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PR00425

Identifier
BRADYKININR  [View Relations]  [View Alignment]  
Accession
PR00425
No. of Motifs
6
Creation Date
16-DEC-1995  (UPDATE 03-JUL-1999)
Title
Bradykinin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00993 BRADYKINNB1R; PR00994 BRADYKINNB2R
INTERPRO; IPR000496
GCRDB; GCR_0170; GCR_0171; GCR_0775; GCR_1054; GCR_2043; GCR_0302

GCRDB; GCR_0508
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. Of these, B2 is the predominant
subtype, mediating slow contraction of various smooth muscles (including
veins, intestine, uterus, trachea and lung), inducing endothelium-dependent
relaxation of arteries and arterioles, and stimulating natriuresis/diuresis
in kidney. BK also induces hyperalgesia through activation of B2 receptors
in sensory nerve fibres and dorsal root ganglion neurons [6].
 
BRADYKININR is a 6-element fingerprint that provides a signature for 
the bradykinin receptors. The fingerprint was derived from an initial 
alignment of 8 sequences: the motifs were drawn from conserved sections 
within either loop or TM regions, focusing on those areas of the alignment 
that characterise the bradykinin receptors but distinguish them from the 
rest of the rhodopsin-like GPCR superfamily - motif 1 spans the C-terminus
of TM domain 2, leading into the first external loop; motif 2 spans the
N-terminal portion of TM domain 3; motifs 3 and 4 span the C-terminus of 
TM domain 4 and the second external loop; motif 5 spans the C-terminus of
TM domain 5, leading into the third cytoplasmic loop; and motif 6 resides
at the C-terminus. A single iteration on OWL26.3 was required to reach
convergence, no further sequences being identified beyond the starting set.
Several partial matches were also found, all of which are superfamily
members that fail to match one or more motifs.
 
An update on SPTR37_9f identified a true set of 10 sequences, and 1
partial match.
Summary Information
  10 codes involving  6 elements
0 codes involving 5 elements
1 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6101010101010
5000000
4110101
3000000
2000000
123456
True Positives
BRB1_HUMAN    BRB1_RABIT    BRB2_HUMAN    BRB2_MOUSE    
BRB2_RABIT BRB2_RAT O35782 O70526
P97583 Q61125
True Positive Partials
Codes involving 4 elements
O42402
Sequence Titles
BRB1_HUMAN  B1 BRADYKININ RECEPTOR (BK-1 RECEPTOR) - HOMO SAPIENS (HUMAN). 
BRB1_RABIT B1 BRADYKININ RECEPTOR (BK-1 RECEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
BRB2_HUMAN B2 BRADYKININ RECEPTOR (BK-2 RECEPTOR) - HOMO SAPIENS (HUMAN).
BRB2_MOUSE B2 BRADYKININ RECEPTOR (BK-2 RECEPTOR) (B2R) - MUS MUSCULUS (MOUSE).
BRB2_RABIT B2 BRADYKININ RECEPTOR (BK-2 RECEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
BRB2_RAT B2 BRADYKININ RECEPTOR (BK-2 RECEPTOR) - RATTUS NORVEGICUS (RAT).
O35782 KININ B1 RECEPTOR - RATTUS NORVEGICUS (RAT).
O70526 BRADYKININ B2 RECEPTOR - CAVIA PORCELLUS (GUINEA PIG).
P97583 B1 BRADYKININ RECEPTOR - RATTUS NORVEGICUS (RAT).
Q61125 BRADYKININ RECEPTOR, BETA (BRADYKININ RECEPTOR B1 SUBTYPE RECEPTOR) - MUS MUSCULUS (MOUSE).

