WORKLIST ENTRIES (1):

MUSCRINICM1R View alignment View Structure    Muscarinic M1 receptor signature
 Type of fingerprint: COMPOUND with 6  elements
Links:
   PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
   PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
   PRINTS; PR00251 BACTRLOPSIN
   PRINTS; PR00243 MUSCARINICR; PR00539 MUSCRINICM2R; PR00540 MUSCRINICM3R
   PRINTS; PR00541 MUSCRINICM4R; PR00542 MUSCRINICM5R
   INTERPRO; IPR002228

 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 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 FINGERPRINT INDEX
  
    6|   5    5    5    5    5    5  
    5|   0    0    0    0    0    0  
    4|   0    0    0    0    0    0  
    3|   0    0    0    0    0    0  
    2|   0    0    0    0    0    0  
   --+-------------------------------
     |   1    2    3    4    5    6  

True positives..
 ACM1_HUMAN     ACM1_MOUSE     ACM1_RAT       ACM1_MACMU     
 ACM1_PIG       


  PROTEIN TITLES
   ACM1_HUMAN       MUSCARINIC ACETYLCHOLINE RECEPTOR M1 - HOMO SAPIENS (HUMAN).
   ACM1_MOUSE       MUSCARINIC ACETYLCHOLINE RECEPTOR M1 - MUS MUSCULUS (MOUSE).
   ACM1_RAT         MUSCARINIC ACETYLCHOLINE RECEPTOR M1 - RATTUS NORVEGICUS (RA
   ACM1_MACMU       MUSCARINIC ACETYLCHOLINE RECEPTOR M1 - MACACA MULATTA (RHESU
   ACM1_PIG         MUSCARINIC ACETYLCHOLINE RECEPTOR M1 (BRAIN) - SUS SCROFA (P

SCAN HISTORY OWL28_0 1 20 NSINGLE SPTR37_9f 2 6 NSINGLE INITIAL MOTIF SETS MUSCRINICM1R1 Length of motif = 17 Motif number = 1 Muscarinic M1 receptor motif I - 1 PCODE ST INT PPAVSPNITVLAPGKGP ACM1_HUMAN 6 6 PPAVSPNITVLAPGKGP ACM1_MOUSE 6 6 PPAVSPNITVLAPGKGP ACM1_PIG 6 6 PPAVSPNITVLAPGKGP ACM1_RAT 6 6 MUSCRINICM1R2 Length of motif = 20 Motif number = 2 Muscarinic M1 receptor motif II - 1 PCODE ST INT RCCRCCRAPRLLQAYSWKEE ACM1_HUMAN 258 235 RCCRCCRAPRLLQAYSWKEE ACM1_MOUSE 258 235 RCCRCCRAPRLLQAYSWKEE ACM1_PIG 258 235 RCCRCCRAPRLLQAYSWKEE ACM1_RAT 258 235 MUSCRINICM1R3 Length of motif = 19 Motif number = 3 Muscarinic M1 receptor motif III - 1 PCODE ST INT DEGSMESLTSSEGEEPGSE ACM1_HUMAN 281 3 DEGSMESLTSSEGEEPGSE ACM1_MOUSE 281 3 DEGSMESLTSSEGEEPGSE ACM1_PIG 281 3 DEGSMESLTSSEGEEPGSE ACM1_RAT 281 3 MUSCRINICM1R4 Length of motif = 18 Motif number = 4 Muscarininc M1 receptor motif IV - 1 PCODE ST INT KMPMVDPEAQAPTKQPPR ACM1_HUMAN 303 3 KMPMVDPEAQAPTKQPPK ACM1_MOUSE 303 3 KMPMVDPEAQAPAKQPPR ACM1_PIG 303 3 KMPMVDSEAQAPTKQPPK ACM1_RAT 303 3 MUSCRINICM1R5 Length of motif = 17 Motif number = 5 Muscarinic M1 receptor motif V - 1 PCODE ST INT GRDRAGKGQKPRGKEQL ACM1_HUMAN 333 12 GRDRGGKGQKPRGKEQL ACM1_MOUSE 333 12 GRERAGKGQKPRGKEQL ACM1_PIG 333 12 GRDRGGKGQKPRGKEQL ACM1_RAT 333 12 MUSCRINICM1R6 Length of motif = 18 Motif number = 6 Muscarinic M1 receptor motif VI - 1 PCODE ST INT RWRKIPKRPGSVHRTPSR ACM1_HUMAN 441 91 RWRKIPKRPGSVHRTPSR ACM1_MOUSE 441 91 RWRKIPKRPGSVHRTPSR ACM1_PIG 441 91 RWRKIPKRPGSVHRTPSR ACM1_RAT 441 91 FINAL MOTIF SETS MUSCRINICM1R1 Length of motif = 17 Motif number = 1 Muscarinic M1 receptor motif I - 2 PCODE ST INT 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 MUSCRINICM1R2 Length of motif = 20 Motif number = 2 Muscarinic M1 receptor motif II - 2 PCODE ST INT 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 MUSCRINICM1R3 Length of motif = 19 Motif number = 3 Muscarinic M1 receptor motif III - 2 PCODE ST INT 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 MUSCRINICM1R4 Length of motif = 18 Motif number = 4 Muscarinic M1 receptor motif IV - 2 PCODE ST INT 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 MUSCRINICM1R5 Length of motif = 17 Motif number = 5 Muscarinic M1 receptor motif V - 2 PCODE ST INT 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 MUSCRINICM1R6 Length of motif = 18 Motif number = 6 Muscarinic M1 receptor motif VI - 2 PCODE ST INT 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

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