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PR00361

Identifier
CALCITONINR  [View Relations]  [View Alignment]  
Accession
PR00361
No. of Motifs
6
Creation Date
15-APR-1995  (UPDATE 06-JUN-1999)
Title
Calcitonin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN

INTERPRO; IPR001688
GCRDB; GCR_0257; GCR_0995
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).

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.
 
CALCITONINR is a 6-element fingerprint that provides a signature for the
calcitonin 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 calcitonin receptors but distinguish them from the rest
of the secretin-like family - motifs 1-3 were drawn from the N-terminal
region leading into the first TM domain; motif 4 lies at the C-terminus of
the second TM domain following into the loop region; motif 5 is N-terminal
to the seventh TM region; and motif 6 was drawn from the C-terminus. Two
iterations on OWL25.2 were required to reach convergence, at which point a
true set comprising 9 sequences was identified. A single partial match was
also found, RNCLR, a new calcitonin-like receptor from rat pulmonary blood
vessels [7].
 
An update on SPTR37_9f identified a true set of 6 sequences.
Summary Information
6 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
6666666
5000000
4000000
3000000
2000000
123456
True Positives
CALR_CAVPO    CALR_HUMAN    CALR_MOUSE    CALR_PIG      
CALR_RABIT CALR_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).
Scan History
OWL25_2    2  120  NSINGLE    
SPTR37_9f 2 8 NSINGLE
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
LDQEPFLYLVGRKKLLDAQ CLRA_RAT 34 34 -
LDQEPFLYLVGRKKLLDAQ RATCR 34 34 -
LEPEPFLYILGKQRMLEAQ CALR_PIG 35 35 -
LDQEPFLYLVGRKKLLDAQ CLRB_RAT 34 34 -
LDQEPFLYLVGRKKLLDAQ RATCR1B 34 34 -
IEPKPFLYVVGRKKMMDAQ CALR_HUMAN 34 34 -

Motif 2 width=18
Element Seqn Id St Int Rpt
KCYDRIQQLPPYEGEGPY CLRA_RAT 54 1 -
KCYDRIQQLPPYEGEGPY CLRB_RAT 54 1 -
KCYDRIQQLPPYEGEGPY RATCR 54 1 -
KCYDRIQQLPPYEGEGPY RATCR1B 54 1 -
KCYDRMQQLPAYQGEGPY CALR_HUMAN 54 1 -
RCYDRMQKLPPYQGEGLY CALR_PIG 55 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
TPEKLKNAYVLYYLA CALR_HUMAN 138 66 -
TPDKLHNAYVLYYLA CLRA_RAT 138 66 -
TPDKLHNAYVLYYLA CLRB_RAT 138 66 -
TPDKLHNAYVSYYLA RATCR 138 66 -
TPDKLHNAYVSYYLA RATCR1B 138 66 -
TPDKLQNAYILYYLA CALR_PIG 139 66 -

Motif 4 width=15
Element Seqn Id St Int Rpt
LVEVVPNGDLVRRDP RATCR 202 49 -
LVEVVPNGDLVRRDP CLRB_RAT 202 49 -
LVVIVPNGELVKRDP CALR_PIG 203 49 -
LVEVVPNGELVRRDP CALR_HUMAN 218 65 -
LVEVVPNGDLVRRDP CLRA_RAT 202 49 -
LVEVVPNGDLVRRDP RATCR1B 202 49 -

Motif 5 width=18
Element Seqn Id St Int Rpt
SNKVLGKIYDYLMHSLIH RATCR 364 147 -
SNKVLGKIYDYLMHSLIH CLRA_RAT 364 147 -
SNKVLGKIYDYLMHSLIH CLRB_RAT 401 184 -
SNKVLGKIYDYLMHSLIH RATCR1B 401 184 -
SNKMLGKIYDYVMHSLIH CALR_HUMAN 380 147 -
STPLLGKIYDYVVHSLIH CALR_PIG 365 147 -

