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PR00563

Identifier
ADRENRGCB3AR  [View Relations]  [View Alignment]  
Accession
PR00563
No. of Motifs
7
Creation Date
15-AUG-1996  (UPDATE 06-JUN-1999)
Title
Beta-3 adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR000681
GCRDB; GCR_00253; GCR_0708; GCR_0287; GCR_0622; GCR_0732; GCR_0051

GCRDB; GCR_0547
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]. 
 
Beta-3 receptors have limited distribution. They are found in low levels
in adipose tissue and the gastrointestinal tract, where they stimulate
lipolysis and increased gut motility [6]. They appear to coexist with beta-2
receptors in skeletal muscle, where the latter predominate. Beta-3 receptors
activate adenylyl cyclase through Gs [6]. 
 
ADRENRGCB3AR is a 7-element fingerprint that provides a signature for the
beta-3 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-terminal regions, focusing on those areas of the
alignment that characterise the beta-3 adrenergic receptors but distinguish 
them from the rest of the rhodopsin-like superfamily - motifs 1 and 2 lie at
the N-terminus; motif 3 spans part of the second TM domain, leading into the
first external loop; motif 4 lies in the second external loop; motifs 5 and 
6 lie in the third cytoplasmic loop; and motif 7 spans the third external
loop. 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, B4AR_MELGA, a turkey beta-4c adrenergic
receptor that matches motifs 3 and 4.
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 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
76666666
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
B3AR_BOVIN    B3AR_CANFA    B3AR_HUMAN    B3AR_MACMU    
B3AR_MOUSE B3AR_RAT
Sequence Titles
B3AR_BOVIN  BETA-3 ADRENERGIC RECEPTOR - BOS TAURUS (BOVINE). 
B3AR_CANFA BETA-3 ADRENERGIC RECEPTOR - CANIS FAMILIARIS (DOG).
B3AR_HUMAN BETA-3 ADRENERGIC RECEPTOR - HOMO SAPIENS (HUMAN).
B3AR_MACMU BETA-3 ADRENERGIC RECEPTOR - MACACA MULATTA (RHESUS MACAQUE).
B3AR_MOUSE BETA-3 ADRENERGIC RECEPTOR - MUS MUSCULUS (MOUSE).
B3AR_RAT BETA-3 ADRENERGIC RECEPTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 7 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
PWPHKNGSLAFWSDAPTLD B3AR_RAT 3 3 -
PWPHENSSAAPWPDTPTLA CPU51098 3 3 -
PWPHENSSLAPWPDLPTLA B3AR_HUMAN 3 3 -
PWPHRNGSLALWSDAPTLD B3AR_MOUSE 3 3 -
PWPPGNSSLTPWPDIPTLA B3AR_BOVIN 3 3 -

Motif 2 width=20
Element Seqn Id St Int Rpt
PNTANASGLPGVPWAVALAG B3AR_BOVIN 22 0 -
PNTANTSGLPGVPWEAALAG B3AR_HUMAN 22 0 -
PNTANTSGLPGVPWAAALAG CPU51098 22 0 -
PSAANTSGLPGVPWAAALAG B3AR_MOUSE 22 0 -
PSAANTSGLPGVPWAAALAG B3AR_RAT 22 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
PPGATLALTGH B3AR_BOVIN 92 50 -
PPGATLALTGH CPU51098 89 47 -
PPAATLALTGH B3AR_HUMAN 92 50 -
PPGATLALTGH B3AR_MOUSE 89 47 -
PPGATLALTGH B3AR_RAT 89 47 -

Motif 4 width=16
Element Seqn Id St Int Rpt
RVGADAEAQECHSNPR B3AR_MOUSE 176 76 -
RVGADAEAQECHSNPR B3AR_RAT 176 76 -
RAGADAEAQLCHGNPR CPU51098 176 76 -
RIGADAEAQRCHSNPR B3AR_BOVIN 179 76 -
RVGADAEAQRCHSNPR B3AR_HUMAN 179 76 -

Motif 5 width=19
Element Seqn Id St Int Rpt
REEVGRFPPQGSPRIRSRS CPU51098 236 44 -
RGELGRFPPEESPPAPSRS B3AR_HUMAN 239 44 -
RRELGRFSPEESPPSPSRS B3AR_MOUSE 236 44 -
RRELGRFPPEESPPAPSRS B3AR_BOVIN 239 44 -
RRELGRFPPEESPRSPSRS B3AR_RAT 236 44 -

