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PR01351

Identifier
CGRPRECEPTOR  [View Relations]  [View Alignment]  
Accession
PR01351
No. of Motifs
7
Creation Date
06-MAY-2000
Title
Calcitonin gene-related peptide type 1 receptor signature
Database References
PRINTS; PR01350 CTRFAMILY
GCRDB; GCR_2024; GCR_0951
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.   
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.  
Molecular cloning and expression of a cDNA encoding the secretin receptor.
EMBO J. 10 1635-1641 (1991).
 
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H.,
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor.
SCIENCE 254 1022-1024 (1991). 
 
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F.,
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
 
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
 
6. NJUKI, F., NICHOLL, C.G., HOWARD, A., MAK, J.C., BARNES, P.J.,
GIRGIS, S.I. AND LEGON, S.A.
A new calcitonin-receptor-like sequence in rat pulmonary blood vessels.
CLIN.SCI. 85(4) 385-388 (1993).
 
7. AIYAR, N., RAND, K., ELSHOURBAGY, N.A., ZENG, Z., ADAMOU, J.E.,
BERGSMA, D.J. AND LI, Y.
A cDNA encoding the calcitonin gene-related peptide type 1 receptor.
J.BIOL.CHEM. 271 11325-11329 (1996). 
 
8. NJUKI, F., NICHOLL, C.G., HOWARD, A., MAK, J.C., BARNES, P.J., 
GIRGIS, S.I. AND LEGON, S.
A new calcitonin-receptor-like sequence in rat pulmonary blood vessels.
CLIN.SCI. 85 385-388 (1993). 
 
9. FLUHMANN, B., MUFF, R., HUNZIKER, W., FISCHER, J.A. AND BORN, W.
A human orphan calcitonin receptor-like structure. 
BIOCHEM.BIOPHYS.RES.COMMUN. 206 341-347 (1995). 

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 secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid   
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-   
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a manner
reminiscent of the rhodopsins and other receptors believed to interact with
G proteins. However, while a similar 3D framework has been proposed to
account for this, there is no significant sequence identity between these
families: the secretin-like receptors thus bear their own unique `7TM'
signature.      
 
Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse
biological effects including potent vasodilator activity [6]. Messenger RNA
for this receptor is predominantly expressed in the lung and heart, with
specific localisation to lung alveolar cells and cardiac myocytes [7]. In 
the rat lung, it is associated with blood vessels; the gene may therefore
play an important role in the maintenance of vascular tone [8]. mRNA is also
found in the cerebellum [9]. The ligand for this receptor-like protein 
remains to be discovered. 
 
CGRPRECEPTOR is a 7-element fingerprint that provides a signature for the
calcitonin gene-related peptide type 1 receptors. The fingerprint was 
derived from an initial alignment of 2 sequences: the motifs were drawn
from conserved regions spanning the full alignment length, focusing on 
those sections that characterise the CGRP receptors but distinguish them
from the rest of the secretin-like GPCR superfamily - motifs 1-4 reside in
the N-terminal putative extracellular domain; motif 5 spans the first
external loop; and motifs 6 and 7 reside in the cytoplasmic C-terminus. A
single iteration on SPTR37_10f was required to reach convergence, no further
sequences being identified beyond the starting set.
Summary Information
2 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
72222222
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
CGRR_HUMAN    CGRR_RAT      
Sequence Titles
CGRR_HUMAN  CALCITONIN GENE-RELATED PEPTIDE TYPE 1 RECEPTOR PRECURSOR (CGRP TYPE 1 RECEPTOR) - HOMO SAPIENS (HUMAN). 
CGRR_RAT CALCITONIN GENE-RELATED PEPTIDE TYPE 1 RECEPTOR PRECURSOR (CGRP TYPE 1 RECEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
SPTR37_10f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
KKCTLYFLVLLPFFMILVTAELEE CGRR_HUMAN 3 3 -
KKCTLCFLFLLLLNMALIAAESEE CGRR_RAT 4 4 -

Motif 2 width=14
Element Seqn Id St Int Rpt
LGVTRNKIMTAQYE CGRR_HUMAN 34 7 -
LGVTRNKIMTAQYE CGRR_RAT 34 6 -

Motif 3 width=12
Element Seqn Id St Int Rpt
QKIMQDPIQQAE CGRR_HUMAN 50 2 -
QKIMQDPIQQGE CGRR_RAT 50 2 -

Motif 4 width=11
Element Seqn Id St Int Rpt
NDVAAGTESMQ CGRR_HUMAN 76 14 -
NDVAAGTESMQ CGRR_RAT 76 14 -

Motif 5 width=13
Element Seqn Id St Int Rpt
TAVANNQALVATN CGRR_HUMAN 196 109 -
TAVANNQALVATN CGRR_RAT 196 109 -

Motif 6 width=17
Element Seqn Id St Int Rpt
QFGNSFSNSEALRSASY CGRR_HUMAN 405 196 -
QFGNGFSHSDALRSASY CGRR_RAT 405 196 -

Motif 7 width=17
Element Seqn Id St Int Rpt
YTVSTISDGPGYSHDCP CGRR_HUMAN 421 -1 -
YTVSTISDVQGYSHDCP CGRR_RAT 421 -1 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
KKCTLYFLVLLPFFMILVTAELEE CGRR_HUMAN 3 3 -
KKCTLCFLFLLLLNMALIAAESEE CGRR_RAT 4 4 -

Motif 2 width=14
Element Seqn Id St Int Rpt
LGVTRNKIMTAQYE CGRR_HUMAN 34 7 -
LGVTRNKIMTAQYE CGRR_RAT 34 6 -

Motif 3 width=12
Element Seqn Id St Int Rpt
QKIMQDPIQQAE CGRR_HUMAN 50 2 -
QKIMQDPIQQGE CGRR_RAT 50 2 -

Motif 4 width=11
Element Seqn Id St Int Rpt
NDVAAGTESMQ CGRR_HUMAN 76 14 -
NDVAAGTESMQ CGRR_RAT 76 14 -

Motif 5 width=13
Element Seqn Id St Int Rpt
TAVANNQALVATN CGRR_HUMAN 196 109 -
TAVANNQALVATN CGRR_RAT 196 109 -

Motif 6 width=17
Element Seqn Id St Int Rpt
QFGNSFSNSEALRSASY CGRR_HUMAN 405 196 -
QFGNGFSHSDALRSASY CGRR_RAT 405 196 -

Motif 7 width=17
Element Seqn Id St Int Rpt
YTVSTISDGPGYSHDCP CGRR_HUMAN 421 -1 -
YTVSTISDVQGYSHDCP CGRR_RAT 421 -1 -