WORKLIST ENTRIES (1):
MUSCRINICM2R View alignment View Structure Muscarinic M2 receptor signature
Type of fingerprint: COMPOUND with 7 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR00243 MUSCARINICR; PR00538 MUSCRINICM1R; PR00540 MUSCRINICM3R
PRINTS; PR00541 MUSCRINICM4R; PR00542 MUSCRINICM5R
INTERPRO; IPR001065
Creation date 01-JUN-1996; UPDATE 07-JUN-1999
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.
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 [1,2]. 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 FINGERPRINT INDEX
7| 4 4 4 4 4 4 4
6| 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0
--+------------------------------------
| 1 2 3 4 5 6 7
True positives..
ACM2_HUMAN ACM2_PIG ACM2_RAT ACM2_CHICK
PROTEIN TITLES
ACM2_HUMAN MUSCARINIC ACETYLCHOLINE RECEPTOR M2 - HOMO SAPIENS (HUMAN).
ACM2_PIG MUSCARINIC ACETYLCHOLINE RECEPTOR M2 (CARDIAC) - SUS SCROFA
ACM2_RAT MUSCARINIC ACETYLCHOLINE RECEPTOR M2 - RATTUS NORVEGICUS (RA
ACM2_CHICK MUSCARINIC ACETYLCHOLINE RECEPTOR M2 - GALLUS GALLUS (CHICKE
SCAN HISTORY
OWL28_0 2 25 NSINGLE
SPTR37_9f 2 5 NSINGLE
INITIAL MOTIF SETS
MUSCRINICM2R1 Length of motif = 17 Motif number = 1
Muscarinic M2 receptor motif I - 1
PCODE ST INT
SSNNGLAITSPYKTFEV ACM2_RAT 7 7
SSNNSLALTSPYKTFEV ACM2_HUMAN 7 7
SSNSGLALTSPYKTFEV ACM2_PIG 7 7
SSENVIALESPYKTIEV ACM2_CHICK 10 10
MUSCRINICM2R2 Length of motif = 19 Motif number = 2
Muscarinic M2 receptor motif II - 1
PCODE ST INT
QDPVSPSLVQGRIVKPNNN ACM2_RAT 228 204
QDPVSPSLVQGRIVKPNNN ACM2_HUMAN 228 204
QEPVSPSLVQGRIVKPNNN ACM2_PIG 228 204
QDPVSPSLVQGKIVKPNNN ACM2_CHICK 231 204
MUSCRINICM2R3 Length of motif = 17 Motif number = 3
Muscarinic M2 receptor motif III - 1
PCODE ST INT
ETCVQGEEKESSNDSTS ACM2_RAT 272 25
ENCVQGEEKESSNDSTS ACM2_HUMAN 272 25
ENCVQGEEKESSNDSTS ACM2_PIG 272 25
ENCVQGEEKDSSNDSTS ACM2_CHICK 275 25
MUSCRINICM2R4 Length of motif = 19 Motif number = 4
Muscarinic M2 receptor motif IV - 1
PCODE ST INT
AVASNMRDDEITQDENTVS ACM2_RAT 291 2
AVASNMRDDEITQDENTVS ACM2_HUMAN 291 2
AVASNMRDDEITQDENTVS ACM2_PIG 291 2
VVPSNTKEDEAAKDASQIS ACM2_CHICK 294 2
MUSCRINICM2R5 Length of motif = 20 Motif number = 5
Muscarinic M2 receptor motif V - 1
PCODE ST INT
HSRDDNSKQTCIKIVTKAQK ACM2_RAT 314 4
HSKDENSKQTCIRIGTKTPK ACM2_HUMAN 314 4
HSKDENSKQTCIKIVTKTQK ACM2_PIG 314 4
