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PR01350

Identifier
CTRFAMILY  [View Relations]  [View Alignment]  
Accession
PR01350
No. of Motifs
9
Creation Date
06-MAY-2000
Title
Calcitonin receptor family signature
Database References
PRINTS; PR01351 CGRPRECEPTOR
GCRDB; GCR_0257; GCR_0995; GCR_2000; GCR_2001; GCR_2119; GCR_2024
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. WATSON, S. AND ARKINSTALL, S.
Calcitonin.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.74-76.
 
7. 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).
 
8. 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). 
 
9. 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). 
 
10. 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.      
 
The major physiological role of calcitonin is to inhibit bone resorption
thereby leading to a reduction in plasma Ca++ [6]. Further, it enhances 
excretion of ions in the kidney, prevents absorption of ions in the 
intestine, and inhibits secretion in endocrine cells (e.g. pancreas and
pituitary). In the CNS, calcitonin has been reported to be analgesic
and to suppress feeding and gastric acid secretion. It is used to treat
Paget's disease of the bone. Calcitonin receptors are found predominantly
on osteoclasts or on immortal cell lines derived from these cells. It is
found in lower amounts in the brain (e.g. in hypothalamus and pituitary
tissues) and in peripheral tissues (e.g. testes, kidney, liver and
lymphocytes). It has also been described in lung and breast cancer cell
lines. The predominant signalling pathway is activation of adenylyl cyclase
through Gs, but calcitonin has also been described to have both stimulatory
and inhibitory actions on the phosphoinositide pathway.
 
Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse
biological effects including potent vasodilator activity [8]. Messenger RNA
for this receptor is predominantly expressed in the lung and heart, with
specific localisation to lung alveolar cells and cardiac myocytes [8]. In 
the rat lung, it is associated with blood vessels; the gene may therefore
play an important role in the maintenance of vascular tone [9]. mRNA is also
found in the cerebellum [10]. The ligand for this receptor-like protein 
remains to be discovered. 
 
CTRFAMILY is a 9-element fingerprint that provides a signature for the
calcitonin receptor family. The fingerprint was derived from an initial 
alignment of 5 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that 
characterise the calcitonin receptor family but distinguish it from the
rest of the secretin-like GPCR superfamily - motifs 1-5 span the N-terminal
putative extracellular domain, motif 5 leading into the first TM domain; 
motif 6 spans the C-terminus of putative TM domain 4; motif 7 includes the
N-terminus of TM domain 7; and motifs 8 and 9 reside at the C-terminus. Two
iterations on SPTR37_10f were required to reach convergence, at which point
a true set comprising 8 sequences was identified.
Summary Information
8 codes involving  9 elements
0 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
9888888888
8000000000
7000000000
6000000000
5000000000
4000000000
3000000000
2000000000
123456789
True Positives
CALR_CAVPO    CALR_HUMAN    CALR_MOUSE    CALR_PIG      
CALR_RABIT CALR_RAT CGRR_HUMAN CGRR_RAT
Sequence Titles
CALR_CAVPO  CALCITONIN RECEPTOR PRECURSOR (CT-R) - CAVIA PORCELLUS (GUINEA PIG). 
CALR_HUMAN CALCITONIN RECEPTOR PRECURSOR (CT-R) - HOMO SAPIENS (HUMAN).
CALR_MOUSE CALCITONIN RECEPTOR PRECURSOR (CT-R) - MUS MUSCULUS (MOUSE).
CALR_PIG CALCITONIN RECEPTOR PRECURSOR (CT-R) - SUS SCROFA (PIG).
CALR_RABIT CALCITONIN RECEPTOR PRECURSOR (CT-R) - ORYCTOLAGUS CUNICULUS (RABBIT).
CALR_RAT CALCITONIN RECEPTOR PRECURSOR (CT-R) (C1A/C1B) - RATTUS NORVEGICUS (RAT).
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  50   NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
QYKCYDRIQQLPPYEGEGPY CALR_RAT 52 52 -
QYKCYDRMQQLPAYQGEGPY CALR_HUMAN 52 52 -
QHRCYDRMQKLPPYQGEGLY CALR_PIG 53 53 -
QYECYQKIMQDPIQQGEGLY CGRR_RAT 45 45 -
QYECYQKIMQDPIQQAEGVY CGRR_HUMAN 45 45 -

Motif 2 width=12
Element Seqn Id St Int Rpt
WDDTPAGVMSYQ CALR_RAT 82 10 -
WDDTPAGVLSYQ CALR_HUMAN 82 10 -
WDDTPAGVLAEQ CALR_PIG 83 10 -
WNDVAAGTESMQ CGRR_RAT 75 10 -
WNDVAAGTESMQ CGRR_HUMAN 75 10 -

