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PR00538

Identifier
MUSCRINICM1R  [View Relations]  [View Alignment]  
Accession
PR00538
No. of Motifs
6
Creation Date
01-JUN-1996  (UPDATE 07-JUN-1999)
Title
Muscarinic M1 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00243 MUSCARINICR
INTERPRO; IPR002228
GCRDB; GCR_0056; GCR_0073; GCR_0079
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 M1 receptor is found in high levels in neuronal cells of the CNS; it
is particularly abundant in the cerebral cortex and hippocampus [7]. Its
distribution largely overlaps with that of M3 and M4 subtypes. In the
periphery, M1 receptors are found in autonomic ganglia and certain
secretory glands, and they are also found in cell lines. No truly
selective agonist has been described [7].
 
MUSCRINICM1R is a 6-element fingerprint that provides a signature for the
muscarinic M1 receptors. The fingerprint was derived from an initial
alignment of 4 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 M1 receptors but distinguish them
from the rest of the muscarinic receptor family - motif 1 lies at the N-
terminus; motifs 2-5 span the third cytoplasmic loop; and motif 6 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 5 sequences.
Summary Information
5 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
6555555
5000000
4000000
3000000
2000000
123456
True Positives
ACM1_HUMAN    ACM1_MACMU    ACM1_MOUSE    ACM1_PIG      
ACM1_RAT
Sequence Titles
ACM1_HUMAN  Muscarinic acetylcholine receptor M1 - Homo sapiens (Human). 
ACM1_MACMU Muscarinic acetylcholine receptor M1 - Macaca mulatta (Rhesus macaque).
ACM1_MOUSE Muscarinic acetylcholine receptor M1 - Mus musculus (Mouse).
ACM1_PIG Muscarinic acetylcholine receptor M1 - Sus scrofa (Pig).
ACM1_RAT Muscarinic acetylcholine receptor M1 - Rattus norvegicus (Rat).
Scan History
OWL28_0    1  20   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
PPAVSPNITVLAPGKGP ACM1_HUMAN 6 6 -
PPAVSPNITVLAPGKGP ACM1_MOUSE 6 6 -
PPAVSPNITVLAPGKGP ACM1_RAT 6 6 -
PPAVSPNITVLAPGKGP ACM1_PIG 6 6 -

Motif 2 width=20
Element Seqn Id St Int Rpt
RCCRCCRAPRLLQAYSWKEE ACM1_HUMAN 258 235 -
RCCRCCRAPRLLQAYSWKEE ACM1_MOUSE 258 235 -
RCCRCCRAPRLLQAYSWKEE ACM1_RAT 258 235 -
RCCRCCRAPRLLQAYSWKEE ACM1_PIG 258 235 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DEGSMESLTSSEGEEPGSE ACM1_HUMAN 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_MOUSE 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_RAT 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_PIG 281 3 -

Motif 4 width=18
Element Seqn Id St Int Rpt
KMPMVDPEAQAPTKQPPR ACM1_HUMAN 303 3 -
KMPMVDPEAQAPTKQPPK ACM1_MOUSE 303 3 -
KMPMVDSEAQAPTKQPPK ACM1_RAT 303 3 -
KMPMVDPEAQAPAKQPPR ACM1_PIG 303 3 -

Motif 5 width=17
Element Seqn Id St Int Rpt
GRDRAGKGQKPRGKEQL ACM1_HUMAN 333 12 -
GRDRGGKGQKPRGKEQL ACM1_MOUSE 333 12 -
GRDRGGKGQKPRGKEQL ACM1_RAT 333 12 -
GRERAGKGQKPRGKEQL ACM1_PIG 333 12 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RWRKIPKRPGSVHRTPSR ACM1_HUMAN 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_MOUSE 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_RAT 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_PIG 441 91 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
PPAVSPNITVLAPGKGP ACM1_HUMAN 6 6 -
PPAVSPNITVLAPGKGP ACM1_MOUSE 6 6 -
PPAVSPNITVLAPGKGP ACM1_RAT 6 6 -
PPAVSPNITVLAPGKGP ACM1_MACMU 6 6 -
PPAVSPNITVLAPGKGP ACM1_PIG 6 6 -

Motif 2 width=20
Element Seqn Id St Int Rpt
RCCRCCRAPRLLQAYSWKEE ACM1_HUMAN 258 235 -
RCCRCCRAPRLLQAYSWKEE ACM1_MOUSE 258 235 -
RCCRCCRAPRLLQAYSWKEE ACM1_RAT 258 235 -
RCCRCCRPPRLLQAYSWKED ACM1_MACMU 258 235 -
RCCRCCRAPRLLQAYSWKEE ACM1_PIG 258 235 -

Motif 3 width=19
Element Seqn Id St Int Rpt
DEGSMESLTSSEGEEPGSE ACM1_HUMAN 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_MOUSE 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_RAT 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_MACMU 281 3 -
DEGSMESLTSSEGEEPGSE ACM1_PIG 281 3 -

Motif 4 width=18
Element Seqn Id St Int Rpt
KMPMVDPEAQAPTKQPPR ACM1_HUMAN 303 3 -
KMPMVDPEAQAPTKQPPK ACM1_MOUSE 303 3 -
KMPMVDSEAQAPTKQPPK ACM1_RAT 303 3 -
KMPMVDPEAQAPTKQPPR ACM1_MACMU 303 3 -
KMPMVDPEAQAPAKQPPR ACM1_PIG 303 3 -

Motif 5 width=17
Element Seqn Id St Int Rpt
GRDRAGKGQKPRGKEQL ACM1_HUMAN 333 12 -
GRDRGGKGQKPRGKEQL ACM1_MOUSE 333 12 -
GRDRGGKGQKPRGKEQL ACM1_RAT 333 12 -
GRDRAGKGQKPRGKEQL ACM1_MACMU 333 12 -
GRERAGKGQKPRGKEQL ACM1_PIG 333 12 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RWRKIPKRPGSVHRTPSR ACM1_HUMAN 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_MOUSE 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_RAT 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_MACMU 441 91 -
RWRKIPKRPGSVHRTPSR ACM1_PIG 441 91 -