Motif 6 width=21
Element Seqn Id St Int Rpt
GMRTAPAGEAPCGPRPARLLP CPU51098 262 7 -
GTCAPPEGVPACGRRPARLLP B3AR_HUMAN 264 6 -
GTPAAPDGVPPCGRRPARLLP B3AR_MOUSE 261 6 -
GPCASPAGVPSYGRRPARLLP B3AR_BOVIN 264 6 -
GTPTASDGVPSCGRRPARLLP B3AR_RAT 261 6 -

Motif 7 width=16
Element Seqn Id St Int Rpt
RALGGPSLVPNSVLLP CPU51098 313 30 -
RALAGPSLVPSGVFIA B3AR_MOUSE 312 30 -
RALGGPSLVPGPAFLA B3AR_HUMAN 315 30 -
RALVGPSLVPSGVFIA B3AR_RAT 312 30 -
RALGGPSLVSGPTFLA B3AR_BOVIN 315 30 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
PWPHRNGSLALWSDAPTLD B3AR_MOUSE 3 3 -
PWPHGNSSLVPWPDVPTLA B3AR_MACMU 3 3 -
PWPPGNSSLTPWPDIPTLA B3AR_BOVIN 3 3 -
PWPHENSSLAPWPDLPTLA B3AR_HUMAN 3 3 -
PWPHKNGSLAFWSDAPTLD B3AR_RAT 3 3 -
PWPHGNGSVASWPAAPTPT B3AR_CANFA 3 3 -

Motif 2 width=20
Element Seqn Id St Int Rpt
PNTANTSGLPGVPWEAALAG B3AR_HUMAN 22 0 -
PSAANTSGLPGVPWAAALAG B3AR_MOUSE 22 0 -
PNTANTSGLPGVPWAAALAG B3AR_MACMU 22 0 -
PNTANASGLPGVPWAVALAG B3AR_BOVIN 22 0 -
PSAANTSGLPGVPWAAALAG B3AR_RAT 22 0 -
PDAANTSGLPGAPWAVALAG B3AR_CANFA 22 0 -

Motif 3 width=11
Element Seqn Id St Int Rpt
PPAATLALTGH B3AR_HUMAN 92 50 -
PPGATLALTGH B3AR_MOUSE 89 47 -
PPAATLVLTGH B3AR_MACMU 92 50 -
PPGATLALTGH B3AR_BOVIN 92 50 -
PPGATLALTGH B3AR_RAT 89 47 -
PPGATLALTGR B3AR_CANFA 92 50 -

Motif 4 width=16
Element Seqn Id St Int Rpt
RIGADAEAQRCHSNPR B3AR_BOVIN 179 76 -
RVGADAEAQRCHSNPR B3AR_HUMAN 179 76 -
RVGADAEAQECHSNPR B3AR_MOUSE 176 76 -
RVGADAEAQRCHSNPR B3AR_MACMU 179 76 -
RVGADAEAQECHSNPR B3AR_RAT 176 76 -
RVGADAEAQRCHSNPH B3AR_CANFA 179 76 -

Motif 5 width=19
Element Seqn Id St Int Rpt
RGELGRFPPEESPPAPSRS B3AR_HUMAN 239 44 -
RRELGRFSPEESPPSPSRS B3AR_MOUSE 236 44 -
RWELGRFPPEESSPALSRS B3AR_MACMU 239 44 -
RRELGRFPPEESPPAPSRS B3AR_BOVIN 239 44 -
RRELGRFPPEESPRSPSRS B3AR_RAT 236 44 -
RRELGRFPPAESPPAASRS B3AR_CANFA 239 44 -

Motif 6 width=21
Element Seqn Id St Int Rpt
GTCAPPEGVPACCRRPARLLP B3AR_MACMU 264 6 -
GTCAPPEGVPACGRRPARLLP B3AR_HUMAN 264 6 -
GTPAAPDGVPPCGRRPARLLP B3AR_MOUSE 261 6 -
GPCASPAGVPSYGRRPARLLP B3AR_BOVIN 264 6 -
GTPTASDGVPSCGRRPARLLP B3AR_RAT 261 6 -
RRCASPAAVPSDRLRPARLLP B3AR_CANFA 264 6 -

Motif 7 width=16
Element Seqn Id St Int Rpt
RALGGPSLVPSPALLA B3AR_CANFA 315 30 -
RALAGPSLVPSGVFIA B3AR_MOUSE 312 30 -
RALGGPSLVPDPAFLA B3AR_MACMU 315 30 -
RALGGPSLVPGPAFLA B3AR_HUMAN 315 30 -
RALGGPSLVSGPTFLA B3AR_BOVIN 315 30 -
RALVGPSLVPSGVFIA B3AR_RAT 312 30 -