SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR00240

Identifier
ADRENRGCA1DR  [View Relations]  [View Alignment]  
Accession
PR00240
No. of Motifs
7
Creation Date
14-AUG-1996  (UPDATE 18-FEB-2000)
Title
Alpha-1D adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR000363
GCRDB; GCR_0123; GCR_0167
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. WATSON, S. AND ARKINSTALL, S.
Adrenaline and noradrenaline.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp32-54.

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]. 
 
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 pharmacological profile of the alpha-1A receptor closely resembles that 
of the alpha-1D receptor [6]. It appears to be widely distributed in the rat, 
with high levels in peripheral tissues (e.g., vas deferens) and in the CNS
(e.g., hippocampus, cerebral cortex and brainstem). The receptor is coupled
to the phosphoinositide pathway through a pertussis-toxin-insensitive
G protein, probably of the Gq/G11 class. It is thought to stimulate
direct entry of extracellular calcium [6]. 
 
ADRENRGCA1DR is a 7-element fingerprint that provides a signature for the
alpha-1D adrenergic receptors. The fingerprint was derived from an initial
alignment of 5 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-1D adrenergic receptors but 
distinguish them from the rest of the rhodopsin-like superfamily - motifs 
1-3 lie at the N-terminus; motif 4 lies in the third cytoplasmic loop; and
motifs 5-7 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-A1 receptor 
that shows significant differences in its N- and C-terminal regions.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
74444444
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
A1AD_HUMAN    A1AD_MOUSE    A1AD_RABIT    A1AD_RAT      
Sequence Titles
A1AD_HUMAN  ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) (ALPHA-1A ADRENERGIC RECEPTOR) - HOMO SAPIENS (HUMAN). 
A1AD_MOUSE ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) (ALPHA-1A ADRENERGIC RECEPTOR) - MUS MUSCULUS (MOUSE).
A1AD_RABIT ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
A1AD_RAT ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) (ALPHA-1A ADRENERGIC RECEPTOR) (RA42) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  25   NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
FRDILSVTFEGPRSSS A1AA_RAT 3 3 -
FRDILSVTFEGPRSSS A53280 3 3 -
FRDILSVTFEGPRSSS RATADRA1A 3 3 -
FRDLLSVSFEGPRPDS A1AA_HUMAN 3 3 -
FRDLLSVSFEGPRPDS JC2331 3 3 -

Motif 2 width=20
Element Seqn Id St Int Rpt
GAVVGTGSGEDNQSSTGEPG A1AA_RAT 49 30 -
GAVVGTGSGEINQSSTGEPG A53280 49 30 -
GAVVGTGSGEDNQSSTGEPG RATADRA1A 49 30 -
GGVVGAGSGEDNRSSAGEPG A1AA_HUMAN 54 35 -
GGVVGAGSGEDNRSSAGEPG JC2331 54 35 -

Motif 3 width=20
Element Seqn Id St Int Rpt
AAASGEVNGSAAVGGLVVSA A1AA_RAT 69 0 -
AAASGEVNGSAAVGGLVVSA A53280 69 0 -
AAASGEVNGSAAVGGLVVSA RATADRA1A 69 0 -
AGAGGDVNGTAAVGGLVVSA A1AA_HUMAN 75 1 -
AGAGGDVNGTAAVGGLVVSA JC2331 75 1 -

Motif 4 width=20
Element Seqn Id St Int Rpt
REPGKASEVVLRIHCRGAAT A1AA_RAT 288 199 -
REPGKASEVVLRIHCRGART A53280 288 199 -
REPGKASEVVLRIHCRGAAT RATADRA1A 288 199 -
RERGKASEVVLRIHCRGAAT A1AA_HUMAN 294 199 -
RERGKASEVVLRIHCRGAAT JC2331 294 199 -

Motif 5 width=20
Element Seqn Id St Int Rpt
RLLGPLQRPTTQLRAKVSSL A1AA_RAT 488 180 -
RLLGPLQRPTTQLRAKVSSL A53280 487 179 -
RLLGPLQRPTTQLRAKVSSL RATADRA1A 487 179 -
RLLGPFRRPTTQLRAKVSSL A1AA_HUMAN 498 184 -
RLLGPFRRPTTQLRAKVSSL JC2331 498 184 -

