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PR00558

Identifier
ADRENRGCA2AR  [View Relations]  [View Alignment]  
Accession
PR00558
No. of Motifs
7
Creation Date
15-AUG-1996  (UPDATE 06-JUN-1999)
Title
Alpha-2A adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR001946
GCRDB; GCR_0046; GCR_0047; GCR_0154; GCR_0200; GCR_0101; GCR_0439
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]. 
 
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 Feature Index
75555555
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
A2AA_CAVPO    A2AA_HUMAN    A2AA_MOUSE    A2AA_PIG      
A2AA_RAT
Sequence Titles
A2AA_CAVPO  ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-2AAR) - CAVIA PORCELLUS (GUINEA PIG). 
A2AA_HUMAN ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-2AAR SUBTYPE C10) - HOMO SAPIENS (HUMAN).
A2AA_MOUSE ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-2AAR) - MUS MUSCULUS (MOUSE).
A2AA_PIG ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-2AAR) - SUS SCROFA (PIG).
A2AA_RAT ALPHA-2A ADRENERGIC RECEPTOR (ALPHA-2A ADRENOCEPTOR) (ALPHA-2AAR) (CA2-47) (ALPHA-2D ADRENERGIC RECEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
PEAGNASWNGTEAPGGGARATPY A2AA_PIG 6 6 -
PDAGNSSWNGTEAPGGGTRATPY A2AA_RAT 6 6 -
PDAGNASWNGTEAPGGGARATPY A2AA_HUMAN 6 6 -
PDAGNSSWNGTEAPGGGTRATPY A2AA_MOUSE 6 6 -
PDAGNASWNGTEAPGGGARATPY HUMADRA2R 6 6 -
PDAGNSSWNGTEAPGGGTRATPY RATRG20 6 6 -
PDSGNASWNGTEGPGGGTRATPY CPU25722 6 6 -
PDAGNASWNGTEAPGGGARATPY HUMADRA 6 6 -

Motif 2 width=24
Element Seqn Id St Int Rpt
ISFEKAGGGGQQPAEPRCEINDQK CPU25722 170 141 -
SIEKKGGGGGPQPAEPRCEINDQK HUMADRA 171 142 -
SIEKKGGGGGPQPAEPRCEINDQK HUMADRA2R 171 142 -
SIEKKGAGGGQQPAEPSCKINDQK RATRG20 171 142 -
SIEKKGAGGGQQPAEPSCKINDQK A2AA_MOUSE 171 142 -
SIEKKGGGGGPQPAEPRCEINDQK A2AA_HUMAN 171 142 -
SIEKKGAGGGQQPAEPSCKINDQK A2AA_RAT 171 142 -
SIEKKAGGGGQQPAEPRCEINDQK A2AA_PIG 171 142 -

Motif 3 width=20
Element Seqn Id St Int Rpt
PSRRGPDAHAAAPPGGAERR CPU25722 230 36 -
PSRRGPDAAAALPGGAERRP A2AA_PIG 231 36 -
PSRRGPDACSAPPGGADRRP A2AA_RAT 231 36 -
PSRRGPDAVAAPPGGTERRP A2AA_HUMAN 231 36 -
PSRRGPDACSAPPGGADRRP A2AA_MOUSE 231 36 -
PSRRGPDAVAAPPGGTERRP HUMADRA 231 36 -
PSRRGPDAVAAPPGGTERRP HUMADRA2R 231 36 -
PSRRGPDACSAPPGGADRRP RATRG20 231 36 -

Motif 4 width=20
Element Seqn Id St Int Rpt
ERGVGPGGAEAEPLPTQVNG CPU25722 256 6 -
ERGAGPTGAEAEPLPTQLNG A2AA_MOUSE 256 5 -
ERSAGPGGAEAEPLPTQLNG A2AA_HUMAN 256 5 -
ERGAGTAGAEAEPLPTQLNG A2AA_RAT 256 5 -
ERGVGRVGAEAEPLPVQLNG A2AA_PIG 256 5 -
ERSAGPGGAEAEPLPTQLNG HUMADRA 256 5 -
ERSAGPGGAEAEPLPTQLNG HUMADRA2R 256 5 -
ERGAGTAGAEAEPLPTQLNG RATRG20 256 5 -

Motif 5 width=19
Element Seqn Id St Int Rpt
EPAPTRPRDGDALDLEESS A2AA_RAT 279 3 -
EPAPAGPRDTDALDLEESS A2AA_HUMAN 279 3 -
EPAPAGPRDADGLDLEESS A2AA_PIG 279 3 -
EPAPAGPRDTDALDLEESS HUMADRA 279 3 -
EPAPAGPRDGDALDLEESS A2AA_MOUSE 279 3 -
EPAPAGPRDAEALDLEESS CPU25722 279 3 -
EPAPTRPRDGDALDLEESS RATRG20 279 3 -
EPAPAGPRDTDALDLEESS HUMADRA2R 279 3 -

Motif 6 width=18
Element Seqn Id St Int Rpt
RPERGPRGKGKARASQVK HUMADRA2R 310 12 -
RPERGPRGKGKARASQVK HUMADRA 310 12 -
RPERGPRGKGKARASQVK A2AA_HUMAN 310 12 -
KPERGPRAKGKTKASQVK A2AA_RAT 310 12 -
RSERGPRAKSKARASQVK A2AA_PIG 310 12 -
RPDRGPRAKGKTRASQVK A2AA_MOUSE 310 12 -
RPERGLRAKSKARASQVK CPU25722 310 12 -
KPERGPRAKGKTKASQVK RATRG20 310 12 -

Motif 7 width=12
Element Seqn Id St Int Rpt
FKKILCRGDRKR A2AA_MOUSE 437 109 -
FKKILCRGDRKR HUMADRA2R 437 109 -
FKKILCRGDRKR RATRG20 437 109 -
FKKILCRGDRKR CPU25722 437 109 -
FKKILCRGDRKR HUMADRA 437 109 -
FKKILCRGDRKR A2AA_PIG 437 109 -
FKKILCRGDRKR A2AA_RAT 437 109 -
FKKILCRGDRKR A2AA_HUMAN 437 109 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
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 -

Motif 2 width=24
Element Seqn Id St Int Rpt
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 -

Motif 3 width=20
Element Seqn Id St Int Rpt
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 -

Motif 4 width=20
Element Seqn Id St Int Rpt
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 -

Motif 5 width=19
Element Seqn Id St Int Rpt
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 -

Motif 6 width=18
Element Seqn Id St Int Rpt
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 -

Motif 7 width=12
Element Seqn Id St Int Rpt
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 -