Motif 3 width=15
Element Seqn Id St Int Rpt
DYFPDFDPTEKVSKY CALR_RAT 97 3 -
DYFPDFDPSEKVTKY CALR_HUMAN 97 3 -
DYFPDFDAAEKVTKY CALR_PIG 98 3 -
DYFQDFDPSEKVTKI CGRR_RAT 90 3 -
DYFQDFDPSEKVTKI CGRR_HUMAN 90 3 -

Motif 4 width=15
Element Seqn Id St Int Rpt
WFRHPDSNRTWSNYT CALR_RAT 118 6 -
WFKHPENNRTWSNYT CALR_HUMAN 118 6 -
WYRHPESNISWSNYT CALR_PIG 119 6 -
WFRHPDSNRTWTNYT CGRR_RAT 111 6 -
WFRHPASNRTWTNYT CGRR_HUMAN 111 6 -

Motif 5 width=21
Element Seqn Id St Int Rpt
NAFTPDKLHNAYVLYYLALVG CALR_RAT 135 2 -
NAFTPEKLKNAYVLYYLAIVG CALR_HUMAN 135 2 -
NAFTPDKLQNAYILYYLAIVG CALR_PIG 136 2 -
NNSTHEKVKTALNLFYLTIIG CGRR_RAT 128 2 -
NVNTHEKVKTALNLFYLTIIG CGRR_HUMAN 128 2 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PIVPTIIHAITRAVYYNDN CALR_RAT 307 151 -
PLVPTTIHAITRAVYFNDN CALR_HUMAN 286 130 -
PLIPTTAHAITRAVLFNDN CALR_PIG 287 130 -
PLLPACIHAIARSLYYNDN CGRR_RAT 263 114 -
PLIPACIHAIARSLYYNDN CGRR_HUMAN 263 114 -

Motif 7 width=21
Element Seqn Id St Int Rpt
WRPSNKVLGKIYDYLMHSLIH CALR_RAT 398 72 -
WRPSNKMLGKIYDYVMHSLIH CALR_HUMAN 377 72 -
WRPSTPLLGKIYDYVVHSLIH CALR_PIG 378 72 -
WRPEGKVAEEVYDYVMHILMH CGRR_RAT 354 72 -
WRPEGKIAEEVYDYIMHILMH CGRR_HUMAN 354 72 -

Motif 8 width=15
Element Seqn Id St Int Rpt
QVTLKRQWAQFKIQW CALR_RAT 436 17 -
QTTVKRQWAQFKIQW CALR_HUMAN 415 17 -
QGALKRQWNQYQAQR CALR_PIG 416 17 -
QAILRRNWNQYKIQF CGRR_RAT 392 17 -
QAILRRNWNQYKIQF CGRR_HUMAN 392 17 -

Motif 9 width=11
Element Seqn Id St Int Rpt
YICHQEPRNPP CALR_RAT 482 31 -
YICHQEPRNEP CALR_HUMAN 457 27 -
YICHQEPREEP CALR_PIG 462 31 -
HDCPTEHLNGK CGRR_RAT 434 27 -
HDCPSEHLNGK CGRR_HUMAN 434 27 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
QYKCYDRIQQLPPYEGEGPY CALR_RAT 52 52 -
QYKCYDRMQQLPAYQGEGPY CALR_HUMAN 52 52 -
QYRCYDRMQQLPPYEGEGPY CALR_CAVPO 52 52 -
QYKCYDRIHQLPSYEGEGLY CALR_MOUSE 52 52 -
QHRCYDRMQKLPPYQGEGLY CALR_PIG 53 53 -
QYECYQKIMQDPIQQGEGLY CGRR_RAT 45 45 -
QYECYQKIMQDPIQQAEGVY CGRR_HUMAN 45 45 -
QYKCYDRMEQLPPYQGEGPY CALR_RABIT 52 52 -

Motif 2 width=12
Element Seqn Id St Int Rpt
WDDTPAGVMSYQ CALR_RAT 82 10 -
WDDTPAGVLSYQ CALR_HUMAN 82 10 -
WDDTPAGVLSVQ CALR_CAVPO 82 10 -
WDDTPAGATAYQ CALR_MOUSE 82 10 -
WDDTPAGVLAEQ CALR_PIG 83 10 -
WNDVAAGTESMQ CGRR_RAT 75 10 -
WNDVAAGTESMQ CGRR_HUMAN 75 10 -
WDDTPAGVLGFQ CALR_RABIT 82 10 -

