WORKLIST ENTRIES (1):

ADRENRGCA2AR View alignment View Structure    Alpha-2A adrenergic 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; PR01103 ADRENERGICR; PR00559 ADRENRGCA2BR; PR00560 ADRENRGCA2CR
   INTERPRO; IPR001946

 Creation date 15-AUG-1996; UPDATE 06-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. WATSON, S. AND ARKINSTALL, S.
   Adrenaline and noradrenaline.
   IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.32-54.

   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]. 
  
   In the periphery, the adrenergic system plays an important role in
   regulating the cardiovascular system [6]. Increased sympathetic discharge
   to the heart increases the rate and force of contraction mediated through 
   beta-1 receptors. Circulating adrenaline also acts on cardiac tissue, and, 
   in addition acts both on alpha-1 adrenoceptors in arterial smooth muscle, 
   stimulating vasoconstriction, and on beta-2 adrenoceptors in vascular beds 
   of skeletal muscle, stimulating vasodilation [6]. In the CNS, noradrenaline 
   is thought to be involved in the regulation of mood, and various psycho-
   active drugs alter noradrenergic function. Numerous drugs exert their 
   actions via adrenoceptors: e.g., beta-2 selective agonists such as 
   salbutamol are used in the acute treatment of asthma, while alpha agonists 
   prolong the action of local anaesthetics, and act as nasal decongestants [6].
  
   Adrenoceptors can be divided into three main classes based on sequence
   similarity, receptor pharmacology and signalling mechanisms. Further 
   subdivisions exist within each class [6]. A large number of agonists and 
   antagonists distinguish between the different classes of adrenoceptor; by
   contrast, relatively small differences in agonist and antagonist affinities
   are demonstrated, especially within the alpha-1 and alpha-2 adrenoceptor
   subtypes [6]. 
  
   A wide distribution of alpha-2A receptor mRNA has been demonstrated by
   Northern analysis, high levels occurring in rat CNS (e.g., hippocampus,
   cerebral cortex, brainstem, pituitary gland and cerebellum), and in
   peripheral tissues (e.g., kidney, aorta, skeletal muscle, spleen and lung)
   [6]. The receptor inhibits adenylyl cyclase and L-type calcium channels, 
   and activates potassium channels through pertussis-toxin-insensitive
   G proteins belonging to the Gi/G0 class [6]. 
   
   ADRENRGCA2AR is a 7-element fingerprint that provides a signature for the
   alpha-2A adrenergic receptors. The fingerprint was derived from an initial
   alignment of 8 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 alpha-2A adrenergic receptors but 
   distinguish them from the rest of the rhodopsin-like superfamily - motif 
   1 lies at the N-terminus; motif 2 spans the second external loop; motifs
   3-6 span the third cytoplasmic loop; and motif 7 lies at the C-terminus.
   A single iteration on OWL28.1 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  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..
 A2AA_MOUSE     A2AA_HUMAN     A2AA_RAT       A2AA_PIG       
 A2AA_CAVPO     


  PROTEIN TITLES
   A2AA_MOUSE       ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-
   A2AA_HUMAN       ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-
   A2AA_RAT         ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-
   A2AA_PIG         ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-
   A2AA_CAVPO       ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-

