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PR00358

Identifier
BOMBESINR  [View Relations]  [View Alignment]  
Accession
PR00358
No. of Motifs
6
Creation Date
12-JUL-1995  (UPDATE 06-JUN-1999)
Title
Bombesin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00237 GPCRRHODOPSN
PRINTS; PR00637 BOMBESIN3R; PR00638 BOMBESIN4R; PR00640 GASTRINRELPR
PRINTS; PR00639 NEUROMEDINBR
INTERPRO; IPR001556
GCRDB; GCR_0187
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.
Bombesin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.60-66.

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].
 
Bombesins are peptide neurotransmitters whose biological activity resides
in a common C-terminal sequence, WAXGHXM [6]. In the periphery, bombesin-
related peptides stimulate smooth muscle and glandular secretion. In the
brain, these peptides are believed to play a role in homeostasis, thermo-
regulation and metabolism, and have been reported to elicit analgesia and
excessive grooming, together with central regulation of a variety of
peripheral effects. 
 
Mammalian bombesins are encoded by 2 genes. The preproGRP gene transcript
encodes a precursor of 147 amino acids, which gives GRP and GRP18-27. The
preproNMB gene transcript encodes a precursor of 117 amino acids, which is
metabolised to neuromedin B. Receptors for these peptides have widespread
distribution in peripheral tissue. High levels are found in smooth muscle
and in the brain. 
 
BOMBESINR is a 6-element fingerprint that provides a signature for the
bombesin receptors. The fingerprint was derived from an initial alignment
of 6 sequences: the motifs were drawn from conserved sections within either
loop or TM regions, focusing on those areas of the alignment that
characterise the bombesin receptors but distinguish them from the rest of
the rhodopsin-like superfamily - motif 1 spans the C-terminus of TM domain
2 leading into the first external loop; motif 2 lies in the N-terminal
region of TM domain 3; motif 3 spans part of the second external loop;
motif 4 was taken from the third cytoplasmic loop; motif 5 spans part of
the third external loop leading into TM domain 7; and motif 6 lies at the
C-terminus. Two iterations on OWL26.0 were required to reach convergence,
at which point a true set comprising 7 sequences was identfied. 
 
An update on SPTR37_9f identified a true set of 9 sequences, and 2
partial matches.
Summary Information
   9 codes involving  6 elements
2 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6999999
5222202
4000000
3000000
2000000
123456
True Positives
BRS3_CAVPO    BRS3_HUMAN    BRS4_BOMOR    GRPR_HUMAN    
GRPR_MOUSE GRPR_RAT NMBR_HUMAN NMBR_RAT
O54799
True Positive Partials
Codes involving 5 elements
O54798 O88790
Sequence Titles
BRS3_CAVPO  Bombesin receptor subtype-3 (BRS-3) - Cavia porcellus (Guinea pig). 
BRS3_HUMAN Bombesin receptor subtype-3 (BRS-3) - Homo sapiens (Human).
BRS4_BOMOR [Phe13]-bombesin receptor (Bombesin receptor subtype-4) (BRS-4) - Bombina orientalis (Oriental fire-bellied toad).
GRPR_HUMAN Gastrin-releasing peptide receptor (GRP-R) (GRP-preferring bombesin receptor) - Homo sapiens (Human).
GRPR_MOUSE Gastrin-releasing peptide receptor (GRP-R) (GRP-preferring bombesin receptor) - Mus musculus (Mouse).
GRPR_RAT Gastrin-releasing peptide receptor (GRP-R) (GRP-preferring bombesin receptor) - Rattus norvegicus (Rat).
NMBR_HUMAN Neuromedin-B receptor (NMB-R) (Neuromedin-B-preferring bombesin receptor) - Homo sapiens (Human).
NMBR_RAT Neuromedin-B receptor (NMB-R) (Neuromedin-B-preferring bombesin receptor) - Rattus norvegicus (Rat).
O54799 NEUROMEDIN B RECEPTOR - MUS MUSCULUS (MOUSE).

