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+ [6]. 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 [7], 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+ [10].
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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