WORKLIST ENTRIES (1):
CTRFAMILY View alignment Calcitonin receptor family signature
Type of fingerprint: COMPOUND with 9 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR00361 CALCITONINR; PR01351 CGRPRECEPTOR
Creation date 06-MAY-2000
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).
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 FINGERPRINT INDEX
9| 8 8 8 8 8 8 8 8 8
8| 0 0 0 0 0 0 0 0 0
7| 0 0 0 0 0 0 0 0 0
6| 0 0 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0 0 0
--+----------------------------------------------
| 1 2 3 4 5 6 7 8 9
True positives..
CALR_RAT CALR_HUMAN CALR_CAVPO CALR_MOUSE
CALR_PIG CGRR_RAT CGRR_HUMAN CALR_RABIT
PROTEIN TITLES
CALR_RAT CALCITONIN RECEPTOR PRECURSOR (CT-R) (C1A/C1B) - RATTUS NORV
CALR_HUMAN CALCITONIN RECEPTOR PRECURSOR (CT-R) - HOMO SAPIENS (HUMAN).
CALR_CAVPO CALCITONIN RECEPTOR PRECURSOR (CT-R) - CAVIA PORCELLUS (GUIN
CALR_MOUSE CALCITONIN RECEPTOR PRECURSOR (CT-R) - MUS MUSCULUS (MOUSE).
CALR_PIG CALCITONIN RECEPTOR PRECURSOR (CT-R) - SUS SCROFA (PIG).
CGRR_RAT CALCITONIN GENE-RELATED PEPTIDE TYPE 1 RECEPTOR PRECURSOR (C
CGRR_HUMAN CALCITONIN GENE-RELATED PEPTIDE TYPE 1 RECEPTOR PRECURSOR (C
CALR_RABIT CALCITONIN RECEPTOR PRECURSOR (CT-R) - ORYCTOLAGUS CUNICULUS
SCAN HISTORY
SPTR37_10f 1 50 NSINGLE
INITIAL MOTIF SETS
CTRFAMILY1 Length of motif = 20 Motif number = 1
Calcitonin receptor family motif I - 1
PCODE ST INT
QHRCYDRMQKLPPYQGEGLY CALR_PIG 53 53
QYKCYDRMQQLPAYQGEGPY CALR_HUMAN 52 52
QYKCYDRIQQLPPYEGEGPY CALR_RAT 52 52
QYECYQKIMQDPIQQAEGVY CGRR_HUMAN 45 45
QYECYQKIMQDPIQQGEGLY CGRR_RAT 45 45
CTRFAMILY2 Length of motif = 12 Motif number = 2
Calcitonin receptor family motif II - 1
PCODE ST INT
WDDTPAGVLAEQ CALR_PIG 83 10
WDDTPAGVLSYQ CALR_HUMAN 82 10
WDDTPAGVMSYQ CALR_RAT 82 10
WNDVAAGTESMQ CGRR_HUMAN 75 10
WNDVAAGTESMQ CGRR_RAT 75 10
CTRFAMILY3 Length of motif = 15 Motif number = 3
Calcitonin receptor family motif III - 1
PCODE ST INT
DYFPDFDAAEKVTKY CALR_PIG 98 3
DYFPDFDPSEKVTKY CALR_HUMAN 97 3
DYFPDFDPTEKVSKY CALR_RAT 97 3
DYFQDFDPSEKVTKI CGRR_HUMAN 90 3
DYFQDFDPSEKVTKI CGRR_RAT 90 3
CTRFAMILY4 Length of motif = 15 Motif number = 4
Calcitonin receptor family motif IV - 1
PCODE ST INT
WYRHPESNISWSNYT CALR_PIG 119 6
WFKHPENNRTWSNYT CALR_HUMAN 118 6
WFRHPDSNRTWSNYT CALR_RAT 118 6
WFRHPASNRTWTNYT CGRR_HUMAN 111 6
WFRHPDSNRTWTNYT CGRR_RAT 111 6
CTRFAMILY5 Length of motif = 21 Motif number = 5
Calcitonin receptor family motif V - 1
PCODE ST INT
NAFTPDKLQNAYILYYLAIVG CALR_PIG 136 2
NAFTPEKLKNAYVLYYLAIVG CALR_HUMAN 135 2
NAFTPDKLHNAYVLYYLALVG CALR_RAT 135 2
NVNTHEKVKTALNLFYLTIIG CGRR_HUMAN 128 2