O42402 ORNITHOKININ RECEPTOR - GALLUS GALLUS (CHICKEN).
Scan History
OWL30_2    1  100  NSINGLE    
SPTR37_9f 2 50 NSINGLE
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
FWAENIWNQFNW BRB1_HUMAN 92 92 -
FWAENVRNQFDW BRB1_RABIT 91 91 -
FWAITISNNFDW BRB2_HUMAN 112 112 -
FWAITIANNFDW BRB2_MOUSE 87 87 -
FWAITIANNFDW BRB2_RAT 87 87 -
FWAENIGNRFNW AF009899 102 102 -
FWQGNIGNRFNW RNU66107 102 102 -
FWAENVGNRFNW JC4681 99 99 -
FWAITIANNFDW CPAJ3243 86 86 -
FWAVTIANHFDW OCU33334 88 88 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VVSGVIKANLFVSI RNU66107 122 8 -
VVSGVIKANLFISI JC4681 119 8 -
VVSGVIKANLFVSI AF009899 122 8 -
MVNTMIQMNMYSSI CPAJ3243 106 8 -
VVNTMIYMNLYSSI OCU33334 108 8 -
VVNTMIYMNLYSSI BRB2_RAT 107 8 -
VVNTMIYMNLYSSI BRB2_MOUSE 107 8 -
VVNAIISMNLYSSI BRB2_HUMAN 132 8 -
IVNGVIKANLFISI BRB1_RABIT 111 8 -
VINGVIKANLFISI BRB1_HUMAN 112 8 -

Motif 3 width=14
Element Seqn Id St Int Rpt
LLLSSPMLVFRTMK OCU33334 162 40 -
GLLSIPTFLLRSIQ BRB1_HUMAN 166 40 -
GLLSTPTFVLRSVR BRB1_RABIT 165 40 -
LLLSSPMLVFRTMK BRB2_HUMAN 186 40 -
LLLSSPMLVFRTMR BRB2_MOUSE 161 40 -
LLLSSPMLVFRTMK BRB2_RAT 161 40 -
GLLSTPTFLLRSVK JC4681 173 40 -
GLLSIPTFLLRSVK AF009899 176 40 -
GLLSIPTFLLRSVK RNU66107 176 40 -
LLLSSPMLVFRTMK CPAJ3243 160 40 -

Motif 4 width=14
Element Seqn Id St Int Rpt
NVTACIIDYPSRSW OCU33334 183 7 -
NVTACVIVYPSRSW BRB2_RAT 182 7 -
NVTACVIVYPSRSW BRB2_MOUSE 182 7 -
NVTACVISYPSLIW BRB2_HUMAN 207 7 -
NVSACILLLPHEAW BRB1_RABIT 184 5 -
NITACILLLPHEAW BRB1_HUMAN 185 5 -
NISACILLFPHEAW JC4681 192 5 -
NVSACILLFPHEAW AF009899 195 5 -
NVSACILLFPHEAW RNU66107 195 5 -
NVTACLIIYPSLTW CPAJ3243 181 7 -

Motif 5 width=13
Element Seqn Id St Int Rpt
ITFCTVRIMQVLR BRB2_RAT 215 19 -
ITFCTVQILQVLR OCU33334 216 19 -
ITFCTVQIMQVLR CPAJ3243 214 19 -
IIFFNYHILASLR RNU66107 228 19 -
IIFFNYHILASLR AF009899 228 19 -
ITFCTVRILQVLR BRB2_MOUSE 215 19 -
ITFCTMQIMQVLR BRB2_HUMAN 240 19 -
ILFFNCHILASLR BRB1_RABIT 217 19 -
IVFFNYHILASLR BRB1_HUMAN 218 19 -
ILYFNFHILASLR JC4681 225 19 -

