WORKLIST ENTRIES (1):
MRGPCRD View alignment Mas-related G protein-coupled receptor D signature
Type of fingerprint: COMPOUND with 7 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN
PRINTS; PR00533 MASONCOGENE; PR02108 MRGPCRFAMILY
PRINTS; PR02109 MRGPCRA; 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. SHINOHARA, T., HARADA, M., OGI, K., MARUYAMA, M., FUJII, R., TANAKA, H.,
FUKUSUMI, S., KOMATSU, H., HOSOYA, M., NOGUCHI, Y., WATANABE, T., MORIYA,
T., ITOH, Y. AND HINUMA, S.
Identification of a G protein-coupled receptor specifically responsive to
beta-alanine.
J.BIOL.CHEM. 279 23559-23564 (2004).
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.
The Mrgrd receptors are thought to be involved with nociceptor function
and development, and are directly involved in the modulation of pain. It
has been demonstrated that beta-alanine can act as an agonist at Mrgrd
receptors [10].
MRGPCRD is a 7-element fingerprint that provides a signature for
mas-related G protein-coupled receptor D. The fingerprint was derived from
an initial alignment of 4 sequences: the motifs were drawn from conserved
sections within N- and C-terminal and loop regions, focusing on those areas
of the alignment that characterise the mas-related type D receptors but
distinguish them from the rest of the mas-related family - motif 1 lies
in the first cytoplasmic loop; motif 2 resides within the first TM domain;
motif 3 spans the end of TM domain 2, leading into the first external loop;
motif 4 lies in the first external loop; motifs 5 and 6 encode the N- and
C-termini of the fifth TM domain; and motif 7 resides at the C terminus.
Two iterations on SPTR57.15_40.15f were required to reach convergence, at
which point a true set comprising 5 sequences was identified.
SUMMARY INFORMATION
5 codes involving 7 elements
0 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
7| 5 5 5 5 5 5 5
6| 0 0 0 0 0 0 0
5| 0 0 0 0 0 0 0
4| 0 0 0 0 0 0 0
3| 0 0 0 0 0 0 0
2| 0 0 0 0 0 0 0
--+------------------------------------
| 1 2 3 4 5 6 7
True positives..
MRGRD_MOUSE Q5UCB4_MOUSE MRGRD_RAT MRGRD_MACFA
MRGRD_HUMAN
PROTEIN TITLES
MRGRD_MOUSE Mas-related G-protein coupled receptor member D - Mus muscul
Q5UCB4_MOUSE MAS-related GPR member D - Mus musculus
MRGRD_RAT Mas-related G-protein coupled receptor member D - Rattus nor
MRGRD_MACFA Mas-related G-protein coupled receptor member D - Macaca fas
MRGRD_HUMAN Mas-related G-protein coupled receptor member D - Homo sapie
SCAN HISTORY
SPTR57.15_40.15f 2 150 NSINGLE
INITIAL MOTIF SETS
MRGPCRD1 Length of motif = 12 Motif number = 1
Mas-related G protein-coupled receptor D motif I - 1
PCODE ST INT
MNQTLNSSGTVE MRGRD_HUMAN 1 1
MNQTLNSSGTAE MRGRD_MACFA 1 1
MNSTLDSSPAPG MRGRD_MOUSE 1 1
MNYTPYSSPAPG MRGRD_RAT 1 1
MRGPCRD2 Length of motif = 10 Motif number = 2
Mas-related G protein-coupled receptor D motif II - 1
PCODE ST INT
TCLCGMAGNS MRGRD_HUMAN 37 24
TCLCGMAGNS MRGRD_MACFA 37 24
TCVGGMAGNS MRGRD_MOUSE 36 23
TCVCGIVGNS MRGRD_RAT 36 23
MRGPCRD3 Length of motif = 13 Motif number = 3
