WORKLIST ENTRIES (1): VASOACTVEIPR View alignment Vasoactive intestinal peptide receptor signature Type of fingerprint: COMPOUND with 4 elements Links: PRINTS; PR00237 GPCRRHODOPSN; PR00247 GPCRCAMP; PR00248 GPCRMGR PRINTS; PR00249 GPCRSECRETIN; PR00250 GPCRSTE2; PR00899 GPCRSTE3 PRINTS; PR00251 BACTRLOPSIN PRINTS; PR01154 VIP1RECEPTOR; PR01155 VIP2RECEPTOR; PR01156 PACAPRECEPTR INTERPRO; IPR001571 Creation date 03-MAR-1996; UPDATE 07-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. Vasoactive intestinal polypeptide family. IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.278-283. 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 . 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 , calcitonin , parathyroid hormone/parathyroid hormone-related peptides  and vasoactive intestinal peptide , 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. Vasoactive intestinal polypeptide (VIP) has a wide physiological profile. In the periphery, it induces relaxation in smooth muscle; inhibits secretion in certain tissues, but stimulates secretion in others; and modulates activity of cells in the immune system . In the CNS, it has a range of both excitatory and inhibitory actions. VIP receptors are distributed widely in the periphery, and occur throughout the gastro- intestinal tract and genitourinary system, other smooth muscles and secretory glands. In the CNS, they are found abundantly in, e.g. the cortex, hippocampus and thalamus . All VIP receptors activate adenylyl cyclase. VASOACTVEIPR is a 4-element fingerprint that provides a signature for the vasoactive intestinal peptide receptors. The fingerprint was derived from an initial alignment of 5 sequences: the motifs were drawn from conserved sections within the N- and C-termini, focusing on those areas of the alignment that characterise the VIP receptors but distinguish them from the rest of the secretin-like family - motifs 1-3 lie in the N-terminal region preceding the first TM domain, and motif 4 lies at the C-terminus. Two iterations on OWL27.0 were required to reach convergence, at which point a true set comprising 6 sequences was identified. Seven partial matches were also found, all of which are members of the secretin-like family. An update on SPTR37_9f identified a true set of 6 sequences. SUMMARY INFORMATION 6 codes involving 4 elements 0 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 4| 6 6 6 6 3| 0 0 0 0 2| 0 0 0 0 --+--------------------- | 1 2 3 4 True positives.. VIPS_MOUSE VIPS_RAT VIPS_HUMAN VIPR_HUMAN VIPR_PIG VIPR_RAT PROTEIN TITLES VIPS_MOUSE VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2 PRECURSOR (VIP- VIPS_RAT VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2 PRECURSOR (VIP- VIPS_HUMAN VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2 PRECURSOR (VIP- VIPR_HUMAN VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 1 PRECURSOR (VIP- VIPR_PIG VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 1 PRECURSOR (VIP- VIPR_RAT VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 1 PRECURSOR (VIP-
SCAN HISTORY OWL27_0 2 100 NSINGLE SPTR37_9f 2 7 NSINGLE INITIAL MOTIF SETS VASOACTVEIPR1 Length of motif = 12 Motif number = 1 VIP receptor motif I - 1 PCODE ST INT PKVFSNFYSRPG VIPS_MOUSE 75 75 PKVFSNFYSRPG VIPS_RAT 75 75 PLIFKLFSSIQG VIPR_HUMAN 87 87 PKVFSNFYSKAG VIPS_HUMAN 76 76 PLIFQLFAPIHG VIPR_RAT 87 87 VASOACTVEIPR2 Length of motif = 16 Motif number = 2 VIP receptor motif II - 1 PCODE ST INT NISKNCTSDGWSETFP VIPS_MOUSE 87 0 NISKNCTSDGWSETFP VIPS_RAT 87 0 NVSRSCTDEGWTHLEP VIPR_HUMAN 100 1 NISKNCTSDGWSETFP VIPS_HUMAN 88 0 NISRSCTEEGWSQLEP VIPR_RAT 100 1 VASOACTVEIPR3 Length of motif = 11 Motif number = 3 VIP receptor motif III - 1 PCODE ST INT DFIDACGYNDP VIPS_MOUSE 103 0 DFIDACGYNDP VIPS_RAT 103 0 PYPIACGLDDK VIPR_HUMAN 117 1 DFVDACGYSDP VIPS_HUMAN 104 0 PYHIACGLNDR VIPR_RAT 117 1 VASOACTVEIPR4 Length of motif = 12 Motif number = 4 VIP receptor motif IV - 1 PCODE ST INT GSRTQSFLQSET VIPS_MOUSE 423 309 GSRTQSFLQSET VIPS_RAT 423 309 ARRSSSFQAEVS VIPR_HUMAN 444 316 ASRAQSFLQTET VIPS_HUMAN 424 309 ARRSSSFQAEVS VIPR_RAT 446 318 FINAL MOTIF SETS VASOACTVEIPR1 Length of motif = 12 Motif number = 1 VIP receptor motif I - 2 PCODE ST INT PKVFSNFYSRPG VIPS_MOUSE 75 75 PKVFSNFYSRPG VIPS_RAT 75 75 PKVFSNFYSKAG VIPS_HUMAN 76 76 PLIFKLFSSIQG VIPR_HUMAN 87 87 PLIFKLFSPTQG VIPR_PIG 88 88 PLIFQLFAPIHG VIPR_RAT 87 87 VASOACTVEIPR2 Length of motif = 16 Motif number = 2 VIP receptor motif II - 2 PCODE ST INT NISKNCTSDGWSETFP VIPS_MOUSE 87 0 NISKNCTSDGWSETFP VIPS_RAT 87 0 NISKNCTSDGWSETFP VIPS_HUMAN 88 0 NVSRSCTDEGWTHLEP VIPR_HUMAN 100 1 NVSRNCTDEGWTPLEP VIPR_PIG 101 1 NISRSCTEEGWSQLEP VIPR_RAT 100 1 VASOACTVEIPR3 Length of motif = 11 Motif number = 3 VIP receptor motif III - 2 PCODE ST INT DFIDACGYNDP VIPS_MOUSE 103 0 DFIDACGYNDP VIPS_RAT 103 0 DFVDACGYSDP VIPS_HUMAN 104 0 PYPIACGLDDK VIPR_HUMAN 117 1 PYPIACGMDDK VIPR_PIG 118 1 PYHIACGLNDR VIPR_RAT 117 1 VASOACTVEIPR4 Length of motif = 12 Motif number = 4 VIP receptor motif IV - 2 PCODE ST INT GSRTQSFLQSET VIPS_MOUSE 423 309 GSRTQSFLQSET VIPS_RAT 423 309 GSRAQSFLQTET VIPS_HUMAN 424 309 ARRSSSFQAEVS VIPR_HUMAN 444 316 ARRSSSFQAEVS VIPR_PIG 445 316 ARRSSSFQAEVS VIPR_RAT 446 318
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