNGTPVNHQALERHGL ACM5_RAT 10 10 -

Motif 2 width=19
Element Seqn Id St Int Rpt
CPRPTLAQRERNQASWSSS ACM5_HUMAN 256 228 -
CPRPSLAQRERNQASWSSS ACM5_RAT 255 228 -

Motif 3 width=19
Element Seqn Id St Int Rpt
WAKAEQLTTCSSYPSSEDE ACM5_HUMAN 294 19 -
WEKAEQVTTCSSYPSSEDE ACM5_RAT 293 19 -

Motif 4 width=21
Element Seqn Id St Int Rpt
KPATDPVLQVVYKSQGKESPG ACM5_HUMAN 314 1 -
KPTTDPVFQMVYKSEAKESPG ACM5_RAT 313 1 -

Motif 5 width=19
Element Seqn Id St Int Rpt
SDYDTPNYLLSPAAAHRPK ACM5_HUMAN 354 19 -
SDYDTPKYFLSPAAAHRLK ACM5_RAT 353 19 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KCVAYKFRLVVKADGNQET ACM5_HUMAN 375 2 -
KCVAYKFRLVVKADGTQET ACM5_RAT 374 2 -

Motif 7 width=18
Element Seqn Id St Int Rpt
GCHKVKIMPCPFPVAKEP ACM5_HUMAN 396 2 -
GCRKVKIMPCSFPVSKDP ACM5_RAT 395 2 -

Motif 8 width=15
Element Seqn Id St Int Rpt
KKVEEKLYWQGNSKL ACM5_HUMAN 517 103 -
KKVEEKLYWQGNSKL ACM5_RAT 516 103 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
TVNGTPVNHQPLERHRL ACM5_HUMAN 11 11 -
TVNGTPVYHQPLERHRL ACM5_MACMU 11 11 -
TVNGTPVNHQALERHGL ACM5_RAT 10 10 -

Motif 2 width=19
Element Seqn Id St Int Rpt
CPRPTLAQRERNQASWSSS ACM5_HUMAN 256 228 -
CPRPTLAQRERNQTSWSSS ACM5_MACMU 256 228 -
CPRPSLAQRERNQASWSSS ACM5_RAT 255 228 -

Motif 3 width=19
Element Seqn Id St Int Rpt
WAKAEQLTTCSSYPSSEDE ACM5_HUMAN 294 19 -
QAKAEQLTTCSSYPSSEDE ACM5_MACMU 294 19 -
WEKAEQVTTCSSYPSSEDE ACM5_RAT 293 19 -

Motif 4 width=21
Element Seqn Id St Int Rpt
KPATDPVLQVVYKSQGKESPG ACM5_HUMAN 314 1 -
KPATDPVLQVVYKSRGKESPG ACM5_MACMU 314 1 -
KPTTDPVFQMVYKSEAKESPG ACM5_RAT 313 1 -

Motif 5 width=19
Element Seqn Id St Int Rpt
SDYDTPNYLLSPAAAHRPK ACM5_HUMAN 354 19 -
HDSDTPNYFLSPAAAHRPK ACM5_MACMU 354 19 -
SDYDTPKYFLSPAAAHRLK ACM5_RAT 353 19 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KCVAYKFRLVVKADGNQET ACM5_HUMAN 375 2 -
KCVAYKFRLVVKADGTQEN ACM5_MACMU 375 2 -
KCVAYKFRLVVKADGTQET ACM5_RAT 374 2 -

Motif 7 width=18
Element Seqn Id St Int Rpt
GCHKVKIMPCPFPVAKEP ACM5_HUMAN 396 2 -
GCHKVKIMPCSFPVAKEP ACM5_MACMU 396 2 -
GCRKVKIMPCSFPVSKDP ACM5_RAT 395 2 -

Motif 8 width=15
Element Seqn Id St Int Rpt
KKVEEKLYWQGNSKL ACM5_HUMAN 517 103 -
KKVEEKLYWQGNSKL ACM5_MACMU 517 103 -
KKVEEKLYWQGNSKL ACM5_RAT 516 103 -