WORKLIST ENTRIES (1): GPR3ORPHANR View alignment View Structure GPR3 orphan 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; PR00644 GPRORPHANR; PR00649 GPR6ORPHANR; PR00650 GPR12ORPHANR INTERPRO; IPR000984 Creation date 10-DEC-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. 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. EIDNE, K.A., ZABAVNIK, J., PETERS, T., YOSHIDA, S., ANDERSON, L. AND TAYLOR, P.L. Cloning, sequencing and tissue distribution of a candidate G protein-coupled receptor from rat pituitary gland. FEBS LETT. 292 243-248 (1991). 7. SONG, Z.H., MODI, W. AND BONNER, T.I. Molecular cloning and chromosomal localization of human genes encoding three closely related G protein-coupled receptors. GENOMICS 28 347-349 (1995). 8. WATSON, S. AND ARKINSTALL, Orphan receptors. IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.223-230. 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]. Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. A new GPCR, GPR12, was isolated from a rat pituitary library, and is found in discrete regions of the brain, pituitary and testis, but is absent in other tissues [6-8]. Three human homologues (GPR12, GPR6 and GPR3) have also been isolated . The 3 genes have been localised to human chromosomal regions 13q12, 6q21 and 1p34.3-p36.1 respectively. GPR3ORPHANR is a 4-element fingerprint that provides a signature for the GPR3 orphan receptors. The fingerprint was derived from an initial alignment of 2 sequences: the motifs were drawn from conserved sections within either loop or N- and C-terminal regions, focusing on those areas of the alignment that characterise the GPR3 receptors but distinguish them from the rest of the GPR family - motifs 1 and 2 span the N-terminus; motif 3 spans the first external loop; and motif 4 resides at the C-terminus. A single iteration on OWL29.0 was required to reach convergence, no further sequences being identified beyond the starting set. A single partial match was found, RATGPCRA, a rat GPR3 fragment lacking motifs 1 and 4. An update on SPTR37_9f identified a true set of 2 sequences. SUMMARY INFORMATION 2 codes involving 4 elements 0 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 4| 2 2 2 2 3| 0 0 0 0 2| 0 0 0 0 --+--------------------- | 1 2 3 4 True positives.. GPR3_HUMAN GPR3_MOUSE PROTEIN TITLES GPR3_HUMAN PROBABLE G PROTEIN-COUPLED RECEPTOR GPR3 (ACCA ORPHAN RECEPT GPR3_MOUSE PROBABLE G PROTEIN-COUPLED RECEPTOR GPR3 (GPCR21) - MUS MUSC
SCAN HISTORY OWL29_0 1 50 NSINGLE SPTR37_9f 2 3 NSINGLE INITIAL MOTIF SETS GPR3ORPHANR1 Length of motif = 18 Motif number = 1 GPR3 motif I - 1 PCODE ST INT WGAGSPLAWLSAGSGNVN GPR3_HUMAN 3 3 WGAGSSMAWFSAGSGSVN GPR3_MOUSE 3 3 GPR3ORPHANR2 Length of motif = 19 Motif number = 2 GPR3 motif II - 1 PCODE ST INT NVSSVGPAEGPTGPAAPLP GPR3_HUMAN 20 -1 NVSSVDPVEEPTGPATLLP GPR3_MOUSE 20 -1 GPR3ORPHANR3 Length of motif = 16 Motif number = 3 GPR3 motif III - 1 PCODE ST INT AAVFCIGSAEMSLVLV GPR3_HUMAN 98 59 AADFCIGSPEMSLMLV GPR3_MOUSE 98 59 GPR3ORPHANR4 Length of motif = 11 Motif number = 4 GPR3 motif IV - 1 PCODE ST INT AVCCCCSSSKI GPR3_HUMAN 310 196 AICCCCSTSKI GPR3_MOUSE 310 196 FINAL MOTIF SETS GPR3ORPHANR1 Length of motif = 18 Motif number = 1 GPR3 motif I - 2 PCODE ST INT WGAGSPLAWLSAGSGNVN GPR3_HUMAN 3 3 WGAGSSMAWFSAGSGSVN GPR3_MOUSE 3 3 GPR3ORPHANR2 Length of motif = 19 Motif number = 2 GPR3 motif II - 2 PCODE ST INT NVSSVGPAEGPTGPAAPLP GPR3_HUMAN 20 -1 NVSSVDPVEEPTGPATLLP GPR3_MOUSE 20 -1 GPR3ORPHANR3 Length of motif = 16 Motif number = 3 GPR3 motif III - 2 PCODE ST INT AAVFCIGSAEMSLVLV GPR3_HUMAN 98 59 AADFCIGSPEMSLMLV GPR3_MOUSE 98 59 GPR3ORPHANR4 Length of motif = 11 Motif number = 4 GPR3 motif IV - 2 PCODE ST INT AVCCCCSSSKI GPR3_HUMAN 310 196 AICCCCSTSKI GPR3_MOUSE 310 196
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