Motif 3 width=15
Element Seqn Id St Int Rpt
DYFPDFDPTEKVSKY CALR_RAT 97 3 -
DYFPDFDPSEKVTKY CALR_HUMAN 97 3 -
DYFPDFDPTEKVTKY CALR_CAVPO 97 3 -
DYFPDFDTAEKVSKY CALR_MOUSE 97 3 -
DYFPDFDAAEKVTKY CALR_PIG 98 3 -
DYFQDFDPSEKVTKI CGRR_RAT 90 3 -
DYFQDFDPSEKVTKI CGRR_HUMAN 90 3 -
DYFPDFDPTEKVTKY CALR_RABIT 97 3 -

Motif 4 width=15
Element Seqn Id St Int Rpt
WFRHPDSNRTWSNYT CALR_RAT 118 6 -
WFKHPENNRTWSNYT CALR_HUMAN 118 6 -
WFKHPENNRTWSNYT CALR_CAVPO 118 6 -
WFRHPDSNRTWSNYT CALR_MOUSE 118 6 -
WYRHPESNISWSNYT CALR_PIG 119 6 -
WFRHPDSNRTWTNYT CGRR_RAT 111 6 -
WFRHPASNRTWTNYT CGRR_HUMAN 111 6 -
WFKHPGNNQTWSNYT CALR_RABIT 118 6 -

Motif 5 width=21
Element Seqn Id St Int Rpt
NAFTPDKLHNAYVLYYLALVG CALR_RAT 135 2 -
NAFTPEKLKNAYVLYYLAIVG CALR_HUMAN 135 2 -
NAFTPEKLQNAYVLYYLAIVG CALR_CAVPO 135 2 -
NAFTSEKLQNAYVLYYLALVG CALR_MOUSE 135 2 -
NAFTPDKLQNAYILYYLAIVG CALR_PIG 136 2 -
NNSTHEKVKTALNLFYLTIIG CGRR_RAT 128 2 -
NVNTHEKVKTALNLFYLTIIG CGRR_HUMAN 128 2 -
NAFTPEKLQNAYVLYYLAIVG CALR_RABIT 135 2 -

Motif 6 width=19
Element Seqn Id St Int Rpt
PIVPTIIHAITRAVYYNDN CALR_RAT 307 151 -
PLVPTTIHAITRAVYFNDN CALR_HUMAN 286 130 -
PLVPTTIHAITRALYFNDN CALR_CAVPO 270 114 -
PIVPTIIHAITRALYYNDN CALR_MOUSE 307 151 -
PLIPTTAHAITRAVLFNDN CALR_PIG 287 130 -
PLLPACIHAIARSLYYNDN CGRR_RAT 263 114 -
PLIPACIHAIARSLYYNDN CGRR_HUMAN 263 114 -
PLVPTTIHAITRAIYFNDN CALR_RABIT 270 114 -

Motif 7 width=21
Element Seqn Id St Int Rpt
WRPSNKVLGKIYDYLMHSLIH CALR_RAT 398 72 -
WRPSNKMLGKIYDYVMHSLIH CALR_HUMAN 377 72 -
WRPSNKVLGKIYDYFMHSLIH CALR_CAVPO 361 72 -
WRPSNKVLGKIYDYLMHSLIH CALR_MOUSE 398 72 -
WRPSTPLLGKIYDYVVHSLIH CALR_PIG 378 72 -
WRPEGKVAEEVYDYVMHILMH CGRR_RAT 354 72 -
WRPEGKIAEEVYDYIMHILMH CGRR_HUMAN 354 72 -
WRPSNKILGKIYDYLMHSLIH CALR_RABIT 361 72 -

Motif 8 width=15
Element Seqn Id St Int Rpt
QVTLKRQWAQFKIQW CALR_RAT 436 17 -
QTTVKRQWAQFKIQW CALR_HUMAN 415 17 -
QTTLKRQWAQFKIQW CALR_CAVPO 399 17 -
QVTLKRQWTQFKIQW CALR_MOUSE 436 17 -
QGALKRQWNQYQAQR CALR_PIG 416 17 -
QAILRRNWNQYKIQF CGRR_RAT 392 17 -
QAILRRNWNQYKIQF CGRR_HUMAN 392 17 -
QTTVKRQWVQFKIQW CALR_RABIT 399 17 -

Motif 9 width=11
Element Seqn Id St Int Rpt
YICHQEPRNPP CALR_RAT 482 31 -
YICHQEPRNEP CALR_HUMAN 457 27 -
YICHQEPRNDP CALR_CAVPO 445 31 -
YICHQEPRNPP CALR_MOUSE 481 30 -
YICHQEPREEP CALR_PIG 462 31 -
HDCPTEHLNGK CGRR_RAT 434 27 -
HDCPSEHLNGK CGRR_HUMAN 434 27 -
YIYHQEPRNDP CALR_RABIT 441 27 -