O54798 BOMBESIN-LIKE RECEPTOR 3 (BOMBESIN RECEPTOR SUBTYPE-3) - MUS MUSCULUS (MOUSE).
O88790 BOMBESIN RECEPTOR SUBTYPE-3 - MUS MUSCULUS (MOUSE).
Scan History
OWL26_0    2  100  NSINGLE    
SPTR37_9f 2 12 NSINGLE
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
CAPVDASRYLADRWLF GRPR_HUMAN 93 93 -
CAPVDASKYLADRWLF GRPR_MOUSE 94 94 -
CVPVDASRYFFDEWVF NMBR_RAT 96 96 -
CVPVDASRYFFDEWMF NMBR_HUMAN 96 96 -
CVPVDATHYLAEGWLF BRS3_HUMAN 100 100 -
CVPVDATHYLAEGWLF BRS3_CAVPO 100 100 -

Motif 2 width=17
Element Seqn Id St Int Rpt
KLIPFIQLTSVGVSVFT GRPR_HUMAN 114 5 -
KLIPFIQLTSVGVSVFT GRPR_MOUSE 115 5 -
KLIPAIQLTSVGVSVFT NMBR_RAT 117 5 -
KLIPVIQLTSVGVSVFT NMBR_HUMAN 117 5 -
KVLSFIRLTSVGVSVFT BRS3_HUMAN 121 5 -
KVLSFIRLTSVGVSVFT BRS3_CAVPO 121 5 -

Motif 3 width=14
Element Seqn Id St Int Rpt
YPHSNELHPKIHSM GRPR_HUMAN 199 68 -
YPHSNELHPKIHSM GRPR_MOUSE 200 68 -
YPQTDELHPKIHSV NMBR_RAT 201 67 -
YPQTDELHPKIHSV NMBR_HUMAN 201 67 -
YPVSKKLLQEIHSL BRS3_HUMAN 206 68 -
YPVSEKLLQEIHAL BRS3_CAVPO 206 68 -

Motif 4 width=19
Element Seqn Id St Int Rpt
NLPVEGNIHVKKQIESRKR GRPR_HUMAN 243 30 -
NLPVEGNIHVKKQIESRKR GRPR_MOUSE 244 30 -
NLPGEYNEHTKKQMETRKR NMBR_RAT 245 30 -
NLPGEYNEHTKKQMETRKR NMBR_HUMAN 245 30 -
NIPTEEQSHARKQIESRKR BRS3_HUMAN 250 30 -
NIPTEEQSHARKQVESRKR BRS3_CAVPO 250 30 -

Motif 5 width=14
Element Seqn Id St Int Rpt
DTSMLHFVTSICAR GRPR_HUMAN 295 33 -
DTSMLHFVTSICAR GRPR_MOUSE 296 33 -
DPSLGHMIVTLVAR NMBR_RAT 297 33 -
DPSLGHMIVTLVAR NMBR_HUMAN 297 33 -
DPSAMHFIFTIFSR BRS3_HUMAN 303 34 -
DSSAIHFIVTIFSR BRS3_CAVPO 303 34 -

Motif 6 width=14
Element Seqn Id St Int Rpt
LSKSFRKQFNTQLL GRPR_HUMAN 325 16 -
LSKSFRKQFNTQLL GRPR_MOUSE 326 16 -
LSESFRKHFNSQLC NMBR_RAT 327 16 -
LSESFRRHFNSQLC NMBR_HUMAN 327 16 -
LSKSFQKHFKAQLF BRS3_HUMAN 333 16 -
LSKTFQKQFKAQLF BRS3_CAVPO 333 16 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
CAPVDASKYLADRWLF GRPR_RAT 94 94 -
CAPVDASRYLADRWLF GRPR_HUMAN 93 93 -
CAPVDASKYLADRWLF GRPR_MOUSE 94 94 -
CVPVDASRYFFDEWVF NMBR_RAT 96 96 -
CVPVDASRYFFDEWVF O54799 96 96 -
CVPVDASRYFFDEWMF NMBR_HUMAN 96 96 -
CVPVDATHYLAEGWLF BRS3_HUMAN 100 100 -
CVPVDATHYLAEGWLF BRS3_CAVPO 100 100 -
CVPVDASRYIVDTWMF BRS4_BOMOR 99 99 -

