WORKLIST ENTRIES (1): P2Y6PRNOCPTR View alignment View Structure P2Y6 purinoceptor 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; PR01157 P2YPURNOCPTR; PR00595 P2Y1PRNOCPTR; PR00594 P2Y2PRNOCPTR PRINTS; PR01065 P2Y3PRNOCPTR; PR01066 P2Y4PRNOCPTR; PR01569 P2Y12PRNCPTR PRINTS; PR01735 P2Y13PRNCPTR INTERPRO; IPR001973 Creation date 31-JAN-1999; UPDATE 29-NOV-2001 1. ATTWOOD, T.K. AND FINDLAY, J.B.C. Fingerprinting G protein-coupled receptors. PROTEIN ENG. 7(2) 195-203 (1994). 2. ATTWOOD, T.K. AND FINDLAY, J.B.C. G protein-coupled receptor fingerprints. 7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993). 3. BIRNBAUMER, L. G proteins in signal transduction. ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990). 4. CASEY, P.J. AND GILMAN, A.G. G protein involvement in receptor-effector coupling. J.BIOL.CHEM. 263(6) 2577-2580 (1988). 5. ATTWOOD, T.K. AND FINDLAY, J.B.C. Design of a discriminating fingerprint for G protein-coupled receptors. PROTEIN ENG. 6(2) 167-176 (1993). 6. WATSON, S. AND ARKINSTALL, S. Adenosine and adenine nucleotides. IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.19-31. 7. COMMUNI, D., JANSSENS, R., SUAREZ-HUERTA, N., ROBAYE, B. AND BOEYNAEMS, J. Advances in signalling by extracellular nucleotides: the role and transduction mechanisms of P2Y receptors. CELL SIGNAL. 12 351-360 (2000). 8. CHANG, K., HANAOKA, K., KUMADA, M. AND TAKUWA, Y. Molecular cloning and functional analysis of a novel P2 nucleotide receptor. J.BIOL.CHEM. 270 26152-26158 (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 [1,2]. 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 rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [3-5]. In addition to their roles in energy metabolism, extracellular nucleotides (such as ATP) can act as signalling molecules to induce a wide variety of biological effects. They are released into the extracellular fluid as a result of cell lysis, exocytosis of nucleotide-containing granules or by efflux through membrane transport proteins, and can function as autocrine and paracrine mediators [6,7]. Nucleotides play a role in synaptic transmission and in platelet-vessel wall interactions. In neurons of the central and peripheral nervous system, ATP is colocalised and cosecreted with more traditional neurotransmitters, such as catecholamines and acetylcholine, and has excitatory effects [6,7]. ATP is also found in high concentrations in the dense granules of platelets, together with ADP. These granules also contain lower levels of other nucleotides, such as adenine dinucleotides, GTP and UTP . In addition, ADP is released from the vascular endothelium following injury and causes activation of platelets . Receptors for adenine nucleotides are collectively termed P2 purinoceptors. They can be further subdivided into two structural classes: P2X receptors are ligand-gated ion channels, while P2Y receptors are G protein-coupled receptors. P2Y receptors have also been identified that are selective for uridine (rather than adenine) nucleotides . cDNA encoding the P2Y6 receptor has been isolated and functionally characterised . The receptor shows 44 and 38% amino acid identity with rat P2U and chicken P2Y receptors, respectively . P2Y6 is functionally coupled to phospholipase C, but not to adenylate cyclase in C6 rat glioma cells transfected with the cloned P2 expression vector . P2Y6 mRNA is abundantly expressed in various rat tissues, including lung, stomach, intestine, spleen, mesentery, heart, and, most prominently, aorta . The receptor displays pharmacological characteristics distinct from any P2Y receptor subtype thus far identified, having a preference for uridine nucleotides, with UDP being 100-fold more potent than UTP . P2Y6PRNOCPTR is a 6-element fingerprint that provides a signature for the P2Y6 purinoceptor. The fingerprint was derived from an initial alignment of 2 sequences: the motifs were drawn from conserved regions spanning the full alignment length, focusing on those sections that characterise the P2Y6 receptors but distinguish them from the rest of the P2Y receptor family - motif 1 resides at the N-terminus; motif 2 spans the C-terminus of TM domain 1, leading into the first cytoplasmic loop; motif 3 lies in the second external loop; motif 4 spans the C-terminus of TM domain 5, leading into the third cytoplasmic loop; motif 5 lies in the third external loop; and motif 6 resides at the C-terminus. A single iteration on OWL31.1 was required to reach convergence, no further sequences being identified beyond the starting set. An update on SPTR37_9f identified no further matches. SUMMARY INFORMATION 2 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| 2 2 2 2 2 2 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.. P2Y6_HUMAN P2Y6_RAT PROTEIN TITLES P2Y6_HUMAN P2Y PURINOCEPTOR 6 (P2Y6) - HOMO SAPIENS (HUMAN). P2Y6_RAT P2Y PURINOCEPTOR 6 (P2Y6) - RATTUS NORVEGICUS (RAT).
