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PR00539

Identifier
MUSCRINICM2R  [View Relations]  [View Alignment]  
Accession
PR00539
No. of Motifs
7
Creation Date
01-JUN-1996  (UPDATE 07-JUN-1999)
Title
Muscarinic M2 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00243 MUSCARINICR
INTERPRO; IPR001065
GCRDB; GCR_0102; GCR_0105
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 M2 receptor is found in low levels in the CNS, where it has a limited
distribution [7]. By contrast, M2 receptors are expressed in high density
in the heart, where they induce a decrease in inotropy and bradycardia [7].
They are also found in smooth muscle. No selective agonist has been
described [7].
 
MUSCRINICM2R is a 7-element fingerprint that provides a signature for the
muscarinic M2 receptors. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved sections
within either loop or N-terminal regions, focusing on those areas of the
alignment that characterise the M2 receptors but distinguish them from the
rest of the muscarinic receptor family - motif 1 lies at the N-terminus,
and motifs 2-7 span 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. A single partial match was also found,
ACM2_BOVIN, an M2 receptor fragment.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
74444444
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
ACM2_CHICK    ACM2_HUMAN    ACM2_PIG      ACM2_RAT      
Sequence Titles
ACM2_CHICK  Muscarinic acetylcholine receptor M2 - Gallus gallus (Chicken). 
ACM2_HUMAN Muscarinic acetylcholine receptor M2 - Homo sapiens (Human).
ACM2_PIG Muscarinic acetylcholine receptor M2 - Sus scrofa (Pig).
ACM2_RAT Muscarinic acetylcholine receptor M2 - Rattus norvegicus (Rat).
Scan History
OWL28_0    2  25   NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
SSNNSLALTSPYKTFEV ACM2_HUMAN 7 7 -
SSNSGLALTSPYKTFEV ACM2_PIG 7 7 -
SSNNGLAITSPYKTFEV ACM2_RAT 7 7 -
SSENVIALESPYKTIEV ACM2_CHICK 10 10 -

Motif 2 width=19
Element Seqn Id St Int Rpt
QDPVSPSLVQGRIVKPNNN ACM2_HUMAN 228 204 -
QEPVSPSLVQGRIVKPNNN ACM2_PIG 228 204 -
QDPVSPSLVQGRIVKPNNN ACM2_RAT 228 204 -
QDPVSPSLVQGKIVKPNNN ACM2_CHICK 231 204 -

Motif 3 width=17
Element Seqn Id St Int Rpt
ENCVQGEEKESSNDSTS ACM2_HUMAN 272 25 -
ENCVQGEEKESSNDSTS ACM2_PIG 272 25 -
ETCVQGEEKESSNDSTS ACM2_RAT 272 25 -
ENCVQGEEKDSSNDSTS ACM2_CHICK 275 25 -

Motif 4 width=19
Element Seqn Id St Int Rpt
AVASNMRDDEITQDENTVS ACM2_HUMAN 291 2 -
AVASNMRDDEITQDENTVS ACM2_PIG 291 2 -
AVASNMRDDEITQDENTVS ACM2_RAT 291 2 -
VVPSNTKEDEAAKDASQIS ACM2_CHICK 294 2 -

Motif 5 width=20
Element Seqn Id St Int Rpt
HSKDENSKQTCIRIGTKTPK ACM2_HUMAN 314 4 -
HSKDENSKQTCIKIVTKTQK ACM2_PIG 314 4 -
HSRDDNSKQTCIKIVTKAQK ACM2_RAT 314 4 -
HLKVENSKLTCIRIVTKSQK ACM2_CHICK 317 4 -

Motif 6 width=15
Element Seqn Id St Int Rpt
DSCTPTNTTVEVVGS ACM2_HUMAN 335 1 -
DSCTPANTTVELVGS ACM2_PIG 335 1 -
DVYTPTSTTVELVGS ACM2_RAT 335 1 -
DCCAPTNTTVEIVGT ACM2_CHICK 338 1 -

Motif 7 width=19
Element Seqn Id St Int Rpt
GDEKQNIVARKIVKMTKQP ACM2_HUMAN 354 4 -
GDEKQNIVARKIVKMTKQP ACM2_PIG 354 4 -
GDEKQNVVARKIVKMPKQP ACM2_RAT 354 4 -
GDEKQNSVARKIVKMTKQP ACM2_CHICK 354 1 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
SSNNSLALTSPYKTFEV ACM2_HUMAN 7 7 -
SSNSGLALTSPYKTFEV ACM2_PIG 7 7 -
SSNNGLAITSPYKTFEV ACM2_RAT 7 7 -
SSENVIALESPYKTIEV ACM2_CHICK 10 10 -

Motif 2 width=19
Element Seqn Id St Int Rpt
QDPVSPSLVQGRIVKPNNN ACM2_HUMAN 228 204 -
QEPVSPSLVQGRIVKPNNN ACM2_PIG 228 204 -
QDPVSPSLVQGRIVKPNNN ACM2_RAT 228 204 -
QDPVSPSLVQGKIVKPNNN ACM2_CHICK 231 204 -

Motif 3 width=17
Element Seqn Id St Int Rpt
ENCVQGEEKESSNDSTS ACM2_HUMAN 272 25 -
ENCVQGEEKESSNDSTS ACM2_PIG 272 25 -
ETCVQGEEKESSNDSTS ACM2_RAT 272 25 -
ENCVQGEEKDSSNDSTS ACM2_CHICK 275 25 -

Motif 4 width=19
Element Seqn Id St Int Rpt
AVASNMRDDEITQDENTVS ACM2_HUMAN 291 2 -
AVASNMRDDEITQDENTVS ACM2_PIG 291 2 -
AVASNMRDDEITQDENTVS ACM2_RAT 291 2 -
VVPSNTKEDEAAKDASQIS ACM2_CHICK 294 2 -

Motif 5 width=20
Element Seqn Id St Int Rpt
HSKDENSKQTCIRIGTKTPK ACM2_HUMAN 314 4 -
HSKDENSKQTCIKIVTKTQK ACM2_PIG 314 4 -
HSRDDNSKQTCIKIVTKAQK ACM2_RAT 314 4 -
HLKVENSKLTCIRIVTKSQK ACM2_CHICK 317 4 -

Motif 6 width=15
Element Seqn Id St Int Rpt
DSCTPTNTTVEVVGS ACM2_HUMAN 335 1 -
DSCTPANTTVELVGS ACM2_PIG 335 1 -
DVYTPTSTTVELVGS ACM2_RAT 335 1 -
DCCAPTNTTVEIVGT ACM2_CHICK 338 1 -

Motif 7 width=19
Element Seqn Id St Int Rpt
GDEKQNIVARKIVKMTKQP ACM2_HUMAN 354 4 -
GDEKQNIVARKIVKMTKQP ACM2_PIG 354 4 -
GDEKQNVVARKIVKMPKQP ACM2_RAT 354 4 -
GDEKQNSVARKIVKMTKQP ACM2_CHICK 354 1 -