HLKVENSKLTCIRIVTKSQK ACM2_CHICK 317 4
MUSCRINICM2R6 Length of motif = 15 Motif number = 6
Muscarinic M2 receptor motif VI - 1
PCODE ST INT
DVYTPTSTTVELVGS ACM2_RAT 335 1
DSCTPTNTTVEVVGS ACM2_HUMAN 335 1
DSCTPANTTVELVGS ACM2_PIG 335 1
DCCAPTNTTVEIVGT ACM2_CHICK 338 1
MUSCRINICM2R7 Length of motif = 19 Motif number = 7
Muscarinic M2 receptor motif VII - 1
PCODE ST INT
GDEKQNVVARKIVKMPKQP ACM2_RAT 354 4
GDEKQNIVARKIVKMTKQP ACM2_HUMAN 354 4
GDEKQNIVARKIVKMTKQP ACM2_PIG 354 4
GDEKQNSVARKIVKMTKQP ACM2_CHICK 354 1
FINAL MOTIF SETS
MUSCRINICM2R1 Length of motif = 17 Motif number = 1
Muscarinic M2 receptor motif I - 2
PCODE ST INT
SSNNSLALTSPYKTFEV ACM2_HUMAN 7 7
SSNSGLALTSPYKTFEV ACM2_PIG 7 7
SSNNGLAITSPYKTFEV ACM2_RAT 7 7
SSENVIALESPYKTIEV ACM2_CHICK 10 10
MUSCRINICM2R2 Length of motif = 19 Motif number = 2
Muscarinic M2 receptor motif II - 2
PCODE ST INT
QDPVSPSLVQGRIVKPNNN ACM2_HUMAN 228 204
QEPVSPSLVQGRIVKPNNN ACM2_PIG 228 204
QDPVSPSLVQGRIVKPNNN ACM2_RAT 228 204
QDPVSPSLVQGKIVKPNNN ACM2_CHICK 231 204
MUSCRINICM2R3 Length of motif = 17 Motif number = 3
Muscarinic M2 receptor motif III - 2
PCODE ST INT
ENCVQGEEKESSNDSTS ACM2_HUMAN 272 25
ENCVQGEEKESSNDSTS ACM2_PIG 272 25
ETCVQGEEKESSNDSTS ACM2_RAT 272 25
ENCVQGEEKDSSNDSTS ACM2_CHICK 275 25
MUSCRINICM2R4 Length of motif = 19 Motif number = 4
Muscarinic M2 receptor motif IV - 2
PCODE ST INT
AVASNMRDDEITQDENTVS ACM2_HUMAN 291 2
AVASNMRDDEITQDENTVS ACM2_PIG 291 2
AVASNMRDDEITQDENTVS ACM2_RAT 291 2
VVPSNTKEDEAAKDASQIS ACM2_CHICK 294 2
MUSCRINICM2R5 Length of motif = 20 Motif number = 5
Muscarinic M2 receptor motif V - 2
PCODE ST INT
HSKDENSKQTCIRIGTKTPK ACM2_HUMAN 314 4
HSKDENSKQTCIKIVTKTQK ACM2_PIG 314 4
HSRDDNSKQTCIKIVTKAQK ACM2_RAT 314 4
HLKVENSKLTCIRIVTKSQK ACM2_CHICK 317 4
MUSCRINICM2R6 Length of motif = 15 Motif number = 6
Muscarinic M2 receptor motif VI - 2
PCODE ST INT
DSCTPTNTTVEVVGS ACM2_HUMAN 335 1
DSCTPANTTVELVGS ACM2_PIG 335 1
DVYTPTSTTVELVGS ACM2_RAT 335 1
DCCAPTNTTVEIVGT ACM2_CHICK 338 1
MUSCRINICM2R7 Length of motif = 19 Motif number = 7
Muscarinic M2 receptor motif VII - 2
PCODE ST INT
GDEKQNIVARKIVKMTKQP ACM2_HUMAN 354 4
GDEKQNIVARKIVKMTKQP ACM2_PIG 354 4
GDEKQNVVARKIVKMPKQP ACM2_RAT 354 4
GDEKQNSVARKIVKMTKQP ACM2_CHICK 354 1
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