SCAN HISTORY OWL31_1 1 100 NSINGLE SPTR37_9f 2 3 NSINGLE INITIAL MOTIF SETS P2Y6PRNOCPTR1 Length of motif = 17 Motif number = 1 P2Y6 purinoceptor motif I - 1 PCODE ST INT ERDNGTIQAPGLPPTTC P2Y6_RAT 2 2 EWDNGTGQALGLPPTTC P2Y6_HUMAN 2 2 P2Y6PRNOCPTR2 Length of motif = 11 Motif number = 2 P2Y6 purinoceptor motif II - 1 PCODE ST INT CVIAQICASRR P2Y6_RAT 46 27 CVITQICTSRR P2Y6_HUMAN 46 27 P2Y6PRNOCPTR3 Length of motif = 13 Motif number = 3 P2Y6 purinoceptor motif III - 1 PCODE ST INT PILSTRYLPYGMA P2Y6_RAT 183 126 PALATHYMPYGMA P2Y6_HUMAN 183 126 P2Y6PRNOCPTR4 Length of motif = 20 Motif number = 4 P2Y6 purinoceptor motif IV - 1 PCODE ST INT CRMARRLCRQDGPAGPVAQE P2Y6_RAT 213 17 CLLACRLCRQDGPAEPVAQE P2Y6_HUMAN 213 17 P2Y6PRNOCPTR5 Length of motif = 14 Motif number = 5 P2Y6 purinoceptor motif V - 1 PCODE ST INT PGVSCPVLETFAAA P2Y6_RAT 269 36 PGVPCTVLEAFAAA P2Y6_HUMAN 269 36 P2Y6PRNOCPTR6 Length of motif = 18 Motif number = 6 P2Y6 purinoceptor motif VI - 1 PCODE ST INT RRQPHDLLQKLTAKWQRQ P2Y6_RAT 309 26 RRRPHELLQKLTAKWQRQ P2Y6_HUMAN 309 26 FINAL MOTIF SETS P2Y6PRNOCPTR1 Length of motif = 17 Motif number = 1 P2Y6 purinoceptor motif I - 2 PCODE ST INT EWDNGTGQALGLPPTTC P2Y6_HUMAN 2 2 ERDNGTIQAPGLPPTTC P2Y6_RAT 2 2 P2Y6PRNOCPTR2 Length of motif = 11 Motif number = 2 P2Y6 purinoceptor motif II - 2 PCODE ST INT CVITQICTSRR P2Y6_HUMAN 46 27 CVIAQICASRR P2Y6_RAT 46 27 P2Y6PRNOCPTR3 Length of motif = 13 Motif number = 3 P2Y6 purinoceptor motif III - 2 PCODE ST INT PALATHYMPYGMA P2Y6_HUMAN 183 126 PILSTRYLPYGMA P2Y6_RAT 183 126 P2Y6PRNOCPTR4 Length of motif = 20 Motif number = 4 P2Y6 purinoceptor motif IV - 2 PCODE ST INT CLLACRLCRQDGPAEPVAQE P2Y6_HUMAN 213 17 CRMARRLCRQDGPAGPVAQE P2Y6_RAT 213 17 P2Y6PRNOCPTR5 Length of motif = 14 Motif number = 5 P2Y6 purinoceptor motif V - 2 PCODE ST INT PGVPCTVLEAFAAA P2Y6_HUMAN 269 36 PGVSCPVLETFAAA P2Y6_RAT 269 36 P2Y6PRNOCPTR6 Length of motif = 18 Motif number = 6 P2Y6 purinoceptor motif VI - 2 PCODE ST INT RRRPHELLQKLTAKWQRQ P2Y6_HUMAN 309 26 RRQPHDLLQKLTAKWQRQ P2Y6_RAT 309 26
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