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PR00993

Identifier
BRADYKINNB1R  [View Relations]  [View Alignment]  
Accession
PR00993
No. of Motifs
8
Creation Date
25-NOV-1998  (UPDATE 06-JUN-1999)
Title
B1 bradykinin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00425 BRADYKININR
INTERPRO; IPR001186
GCRDB; GCR_1054; GCR_2043
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,
Bradykinin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, pp67-70.

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]. 
 
Bradykinins (BKs) are a family of short, structurally similar peptides that 
activate sensory fibres, contract venous smooth muscle, stimulate release
of cytokines, induce connective tissue proliferation and mediate endo-
thelium-dependent vasodilation [6]. BK antagonists are of potential use
in the treatment of inflammation, asthma, mild pain and endotoxic shock.
BK receptors are widespread in peripheral tissues, and at least 3 different
receptor subtypes have been proposed, designated B1, B2 and B3. 
 
B2 is the predominant bradykinin subtype. The B1 receptor has limited
distribution in the periphery, but has not been described in the CNS [6].
It stimulates contraction of rabbit aorta and rat duodenum, and mediates
relaxation of rabbit mesenteric and coeliac arteries [6]. In rabbit 
vascular smooth muscle, the expression of B1 receptors is increased
following various pathological insults, in vitro or in vivo [6]. In the
majority of tissues, bradykinin induces activation of phosphoinositide
metabolism via a pertussis-toxin-insensitive G protein, probably of the
Gq/G11 class [6]. It has also been reported to inhibit adenylyl cyclase
through a persussis-toxin-insensitive G protein, and to raise levels of
cGMP and open ion channels. It also stimulates PLA2, possibly by direct
activation of a G protein.
 
BRADYKINNB1R is an 8-element fingerprint that provides a signature for 
the B1 bradykinin receptors. The fingerprint was derived from an initial 
alignment of 5 sequences: the motifs were drawn from conserved sections 
within either loop or TM regions, focusing on those areas of the alignment 
that characterise the B1 bradykinin receptors but distinguish them from the 
rest of the bradykinin receptor family - motifs 1 and 2 span the N-terminus,
leading into TM domain 1; motif 3 encodes the central portion of TM domain
3; motif 4 spans the C-terminus of TM domain 4, leading into the second
external loop; motif 5 spans the C-terminus of the second cytoplasmic loop
and the N-terminal portion of TM domain 5; motifs 6 and 7 span the 
C-terminus of TM domain 5, the third cytoplasmic loop and the N-terminal
portion of TM domain 6; and motif 8 spans the C-terminus of TM domain 6,
leading into the third external loop. A single iteration on OWL30.2 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  8 elements
0 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
855555555
700000000
600000000
500000000
400000000
300000000
200000000
12345678
True Positives
BRB1_HUMAN    BRB1_RABIT    O35782        P97583        
Q61125
Sequence Titles
BRB1_HUMAN  B1 BRADYKININ RECEPTOR (BK-1 RECEPTOR) - HOMO SAPIENS (HUMAN). 
BRB1_RABIT B1 BRADYKININ RECEPTOR (BK-1 RECEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
O35782 KININ B1 RECEPTOR - RATTUS NORVEGICUS (RAT).
P97583 B1 BRADYKININ RECEPTOR - RATTUS NORVEGICUS (RAT).
Q61125 BRADYKININ RECEPTOR, BETA (BRADYKININ RECEPTOR B1 SUBTYPE RECEPTOR) - MUS MUSCULUS (MOUSE).
Scan History
OWL30_2    1  100  NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
LELQPSNQSQLAPPN BRB1_RABIT 7 7 -
LELQPSNRSLQAPAN RNU66107 7 7 -
LKLQPSNQSQQAPPN JC4681 7 7 -
LELQPSNRSLQAPAN AF009899 7 7 -
LELQSSNQSQLFPQN BRB1_HUMAN 8 8 -

Motif 2 width=17
Element Seqn Id St Int Rpt
NITSCESALEDWDLLYR RNU66107 21 -1 -
NATACDNAPEAWDLLHR BRB1_HUMAN 22 -1 -
NATSCSGAPDAWDLLHR BRB1_RABIT 21 -1 -
NITSCEGAPEAWDLLCR JC4681 21 -1 -
NITSCESALEDWDLLYR AF009899 21 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FISIFLVVAISQ BRB1_HUMAN 122 83 -
FISIFLVVAISQ JC4681 129 91 -
FVSIFLVVAISQ AF009899 132 94 -
FVSIFLVVAISQ RNU66107 132 94 -
FISIFLVVAISQ BRB1_RABIT 121 83 -

Motif 4 width=16
Element Seqn Id St Int Rpt
IPTFLLRSIQAVPDLN BRB1_HUMAN 170 36 -
IPTFLLRSVKVVPDLN RNU66107 180 36 -
IPTFLLRSVKVVPDLN AF009899 180 36 -
TPTFLLRSVKVVPDLN JC4681 177 36 -
TPTFVLRSVRAVPELN BRB1_RABIT 169 36 -

