WORKLIST ENTRIES (1): MRGPCRA View alignment Mas-related G protein-coupled receptor A signature Type of fingerprint: COMPOUND with 3 elements Links: PRINTS; PR00237 GPCRRHODOPSN PRINTS; PR00533 MASONCOGENE; PR02108 MRGPCRFAMILY PRINTS; PR02110 MRGPCRD; PR02111 MRGPCRE PRINTS; PR02112 MRGPCRF; PR02113 MRGPCRH INTERPRO; IPR000820 Creation date 05-APR-2011 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. LEMBO, P.M.C., GRAZZINI E., GROBLWESKI, T., O'DONNELL, D., ROY, M.-O., ZHANG, J., HOFFERT, C., CAO, J., SCHMIDT, R., PELLETIER, M., LABARRE, M., GOSSELIN, M., FORTIN, Y., BANVILLE, D., SHEN, S., STROEM, P., PAYZA, K., DRAY, A., WALKER, P. AND AHMAD, S. Proenkephalin A gene products activate a new family of sensory neuron- specific GPCRs. NAT.NEUROSCI. 5 201-209 (2002). 7. LIU, Q., TANG, Z., SURDENIKOVA, L., KIM, S., PATEL, K.N., KIM, A., RU, F., GUAN, Y., WENG, H.J., GENG, Y., UNDEM, B.J., KOLLARIK, M., CHEN, Z.F., ANDERSON, D.J. AND DONG, X. Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. CELL 139 1353-1365 (2009). 8. ROBAS, N., MEAD, E. AND FIDOCK, M. MrgX2 is a high potency cortistatin receptor expressed in dorsal root ganglion. J.BIOL.CHEM. 278 44400-44404 (2003). 9. YANG, S., LIU, Y., LIN, A.A., CAVALLI-SFORZA, L.L., ZHAO, Z. AND SU, B. Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in nociception. GENE 352 30-35 (2005). 10. HAN, S.-K., DONG, X., HWANG, J.-I., ZYLKA, M.J., ANDERSON, D.J. AND SIMON,M.I. Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. PROC.NATL.ACAD.SCI.U.S.A. 99 14740-14745 (2002). 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]. Mas oncogene is expressed at high levels in the CNS. Members of the family of mas-related receptors have been indicated in the development, regulation and function of nociceptive neurons, specifically in the modulation of pain. Most members are orphaned, with no endogeneous ligand identified; however, some have been cloned. MRGX1 is potently activated by enkephalins, including BAM22, in stably transfected cells, resulting in a large dose-dependent release of intracellular Ca2+ . Cortistatin-14 acts as a potent ligand for MRGX2. Stimulation by cortistatin-14 in receptor-expressing cells increases intracellular Ca2+, acting in part of the calcium signalling pathway [8-9]. Members of the family can also be activated via chloroquine, inducing a histamine-independent itch response , although their exact functions are currently unknown. Mrga receptors are found to be expressed only in specific subsets of sensory neurons that are known to detect painful stimuli. They are coupled to the Galpha(q/11) signalling pathway, and are potently activated by members of the rf-amide(npff/npaf) neuropeptide family. Stimulation by rf-amide agonists results in a dose-dependent release of free cytoplasmic Ca2+ . MRGPCRA is a 3-element fingerprint that provides a signature for mas-related G protein-coupled receptor A. The fingerprint was derived from an initial alignment of 8 sequences: the motifs were drawn from conserved sections within the C-terminal, loop and TM regions, focusing on those areas of the alignment that characterise the mas-related type A receptors but distinguish them from the rest of the mas-related family - motif 1 lies in the second half of TM domain 2, leading into the first external loop; motif 2 lies within the third TM domain; and motif 3 resides at the C-terminus. Two iterations on SPTR57.15_40.15f were required to reach convergence, at which point a true set comprising 13 sequences was identified. SUMMARY INFORMATION 13 codes involving 3 elements 0 codes involving 2 elements COMPOSITE FINGERPRINT INDEX 3| 13 13 13 2| 0 0 0 --+---------------- | 1 2 3 True positives.. B7ZP12_MOUSE MRGA8_MOUSE MRGA4_MOUSE Q1RLL1_MOUSE MRGA3_MOUSE MRGA2_MOUSE Q3U1A9_MOUSE