Motif 6 width=21
Element Seqn Id St Int Rpt
HKIRSGARRAETACALRSEVE A1AA_RAT 509 1 -
HKIRSGARRAETACALRSEVE A53280 508 1 -
HKIRSGARRAETACALRSEVE RATADRA1A 508 1 -
KIRAGGAQRAEAACAQRSEVE A1AA_HUMAN 520 2 -
KIPAGGAQRAEAACAQRSEVE JC2331 520 2 -

Motif 7 width=22
Element Seqn Id St Int Rpt
PQDGAEAVICQAYEPGDYSNLR A1AA_RAT 536 6 -
PQDGAEAVICQAYEPGDYSNLR A53280 535 6 -
PQDGAEAVICQAYEPGDYSNLR RATADRA1A 535 6 -
PHEVAEGATCQAYELADYSNLR A1AA_HUMAN 547 6 -
PHEVAEGATCQAYELADYSNLR JC2331 547 6 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
FRDILSVTFEGPRSSS A1AD_RAT 3 3 -
FRDILSVTFEGPRASS A1AD_MOUSE 3 3 -
FRDLLSVSFEGPRPDS A1AD_HUMAN 3 3 -
FRDLLSVTFEGPRPDI A1AD_RABIT 3 3 -

Motif 2 width=20
Element Seqn Id St Int Rpt
GAVVGTGSGEDNQSSTGEPG A1AD_RAT 49 30 -
SAVVGTGSGEDNQSSTAEAG A1AD_MOUSE 49 30 -
GGVVGAGSGEDNRSSAGEPG A1AD_HUMAN 54 35 -
GSVVGAGSGEDNRSSAGEPG A1AD_RABIT 59 40 -

Motif 3 width=20
Element Seqn Id St Int Rpt
AAASGEVNGSAAVGGLVVSA A1AD_RAT 69 0 -
AAASGEVNGSAAVGGLVVSA A1AD_MOUSE 69 0 -
AGAGGDVNGTAAVGGLVVSA A1AD_HUMAN 75 1 -
AGGGGEVNGTAAVGGLVVSA A1AD_RABIT 80 1 -

Motif 4 width=20
Element Seqn Id St Int Rpt
REPGKASEVVLRIHCRGAAT A1AD_RAT 288 199 -
REPGKASEVVLRIHCRGAAT A1AD_MOUSE 288 199 -
RERGKASEVVLRIHCRGAAT A1AD_HUMAN 294 199 -
RERGKASEVVLRIHCRGAAS A1AD_RABIT 299 199 -

Motif 5 width=20
Element Seqn Id St Int Rpt
RLLGPLQRPTTQLRAKVSSL A1AD_RAT 488 180 -
RLLGPLQRPTTQLRAKVSSL A1AD_MOUSE 488 180 -
RLLGPFRRPTTQLRAKVSSL A1AD_HUMAN 498 184 -
RLLGPLRRPTTQLRAKVSSL A1AD_RABIT 502 183 -

Motif 6 width=21
Element Seqn Id St Int Rpt
HKIRSGARRAETACALRSEVE A1AD_RAT 509 1 -
KFRSGGARRAETACALRSEVE A1AD_MOUSE 510 2 -
KIRAGGAQRAEAACAQRSEVE A1AD_HUMAN 520 2 -
KIRAGGAQRAEAACALRSEVE A1AD_RABIT 524 2 -

Motif 7 width=22
Element Seqn Id St Int Rpt
PQDGAEAVICQAYEPGDYSNLR A1AD_RAT 536 6 -
PQDGAEAVICQAYEPGDLSNLR A1AD_MOUSE 537 6 -
PHEVAEGATCQAYELADYSNLR A1AD_HUMAN 547 6 -
ARDVAEDNTCQAYELADYRNLR A1AD_RABIT 551 6 -