NNSTHEKVKTALNLFYLTIIG CGRR_RAT 128 2
CTRFAMILY6 Length of motif = 19 Motif number = 6
Calcitonin receptor family motif VI - 1
PCODE ST INT
PLIPTTAHAITRAVLFNDN CALR_PIG 287 130
PLVPTTIHAITRAVYFNDN CALR_HUMAN 286 130
PIVPTIIHAITRAVYYNDN CALR_RAT 307 151
PLIPACIHAIARSLYYNDN CGRR_HUMAN 263 114
PLLPACIHAIARSLYYNDN CGRR_RAT 263 114
CTRFAMILY7 Length of motif = 21 Motif number = 7
Calcitonin receptor family motif VII - 1
PCODE ST INT
WRPSTPLLGKIYDYVVHSLIH CALR_PIG 378 72
WRPSNKMLGKIYDYVMHSLIH CALR_HUMAN 377 72
WRPSNKVLGKIYDYLMHSLIH CALR_RAT 398 72
WRPEGKIAEEVYDYIMHILMH CGRR_HUMAN 354 72
WRPEGKVAEEVYDYVMHILMH CGRR_RAT 354 72
CTRFAMILY8 Length of motif = 15 Motif number = 8
Calcitonin receptor family motif VIII - 1
PCODE ST INT
QGALKRQWNQYQAQR CALR_PIG 416 17
QTTVKRQWAQFKIQW CALR_HUMAN 415 17
QVTLKRQWAQFKIQW CALR_RAT 436 17
QAILRRNWNQYKIQF CGRR_HUMAN 392 17
QAILRRNWNQYKIQF CGRR_RAT 392 17
CTRFAMILY9 Length of motif = 11 Motif number = 9
Calcitonin receptor family motif IX - 1
PCODE ST INT
YICHQEPREEP CALR_PIG 462 31
YICHQEPRNEP CALR_HUMAN 457 27
YICHQEPRNPP CALR_RAT 482 31
HDCPSEHLNGK CGRR_HUMAN 434 27
HDCPTEHLNGK CGRR_RAT 434 27
FINAL MOTIF SETS
CTRFAMILY1 Length of motif = 20 Motif number = 1
Calcitonin receptor family motif I - 2
PCODE ST INT
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
CTRFAMILY2 Length of motif = 12 Motif number = 2
Calcitonin receptor family motif II - 2
PCODE ST INT
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
CTRFAMILY3 Length of motif = 15 Motif number = 3
Calcitonin receptor family motif III - 2
PCODE ST INT
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
CTRFAMILY4 Length of motif = 15 Motif number = 4
Calcitonin receptor family motif IV - 2
PCODE ST INT
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
CTRFAMILY5 Length of motif = 21 Motif number = 5
Calcitonin receptor family motif V - 2
PCODE ST INT
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
CTRFAMILY6 Length of motif = 19 Motif number = 6
Calcitonin receptor family motif VI - 2
PCODE ST INT
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
CTRFAMILY7 Length of motif = 21 Motif number = 7
Calcitonin receptor family motif VII - 2
PCODE ST INT
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
CTRFAMILY8 Length of motif = 15 Motif number = 8
Calcitonin receptor family motif VIII - 2
PCODE ST INT
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
CTRFAMILY9 Length of motif = 11 Motif number = 9
Calcitonin receptor family motif IX - 2
PCODE ST INT
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
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