WORKLIST ENTRIES (1):
MRGPCRE View alignment Mas-related G protein-coupled receptor E signature
Type of fingerprint: COMPOUND with 7 elements
Links:
PRINTS; PR00237 GPCRRHODOPSN
PRINTS; PR00533 MASONCOGENE; PR02108 MRGPCRFAMILY
PRINTS; PR02109 MRGPCRA; PR02110 MRGPCRD
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).
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 Mrgre receptors are thought to be involved with nociceptor function
and development, and are directly involved in the modulation of pain. They
are currently orphaned, no specific binding ligand having been identified.
MRGPCRE is a 7-element fingerprint that provides a signature for
mas-related G protein-coupled receptor E. 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 E receptors but
distinguish them from the rest of the mas-related family - motif 1 lies at
the N terminus, leading into the first TM domain; motif 2 is located within
the second TM domain, leading into the first external loop; motif 3 spans
the end of TM domain 4, leading into the second external loop; motif 4 lies
within TM domain 5; motif 5 is located in the third cytoplasmic loop,
leading into TM domain 6; motif 6 spans the third external loop, leading
into TM domain 7; 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 7 sequences was identified.
SUMMARY INFORMATION
7 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| 7 7 7 7 7 7 7
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..
A8MZL3_HUMAN MRGRE_HUMAN MRGRE_MACFA B4DF56_HUMAN
MRGRE_RAT MRGRE_MOUSE Q4V9R2_MOUSE
PROTEIN TITLES
A8MZL3_HUMAN HCG2039161 - Homo sapiens
MRGRE_HUMAN Mas-related G-protein coupled receptor member E - Homo sapie
MRGRE_MACFA Mas-related G-protein coupled receptor member E - Macaca fas
B4DF56_HUMAN cDNA FLJ59015, highly similar to Mas-related G-protein coupl
MRGRE_RAT Mas-related G-protein coupled receptor member E - Rattus nor
MRGRE_MOUSE Mas-related G-protein coupled receptor member E - Mus muscul
Q4V9R2_MOUSE MAS-related GPR, member E - Mus musculus
SCAN HISTORY
SPTR57.15_40.15f 2 300 NSINGLE
INITIAL MOTIF SETS
MRGPCRE1 Length of motif = 13 Motif number = 1
Mas-related G protein-coupled receptor E motif I - 1
PCODE ST INT
DMAFNLTILSLTE MRGRE_RAT 15 15
DVAFNLIILSLTE MRGRE_HUMAN 19 19
DVAFNLVILSLTE MRGRE_MACFA 19 19
EMAFNLTILSLTE MRGRE_MOUSE 16 16
MRGPCRE2 Length of motif = 10 Motif number = 2
Mas-related G protein-coupled receptor E motif II - 1
PCODE ST INT
CCHMVAIIPE MRGRE_RAT 69 41
GCHMVAIVPD MRGRE_HUMAN 73 41
GCHMVAIIPD MRGRE_MACFA 73 41
CCHMVAIIPE MRGRE_MOUSE 70 41
MRGPCRE3 Length of motif = 20 Motif number = 3
Mas-related G protein-coupled receptor E motif III - 1
PCODE ST INT
CLLLDLLLSGACTQFFGAPS MRGRE_RAT 146 67
CLLLHLLLSGACTQFFGEPS MRGRE_HUMAN 150 67
CLLLHLLLSGACTQFFGEPS MRGRE_MACFA 150 67
CLLLDLLLSGACTQFFGAPS MRGRE_MOUSE 147 67
MRGPCRE4 Length of motif = 16 Motif number = 4
Mas-related G protein-coupled receptor E motif IV - 1
PCODE ST INT
WLVVAVLLAALCCTMC MRGRE_RAT 173 7
WLVAAVLLALLCCTMC MRGRE_HUMAN 177 7
WLVAAVLLAVLCCTMC MRGRE_MACFA 177 7
WLVVAVLLAALCCTMC MRGRE_MOUSE 174 7
MRGPCRE5 Length of motif = 14 Motif number = 5
Mas-related G protein-coupled receptor E motif V - 1
PCODE ST INT