SCAN HISTORY OWL28_1 1 50 NSINGLE SPTR37_9f 2 6 NSINGLE INITIAL MOTIF SETS ADRENRGCA2AR1 Length of motif = 23 Motif number = 1 A2A adrenergic receptor motif I - 1 PCODE ST INT PDAGNASWNGTEAPGGGARATPY A2AA_HUMAN 6 6 PDAGNSSWNGTEAPGGGTRATPY A2AA_MOUSE 6 6 PDAGNSSWNGTEAPGGGTRATPY A2AA_RAT 6 6 PDAGNASWNGTEAPGGGARATPY HUMADRA 6 6 PDAGNASWNGTEAPGGGARATPY HUMADRA2R 6 6 PDAGNSSWNGTEAPGGGTRATPY RATRG20 6 6 PEAGNASWNGTEAPGGGARATPY A2AA_PIG 6 6 PDSGNASWNGTEGPGGGTRATPY CPU25722 6 6 ADRENRGCA2AR2 Length of motif = 24 Motif number = 2 A2A adrenergic receptor motif II - 1 PCODE ST INT SIEKKGGGGGPQPAEPRCEINDQK A2AA_HUMAN 171 142 SIEKKGAGGGQQPAEPSCKINDQK A2AA_MOUSE 171 142 SIEKKGAGGGQQPAEPSCKINDQK A2AA_RAT 171 142 SIEKKGGGGGPQPAEPRCEINDQK HUMADRA 171 142 SIEKKGGGGGPQPAEPRCEINDQK HUMADRA2R 171 142 SIEKKGAGGGQQPAEPSCKINDQK RATRG20 171 142 SIEKKAGGGGQQPAEPRCEINDQK A2AA_PIG 171 142 ISFEKAGGGGQQPAEPRCEINDQK CPU25722 170 141 ADRENRGCA2AR3 Length of motif = 20 Motif number = 3 A2A adrenergic receptor motif III - 1 PCODE ST INT PSRRGPDAVAAPPGGTERRP A2AA_HUMAN 231 36 PSRRGPDACSAPPGGADRRP A2AA_MOUSE 231 36 PSRRGPDACSAPPGGADRRP A2AA_RAT 231 36 PSRRGPDAVAAPPGGTERRP HUMADRA 231 36 PSRRGPDAVAAPPGGTERRP HUMADRA2R 231 36 PSRRGPDACSAPPGGADRRP RATRG20 231 36 PSRRGPDAAAALPGGAERRP A2AA_PIG 231 36 PSRRGPDAHAAAPPGGAERR CPU25722 230 36 ADRENRGCA2AR4 Length of motif = 20 Motif number = 4 A2A adrenergic receptor motif IV - 1 PCODE ST INT ERSAGPGGAEAEPLPTQLNG A2AA_HUMAN 256 5 ERGAGPTGAEAEPLPTQLNG A2AA_MOUSE 256 5 ERGAGTAGAEAEPLPTQLNG A2AA_RAT 256 5 ERSAGPGGAEAEPLPTQLNG HUMADRA 256 5 ERSAGPGGAEAEPLPTQLNG HUMADRA2R 256 5 ERGAGTAGAEAEPLPTQLNG RATRG20 256 5 ERGVGRVGAEAEPLPVQLNG A2AA_PIG 256 5 ERGVGPGGAEAEPLPTQVNG CPU25722 256 6 ADRENRGCA2AR5 Length of motif = 19 Motif number = 5 A2A adrenergic receptor motif V - 1 PCODE ST INT EPAPAGPRDTDALDLEESS A2AA_HUMAN 279 3 EPAPAGPRDGDALDLEESS A2AA_MOUSE 279 3 EPAPTRPRDGDALDLEESS A2AA_RAT 279 3 EPAPAGPRDTDALDLEESS HUMADRA 279 3 EPAPAGPRDTDALDLEESS HUMADRA2R 279 3 EPAPTRPRDGDALDLEESS RATRG20 279 3 EPAPAGPRDADGLDLEESS A2AA_PIG 279 3 EPAPAGPRDAEALDLEESS CPU25722 279 3 ADRENRGCA2AR6 Length of motif = 18 Motif number = 6 A2A adrenergic receptor motif VI - 1 PCODE ST INT RPERGPRGKGKARASQVK A2AA_HUMAN 310 12 RPDRGPRAKGKTRASQVK A2AA_MOUSE 310 12 KPERGPRAKGKTKASQVK A2AA_RAT 310 12 RPERGPRGKGKARASQVK HUMADRA 310 12 RPERGPRGKGKARASQVK HUMADRA2R 310 12 KPERGPRAKGKTKASQVK RATRG20 310 12 RSERGPRAKSKARASQVK A2AA_PIG 310 12 RPERGLRAKSKARASQVK