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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