WORKLIST ENTRIES (1):
MUSCRINICM4R View alignment View Structure Muscarinic M4 receptor signature
Type of fingerprint: COMPOUND with 5 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR00243 MUSCARINICR; PR00538 MUSCRINICM1R; PR00539 MUSCRINICM2R
PRINTS; PR00540 MUSCRINICM3R; PR00542 MUSCRINICM5R
INTERPRO; IPR001432
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 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 FINGERPRINT INDEX
5| 5 5 5 5 5
4| 0 0 0 0 0
3| 0 0 0 0 0
2| 0 0 0 0 0
--+--------------------------
| 1 2 3 4 5
True positives..
ACM4_RAT ACM4_MOUSE ACM4_HUMAN ACM4_CHICK
ACM4_XENLA
PROTEIN TITLES
ACM4_RAT MUSCARINIC ACETYLCHOLINE RECEPTOR M4 - RATTUS NORVEGICUS (RA
ACM4_MOUSE MUSCARINIC ACETYLCHOLINE RECEPTOR M4 - MUS MUSCULUS (MOUSE).
ACM4_HUMAN MUSCARINIC ACETYLCHOLINE RECEPTOR M4 - HOMO SAPIENS (HUMAN).
ACM4_CHICK MUSCARINIC ACETYLCHOLINE RECEPTOR M4 - GALLUS GALLUS (CHICKE
ACM4_XENLA MUSCARINIC ACETYLCHOLINE RECEPTOR M4 - XENOPUS LAEVIS (AFRIC
SCAN HISTORY
OWL28_0 2 100 NSINGLE
SPTR37_9f 2 6 NSINGLE
INITIAL MOTIF SETS
MUSCRINICM4R1 Length of motif = 11 Motif number = 1
Muscarinic M4 receptor motif I - 1
PCODE ST INT
VHKHRPEGPKE ACM4_HUMAN 226 226
VHKHRPEGPKE ACM4_MOUSE 225 225
VHKHRPEGPKE ACM4_RAT 225 225
VRRHKPESRKE ACM4_CHICK 236 236
MUSCRINICM4R2 Length of motif = 16 Motif number = 2
Muscarinic M4 receptor motif II - 1
PCODE ST INT
KKAKTLAFLKSPLMKQ ACM4_HUMAN 237 0
KKAKTLAFLKSPLMKP ACM4_MOUSE 236 0
KKAKTLAFLKSPLMKP ACM4_RAT 236 0
RKGKSLSFFKAPPVKQ ACM4_CHICK 247 0
MUSCRINICM4R3 Length of motif = 21 Motif number = 3
Muscarinic M4 receptor motif III - 1
PCODE ST INT
KDTSNESSSGSATQNTKERPA ACM4_HUMAN 290 37
KDTSNESSSGSATQNTKERPP ACM4_MOUSE 289 37
KDTSNESSSGSATQNTKERPP ACM4_RAT 289 37
KETSNESSTVSMTQTTKDKPT ACM4_CHICK 300 37
MUSCRINICM4R4 Length of motif = 19 Motif number = 4
Muscarinic M4 receptor motif IV - 1
PCODE ST INT
NPASRWSKIQIVTKQTGNE ACM4_HUMAN 334 23
NPASKWSKIQIVTKQTGSE ACM4_MOUSE 334 24
NPASKWSKIQIVTKQTGNE ACM4_RAT 333 23
NPTSKWSKIKIVTKQTGTE ACM4_CHICK 338 17
MUSCRINICM4R5 Length of motif = 11 Motif number = 5
Muscarinic M4 receptor motif V - 1
PCODE ST INT
ANVARKFASIA ACM4_HUMAN 371 18
ANVARKFASIA ACM4_MOUSE 371 18
ANVARKFASIA ACM4_RAT 370 18
ANVARKFASIA ACM4_CHICK 382 25
FINAL MOTIF SETS
MUSCRINICM4R1 Length of motif = 11 Motif number = 1
Muscarinic M4 receptor motif I - 2
PCODE ST INT
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
MUSCRINICM4R2 Length of motif = 16 Motif number = 2
Muscarinic M4 receptor motif II - 2
PCODE ST INT
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
MUSCRINICM4R3 Length of motif = 21 Motif number = 3
Muscarinic M4 receptor motif III - 2
PCODE ST INT
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
MUSCRINICM4R4 Length of motif = 19 Motif number = 4
Muscarinic M4 receptor motif IV - 2
PCODE ST INT
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
MUSCRINICM4R5 Length of motif = 11 Motif number = 5
Muscarinic M4 receptor motif V - 2
PCODE ST INT
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
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