CPU25722 310 12 ADRENRGCA2AR7 Length of motif = 12 Motif number = 7 A2A adrenergic receptor motif VII - 1 PCODE ST INT FKKILCRGDRKR A2AA_HUMAN 437 109 FKKILCRGDRKR A2AA_MOUSE 437 109 FKKILCRGDRKR A2AA_RAT 437 109 FKKILCRGDRKR HUMADRA 437 109 FKKILCRGDRKR HUMADRA2R 437 109 FKKILCRGDRKR RATRG20 437 109 FKKILCRGDRKR A2AA_PIG 437 109 FKKILCRGDRKR CPU25722 437 109 FINAL MOTIF SETS ADRENRGCA2AR1 Length of motif = 23 Motif number = 1 A2A adrenergic receptor motif I - 2 PCODE ST INT PDAGNSSWNGTEAPGGGTRATPY A2AA_MOUSE 6 6 PDAGNASWNGTEAPGGGARATPY A2AA_HUMAN 6 6 PDAGNSSWNGTEAPGGGTRATPY A2AA_RAT 6 6 PEAGNASWNGTEAPGGGARATPY A2AA_PIG 6 6 PDSGNASWNGTEGPGGGTRATPY A2AA_CAVPO 6 6 ADRENRGCA2AR2 Length of motif = 24 Motif number = 2 A2A adrenergic receptor motif II - 2 PCODE ST INT SIEKKGAGGGQQPAEPSCKINDQK A2AA_MOUSE 171 142 SIEKKGGGGGPQPAEPRCEINDQK A2AA_HUMAN 171 142 SIEKKGAGGGQQPAEPSCKINDQK A2AA_RAT 171 142 SIEKKAGGGGQQPAEPRCEINDQK A2AA_PIG 171 142 ISFEKAGGGGQQPAEPRCEINDQK A2AA_CAVPO 170 141 ADRENRGCA2AR3 Length of motif = 20 Motif number = 3 A2A adrenergic receptor motif III - 2 PCODE ST INT PSRRGPDACSAPPGGADRRP A2AA_MOUSE 231 36 PSRRGPDAVAAPPGGTERRP A2AA_HUMAN 231 36 PSRRGPDACSAPPGGADRRP A2AA_RAT 231 36 PSRRGPDAAAALPGGAERRP A2AA_PIG 231 36 PSRRGPDAHAAAPPGGAERR A2AA_CAVPO 230 36 ADRENRGCA2AR4 Length of motif = 20 Motif number = 4 A2A adrenergic receptor motif IV - 2 PCODE ST INT ERGAGPTGAEAEPLPTQLNG A2AA_MOUSE 256 5 ERSAGPGGAEAEPLPTQLNG A2AA_HUMAN 256 5 ERGAGTAGAEAEPLPTQLNG A2AA_RAT 256 5 ERGVGRVGAEAEPLPVQLNG A2AA_PIG 256 5 ERGVGPGGAEAEPLPTQVNG A2AA_CAVPO 256 6 ADRENRGCA2AR5 Length of motif = 19 Motif number = 5 A2A adrenergic receptor motif V - 2 PCODE ST INT EPAPAGPRDGDALDLEESS A2AA_MOUSE 279 3 EPAPAGPRDTDALDLEESS A2AA_HUMAN 279 3 EPAPTRPRDGDALDLEESS A2AA_RAT 279 3 EPAPAGPRDADGLDLEESS A2AA_PIG 279 3 EPAPAGPRDAEALDLEESS A2AA_CAVPO 279 3 ADRENRGCA2AR6 Length of motif = 18 Motif number = 6 A2A adrenergic receptor motif VI - 2 PCODE ST INT RPDRGPRAKGKTRASQVK A2AA_MOUSE 310 12 RPERGPRGKGKARASQVK A2AA_HUMAN 310 12 KPERGPRAKGKTKASQVK A2AA_RAT 310 12 RSERGPRAKSKARASQVK A2AA_PIG 310 12 RPERGLRAKSKARASQVK A2AA_CAVPO 310 12 ADRENRGCA2AR7 Length of motif = 12 Motif number = 7 A2A adrenergic receptor motif VII - 2 PCODE ST INT FKKILCRGDRKR A2AA_MOUSE 437 109 FKKILCRGDRKR A2AA_HUMAN 437 109 FKKILCRGDRKR A2AA_RAT 437 109 FKKILCRGDRKR A2AA_PIG 437 109 FKKILCRGDRKR A2AA_CAVPO 437 109

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