SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR00540

Identifier
MUSCRINICM3R  [View Relations]  [View Alignment]  
Accession
PR00540
No. of Motifs
7
Creation Date
01-JUN-1996  (UPDATE 07-JUN-1999)
Title
Muscarinic M3 receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00243 MUSCARINICR
INTERPRO; IPR001183
GCRDB; GCR_0104
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 M3 receptor is found in high levels in neuronal cells of the CNS [7];
its distribution largely overlaps with that of M1 and M4 subtypes. It is
also found in peripheral ganglia, exocrine glands, smooth muscle, vascular
endothelium, and in cell lines. No selective agonist has been described [7].
 
MUSCRINICM3R is a 7-element fingerprint that provides a signature for the
muscarinic M3 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 M3 receptors but distinguish them
from the rest of the muscarinic receptor family - motif 1 lies at the N-
terminus; motifs 2-6 span the third cytoplasmic loop; and motif 7 lies
at the C-terminus. Two iterations on OWL28.0 were required to reach
convergence, at which point a true set comprising 6 sequences was
identified. A single partial match was also found, BOVMRM3SUB, an M3
receptor fragment.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 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
75555555
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
ACM3_BOVIN    ACM3_CHICK    ACM3_HUMAN    ACM3_PIG      
ACM3_RAT
Sequence Titles
ACM3_BOVIN  Muscarinic acetylcholine receptor M3 - Bos taurus (Bovine). 
ACM3_CHICK Muscarinic acetylcholine receptor M3 - Gallus gallus (Chicken).
ACM3_HUMAN Muscarinic acetylcholine receptor M3 - Homo sapiens (Human).
ACM3_PIG Muscarinic acetylcholine receptor M3 - Sus scrofa (Pig).
ACM3_RAT Muscarinic acetylcholine receptor M3 - Rattus norvegicus (Rat).
Scan History
OWL28_0    2  50   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
PLFPNISSSWIHGPSDAGLP ACM3_PIG 11 11 -
PLFPNISSSWIHGPSDTGLP ACM3_BOVIN 11 11 -
PLFPNISSSWIHSPSDAGLP ACM3_HUMAN 11 11 -
PLFPNISSSWVHSPSEAGLP ACM3_RAT 11 11 -

Motif 2 width=22
Element Seqn Id St Int Rpt
TEAEAENFVHPTGSSRSCSSYE ACM3_PIG 273 242 -
TEAEAENFVHPTGSSRSCSSYE ACM3_BOVIN 273 242 -
TEAETENFVHPTGSSRSCSSYE ACM3_HUMAN 273 242 -
TEAEAENFVHPTGSSRSCSSYE ACM3_RAT 272 241 -

Motif 3 width=20
Element Seqn Id St Int Rpt
KRSARRKYGRCHFWFTTKSW ACM3_PIG 301 6 -
KRSARRKYGRCHFWFTTKSW ACM3_BOVIN 301 6 -
KRSNRRKYGRCHFWFTTKSW ACM3_HUMAN 301 6 -
KRSSRRKYGRCHFWFTTKSW ACM3_RAT 300 6 -

Motif 4 width=20
Element Seqn Id St Int Rpt
DIGSETRAIYSIVLKLPGHS ACM3_PIG 356 35 -
DIGSETRAIYSIVLKLPGHS ACM3_BOVIN 356 35 -
DIGSETRAIYSIVLKLPGHS ACM3_HUMAN 356 35 -
DIGSETRAIYSIVLKLPGHS ACM3_RAT 355 35 -

Motif 5 width=19
Element Seqn Id St Int Rpt
FSKLPIQLESAVDTAKASD ACM3_PIG 424 48 -
FSKLPIQLESAVDTAKASD ACM3_BOVIN 424 48 -
FSKLPIQLESAVDTAKTSD ACM3_HUMAN 424 48 -
FTKLPIQLESAVDTGKTSD ACM3_RAT 423 48 -

