WORKLIST ENTRIES (1):
ADRENRGCA1DR View alignment View Structure Alpha-1D 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; PR00556 ADRENRGCA1BR; PR00557 ADRENRGCA1AR
INTERPRO; IPR000363
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 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 FINGERPRINT INDEX
7| 4 4 4 4 4 4 4
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..
A1AD_RAT A1AD_MOUSE A1AD_HUMAN A1AD_RABIT
PROTEIN TITLES
A1AD_RAT ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) (ALPHA-
A1AD_MOUSE ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) (ALPHA-
A1AD_HUMAN ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) (ALPHA-
A1AD_RABIT ALPHA-1D ADRENERGIC RECEPTOR (ALPHA 1D-ADRENOCEPTOR) - ORYCT
SCAN HISTORY
OWL28_1 1 25 NSINGLE
SPTR37_9f 2 5 NSINGLE
INITIAL MOTIF SETS
ADRENRGCA1DR1 Length of motif = 16 Motif number = 1
A1D adrenergic receptor motif I - 1
PCODE ST INT
FRDILSVTFEGPRSSS A1AA_RAT 3 3
FRDILSVTFEGPRSSS A53280 3 3
FRDILSVTFEGPRSSS RATADRA1A 3 3
FRDLLSVSFEGPRPDS A1AA_HUMAN 3 3
FRDLLSVSFEGPRPDS JC2331 3 3
ADRENRGCA1DR2 Length of motif = 20 Motif number = 2
A1D adrenergic receptor motif II - 1
PCODE ST INT
GAVVGTGSGEDNQSSTGEPG A1AA_RAT 49 30
GAVVGTGSGEINQSSTGEPG A53280 49 30
GAVVGTGSGEDNQSSTGEPG RATADRA1A 49 30
GGVVGAGSGEDNRSSAGEPG A1AA_HUMAN 54 35
GGVVGAGSGEDNRSSAGEPG JC2331 54 35
ADRENRGCA1DR3 Length of motif = 20 Motif number = 3
A1D adrenergic receptor motif III - 1
PCODE ST INT
AAASGEVNGSAAVGGLVVSA A1AA_RAT 69 0
AAASGEVNGSAAVGGLVVSA A53280 69 0
AAASGEVNGSAAVGGLVVSA RATADRA1A 69 0
AGAGGDVNGTAAVGGLVVSA A1AA_HUMAN 75 1
AGAGGDVNGTAAVGGLVVSA JC2331 75 1
ADRENRGCA1DR4 Length of motif = 20 Motif number = 4
A1D adrenergic receptor motif IV - 1
PCODE ST INT
REPGKASEVVLRIHCRGAAT A1AA_RAT 288 199
REPGKASEVVLRIHCRGART A53280 288 199
REPGKASEVVLRIHCRGAAT RATADRA1A 288 199
RERGKASEVVLRIHCRGAAT A1AA_HUMAN 294 199
RERGKASEVVLRIHCRGAAT JC2331 294 199
ADRENRGCA1DR5 Length of motif = 20 Motif number = 5
A1A adrenergic recepto motif V - 1
PCODE ST INT
RLLGPLQRPTTQLRAKVSSL A1AA_RAT 488 180
RLLGPLQRPTTQLRAKVSSL A53280 487 179
RLLGPLQRPTTQLRAKVSSL RATADRA1A 487 179
RLLGPFRRPTTQLRAKVSSL A1AA_HUMAN 498 184
RLLGPFRRPTTQLRAKVSSL JC2331 498 184
ADRENRGCA1DR6 Length of motif = 21 Motif number = 6
A1D adrenergic receptor motif VI - 1
PCODE ST INT