Mas-related G protein-coupled receptor D motif III - 1
PCODE ST INT
FSMASTLSLETQP MRGRD_HUMAN 77 30
FCMAAMLSLETQP MRGRD_MACFA 77 30
FCMASMLSLETGP MRGRD_MOUSE 77 31
LCMASLLSLETGP MRGRD_RAT 77 31
MRGPCRD4 Length of motif = 16 Motif number = 4
Mas-related G protein-coupled receptor D motif IV - 1
PCODE ST INT
VNTTDKVHELMKRLMY MRGRD_HUMAN 91 1
VSTTDKVHELMKRLKY MRGRD_MACFA 91 1
VNISAKIYEGMRRIKY MRGRD_MOUSE 93 3
ASTSARVYEGMKRIKY MRGRD_RAT 93 3
MRGPCRD5 Length of motif = 12 Motif number = 5
Mas-related G protein-coupled receptor D motif V - 1
PCODE ST INT
QAALIMGVLTPV MRGRD_HUMAN 182 75
QAALIMGVLTPV MRGRD_MACFA 182 75
FNSLILGIFMPV MRGRD_MOUSE 184 75
FNSLILGIFMPV MRGRD_RAT 184 75
MRGPCRD6 Length of motif = 10 Motif number = 6
Mas-related G protein-coupled receptor D motif VI - 1
PCODE ST INT
FVWVRRSSQQ MRGRD_HUMAN 202 8
FVRVRRSSQQ MRGRD_MACFA 202 8
FIRVRKNSLM MRGRD_MOUSE 204 8
FIRMRKNSLL MRGRD_RAT 204 8
MRGPCRD7 Length of motif = 12 Motif number = 7
Mas-related G protein-coupled receptor D motif VII - 1
PCODE ST INT
EGGETPTVGTNE MRGRD_HUMAN 307 95
EGGETPTTGTNE MRGRD_MACFA 306 94
EGRETPSTCTND MRGRD_MOUSE 308 94
EGRETPSTCTND MRGRD_RAT 306 92
FINAL MOTIF SETS
MRGPCRD1 Length of motif = 12 Motif number = 1
Mas-related G protein-coupled receptor D motif - 2
PCODE ST INT
MNSTLDSSPAPG MRGRD_MOUSE 1 1
MNSTLDSSPAPG Q5UCB4_MOUSE 1 1
MNYTPYSSPAPG MRGRD_RAT 1 1
MNQTLNSSGTAE MRGRD_MACFA 1 1
MNQTLNSSGTVE MRGRD_HUMAN 1 1
MRGPCRD2 Length of motif = 10 Motif number = 2
Mas-related G protein-coupled receptor D motif II - 2
PCODE ST INT
TCVGGMAGNS MRGRD_MOUSE 36 23
TCVGGMAGNS Q5UCB4_MOUSE 36 23
TCVCGIVGNS MRGRD_RAT 36 23
TCLCGMAGNS MRGRD_MACFA 37 24
TCLCGMAGNS MRGRD_HUMAN 37 24
MRGPCRD3 Length of motif = 13 Motif number = 3
Mas-related G protein-coupled receptor D motif - 2
PCODE ST INT
FCMASMLSLETGP MRGRD_MOUSE 77 31
FCMASMLSLETGP Q5UCB4_MOUSE 77 31
LCMASLLSLETGP MRGRD_RAT 77 31
FCMAAMLSLETQP MRGRD_MACFA 77 30
FSMASTLSLETQP MRGRD_HUMAN 77 30
MRGPCRD4 Length of motif = 16 Motif number = 4
Mas-related G protein-coupled receptor D motif - 2
PCODE ST INT
VNISAKIYEGMRRIKY MRGRD_MOUSE 93 3
VNISAKIYEGMRRIKY Q5UCB4_MOUSE 93 3
ASTSARVYEGMKRIKY MRGRD_RAT 93 3
VSTTDKVHELMKRLKY MRGRD_MACFA 91 1
VNTTDKVHELMKRLMY MRGRD_HUMAN 91 1
MRGPCRD5 Length of motif = 12 Motif number = 5
Mas-related G protein-coupled receptor D motif V - 2
PCODE ST INT
FNSLILGIFMPV MRGRD_MOUSE 184 75
FNSLILGIFMPV Q5UCB4_MOUSE 184 75
FNSLILGIFMPV MRGRD_RAT 184 75
QAALIMGVLTPV MRGRD_MACFA 182 75
QAALIMGVLTPV MRGRD_HUMAN 182 75
MRGPCRD6 Length of motif = 10 Motif number = 6
Mas-related G protein-coupled receptor D motif VI - 2
PCODE ST INT
FIRVRKNSLM MRGRD_MOUSE 204 8
FIRVRKNSLM Q5UCB4_MOUSE 204 8
FIRMRKNSLL MRGRD_RAT 204 8
FVRVRRSSQQ MRGRD_MACFA 202 8
FVWVRRSSQQ MRGRD_HUMAN 202 8
MRGPCRD7 Length of motif = 12 Motif number = 7
Mas-related G protein-coupled receptor D motif VII - 2
PCODE ST INT
EGRETPSTCTND MRGRD_MOUSE 308 94
EGRETPSTCTND Q5UCB4_MOUSE 308 94
EGRETPSTCTND MRGRD_RAT 306 92
EGGETPTTGTNE MRGRD_MACFA 306 94
EGGETPTVGTNE MRGRD_HUMAN 307 95
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