WORKLIST ENTRIES (1):

ADRENRGCA1AR View alignment View Structure    Alpha-1A adrenergic 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; PR01103 ADRENERGICR; PR00240 ADRENRGCA1DR; PR00556 ADRENRGCA1BR
   INTERPRO; IPR001004

 Creation date 14-AUG-1996; UPDATE 18-FEB-2000

   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]. 
  
   The alpha-1A receptor has not been detected in rat or bovine tissues by
   Northern analysis [6]. Its expression is thus either very low, or highly
   specialised in tissue distribution [6]. The receptor is coupled to the 
   phosphoinositide pathway through a pertussis-toxin-insensitive G protein, 
   probably of the Gq/G11 class [6]. 
   
   ADRENRGCA1AR is a 6-element fingerprint that provides a signature for the
   alpha-1A 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-1A adrenergic receptors but 
   distinguish them from the rest of the rhodopsin-like superfamily - motif 
   1 lies at the N-terminus; motifs 2 and 3 lie in the third cytoplasmic loop; 
   and motifs 4-6 span the C-terminus. A single iteration on OWL28.1 was 
   required to reach convergence, no further sequences being identified beyond 
   the starting set. A single partial match was also found, an alpha-1C 
   receptor fragment that matches motifs 2 and 3.
  
   An update on SPTR37_9f identified a true set of 8 sequences.

  SUMMARY INFORMATION
      8 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|   8    8    8    8    8    8  
    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..
 A1AA_HUMAN     Q13729         Q13675         O60451         
 A1AA_RABIT     A1AA_RAT       O54913         A1AA_BOVIN     


  PROTEIN TITLES
   A1AA_HUMAN       ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-
   Q13729           ALPHA 1C ADRENERGIC RECEPTOR ISOFORM 3 - HOMO SAPIENS (HUMAN
   Q13675           ALPHA 1C ADRENERGIC RECEPTOR ISOFORM 2 - HOMO SAPIENS (HUMAN
   O60451           ALPHA 1A ADRENERGIC RECEPTOR ISOFORM 4 - HOMO SAPIENS (HUMAN
   A1AA_RABIT       ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-
   A1AA_RAT         ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-
   O54913           ALPHA 1A-ADRENERGIC RECEPTOR - MUS MUSCULUS (MOUSE).
   A1AA_BOVIN       ALPHA-1A ADRENERGIC RECEPTOR (ALPHA 1A-ADRENOCEPTOR) (ALPHA-