Motif 6 width=20
Element Seqn Id St Int Rpt
ATLPLSFKEATLAKRFALKT ACM3_PIG 452 9 -
ATLPLSFKEATLAKRFALKT ACM3_BOVIN 452 9 -
ATLPLSFKEATLAKRFALKT ACM3_HUMAN 452 9 -
ATLPLSFKEATLAKRFALKT ACM3_RAT 451 9 -

Motif 7 width=19
Element Seqn Id St Int Rpt
RKQQYQQRQSVIFHKRVPE ACM3_PIG 569 97 -
RKQQYQQRQSVIFHKRVPE ACM3_BOVIN 569 97 -
RKQQYQQRQSVIFHKRAPE ACM3_HUMAN 569 97 -
RKQQYQQRQSVIFHKRVPE ACM3_RAT 568 97 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
PLFPNISSSWIHGPSDAGLP ACM3_PIG 11 11 -
PLFPNISSSWIHGPSDTGLP ACM3_BOVIN 11 11 -
PLFPNISSSWIHSPSDAGLP ACM3_HUMAN 11 11 -
PLFPNISSSWVHSPSEAGLP ACM3_RAT 11 11 -
PLFSNVSSFWKRDSHGPGLL ACM3_CHICK 50 50 -

Motif 2 width=22
Element Seqn Id St Int Rpt
TEAEAENFVHPTGSSRSCSSYE ACM3_PIG 273 242 -
TEAEAENFVHPTGSSRSCSSYE ACM3_BOVIN 273 242 -
TEAETENFVHPTGSSRSCSSYE ACM3_HUMAN 273 242 -
TEAEAENFVHPTGSSRSCSSYE ACM3_RAT 272 241 -
SEAETARFVHQTGSSRSLSSYE ACM3_CHICK 321 251 -

Motif 3 width=20
Element Seqn Id St Int Rpt
KRSARRKYGRCHFWFTTKSW ACM3_PIG 301 6 -
KRSARRKYGRCHFWFTTKSW ACM3_BOVIN 301 6 -
KRSNRRKYGRCHFWFTTKSW ACM3_HUMAN 301 6 -
KRSSRRKYGRCHFWFTTKSW ACM3_RAT 300 6 -
KRSSRRKYRRCHFWLTMKSW ACM3_CHICK 349 6 -

Motif 4 width=20
Element Seqn Id St Int Rpt
DIGSETRAIYSIVLKLPGHS ACM3_PIG 356 35 -
DIGSETRAIYSIVLKLPGHS ACM3_BOVIN 356 35 -
DIGSETRAIYSIVLKLPGHS ACM3_HUMAN 356 35 -
DIGSETRAIYSIVLKLPGHS ACM3_RAT 355 35 -
DITAETRAIYSIVLKLPGHS ACM3_CHICK 404 35 -

Motif 5 width=19
Element Seqn Id St Int Rpt
FSKLPIQLESAVDTAKASD ACM3_PIG 424 48 -
FSKLPIQLESAVDTAKASD ACM3_BOVIN 424 48 -
FSKLPIQLESAVDTAKTSD ACM3_HUMAN 424 48 -
FTKLPIQLESAVDTGKTSD ACM3_RAT 423 48 -
FSKLPIQPGSAETATASDG ACM3_CHICK 475 51 -

Motif 6 width=20
Element Seqn Id St Int Rpt
ATLPLSFKEATLAKRFALKT ACM3_PIG 452 9 -
ATLPLSFKEATLAKRFALKT ACM3_BOVIN 452 9 -
ATLPLSFKEATLAKRFALKT ACM3_HUMAN 452 9 -
ATLPLSFKEATLAKRFALKT ACM3_RAT 451 9 -
AALPLSFKEATLAKKFALKT ACM3_CHICK 502 8 -

Motif 7 width=19
Element Seqn Id St Int Rpt
RKQQYQQRQSVIFHKRVPE ACM3_PIG 569 97 -
RKQQYQQRQSVIFHKRVPE ACM3_BOVIN 569 97 -
RKQQYQQRQSVIFHKRAPE ACM3_HUMAN 569 97 -
RKQQYQQRQSVIFHKRVPE ACM3_RAT 568 97 -
RKQQYQQRQSVIFHKRIPR ACM3_CHICK 618 96 -