SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR00562

Identifier
ADRENRGCB2AR  [View Relations]  [View Alignment]  
Accession
PR00562
No. of Motifs
7
Creation Date
15-AUG-1996  (UPDATE 06-JUN-1999)
Title
Beta-2 adrenergic receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR01103 ADRENERGICR
INTERPRO; IPR000332
GCRDB; GCR_0094; GCR_0122; GCR_0128; GCR_0035; GCR_0049; GCR_0050

GCRDB; GCR_0052
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-1 and beta-2 receptors often coexist, but one subtype normally
predominates [6]. Beta-2 receptors mediate relaxation of smooth muscle
(including vascular beds, bronchus, intestine and uterus); they mediate
glycogenlysis and glucogenesis in the liver and regulate cell metabolism in
skeletal muscle; they inhibit the activity of leukocytes and other blood
cells; and they are found in the heart, but their physiological role here
is unclear [6]. The receptors are located presynaptically in nerves, where
they facilitate neurotransmitter release, and in the brain, where they
regulate a variety of physiological processes. Beta-2 receptors activate
adenylyl cyclase through Gs [6]. 
 
ADRENRGCB2AR is a 7-element fingerprint that provides a signature for the
beta-2 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 beta-2 adrenergic receptors but
distinguish them from the rest of the rhodopsin-like superfamily - motif 
1 lies at the N-terminus; motifs 2 and 3 lie in the third cytoplasmic loop;
motif 4 spans the third external loop; and motifs 5-7 lie at 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, S31617, a bovine beta-2 adrenergic receptor fragment.
 
An update on SPTR37_9f identified a true set of 8 sequences.
Summary Information
8 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
78888888
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
B2AR_BOVIN    B2AR_CANFA    B2AR_HUMAN    B2AR_MACMU    
B2AR_MESAU B2AR_MOUSE B2AR_PIG B2AR_RAT
Sequence Titles
B2AR_BOVIN  BETA-2 ADRENERGIC RECEPTOR - BOS TAURUS (BOVINE). 
B2AR_CANFA BETA-2 ADRENERGIC RECEPTOR - CANIS FAMILIARIS (DOG).
B2AR_HUMAN BETA-2 ADRENERGIC RECEPTOR - HOMO SAPIENS (HUMAN).
B2AR_MACMU BETA-2 ADRENERGIC RECEPTOR - MACACA MULATTA (RHESUS MACAQUE).
B2AR_MESAU BETA-2 ADRENERGIC RECEPTOR - MESOCRICETUS AURATUS (GOLDEN HAMSTER).
B2AR_MOUSE BETA-2 ADRENERGIC RECEPTOR - MUS MUSCULUS (MOUSE).
B2AR_PIG BETA-2 ADRENERGIC RECEPTOR - SUS SCROFA (PIG).
B2AR_RAT BETA-2 ADRENERGIC RECEPTOR - RATTUS NORVEGICUS (RAT).
Scan History
OWL28_1    1  50   NSINGLE    
SPTR37_9f 2 9 NSINGLE
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
FLLAPNRSHAPDHDVTQQRDE B2AR_HUMAN 10 10 -
FLLTTNGSHVPDHDVTEERDE B2AR_MESAU 10 10 -
FLLAPNGSRAPGHDITQERDE B2AR_RAT 10 10 -
FLLAPNGSRAPDHDVTQERDE B2AR_MOUSE 10 10 -
FLLAPNGSRAPHHDVTQERDE MMB2ARG 10 10 -
FLLAPNGSRAPGHDITQERDE RATMTA 10 10 -
FLLAPNGSHAPDQGDSQERSE CFB2AR 10 10 -
FLLAPNGSHAPDHDVTQERDE MACB2AR 10 10 -

Motif 2 width=18
Element Seqn Id St Int Rpt
DRSEGRFHAQNLSQVEQD CFB2AR 234 203 -
DKSEGRFHAQNLSQVEQD MACB2AR 234 203 -
DKSEGRFHAQNLSQVEQD MMB2ARG 234 203 -
DKSEGRFHAQNLSQVEQD RATMTA 234 203 -
DKSEGRFHAQNLSQVEQD B2AR_MOUSE 234 203 -
DKSEGRFHAQNLSQVEQD B2AR_RAT 234 203 -
DKSEGRFHSPNLGQVEQD B2AR_MESAU 234 203 -
DKSEGRFHVQNLSQVEQD B2AR_HUMAN 234 203 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GRSGHGHRRSSKFCLKE CFB2AR 252 0 -
GRTGHGLRRSSKFCLKE B2AR_HUMAN 252 0 -
GRSGHGLRRSSKFCLKE B2AR_MESAU 252 0 -
GRSGHGLRSSSKFCLKE B2AR_RAT 252 0 -
GRSGHGLRRSSKFCLKE B2AR_MOUSE 252 0 -
GRTGHGLRRSSKFCLKE MACB2AR 252 0 -
GRTGHGLRRSSKFCLKE MMB2ARG 252 0 -
GRSGHGLRSSFKFCLKE RATMTA 252 0 -