Motif 2 width=17
Element Seqn Id St Int Rpt
KLIPFIQLTSVGVSVFT GRPR_RAT 115 5 -
KLIPFIQLTSVGVSVFT GRPR_HUMAN 114 5 -
KLIPFIQLTSVGVSVFT GRPR_MOUSE 115 5 -
KLIPAIQLTSVGVSVFT NMBR_RAT 117 5 -
KLIPAIQLTSVGVSVFT O54799 117 5 -
KLIPVIQLTSVGVSVFT NMBR_HUMAN 117 5 -
KVLSFIRLTSVGVSVFT BRS3_HUMAN 121 5 -
KVLSFIRLTSVGVSVFT BRS3_CAVPO 121 5 -
KIISFIQLTSVGVSVFT BRS4_BOMOR 120 5 -

Motif 3 width=14
Element Seqn Id St Int Rpt
YPHSNELHPKIHSM GRPR_RAT 200 68 -
YPHSNELHPKIHSM GRPR_HUMAN 199 68 -
YPHSNELHPKIHSM GRPR_MOUSE 200 68 -
YPQTDELHPKIHSV NMBR_RAT 201 67 -
YPQTDELHPKIHSV O54799 201 67 -
YPQTDELHPKIHSV NMBR_HUMAN 201 67 -
YPVSKKLLQEIHSL BRS3_HUMAN 206 68 -
YPVSEKLLQEIHAL BRS3_CAVPO 206 68 -
YPVSEKILQETHSL BRS4_BOMOR 205 68 -

Motif 4 width=19
Element Seqn Id St Int Rpt
NLPVEGNIHVKKQIESRKR GRPR_RAT 244 30 -
NLPVEGNIHVKKQIESRKR GRPR_HUMAN 243 30 -
NLPVEGNIHVKKQIESRKR GRPR_MOUSE 244 30 -
NLPGEYNEHTKKQMETRKR NMBR_RAT 245 30 -
NLPGEYNEHTKKQMETRKR O54799 245 30 -
NLPGEYNEHTKKQMETRKR NMBR_HUMAN 245 30 -
NIPTEEQSHARKQIESRKR BRS3_HUMAN 250 30 -
NIPTEEQSHARKQVESRKR BRS3_CAVPO 250 30 -
NMPAEEHTHARKQIESRKR BRS4_BOMOR 249 30 -

Motif 5 width=14
Element Seqn Id St Int Rpt
DTSMLHFITSICAR GRPR_RAT 296 33 -
DTSMLHFVTSICAR GRPR_HUMAN 295 33 -
DTSMLHFVTSICAR GRPR_MOUSE 296 33 -
DPSLGHMIVTLVAR NMBR_RAT 297 33 -
DPSLGHMIVTLVAR O54799 297 33 -
DPSLGHMIVTLVAR NMBR_HUMAN 297 33 -
DPSAMHFIFTIFSR BRS3_HUMAN 303 34 -
DSSAIHFIVTIFSR BRS3_CAVPO 303 34 -
NSSAFHLSATIFAR BRS4_BOMOR 302 34 -

Motif 6 width=14
Element Seqn Id St Int Rpt
LSKSFRKQFNTQLL GRPR_RAT 326 16 -
LSKSFRKQFNTQLL GRPR_HUMAN 325 16 -
LSKSFRKQFNTQLL GRPR_MOUSE 326 16 -
LSESFRKHFNSQLC NMBR_RAT 327 16 -
LSESFRKHFNSQLC O54799 327 16 -
LSESFRRHFNSQLC NMBR_HUMAN 327 16 -
LSKSFQKHFKAQLF BRS3_HUMAN 333 16 -
LSKTFQKQFKAQLF BRS3_CAVPO 333 16 -
LSRSFRQHFKKQVY BRS4_BOMOR 332 16 -