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MRGPRE

Family: Class A Orphans

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Tissue Distribution
Functional Assays
Physiological Consequences of Altering Gene Expression
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 311 11p15.5 MRGPRE MAS-related GPR, member E
Mouse 7 310 7 F5 Mrgpre MAS-related GPR, member E
Rat 7 309 1 Mrgpre MAS-related GPR, member E
Previous and Unofficial Names
mrgE
GPR167
MGC138408
MRGPRE
MRGE
G protein-coupled receptor 167
G-protein coupled receptor 167
mas-related G protein-coupled MRGE
mas-related G-protein coupled receptor member E
MAS-related GPR, member E
MAS-related G-protein coupled receptor, member E
MAS-related gene E
C130069N09Rik
Database Links
Ensembl ENSG00000184350 (Hs), ENSMUSG00000048965 (Mm), ENSRNOG00000020735 (Rn)
Entrez Gene 116534 (Hs), 244238 (Mm), 404660 (Rn)
GeneCards MRGPRE (Hs)
GenitoUrinary Development Molecular Anatomy Project Mrgpre (Mm)
HomoloGene 18469 (Hs)
Human Protein Reference Database 19193 (Hs)
InterPro Q86SM8 (Hs), Q91ZB7 (Mm), Q7TN40 (Rn)
KEGG Gene hsa:116534 (Hs), mmu:244238 (Mm), rno:404660 (Rn)
PharmGKB Gene PA134939296 (Hs)
Protein Ontology (PRO) PRO:000001603 (Hs)
RefSeq Nucleotide NM_001039165 (Hs), NM_175534 (Mm), NM_001002288 (Rn)
RefSeq Protein NP_001034254 (Hs), NP_780743 (Mm), NP_001002288 (Rn)
TreeFam ENSG00000184350 (Hs), ENSMUSG00000048965 (Mm), ENSRNOG00000020735 (Rn)
UniGene Hs. 190988 (Hs)
UniProt Q86SM8 (Hs), Q91ZB7 (Mm), Q7TN40 (Rn)
Wikipedia MRGPRE
Orphan and other 7TM receptors
Tissue Distribution
Placenta, brain (medulla, cerebellum: purkinje and golgi neurons, cerebral cortex)
Species:  Human
Technique:  Northern blot
References:  11
Dorsal root ganglion
Species:  Human
Technique:  Northern blot
References:  11
Brain
Species:  Mouse
Technique:  Northern blot
References:  11
Ileum
Species:  Mouse
Technique:  RT-PCR
References:  1
Ileum (neuronal somata, nerve fibres of tunica muscularis, lamina propria and enteri plexuses)
Species:  Mouse
Technique:  Immunohistochemistry
References:  1
Dorsal root ganglion, spinal cord, sciatic nerve
Species:  Rat
Technique:  RT-PCR
References:  8
Tissue Distribution Comments
MRGPRE broadly expressed in the mouse brain and is not restricted to nociceptive neurons [9]. MRGPRE positive nerve fibres in the lamina propria of villi extensively expressed with CGRP [1].
Functional Assays
Chronic constriction injury of sciatic nerve
Species:  None
Tissue:  Sciatic nerve
Response measured:  Reduced expression of Mrgpre
References:  3
Physiological Consequences of Altering Gene Expression
Deletion of MRGPRE increases MRGPRF expression in the spinal cord
Species:  Mouse
Tissue:  Spinal cord
Technique:  Gene knockout
References:  3
Development but not maintainance of neuropathic pain is affected by receptor knockout, resulting in delayed allodynia onset.
Species:  Mouse
Tissue:  Global knockout (brain, dorsal root ganglion and spinal cord tested)
Technique:  Gene knockout
References:  3
Clinically-Relevant Mutations and Pathophysiology
Comments:  MRGPRE expression significantly downregulated in the ileum of a mouse model of Schistosoma mansoni induced intestinal schistosomiasis.
References:  1
Mutations not determined
Biologically Significant Variants
G159S
SNP accession:  rs4391795 
Type:  Naturally occurring SNPs.
Species:  Human
References: 
G15S
SNP accession:  rs12295710 
Type:  Naturally occurring SNPs.
Species:  Human
References: 
R287Q, low frequency (<10% in all tested populations)
SNP accession:  rs78549252 
Type:  Naturally occurring SNPs.
Species:  Human
References: 
General Comments
Rat MRGPRE is capable of forming a functional heterodimer with rat MRGPRD, restricting beta-alanine induced internalisation and reducing beta-alanine mediated [Ca2+] release at rMRGPRD [8].