SCAN HISTORY OWL28_1 1 50 NSINGLE SPTR37_9f 2 9 NSINGLE INITIAL MOTIF SETS ADRENRGCA1AR1 Length of motif = 23 Motif number = 1 A1A adrenergic receptor motif I - 1 PCODE ST INT FLSGNASDSSNCTQPPAPVNISK A1AC_HUMAN 3 3 FLSGNASDSSNCTQPPAPVNISK JN0765 3 3 FLSGNASDSSNCTQPPAPVNISK JC2333 3 3 FLSGNASDSSNCTQPPAPVNISK HSU02569 3 3 FLSGNASDSSNCTQPPAPVNISK HUMA1CAR2 3 3 FLSGNASDSSNCTHPPPPVNISK A1AC_BOVIN 3 3 LLSENASEGSNCTHPPAPVNISK A1AC_RAT 3 3 LLSENASEGSNCTHPPAPVNISK RNU13368 3 3 ADRENRGCA1AR2 Length of motif = 16 Motif number = 2 A1A adrenergic receptor motif II - 1 PCODE ST INT KSGLKTDKSDSEQVTL A1AC_HUMAN 219 193 KSGLKTDKSDSEQVTL JN0765 219 193 KSGLKTDKSDSEQVTL JC2333 219 193 KSGLKTDKSDSEQVTL HSU02569 219 193 KSGLKTDKSDSEQVTL HUMA1CAR2 219 193 KSGLKTDKSDSEQVTL A1AC_BOVIN 219 193 KSGLKTDKSDSEQVTL A1AC_RAT 219 193 KSGLKTDKSDSEQVTL RNU13368 219 193 ADRENRGCA1AR3 Length of motif = 18 Motif number = 3 A1A adrenergic receptor motif III - 1 PCODE ST INT RKNAPAGGSGMASAKTKT A1AC_HUMAN 238 3 RKNAPAGGSGMASAKTKT JN0765 238 3 RKNAPAGGSGHASAKTKT JC2333 238 3 RKNAPAGGSGMASAKTKT HSU02569 238 3 RKNAPAGGSGMASAKTKT HUMA1CAR2 238 3 RKNAQVGGSGVTSAKNKT A1AC_BOVIN 238 3 RKNVPAEGGGVSSAKNKT A1AC_RAT 238 3 RKNVPAEGGGVSSAKNKT RNU13368 238 3 ADRENRGCA1AR4 Length of motif = 18 Motif number = 4 A1A adrenergic receptor motif IV - 1 PCODE ST INT LGYTLHPPSQAVEGQHKD A1AC_HUMAN 356 100 LGYTLHPPSQAVEGQHKD JN0765 356 100 LGYTLHPPSQAVEGQHKD JC2333 356 100 LGYPLHPPSQAVEGQHKD HSU02569 356 100 LGYTLHPPSQAVEGQHKD HUMA1CAR2 356 100 LGYTLHAPSHVLEGQHKD A1AC_BOVIN 356 100 LGYTLHPPSQALEGQHRD A1AC_RAT 356 100 LGYTLHPPSQALEGQHRD RNU13368 356 100 ADRENRGCA1AR5 Length of motif = 20 Motif number = 5 A1A adrenergic receptor motif V - 1 PCODE ST INT RIPVGSRETFYRISKTDGVC A1AC_HUMAN 376 2 RIPVGSRETFYRISKTDGVC JN0765 376 2 RIPVGSRETFYRISKTDGVC JC2333 376 2 RIPVGSRETFYRISKTDGVC HSU02569 376 2 RIPVGSRETFYRISKTDGVC HUMA1CAR2 376 2 RIPVGSAETFYKISKTDGVC A1AC_BOVIN 376 2 RIPVGSGETFYKISKTDGVC A1AC_RAT 376 2 RIPVGSGETFYKISKTDGVC RNU13368 376 2 ADRENRGCA1AR6 Length of motif = 20 Motif number = 6 A1A adrenergic receptor motif VI - 1 PCODE ST INT FSSMPRGSARITVSKDQSSC A1AC_HUMAN 400 4 FSSMPRGSARITVSKDQSSC JN0765 400 4 FSSMPRGSARITVSKDQSSC JC2333 400 4 FSSMPRGSARITVSKDQSSC HSU02569 400 4 FSSMPRGSARITVSKDQSSC HUMA1CAR2 400 4 FSSLPRGSARMAVARDPSAC A1AC_BOVIN 400 4 FSSMPQGSARITVPKDQSAC A1AC_RAT 400 4 FSSMPQGSARITVPKDQSAC RNU13368 400 4 FINAL MOTIF SETS ADRENRGCA1AR1 Length of motif = 23 Motif number = 1 A1A adrenergic receptor motif I - 2 PCODE ST INT FLSGNASDSSNCTQPPAPVNISK A1AA_HUMAN 3 3 FLSGNASDSSNCTQPPAPVNISK Q13729 3 3 FLSGNASDSSNCTQPPAPVNISK Q13675 3 3 FLSGNASDSSNCTQPPAPVNISK O60451 3 3 FLSGNASDSSNCTHPPAPVNISK A1AA_RABIT 3 3 LLSENASEGSNCTHPPAPVNISK A1AA_RAT 3 3 LLSENASEGSNCTHPPAQVNISK O54913 3 3 FLSGNASDSSNCTHPPPPVNISK A1AA_BOVIN 3 3 ADRENRGCA1AR2 Length of motif = 16 Motif number = 2 A1A adrenergic receptor motif II - 2 PCODE ST INT KSGLKTDKSDSEQVTL A1AA_HUMAN 219 193 KSGLKTDKSDSEQVTL Q13729 219 193 KSGLKTDKSDSEQVTL Q13675 219 193 KSGLKTDKSDSEQVTL O60451 219 193 KSGLKTDKSDSEQVTL A1AA_RABIT 219 193 KSGLKTDKSDSEQVTL A1AA_RAT 219 193 KSGLKTDKSDSEQVTL O54913 219 193 KSGLKTDKSDSEQVTL A1AA_BOVIN 219 193 ADRENRGCA1AR3 Length of motif = 18 Motif number = 3 A1A adrenergic receptor motif III - 2 PCODE ST INT RKNAPAGGSGMASAKTKT A1AA_HUMAN 238 3 RKNAPAGGSGMASAKTKT Q13729 238 3 RKNAPAGGSGMASAKTKT Q13675 238 3 RKNAPAGGSGMASAKTKT O60451 238 3 RKNAPAGGSGVASAKNKT A1AA_RABIT 238 3 RKNVPAEGGGVSSAKNKT A1AA_RAT 238 3 RKNVPAEGSGVSSAKNKT O54913 238 3 RKNAQVGGSGVTSAKNKT A1AA_BOVIN 238 3 ADRENRGCA1AR4 Length of motif = 18 Motif number = 4 A1A adrenergic receptor motif IV - 2 PCODE ST INT LGYTLHPPSQAVEGQHKD A1AA_HUMAN 356 100 LGYTLHPPSQAVEGQHKD Q13729 356 100 LGYTLHPPSQAVEGQHKD Q13675 356 100 LGYTLHPPSQAVEGQHKD O60451 356 100 LGYTLHAPSQALEGQHKD A1AA_RABIT 356 100 LGYTLHPPSQALEGQHRD A1AA_RAT 356 100 LGYTLHPPSQAVEEQHRG O54913 356 100 LGYTLHAPSHVLEGQHKD A1AA_BOVIN 356 100 ADRENRGCA1AR5 Length of motif = 20 Motif number = 5 A1A adrenergic receptor motif V - 2 PCODE ST INT RIPVGSRETFYRISKTDGVC A1AA_HUMAN 376 2 RIPVGSRETFYRISKTDGVC Q13729 376 2 RIPVGSRETFYRISKTDGVC Q13675 376 2 RIPVGSRETFYRISKTDGVC O60451 376 2 RIPVGSGETFYKISKTDGVC A1AA_RABIT 376 2 RIPVGSGETFYKISKTDGVC A1AA_RAT 376 2 RIPVGSGETFYKISKTDGVC O54913 376 2 RIPVGSAETFYKISKTDGVC A1AA_BOVIN 376 2 ADRENRGCA1AR6 Length of motif = 20 Motif number = 6 A1A adrenergic receptor motif VI - 2 PCODE ST INT FSSMPRGSARITVSKDQSSC A1AA_HUMAN 400 4 FSSMPRGSARITVSKDQSSC Q13729 400 4 FSSMPRGSARITVSKDQSSC Q13675 400 4 FSSMPRGSARITVSKDQSSC O60451 400 4 FSSMPRGSARITVPKDQSAC A1AA_RABIT 400 4 FSSMPQGSARITVPKDQSAC A1AA_RAT 400 4 FSSMPQGSARITMPKDQSAC O54913 400 4 FSSLPRGSARMAVARDPSAC A1AA_BOVIN 400 4

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