WORKLIST ENTRIES (1):
CALCITONINR View alignment Calcitonin receptor signature
Type of fingerprint: COMPOUND with 6 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR
PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3
PRINTS; PR00251 BACTRLOPSIN
PRINTS; PR01350 CTRFAMILY; PR01351 CGRPRECEPTOR
INTERPRO; IPR001688
Creation date 15-APR-1995; UPDATE 06-JUN-1999
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).
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 FINGERPRINT INDEX
6| 6 6 6 6 6 6
5| 0 0 0 0 0 0
4| 0 0 0 0 0 0
3| 0 0 0 0 0 0
2| 0 0 0 0 0 0
--+-------------------------------
| 1 2 3 4 5 6
True positives..
CALR_RAT CALR_RABIT CALR_HUMAN CALR_MOUSE
CALR_CAVPO CALR_PIG
PROTEIN TITLES
CALR_RAT CALCITONIN RECEPTOR PRECURSOR (CT-R) (C1A/C1B) - RATTUS NORV
CALR_RABIT CALCITONIN RECEPTOR PRECURSOR (CT-R) - ORYCTOLAGUS CUNICULUS
CALR_HUMAN CALCITONIN RECEPTOR PRECURSOR (CT-R) - HOMO SAPIENS (HUMAN).
CALR_MOUSE CALCITONIN RECEPTOR PRECURSOR (CT-R) - MUS MUSCULUS (MOUSE).
CALR_CAVPO CALCITONIN RECEPTOR PRECURSOR (CT-R) - CAVIA PORCELLUS (GUIN
CALR_PIG CALCITONIN RECEPTOR PRECURSOR (CT-R) - SUS SCROFA (PIG).
SCAN HISTORY
OWL25_2 2 120 NSINGLE
SPTR37_9f 2 8 NSINGLE
INITIAL MOTIF SETS
CALCITONINR1 Length of motif = 19 Motif number = 1
Calcitonin receptor motif I - 1
PCODE ST INT
LDQEPFLYLVGRKKLLDAQ CLRA_RAT 34 34
LDQEPFLYLVGRKKLLDAQ CLRB_RAT 34 34
LDQEPFLYLVGRKKLLDAQ RATCR 34 34
LDQEPFLYLVGRKKLLDAQ RATCR1B 34 34
IEPKPFLYVVGRKKMMDAQ CALR_HUMAN 34 34
LEPEPFLYILGKQRMLEAQ CALR_PIG 35 35
CALCITONINR2 Length of motif = 18 Motif number = 2
Calcitonin receptor motif II - 1
PCODE ST INT
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
CALCITONINR3 Length of motif = 15 Motif number = 3
Calcitonin receptor motif III - 1
PCODE ST INT
TPDKLHNAYVLYYLA CLRA_RAT 138 66
TPDKLHNAYVLYYLA CLRB_RAT 138 66
TPDKLHNAYVSYYLA RATCR 138 66
TPDKLHNAYVSYYLA RATCR1B 138 66
TPEKLKNAYVLYYLA CALR_HUMAN 138 66
TPDKLQNAYILYYLA CALR_PIG 139 66
CALCITONINR4 Length of motif = 15 Motif number = 4
Calcitonin receptor motif IV - 1
PCODE ST INT
LVEVVPNGDLVRRDP CLRA_RAT 202 49
LVEVVPNGDLVRRDP CLRB_RAT 202 49
LVEVVPNGDLVRRDP RATCR 202 49
LVEVVPNGDLVRRDP RATCR1B 202 49
LVEVVPNGELVRRDP CALR_HUMAN 218 65
LVVIVPNGELVKRDP CALR_PIG 203 49
CALCITONINR5 Length of motif = 18 Motif number = 5
Calcitonin receptor motif V - 1
PCODE ST INT
SNKVLGKIYDYLMHSLIH CLRA_RAT 364 147
SNKVLGKIYDYLMHSLIH CLRB_RAT 401 184
SNKVLGKIYDYLMHSLIH RATCR 364 147
SNKVLGKIYDYLMHSLIH RATCR1B 401 184
SNKMLGKIYDYVMHSLIH CALR_HUMAN 380 147
STPLLGKIYDYVVHSLIH CALR_PIG 365 147
CALCITONINR6 Length of motif = 23 Motif number = 6
Calcitonin receptor motif VI - 1
PCODE ST INT
AVAFAEPGGLPIYICHQEPRNPP CLRA_RAT 433 51
AVAFAEPGGLPIYICHQEPRNPP CLRB_RAT 470 51
AVAFAEPGGRPIYICHQEPRNPP RATCR 432 50
AVAFAEPGGRPIYICHQEPRNPP RATCR1B 469 50
AAAAAEAGDIPIYICHQEPRNEP CALR_HUMAN 445 47
AAALAETVEIPVYICHQEPREEP CALR_PIG 434 51
FINAL MOTIF SETS
CALCITONINR1 Length of motif = 19 Motif number = 1
Calcitonin receptor motif I - 2
PCODE ST INT
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
CALCITONINR2 Length of motif = 18 Motif number = 2
Calcitonin receptor motif II - 2
PCODE ST INT
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
CALCITONINR3 Length of motif = 15 Motif number = 3
Calcitonin receptor motif III - 2
PCODE ST INT
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
CALCITONINR4 Length of motif = 15 Motif number = 4
Calcitonin receptor motif IV - 2
PCODE ST INT
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 219 65
CALCITONINR5 Length of motif = 18 Motif number = 5
Calcitonin receptor motif V - 2
PCODE ST INT
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 381 147
CALCITONINR6 Length of motif = 23 Motif number = 6
Calcitonin receptor motif VI - 2
PCODE ST INT
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 450 51
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