MRGA7_MOUSE MRGA1_MOUSE MRGRA_RAT MRGA5_MOUSE MRGA6_MOUSE A2T114_MOUSE PROTEIN TITLES B7ZP12_MOUSE Putative uncharacterized protein - Mus musculus MRGA8_MOUSE Mas-related G-protein coupled receptor member A8 - Mus muscu MRGA4_MOUSE Mas-related G-protein coupled receptor member A4 - Mus muscu Q1RLL1_MOUSE MAS-related GPR, member A4 - Mus musculus MRGA3_MOUSE Mas-related G-protein coupled receptor member A3 - Mus muscu MRGA2_MOUSE Mas-related G-protein coupled receptor member A2 - Mus muscu Q3U1A9_MOUSE Putative uncharacterized protein - Mus musculus MRGA7_MOUSE Mas-related G-protein coupled receptor member A7 - Mus muscu MRGA1_MOUSE Mas-related G-protein coupled receptor member A1 - Mus muscu MRGRA_RAT Mas-related G-protein coupled receptor member A - Rattus nor MRGA5_MOUSE Mas-related G-protein coupled receptor member A5 - Mus muscu MRGA6_MOUSE Mas-related G-protein coupled receptor member A6 - Mus muscu A2T114_MOUSE G-protein coupled adenine receptor - Mus musculus
SCAN HISTORY SPTR57.15_40.15f 2 300 NSINGLE INITIAL MOTIF SETS MRGPCRA1 Length of motif = 14 Motif number = 1 Mas-related G protein-coupled receptor A motif I - 1 PCODE ST INT LGHIIDSILLLLNV MRGA1_MOUSE 63 63 LSSIIASTLFLLKV MRGA2_MOUSE 63 63 LCHIIDSMLLLLTV MRGA5_MOUSE 62 62 LCHIINSIMFLLKV MRGA8_MOUSE 63 63 LCHIIDSTLLLLKF MRGRA_RAT 63 63 LCHIIASTEHILTF MRGA6_MOUSE 59 59 LCHFINSAMFLLKV MRGA7_MOUSE 63 63 LCHIINSTVDLLKF MRGA3_MOUSE 63 63 MRGPCRA2 Length of motif = 10 Motif number = 2 Mas-related G protein-coupled receptor A motif II - 1 PCODE ST INT CFYTIMMVLY MRGA1_MOUSE 85 8 CFNTIMMVVY MRGA2_MOUSE 86 9 YFYTIMTVPY MRGA5_MOUSE 85 9 CFYTIMIVLY MRGA8_MOUSE 86 9 CFNTVMMVPY MRGRA_RAT 86 9 CLYTFRVLLY MRGA6_MOUSE 82 9 CFYTIKMVLY MRGA7_MOUSE 86 9 CFHTIKRVLY MRGA3_MOUSE 86 9 MRGPCRA3 Length of motif = 13 Motif number = 3 Mas-related G protein-coupled receptor A motif III - 1 PCODE ST INT KIMVEMSRSKSEP MRGA1_MOUSE 292 197 ENMVEMSSNKAEP MRGA2_MOUSE 293 197 ENMVEMSRNIPKP MRGA5_MOUSE 292 197 ENMVEMSRSKAEP MRGA8_MOUSE 293 197 ENTVEMSSSKVEP MRGRA_RAT 292 196 ENMVEMSRNKAEL MRGA6_MOUSE 289 197 ENMVEMSRIKAEQ MRGA7_MOUSE 293 197 ENMVEMSRNKAEP MRGA3_MOUSE 290 194 FINAL MOTIF SETS MRGPCRA1 Length of motif = 14 Motif number = 1 Mas-related G protein-coupled receptor A motif I - 2 PCODE ST INT LCHIINSTMLLLKV B7ZP12_MOUSE 71 71 LCHIINSIMFLLKV MRGA8_MOUSE 63 63 LCHIINSTMLLLKV MRGA4_MOUSE 71 71 LCHIINSTMLLLKV Q1RLL1_MOUSE 71 71 LCHIINSTVDLLKF MRGA3_MOUSE 63 63 LSSIIASTLFLLKV MRGA2_MOUSE 63 63 LSSIIASTLFLLKV Q3U1A9_MOUSE 89 89 LCHFINSAMFLLKV MRGA7_MOUSE 63 63 LGHIIDSILLLLNV MRGA1_MOUSE 63 63 LCHIIDSTLLLLKF MRGRA_RAT 63 63 LCHIIDSMLLLLTV MRGA5_MOUSE 62 62 LCHIIASTEHILTF MRGA6_MOUSE 59 59 LCRIIASTQKLLTF A2T114_MOUSE 90 90 MRGPCRA2 Length of motif = 10 Motif number = 2 Mas-related G protein-coupled receptor A motif II - 2 PCODE ST INT CFDIIMMVLY B7ZP12_MOUSE 94 9 CFYTIMIVLY MRGA8_MOUSE 86 9 CFDIIMTVLY MRGA4_MOUSE 94 9 CFDIIMTVLY Q1RLL1_MOUSE 94 9 CFHTIKRVLY MRGA3_MOUSE 86 9 CFNTIMMVVY MRGA2_MOUSE 86 9 CFNTIMMVVY Q3U1A9_MOUSE 112 9 CFYTIKMVLY MRGA7_MOUSE 86 9 CFYTIMMVLY MRGA1_MOUSE 85 8 CFNTVMMVPY MRGRA_RAT 86 9 YFYTIMTVPY MRGA5_MOUSE 85 9 CLYTFRVLLY MRGA6_MOUSE 82 9 CLYTFRVILY A2T114_MOUSE 113 9 MRGPCRA3 Length of motif = 13 Motif number = 3 Mas-related G protein-coupled receptor A motif III - 2 PCODE ST INT ENMVEMSRSKAEP B7ZP12_MOUSE 301 197 ENMVEMSRSKAEP MRGA8_MOUSE 293 197 ENMVEMSRSKAEP MRGA4_MOUSE 301 197 ENMVEMSRSKAEP Q1RLL1_MOUSE 301 197 ENMVEMSRNKAEP MRGA3_MOUSE 290 194 ENMVEMSSNKAEP MRGA2_MOUSE 293 197 ENMVEMSSNKAEP Q3U1A9_MOUSE 319 197 ENMVEMSRIKAEQ MRGA7_MOUSE 293 197 KIMVEMSRSKSEP MRGA1_MOUSE 292 197 ENTVEMSSSKVEP MRGRA_RAT 292 196 ENMVEMSRNIPKP MRGA5_MOUSE 292 197 ENMVEMSRNKAEL MRGA6_MOUSE 289 197 EHMVEMSKSKAEP A2T114_MOUSE 320 197
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