Motif 6 width=23
Element Seqn Id St Int Rpt
AVAFAEPGGLPIYICHQEPRNPP CLRB_RAT 470 51 -
AVAFAEPGGLPIYICHQEPRNPP CLRA_RAT 433 51 -
AAAAAEAGDIPIYICHQEPRNEP CALR_HUMAN 445 47 -
AAALAETVEIPVYICHQEPREEP CALR_PIG 434 51 -
AVAFAEPGGRPIYICHQEPRNPP RATCR1B 469 50 -
AVAFAEPGGRPIYICHQEPRNPP RATCR 432 50 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
LDQEPFLYLVGRKKLLDAQ CALR_RAT 34 34 -
VEPEPFLYVIGRKKLMDAQ CALR_RABIT 34 34 -
IEPKPFLYVVGRKKMMDAQ CALR_HUMAN 34 34 -
LDQEPFLYLVGRKKLLDAQ CALR_MOUSE 34 34 -
FEPEPYLYSVGRKKLVDAQ CALR_CAVPO 34 34 -
LEPEPFLYILGKQRMLEAQ CALR_PIG 35 35 -

Motif 2 width=18
Element Seqn Id St Int Rpt
KCYDRIQQLPPYEGEGPY CALR_RAT 54 1 -
KCYDRMEQLPPYQGEGPY CALR_RABIT 54 1 -
KCYDRMQQLPAYQGEGPY CALR_HUMAN 54 1 -
KCYDRIHQLPSYEGEGLY CALR_MOUSE 54 1 -
RCYDRMQQLPPYEGEGPY CALR_CAVPO 54 1 -
RCYDRMQKLPPYQGEGLY CALR_PIG 55 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
TPDKLHNAYVLYYLA CALR_RAT 138 66 -
TPEKLQNAYVLYYLA CALR_RABIT 138 66 -
TPEKLKNAYVLYYLA CALR_HUMAN 138 66 -
TSEKLQNAYVLYYLA CALR_MOUSE 138 66 -
TPEKLQNAYVLYYLA CALR_CAVPO 138 66 -
TPDKLQNAYILYYLA CALR_PIG 139 66 -

Motif 4 width=15
Element Seqn Id St Int Rpt
LVEVVPNGDLVRRDP CALR_RAT 202 49 -
LVEVVPNGELVRRDP CALR_RABIT 202 49 -
LVEVVPNGELVRRDP CALR_HUMAN 218 65 -
LVEVVPNGDLVRRDP CALR_MOUSE 202 49 -
LVEVVPNGELVRKDP CALR_CAVPO 202 49 -
LVVIVPNGELVKRDP CALR_PIG 203 49 -

Motif 5 width=18
Element Seqn Id St Int Rpt
SNKVLGKIYDYLMHSLIH CALR_RAT 401 184 -
SNKILGKIYDYLMHSLIH CALR_RABIT 364 147 -
SNKMLGKIYDYVMHSLIH CALR_HUMAN 380 147 -
SNKVLGKIYDYLMHSLIH CALR_MOUSE 401 184 -
SNKVLGKIYDYFMHSLIH CALR_CAVPO 364 147 -
STPLLGKIYDYVVHSLIH CALR_PIG 365 147 -

Motif 6 width=23
Element Seqn Id St Int Rpt
AVAFAEPGGLPIYICHQEPRNPP CALR_RAT 470 51 -
TAASAEEGGIPVYIYHQEPRNDP CALR_RABIT 429 47 -
AAAAAEAGDIPIYICHQEPRNEP CALR_HUMAN 445 47 -
AVAFAEPDGLPIYICHQEPRNPP CALR_MOUSE 469 50 -
AAAEAGGDNIPVYICHQEPRNDP CALR_CAVPO 433 51 -
AAALAETVEIPVYICHQEPREEP CALR_PIG 434 51 -