Motif 6 width=13
Element Seqn Id St Int Rpt
VFVGRLFRTKVWE BRB1_HUMAN 313 82 -
VIVGKRFRKKSRE OCU33334 309 80 -
VIVGKRFRKKSRE CPAJ3243 306 79 -
VFAGRLLKTRVLG RNU66107 323 82 -
VFAGRLLKTRVLG AF009899 323 82 -
VIVGKRFRKKSRE BRB2_RAT 308 80 -
VIVGKRFRKKSRE BRB2_MOUSE 308 80 -
VIVGKRFRKKSWE BRB2_HUMAN 333 80 -
VFVGRLFRTKVWE BRB1_RABIT 312 82 -
VFAGRLFKTRVLG JC4681 320 82 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
FWAVTIANHFDW BRB2_RABIT 88 88 -
FWAITIANNFDW BRB2_RAT 87 87 -
FWAITIANNFDW BRB2_MOUSE 87 87 -
FWAITISNNFDW BRB2_HUMAN 112 112 -
FWAENVRNQFDW BRB1_RABIT 91 91 -
FWAITIANNFDW O70526 86 86 -
FWAENIWNQFNW BRB1_HUMAN 92 92 -
FWAENIGNRFNW O35782 102 102 -
FWQGNIGNRFNW P97583 102 102 -
FWAENVGNRFNW Q61125 99 99 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VVNTMIYMNLYSSI BRB2_RABIT 108 8 -
VVNTMIYMNLYSSI BRB2_RAT 107 8 -
VVNTMIYMNLYSSI BRB2_MOUSE 107 8 -
VVNAIISMNLYSSI BRB2_HUMAN 132 8 -
IVNGVIKANLFISI BRB1_RABIT 111 8 -
MVNTMIQMNMYSSI O70526 106 8 -
VINGVIKANLFISI BRB1_HUMAN 112 8 -
VVSGVIKANLFVSI O35782 122 8 -
VVSGVIKANLFVSI P97583 122 8 -
VVSGVIKANLFISI Q61125 119 8 -

Motif 3 width=14
Element Seqn Id St Int Rpt
LLLSSPMLVFRTMK BRB2_RABIT 162 40 -
LLLSSPMLVFRTMK BRB2_RAT 161 40 -
LLLSSPMLVFRTMR BRB2_MOUSE 161 40 -
LLLSSPMLVFRTMK BRB2_HUMAN 186 40 -
GLLSTPTFVLRSVR BRB1_RABIT 165 40 -
LLLSSPMLVFRTMK O70526 160 40 -
GLLSIPTFLLRSIQ BRB1_HUMAN 166 40 -
GLLSIPTFLLRSVK O35782 176 40 -
GLLSIPTFLLRSVK P97583 176 40 -
GLLSTPTFLLRSVK Q61125 173 40 -

Motif 4 width=14
Element Seqn Id St Int Rpt
NVTACIIDYPSRSW BRB2_RABIT 183 7 -
NVTACVIVYPSRSW BRB2_RAT 182 7 -
NVTACVIVYPSRSW BRB2_MOUSE 182 7 -
NVTACVISYPSLIW BRB2_HUMAN 207 7 -
NVSACILLLPHEAW BRB1_RABIT 184 5 -
NVTACLIIYPSLTW O70526 181 7 -
NITACILLLPHEAW BRB1_HUMAN 185 5 -
NVSACILLFPHEAW O35782 195 5 -
NVSACILLFPHEAW P97583 195 5 -
NISACILLFPHEAW Q61125 192 5 -

Motif 5 width=13
Element Seqn Id St Int Rpt
ITFCTVQILQVLR BRB2_RABIT 216 19 -
ITFCTVRIMQVLR BRB2_RAT 215 19 -
ITFCTVRILQVLR BRB2_MOUSE 215 19 -
ITFCTMQIMQVLR BRB2_HUMAN 240 19 -
ILFFNCHILASLR BRB1_RABIT 217 19 -
ITFCTVQIMQVLR O70526 214 19 -
IVFFNYHILASLR BRB1_HUMAN 218 19 -
IIFFNYHILASLR O35782 228 19 -
IIFFNYHILASLR P97583 228 19 -
ILYFNFHILASLR Q61125 225 19 -

Motif 6 width=13
Element Seqn Id St Int Rpt
VIVGKRFRKKSRE BRB2_RABIT 309 80 -
VIVGKRFRKKSRE BRB2_RAT 308 80 -
VIVGKRFRKKSRE BRB2_MOUSE 308 80 -
VIVGKRFRKKSWE BRB2_HUMAN 333 80 -
VFVGRLFRTKVWE BRB1_RABIT 312 82 -
VIVGKRFRKKSRE O70526 306 79 -
VFVGRLFRTKVWE BRB1_HUMAN 313 82 -
VFAGRLLKTRVLG O35782 323 82 -
VFAGRLLKTRVLG P97583 323 82 -
VFAGRLFKTRVLG Q61125 320 82 -