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PR00541

Identifier
MUSCRINICM4R  [View Relations]  [View Alignment]  
Accession
PR00541
No. of Motifs
5
Creation Date
01-JUN-1996  (UPDATE 07-JUN-1999)
Title
Muscarinic M4 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00243 MUSCARINICR
INTERPRO; IPR001432
GCRDB; GCR_0120
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.
 
The M4 receptor is found in high levels in neuronal cells of the CNS [7];
its distribution largely overlaps with that of M1 and M3 subtypes. It is
also found in cell lines. No selective agonist has been described [7].
 
MUSCRINICM4R is a 5-element fingerprint that provides a signature for the
muscarinic M4 receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved sections
within the third cytoplasmic loop. Two iterations on OWL28.0 were required
to reach convergence, at which point a true set comprising 5 sequences was
identified. Two partial matches were also found (S74916 and ACM4_BOVIN), 
both of which are M4 receptor fragments.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
555555
400000
300000
200000
12345
True Positives
ACM4_CHICK    ACM4_HUMAN    ACM4_MOUSE    ACM4_RAT      
ACM4_XENLA
Sequence Titles
ACM4_CHICK  Muscarinic acetylcholine receptor M4 - Gallus gallus (Chicken). 
ACM4_HUMAN Muscarinic acetylcholine receptor M4 - Homo sapiens (Human).
ACM4_MOUSE Muscarinic acetylcholine receptor M4 (Mm4 mAChR) - Mus musculus (Mouse).
ACM4_RAT Muscarinic acetylcholine receptor M4 - Rattus norvegicus (Rat).
ACM4_XENLA Muscarinic acetylcholine receptor M4 - Xenopus laevis (African clawed frog).
Scan History
OWL28_0    2  100  NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
VHKHRPEGPKE ACM4_RAT 225 225 -
VHKHRPEGPKE ACM4_MOUSE 225 225 -
VHKHRPEGPKE ACM4_HUMAN 226 226 -
VRRHKPESRKE ACM4_CHICK 236 236 -

Motif 2 width=16
Element Seqn Id St Int Rpt
KKAKTLAFLKSPLMKP ACM4_RAT 236 0 -
KKAKTLAFLKSPLMKP ACM4_MOUSE 236 0 -
KKAKTLAFLKSPLMKQ ACM4_HUMAN 237 0 -
RKGKSLSFFKAPPVKQ ACM4_CHICK 247 0 -

Motif 3 width=21
Element Seqn Id St Int Rpt
KDTSNESSSGSATQNTKERPP ACM4_RAT 289 37 -
KDTSNESSSGSATQNTKERPP ACM4_MOUSE 289 37 -
KDTSNESSSGSATQNTKERPA ACM4_HUMAN 290 37 -
KETSNESSTVSMTQTTKDKPT ACM4_CHICK 300 37 -

Motif 4 width=19
Element Seqn Id St Int Rpt
NPASKWSKIQIVTKQTGNE ACM4_RAT 333 23 -
NPASKWSKIQIVTKQTGSE ACM4_MOUSE 334 24 -
NPASRWSKIQIVTKQTGNE ACM4_HUMAN 334 23 -
NPTSKWSKIKIVTKQTGTE ACM4_CHICK 338 17 -

Motif 5 width=11
Element Seqn Id St Int Rpt
ANVARKFASIA ACM4_RAT 370 18 -
ANVARKFASIA ACM4_MOUSE 371 18 -
ANVARKFASIA ACM4_HUMAN 371 18 -
ANVARKFASIA ACM4_CHICK 382 25 -
Final Motifs
Motif 1  width=11
Element Seqn Id St Int Rpt
VHKHRPEGPKE ACM4_RAT 225 225 -
VHKHRPEGPKE ACM4_MOUSE 225 225 -
VHKHRPEGPKE ACM4_HUMAN 226 226 -
VRRHKPESRKE ACM4_CHICK 236 236 -
VRRHCPETRQE ACM4_XENLA 227 227 -

Motif 2 width=16
Element Seqn Id St Int Rpt
KKAKTLAFLKSPLMKP ACM4_RAT 236 0 -
KKAKTLAFLKSPLMKP ACM4_MOUSE 236 0 -
KKAKTLAFLKSPLMKQ ACM4_HUMAN 237 0 -
RKGKSLSFFKAPPVKQ ACM4_CHICK 247 0 -
EKKKPISSMKSLLIKQ ACM4_XENLA 237 -1 -

Motif 3 width=21
Element Seqn Id St Int Rpt
KDTSNESSSGSATQNTKERPP ACM4_RAT 289 37 -
KDTSNESSSGSATQNTKERPP ACM4_MOUSE 289 37 -
KDTSNESSSGSATQNTKERPA ACM4_HUMAN 290 37 -
KETSNESSTVSMTQTTKDKPT ACM4_CHICK 300 37 -
KETSNESSSASLSHNPPEKQP ACM4_XENLA 290 37 -

Motif 4 width=19
Element Seqn Id St Int Rpt
NPASKWSKIQIVTKQTGNE ACM4_RAT 333 23 -
NPASKWSKIQIVTKQTGSE ACM4_MOUSE 334 24 -
NPASRWSKIQIVTKQTGNE ACM4_HUMAN 334 23 -
NPTSKWSKIKIVTKQTGTE ACM4_CHICK 338 17 -
NTASKWSKIKIVTKQTGNE ACM4_XENLA 334 23 -

Motif 5 width=11
Element Seqn Id St Int Rpt
ANVARKFASIA ACM4_RAT 370 18 -
ANVARKFASIA ACM4_MOUSE 371 18 -
ANVARKFASIA ACM4_HUMAN 371 18 -
ANVARKFASIA ACM4_CHICK 382 25 -
VNVARKFASIA ACM4_XENLA 376 23 -