Motif 4 width=17
Element Seqn Id St Int Rpt
IVHVIQDNLIPKEVYIL CFB2AR 294 25 -
IVHVIRDNLIPKEVYIL B2AR_MOUSE 294 25 -
IVHVIRANLIPKEVYIL B2AR_RAT 294 25 -
IVHVIQDNLIPKEVYIL B2AR_MESAU 294 25 -
IVHVIQDNLIRKEVYIL B2AR_HUMAN 294 25 -
IVHVIQDNLIPKEVYIL MACB2AR 294 25 -
IVHVIRDNLIPKEVYIL MMB2ARG 294 25 -
IVHVIRANLIPKEVYIL RATMTA 294 25 -

Motif 5 width=19
Element Seqn Id St Int Rpt
LRRSSSKAYGNGYSSNSNG B2AR_MESAU 342 31 -
LRRSSSKTYGNGYSSNSNG B2AR_RAT 342 31 -
LRRSSLKAYGNGYSSNGNT B2AR_HUMAN 342 31 -
LRRSSLKACGNGYSSNSNG MACB2AR 342 31 -
LRRSSSKTYGNGYSSNSNG B2AR_MOUSE 342 31 -
LRRSSLKAYGNGYSNNSNS CFB2AR 342 31 -
LRRSSSKTYGNGYSSNSNG RATMTA 342 31 -
LRRSSFETYGNGYSSNSNG MMB2ARG 342 31 -

Motif 6 width=20
Element Seqn Id St Int Rpt
GEPNTCQLGQEREQELLCED MMB2ARG 366 5 -
GEQSGYHLEQEKENKLLCED MACB2AR 363 2 -
GEQSAYQLGQEKENELLCEE B2AR_RAT 366 5 -
GEASGCQLGQEKESERLCED B2AR_MESAU 366 5 -
GEQSGYHVEQEKENKLLCED B2AR_HUMAN 361 0 -
GEPNTCQLGQEREQELLCED B2AR_MOUSE 366 5 -
GEHSGCHLGQEKDSELLCED CFB2AR 366 5 -
GEQSAYQLGQEKENELLCEE RATMTA 366 5 -

Motif 7 width=20
Element Seqn Id St Int Rpt
FVNCQGTVPSLSVDSQGRNC B2AR_MOUSE 392 6 -
FVNCQGTVPSLSVDSQGRNC MMB2ARG 392 6 -
FVNCQGTVPSLSIDSQGRNC RATMTA 392 6 -
TEDRQGTVPSDSVDSQGRNC CFB2AR 389 3 -
FVGHQGTVPSDNIDSQGRSC MACB2AR 389 6 -
FVGHQGTVPSDNIDSQGRNC B2AR_HUMAN 387 6 -
FVNCQGTVPSLSLDSQGRNC B2AR_MESAU 392 6 -
FVNCQGTVPSLSIDSQGRNC B2AR_RAT 392 6 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
FLLAPNGSHAPDHDVTQERDE B2AR_MACMU 10 10 -
FLLAPNGSRAPDHDVTQERDE B2AR_MOUSE 10 10 -
FLLAPNGSRAPGHDITQERDE B2AR_RAT 10 10 -
FLLTTNGSHVPDHDVTEERDE B2AR_MESAU 10 10 -
FLLAPNRSHAPDHDVTQQRDE B2AR_HUMAN 10 10 -
FLLAPNGSHAPDQGDSQERSE B2AR_CANFA 10 10 -
FLLAPNASHAPDQNVTLERDE B2AR_BOVIN 10 10 -
FLLAPNGSHAPDQDVPQERDE B2AR_PIG 10 10 -