Motif 5 width=12
Element Seqn Id St Int Rpt
HEAWHFARMVEL RNU66107 205 9 -
HEAWHFARMVEL AF009899 205 9 -
HEAWHFVRMVEL JC4681 202 9 -
HEAWHFARIVEL BRB1_HUMAN 195 9 -
HEAWHWLRMVEL BRB1_RABIT 194 9 -

Motif 6 width=16
Element Seqn Id St Int Rpt
VFFNYHILASLRTREE BRB1_HUMAN 219 12 -
IFFNYHILASLRGQKE RNU66107 229 12 -
LYFNFHILASLRGQKE JC4681 226 12 -
LFFNCHILASLRRRGE BRB1_RABIT 218 12 -
IFFNYHILASLRGQKE AF009899 229 12 -

Motif 7 width=18
Element Seqn Id St Int Rpt
RCGGPKGSKTTGLILTLV AF009899 249 4 -
RCGGPKDSKTMGLILTLV JC4681 246 4 -
RCGGPKGSKTTGLILTLV RNU66107 249 4 -
RCGGPRDSKSTALILTLV BRB1_RABIT 238 4 -
RVRGPKDSKTTALILTLV BRB1_HUMAN 239 4 -

Motif 8 width=20
Element Seqn Id St Int Rpt
HFFAFLDFLVQVRVIQDCFW JC4681 274 10 -
HFFAFLECLWQVHAIGGCFW BRB1_RABIT 266 10 -
HFFAFLEFLFQVQAVRGCFW BRB1_HUMAN 267 10 -
HFFAFLDFLVQVRVIQDCSW RNU66107 277 10 -
HFFAFLDFLVQVRVIQDCSW AF009899 277 10 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
LELQSSNQSQLFPQN BRB1_HUMAN 8 8 -
LELQPSNRSLQAPAN O35782 7 7 -
LELQPSNRSLQAPAN P97583 7 7 -
LKLQPSNQSQQAPPN Q61125 7 7 -
LELQPSNQSQLAPPN BRB1_RABIT 7 7 -

Motif 2 width=17
Element Seqn Id St Int Rpt
NATSCSGAPDAWDLLHR BRB1_RABIT 21 -1 -
NITSCESALEDWDLLYR O35782 21 -1 -
NITSCESALEDWDLLYR P97583 21 -1 -
NITSCEGAPEAWDLLCR Q61125 21 -1 -
NATACDNAPEAWDLLHR BRB1_HUMAN 22 -1 -

Motif 3 width=12
Element Seqn Id St Int Rpt
FISIFLVVAISQ BRB1_RABIT 121 83 -
FVSIFLVVAISQ O35782 132 94 -
FVSIFLVVAISQ P97583 132 94 -
FISIFLVVAISQ Q61125 129 91 -
FISIFLVVAISQ BRB1_HUMAN 122 83 -

Motif 4 width=16
Element Seqn Id St Int Rpt
IPTFLLRSVKVVPDLN O35782 180 36 -
IPTFLLRSVKVVPDLN P97583 180 36 -
TPTFLLRSVKVVPDLN Q61125 177 36 -
TPTFVLRSVRAVPELN BRB1_RABIT 169 36 -
IPTFLLRSIQAVPDLN BRB1_HUMAN 170 36 -

Motif 5 width=12
Element Seqn Id St Int Rpt
HEAWHFARMVEL O35782 205 9 -
HEAWHFARMVEL P97583 205 9 -
HEAWHFVRMVEL Q61125 202 9 -
HEAWHWLRMVEL BRB1_RABIT 194 9 -
HEAWHFARIVEL BRB1_HUMAN 195 9 -

Motif 6 width=16
Element Seqn Id St Int Rpt
IFFNYHILASLRGQKE O35782 229 12 -
IFFNYHILASLRGQKE P97583 229 12 -
LYFNFHILASLRGQKE Q61125 226 12 -
LFFNCHILASLRRRGE BRB1_RABIT 218 12 -
VFFNYHILASLRTREE BRB1_HUMAN 219 12 -

Motif 7 width=18
Element Seqn Id St Int Rpt
RCGGPKGSKTTGLILTLV O35782 249 4 -
RCGGPKGSKTTGLILTLV P97583 249 4 -
RCGGPKDSKTMGLILTLV Q61125 246 4 -
RCGGPRDSKSTALILTLV BRB1_RABIT 238 4 -
RVRGPKDSKTTALILTLV BRB1_HUMAN 239 4 -

Motif 8 width=20
Element Seqn Id St Int Rpt
HFFAFLDFLVQVRVIQDCSW O35782 277 10 -
HFFAFLDFLVQVRVIQDCSW P97583 277 10 -
HFFAFLDFLVQVRVIQDCFW Q61125 274 10 -
HFFAFLECLWQVHAIGGCFW BRB1_RABIT 266 10 -
HFFAFLEFLFQVQAVRGCFW BRB1_HUMAN 267 10 -