HKIRSGARRAETACALRSEVE A1AA_RAT 509 1
HKIRSGARRAETACALRSEVE A53280 508 1
HKIRSGARRAETACALRSEVE RATADRA1A 508 1
KIRAGGAQRAEAACAQRSEVE A1AA_HUMAN 520 2
KIPAGGAQRAEAACAQRSEVE JC2331 520 2
ADRENRGCA1DR7 Length of motif = 22 Motif number = 7
A1D adrenergic receptor motif VII - 1
PCODE ST INT
PQDGAEAVICQAYEPGDYSNLR A1AA_RAT 536 6
PQDGAEAVICQAYEPGDYSNLR A53280 535 6
PQDGAEAVICQAYEPGDYSNLR RATADRA1A 535 6
PHEVAEGATCQAYELADYSNLR A1AA_HUMAN 547 6
PHEVAEGATCQAYELADYSNLR JC2331 547 6
FINAL MOTIF SETS
ADRENRGCA1DR1 Length of motif = 16 Motif number = 1
A1D adrenergic receptor motif I - 2
PCODE ST INT
FRDILSVTFEGPRSSS A1AD_RAT 3 3
FRDILSVTFEGPRASS A1AD_MOUSE 3 3
FRDLLSVSFEGPRPDS A1AD_HUMAN 3 3
FRDLLSVTFEGPRPDI A1AD_RABIT 3 3
ADRENRGCA1DR2 Length of motif = 20 Motif number = 2
A1D adrenergic receptor motif II - 2
PCODE ST INT
GAVVGTGSGEDNQSSTGEPG A1AD_RAT 49 30
SAVVGTGSGEDNQSSTAEAG A1AD_MOUSE 49 30
GGVVGAGSGEDNRSSAGEPG A1AD_HUMAN 54 35
GSVVGAGSGEDNRSSAGEPG A1AD_RABIT 59 40
ADRENRGCA1DR3 Length of motif = 20 Motif number = 3
A1D adrenergic receptor motif III - 2
PCODE ST INT
AAASGEVNGSAAVGGLVVSA A1AD_RAT 69 0
AAASGEVNGSAAVGGLVVSA A1AD_MOUSE 69 0
AGAGGDVNGTAAVGGLVVSA A1AD_HUMAN 75 1
AGGGGEVNGTAAVGGLVVSA A1AD_RABIT 80 1
ADRENRGCA1DR4 Length of motif = 20 Motif number = 4
A1D adrenergic receptor motif IV - 2
PCODE ST INT
REPGKASEVVLRIHCRGAAT A1AD_RAT 288 199
REPGKASEVVLRIHCRGAAT A1AD_MOUSE 288 199
RERGKASEVVLRIHCRGAAT A1AD_HUMAN 294 199
RERGKASEVVLRIHCRGAAS A1AD_RABIT 299 199
ADRENRGCA1DR5 Length of motif = 20 Motif number = 5
A1D adrenergic receptor motif V - 2
PCODE ST INT
RLLGPLQRPTTQLRAKVSSL A1AD_RAT 488 180
RLLGPLQRPTTQLRAKVSSL A1AD_MOUSE 488 180
RLLGPFRRPTTQLRAKVSSL A1AD_HUMAN 498 184
RLLGPLRRPTTQLRAKVSSL A1AD_RABIT 502 183
ADRENRGCA1DR6 Length of motif = 21 Motif number = 6
A1D adrenergic receptor motif VI - 2
PCODE ST INT
HKIRSGARRAETACALRSEVE A1AD_RAT 509 1
KFRSGGARRAETACALRSEVE A1AD_MOUSE 510 2
KIRAGGAQRAEAACAQRSEVE A1AD_HUMAN 520 2
KIRAGGAQRAEAACALRSEVE A1AD_RABIT 524 2
ADRENRGCA1DR7 Length of motif = 22 Motif number = 7
A1D adrenergic receptor motif VII - 2
PCODE ST INT
PQDGAEAVICQAYEPGDYSNLR A1AD_RAT 536 6
PQDGAEAVICQAYEPGDLSNLR A1AD_MOUSE 537 6
PHEVAEGATCQAYELADYSNLR A1AD_HUMAN 547 6
ARDVAEDNTCQAYELADYRNLR A1AD_RABIT 551 6
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