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PR00559

Identifier
ADRENRGCA2BR  [View Relations]  [View Alignment]  
Accession
PR00559
No. of Motifs
6
Creation Date
15-AUG-1996  (UPDATE 06-JUN-1999)
Title
Alpha-2B adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR000207
GCRDB; GCR_0115; GCR_0395; GCR_0443; GCR_0472; GCR_0041; GCR_0045
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 limited distribution of alpha-2B receptor mRNA has been demonstrated by
Northern analysis, it being found for example in only 2 peripheral tissues 
(liver and kidney), and not in the brain [6]. The receptor inhibits adenylyl
cyclase and L-type calcium channels through a pertussis-toxin-insensitive
G protein belonging to the Gi/G0 class [6]. 
 
ADRENRGCA2BR is a 6-element fingerprint that provides a signature for the
alpha-2B adrenergic receptors. The fingerprint was derived from an initial
alignment of 5 sequences: the motifs were drawn from conserved sections
within either loop or C-terminal regions, focusing on those areas of the
alignment that characterise the alpha-2B adrenergic receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motifs 
1-4 lie at the N-terminus; motif 5 spans the third external loop; and motif
6 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. Two partial matches were also found, HUMA2C2 and S67316, both of
which are alpha-2 adrenergic receptor fragments.
 
An update on SPTR37_9f identified a true set of 4 sequences.
Summary Information
4 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
6444444
5000000
4000000
3000000
2000000
123456
True Positives
A2AB_CAVPO    A2AB_HUMAN    A2AB_MOUSE    A2AB_RAT      
Sequence Titles
A2AB_CAVPO  ALPHA-2B ADRENERGIC RECEPTOR (ALPHA-2B ADRENOCEPTOR) - CAVIA PORCELLUS (GUINEA PIG). 
A2AB_HUMAN ALPHA-2B ADRENERGIC RECEPTOR (ALPHA-2B ADRENOCEPTOR) (SUBTYPE C2) - HOMO SAPIENS (HUMAN).
A2AB_MOUSE ALPHA-2B ADRENERGIC RECEPTOR (ALPHA-2B ADRENOCEPTOR) - MUS MUSCULUS (MOUSE).
A2AB_RAT ALPHA-2B ADRENERGIC RECEPTOR (ALPHA-2B ADRENOCEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  100  NSINGLE    
SPTR37_9f 2 5 NSINGLE
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EVNGHSKSTGEKEEGETPED A2AB_HUMAN 245 245 -
EANGHPKPPREKEEGETPED A2AB_MOUSE 253 253 -
EANGHPKPPREKEEGETPED A2AB_RAT 251 251 -
EANGHPKPTGEKEEGETSED CPU25723 245 245 -
EANGHPKPPREXEEGETPED RNA2BARA 246 246 -

Motif 2 width=19
Element Seqn Id St Int Rpt
RALPPTWSALPRSGQGQKK A2AB_RAT 274 3 -
RALPPTWSALPRSGQGQKK RNA2BARA 269 3 -
RTLPPSWAALPTSGQGQKK CPU25723 268 3 -
RALPPNWSALPRSVQDQKK A2AB_MOUSE 276 3 -
RALPPSWAALPNSGQGQKE A2AB_HUMAN 268 3 -

Motif 3 width=18
Element Seqn Id St Int Rpt
ECEPQTLPASPASVFNPP A2AB_MOUSE 314 19 -
ECEPQAAPGLPASMCSPS CPU25723 307 20 -
ECEPQTLPASPASVCNPP RNA2BARA 307 19 -
ECEPQTLPASPASVCNPP A2AB_RAT 312 19 -
ECEPQAVPVSPASACSPP A2AB_HUMAN 309 22 -

Motif 4 width=20
Element Seqn Id St Int Rpt
RGQVLLGKNVGVASGQWWRR A2AB_RAT 343 13 -
RGQVLLGRGVGAIGGQWWRR A2AB_HUMAN 340 13 -
RGQVLLGRGVGAVDGQWWRR CPU25723 338 13 -
RGQVLLGKNVGVASGQWWRR RNA2BARA 338 13 -
RGQVLLSKNVGVASGQWWRR A2AB_MOUSE 345 13 -

Motif 5 width=21
Element Seqn Id St Int Rpt
TYSLGAICPQHCKVPHGLFQF CPU25723 388 30 -
SYSLGAICPQHCKVPHGLFQF A2AB_RAT 393 30 -
SYSLGAICPQHCKVPHGLFQF A2AB_MOUSE 395 30 -
SYSLGAICPKHCKVPHGLFQF A2AB_HUMAN 390 30 -
SYSLGAICPQHCKVPHGLFQF RNA2BARA 388 30 -

Motif 6 width=12
Element Seqn Id St Int Rpt
FRRILCRPWTQT A2AB_RAT 440 26 -
FRRILCRPWTQT A2AB_HUMAN 437 26 -
FRRILCRQWTQT A2AB_MOUSE 442 26 -
FRRILCRQWTQT CPU25723 435 26 -
FRRILCRPWTQT RNA2BARA 435 26 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EANGHPKPPREKEEGETPED A2AB_RAT 251 251 -
EANGHPKPPREKEEGETPED A2AB_MOUSE 253 253 -
EVNGHSKSTGEKEEGETPED A2AB_HUMAN 245 245 -
EANGHPKPTGEKEEGETSED A2AB_CAVPO 245 245 -

Motif 2 width=19
Element Seqn Id St Int Rpt
RALPPTWSALPRSGQGQKK A2AB_RAT 274 3 -
RALPPNWSALPRSVQDQKK A2AB_MOUSE 276 3 -
RALPPSWAALPNSGQGQKE A2AB_HUMAN 268 3 -
RTLPPSWAALPTSGQGQKK A2AB_CAVPO 268 3 -

Motif 3 width=18
Element Seqn Id St Int Rpt
ECEPQTLPASPASVCNPP A2AB_RAT 312 19 -
ECEPQTLPASPASVFNPP A2AB_MOUSE 314 19 -
ECEPQAVPVSPASACSPP A2AB_HUMAN 309 22 -
ECEPQAAPGLPASMCSPS A2AB_CAVPO 307 20 -

Motif 4 width=20
Element Seqn Id St Int Rpt
RGQVLLGKNVGVASGQWWRR A2AB_RAT 343 13 -
RGQVLLSKNVGVASGQWWRR A2AB_MOUSE 345 13 -
RGQVLLGRGVGAIGGQWWRR A2AB_HUMAN 340 13 -
RGQVLLGRGVGAVDGQWWRR A2AB_CAVPO 338 13 -

Motif 5 width=21
Element Seqn Id St Int Rpt
SYSLGAICPQHCKVPHGLFQF A2AB_RAT 393 30 -
SYSLGAICPQHCKVPHGLFQF A2AB_MOUSE 395 30 -
SYSLGAICPKHCKVPHGLFQF A2AB_HUMAN 390 30 -
TYSLGAICPQHCKVPHGLFQF A2AB_CAVPO 388 30 -

Motif 6 width=12
Element Seqn Id St Int Rpt
FRRILCRPWTQT A2AB_RAT 440 26 -
FRRILCRQWTQT A2AB_MOUSE 442 26 -
FRRILCRPWTQT A2AB_HUMAN 437 26 -
FRRILCRQWTQT A2AB_CAVPO 435 26 -