WORKLIST ENTRIES (1):

MUSCRINICM3R View alignment View Structure    Muscarinic M3 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; PR00539 MUSCRINICM2R
   PRINTS; PR00541 MUSCRINICM4R; PR00542 MUSCRINICM5R
   INTERPRO; IPR001183

 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 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 FINGERPRINT INDEX
  
    7|   5    5    5    5    5    5    5  
    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..
 ACM3_PIG       ACM3_BOVIN     ACM3_HUMAN     ACM3_RAT       
 ACM3_CHICK     


  PROTEIN TITLES
   ACM3_PIG         MUSCARINIC ACETYLCHOLINE RECEPTOR M3 - SUS SCROFA (PIG).
   ACM3_BOVIN       MUSCARINIC ACETYLCHOLINE RECEPTOR M3 - BOS TAURUS (BOVINE).
   ACM3_HUMAN       MUSCARINIC ACETYLCHOLINE RECEPTOR M3 - HOMO SAPIENS (HUMAN).
   ACM3_RAT         MUSCARINIC ACETYLCHOLINE RECEPTOR M3 - RATTUS NORVEGICUS (RA
   ACM3_CHICK       MUSCARINIC ACETYLCHOLINE RECEPTOR M3 - GALLUS GALLUS (CHICKE

SCAN HISTORY OWL28_0 2 50 NSINGLE SPTR37_9f 2 6 NSINGLE INITIAL MOTIF SETS MUSCRINICM3R1 Length of motif = 20 Motif number = 1 Muscarinic M3 receptor motif I - 1 PCODE ST INT PLFPNISSSWIHSPSDAGLP ACM3_HUMAN 11 11 PLFPNISSSWIHGPSDAGLP ACM3_PIG 11 11 PLFPNISSSWVHSPSEAGLP ACM3_RAT 11 11 PLFPNISSSWIHGPSDTGLP ACM3_BOVIN 11 11 MUSCRINICM3R2 Length of motif = 22 Motif number = 2 Muscarinic M3 receptor motif II - 1 PCODE ST INT TEAETENFVHPTGSSRSCSSYE ACM3_HUMAN 273 242 TEAEAENFVHPTGSSRSCSSYE ACM3_PIG 273 242 TEAEAENFVHPTGSSRSCSSYE ACM3_RAT 272 241 TEAEAENFVHPTGSSRSCSSYE ACM3_BOVIN 273 242 MUSCRINICM3R3 Length of motif = 20 Motif number = 3 Muscarinic M3 receptor motif III - 1 PCODE ST INT KRSNRRKYGRCHFWFTTKSW ACM3_HUMAN 301 6 KRSARRKYGRCHFWFTTKSW ACM3_PIG 301 6 KRSSRRKYGRCHFWFTTKSW ACM3_RAT 300 6 KRSARRKYGRCHFWFTTKSW ACM3_BOVIN 301 6 MUSCRINICM3R4 Length of motif = 20 Motif number = 4 Muscarinic M3 receptor motif IV - 1 PCODE ST INT DIGSETRAIYSIVLKLPGHS ACM3_HUMAN 356 35 DIGSETRAIYSIVLKLPGHS ACM3_PIG 356 35 DIGSETRAIYSIVLKLPGHS ACM3_RAT 355 35 DIGSETRAIYSIVLKLPGHS ACM3_BOVIN 356 35 MUSCRINICM3R5 Length of motif = 19 Motif number = 5 Muscarinic M3 receptor motif V - 1 PCODE ST INT FSKLPIQLESAVDTAKTSD ACM3_HUMAN 424 48 FSKLPIQLESAVDTAKASD ACM3_PIG 424 48 FTKLPIQLESAVDTGKTSD ACM3_RAT 423 48 FSKLPIQLESAVDTAKASD ACM3_BOVIN 424 48 MUSCRINICM3R6 Length of motif = 20 Motif number = 6 Muscarinic M3 receptor motif VI - 1 PCODE ST INT ATLPLSFKEATLAKRFALKT ACM3_HUMAN 452 9 ATLPLSFKEATLAKRFALKT ACM3_PIG 452 9 ATLPLSFKEATLAKRFALKT ACM3_RAT 451 9 ATLPLSFKEATLAKRFALKT ACM3_BOVIN 452 9 MUSCRINICM3R7 Length of motif = 19 Motif number = 7 Muscarinic M3 receptor motif VII - 1 PCODE ST INT RKQQYQQRQSVIFHKRAPE ACM3_HUMAN 569 97 RKQQYQQRQSVIFHKRVPE ACM3_PIG 569 97 RKQQYQQRQSVIFHKRVPE ACM3_RAT 568 97 RKQQYQQRQSVIFHKRVPE ACM3_BOVIN 569 97 FINAL MOTIF SETS MUSCRINICM3R1 Length of motif = 20 Motif number = 1 Muscarinic M3 receptor motif I - 2 PCODE ST INT 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 MUSCRINICM3R2 Length of motif = 22 Motif number = 2 Muscarinic M3 receptor motif II - 2 PCODE ST INT 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 MUSCRINICM3R3 Length of motif = 20 Motif number = 3 Muscarinic M3 receptor motif III - 2 PCODE ST INT 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 MUSCRINICM3R4 Length of motif = 20 Motif number = 4 Muscarinic M3 receptor motif IV - 2 PCODE ST INT 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 MUSCRINICM3R5 Length of motif = 19 Motif number = 5 Muscarinic M3 receptor motif V - 2 PCODE ST INT 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 MUSCRINICM3R6 Length of motif = 20 Motif number = 6 Muscarinic M3 receptor motif VI - 2 PCODE ST INT 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 MUSCRINICM3R7 Length of motif = 19 Motif number = 7 Muscarinic M3 receptor motif VII - 2 PCODE ST INT 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

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