Motif 2 width=18
Element Seqn Id St Int Rpt
DKSEGRFHAQNLSQVEQD B2AR_MACMU 234 203 -
DKSEGRFHAQNLSQVEQD B2AR_MOUSE 234 203 -
DKSEGRFHAQNLSQVEQD B2AR_RAT 234 203 -
DKSEGRFHSPNLGQVEQD B2AR_MESAU 234 203 -
DKSEGRFHVQNLSQVEQD B2AR_HUMAN 234 203 -
DRSEGRFHAQNLSQVEQD B2AR_CANFA 234 203 -
DKSEGRFHAQNVSQVEQD B2AR_BOVIN 234 203 -
DKSEGRFHAQNLSQAEQD B2AR_PIG 234 203 -

Motif 3 width=17
Element Seqn Id St Int Rpt
GRTGHGLRRSSKFCLKE B2AR_MACMU 252 0 -
GRSGHGLRRSSKFCLKE B2AR_MOUSE 252 0 -
GRSGHGLRSSSKFCLKE B2AR_RAT 252 0 -
GRSGHGLRRSSKFCLKE B2AR_MESAU 252 0 -
GRTGHGLRRSSKFCLKE B2AR_HUMAN 252 0 -
GRSGHGHRRSSKFCLKE B2AR_CANFA 252 0 -
GRSGLGQRRTSKFYLKE B2AR_BOVIN 252 0 -
GRSGPGHRRSSKFCLKE B2AR_PIG 252 0 -

Motif 4 width=17
Element Seqn Id St Int Rpt
IVHVIQDNLIPKEVYIL B2AR_MACMU 294 25 -
IVHVIRDNLIPKEVYIL B2AR_MOUSE 294 25 -
IVHVIRANLIPKEVYIL B2AR_RAT 294 25 -
IVHVIQDNLIPKEVYIL B2AR_MESAU 294 25 -
IVHVIQDNLIRKEVYIL B2AR_HUMAN 294 25 -
IVHVIQDNLIPKEVYIL B2AR_CANFA 294 25 -
IVHVIKDNLIRKEIYIL B2AR_BOVIN 294 25 -
IVHGIHDNLIPKEVYIL B2AR_PIG 294 25 -

Motif 5 width=19
Element Seqn Id St Int Rpt
LRRSSLKACGNGYSSNSNG B2AR_MACMU 342 31 -
LRRSSSKTYGNGYSSNSNG B2AR_MOUSE 342 31 -
LRRSSSKTYGNGYSSNSNG B2AR_RAT 342 31 -
LRRSSSKAYGNGYSSNSNG B2AR_MESAU 342 31 -
LRRSSLKAYGNGYSSNGNT B2AR_HUMAN 342 31 -
LRRSSLKAYGNGYSNNSNS B2AR_CANFA 342 31 -
LRRSSLKAYGNGCSSNSND B2AR_BOVIN 342 31 -
LHRSSLKAYGNGCSSNSNG B2AR_PIG 342 31 -

Motif 6 width=20
Element Seqn Id St Int Rpt
GEQSGYHLEQEKENKLLCED B2AR_MACMU 363 2 -
GEPNTCQLGQEREQELLCED B2AR_MOUSE 366 5 -
GEQSAYQLGQEKENELLCEE B2AR_RAT 366 5 -
GEASGCQLGQEKESERLCED B2AR_MESAU 366 5 -
GEQSGYHVEQEKENKLLCED B2AR_HUMAN 361 0 -
GEHSGCHLGQEKDSELLCED B2AR_CANFA 366 5 -
GEQSGYHLGEEKDSELLCED B2AR_BOVIN 366 5 -
GEQSGCYLGEEKDSERLCED B2AR_PIG 366 5 -

Motif 7 width=20
Element Seqn Id St Int Rpt
FVGHQGTVPSDNIDSQGRSC B2AR_MACMU 389 6 -
FVNCQGTVPSLSVDSQGRNC B2AR_MOUSE 392 6 -
FVNCQGTVPSLSIDSQGRNC B2AR_RAT 392 6 -
FVNCQGTVPSLSLDSQGRNC B2AR_MESAU 392 6 -
FVGHQGTVPSDNIDSQGRNC B2AR_HUMAN 387 6 -
TEDRQGTVPSDSVDSQGRNC B2AR_CANFA 389 3 -
FVNQQGTVPSDSIDSQGRNC B2AR_BOVIN 392 6 -
CAHRQGTVPDDSTDSQGRNC B2AR_PIG 392 6 -