ERGPERHQPRGFPT MRGRE_RAT 199 10
ERGPQRPPPRGFPG MRGRE_HUMAN 203 10
ERGPQRPPPRGFPT MRGRE_MACFA 203 10
ERGPERHQPRGFPT MRGRE_MOUSE 200 10
MRGPCRE6 Length of motif = 17 Motif number = 6
Mas-related G protein-coupled receptor E motif VI - 1
PCODE ST INT
SKNLSWHTPLYFYHFSF MRGRE_RAT 234 21
SRNLLWYIPHYFYHFSF MRGRE_HUMAN 238 21
SRNLLWHIPHYFYHFSF MRGRE_MACFA 238 21
SKNLSWHIPLYFYHFSF MRGRE_MOUSE 235 21
MRGPCRE7 Length of motif = 13 Motif number = 7
Mas-related G protein-coupled receptor E motif VII - 1
PCODE ST INT
GAVREASQGGLVD MRGRE_RAT 294 43
GAVRETSRRGLVD MRGRE_HUMAN 296 41
GAVRETSRRGLVD MRGRE_MACFA 296 41
GAGREASQGGLVD MRGRE_MOUSE 295 43
FINAL MOTIF SETS
MRGPCRE1 Length of motif = 13 Motif number = 1
Mas-related G protein-coupled receptor E motif - 2
PCODE ST INT
DVAFNLIILSLTE A8MZL3_HUMAN 20 20
DVAFNLIILSLTE MRGRE_HUMAN 19 19
DVAFNLVILSLTE MRGRE_MACFA 19 19
DVAFNLIILSLTE B4DF56_HUMAN 20 20
DMAFNLTILSLTE MRGRE_RAT 15 15
EMAFNLTILSLTE MRGRE_MOUSE 16 16
EMAFNLTILSLTE Q4V9R2_MOUSE 16 16
MRGPCRE2 Length of motif = 10 Motif number = 2
Mas-related G protein-coupled receptor E motif II - 2
PCODE ST INT
GCHMVAIVPD A8MZL3_HUMAN 74 41
GCHMVAIVPD MRGRE_HUMAN 73 41
GCHMVAIIPD MRGRE_MACFA 73 41
GCHMVAIVPD B4DF56_HUMAN 74 41
CCHMVAIIPE MRGRE_RAT 69 41
CCHMVAIIPE MRGRE_MOUSE 70 41
CCHMVAIIPE Q4V9R2_MOUSE 70 41
MRGPCRE3 Length of motif = 20 Motif number = 3
Mas-related G protein-coupled receptor E motif III - 2
PCODE ST INT
CLLLHLLLSGACTQFFGEPS A8MZL3_HUMAN 151 67
CLLLHLLLSGACTQFFGEPS MRGRE_HUMAN 150 67
CLLLHLLLSGACTQFFGEPS MRGRE_MACFA 150 67
CLLLHLLLSSACTQFFGEPS B4DF56_HUMAN 151 67
CLLLDLLLSGACTQFFGAPS MRGRE_RAT 146 67
CLLLDLLLSGACTQFFGAPS MRGRE_MOUSE 147 67
CLLLDLLLSGACTQFFGAPS Q4V9R2_MOUSE 147 67
MRGPCRE4 Length of motif = 16 Motif number = 4
Mas-related G protein-coupled receptor E motif IV - 2
PCODE ST INT
WLVAAVLLALLCCTMC A8MZL3_HUMAN 178 7
WLVAAVLLALLCCTMC MRGRE_HUMAN 177 7
WLVAAVLLAVLCCTMC MRGRE_MACFA 177 7
WLVAAVLLALLCCTMC B4DF56_HUMAN 178 7
WLVVAVLLAALCCTMC MRGRE_RAT 173 7
WLVVAVLLAALCCTMC MRGRE_MOUSE 174 7
WLVVAVLLAALCCTMC Q4V9R2_MOUSE 174 7
MRGPCRE5 Length of motif = 14 Motif number = 5
Mas-related G protein-coupled receptor E motif V - 2
PCODE ST INT
ERGPQRPPPRGFPG A8MZL3_HUMAN 204 10
ERGPQRPPPRGFPG MRGRE_HUMAN 203 10
ERGPQRPPPRGFPT MRGRE_MACFA 203 10
ERGPQRPPPRGFPG B4DF56_HUMAN 204 10
ERGPERHQPRGFPT MRGRE_RAT 199 10
ERGPERHQPRGFPT MRGRE_MOUSE 200 10
ERGPERHQPRGFPT Q4V9R2_MOUSE 200 10
MRGPCRE6 Length of motif = 17 Motif number = 6
Mas-related G protein-coupled receptor E motif - 2
PCODE ST INT
SRNLLWYIPHYFYHFSF A8MZL3_HUMAN 239 21
SRNLLWYIPHYFYHFSF MRGRE_HUMAN 238 21
SRNLLWHIPHYFYHFSF MRGRE_MACFA 238 21
SRNLLWYIPHYFYHFSF B4DF56_HUMAN 239 21
SKNLSWHTPLYFYHFSF MRGRE_RAT 234 21
SKNLSWHIPLYFYHFSF MRGRE_MOUSE 235 21
SKNLSWHIPLYFYHFSF Q4V9R2_MOUSE 235 21
MRGPCRE7 Length of motif = 13 Motif number = 7
Mas-related G protein-coupled receptor E motif - 2
PCODE ST INT
GAVRETSRRGLVD A8MZL3_HUMAN 297 41
GAVRETSRRGLVD MRGRE_HUMAN 296 41
GAVRETSRRGLVD MRGRE_MACFA 296 41
GAVRETSRRGLVD B4DF56_HUMAN 297 41
GAVREASQGGLVD MRGRE_RAT 294 43
GAGREASQGGLVD MRGRE_MOUSE 295 43
GAGREASQGGLVD Q4V9R2_MOUSE 295 43
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