Of the eight human Mas-related GPCRs (MRGs), four (MRGPRD, MRGPRE, MRGPRF and MRGPRG) have clear orthologues in rodents, whereas the cluster of genes including human MRGPRX1, MRGPRX2, MRGPRX3 and MRGPRX4 is found only in primates and is replaced in rodents with a family of genes (>25 in mice, ~10 in rats) which have no obvious human counterparts [4]. Certain rodent MRGs have been reported to respond to adenine [2] and to RF-amide peptides including neuropeptide FF [5-6] but the relevance of these findings to man is unclear. MRGs are expressed predominantly in small diameter sensory neurons of the dorsal root ganglia, where there is emerging evidence that they may be mediators of histamine-independent itch [7,10].
Available Assays
DiscoveRx PathHunter® CHO-K1 MRGPRE (Orphan) High Expression β-Arrestin Cell Line Human Cat No. 93-0438C2A
DiscoveRx PathHunter® eXpress MRGPRE CHO-K1 β-Arrestin (Orphan) GPCR Assay Human Cat No. 93-0438E2ACP1

REFERENCES

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1. Avula, LR; Buckinx, R; Alpaerts, K; Costagliola, A; Adriaensen, D; Van Nassauw, L; Timmermans, JP. (2011) The effect of inflammation on the expression and distribution of the MAS-related gene receptors MrgE and MrgF in the murine ileum. Histochem. Cell Biol., 136 (5): 569-85. [PMID:21912971]

2. Bender, E; Buist, A; Jurzak, M; Langlois, X; Baggerman, G; Verhasselt, P; Ercken, M; Guo, HQ; Wintmolders, C; Van den Wyngaert, I; et al.. (2002) Characterization of an orphan G protein-coupled receptor localized in the dorsal root ganglia reveals adenine as a signaling molecule. Proc. Natl. Acad. Sci. U.S.A., 99 (13): 8573-8. [PMID:12084918]

3. Cox, PJ; Pitcher, T; Trim, SA; Bell, CH; Qin, W; Kinloch, RA. (2008) The effect of deletion of the orphan G - protein coupled receptor (GPCR) gene MrgE on pain-like behaviours in mice. Mol Pain, 4: 2. [PMID:18197975]

4. Dong, X; Han, S; Zylka, MJ; Simon, MI; Anderson, DJ. (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell, 106 (5): 619-32. [PMID:11551509]

5. Han, SK; Dong, X; Hwang, JI; Zylka, MJ; Anderson, DJ; Simon, MI. (2002) 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 (23): 14740-5. [PMID:12397184]

6. Lee, MG; Dong, X; Liu, Q; Patel, KN; Choi, OH; Vonakis, B; Undem, BJ. (2008) Agonists of the MAS-related gene (Mrgs) orphan receptors as novel mediators of mast cell-sensory nerve interactions. J. Immunol., 180 (4): 2251-5. [PMID:18250432]

7. Liu, Q; Tang, Z; Surdenikova, L; Kim, S; Patel, KN; Kim, A; Ru, F; Guan, Y; Weng, HJ; Geng, Y; Undem, BJ; Kollarik, M; Chen, ZF; Anderson, DJ; Dong, X. (2009) Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell, 139 (7): 1353-65. [PMID:20004959]

8. Milasta, S; Pediani, J; Appelbe, S; Trim, S; Wyatt, M; Cox, P; Fidock, M; Milligan, G. (2006) Interactions between the Mas-related receptors MrgD and MrgE alter signalling and trafficking of MrgD. Mol. Pharmacol., 69 (2): 479-91. [PMID:16282220]

9. Okubo, S; Kurebayashi, J; Otsuki, T; Yamamoto, Y; Tanaka, K; Sonoo, H. (2004) Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI 182,780) in breast cancer cells. Br. J. Cancer, 90 (1): 236-44. [PMID:14710235]

10. Wilson, SR; Gerhold, KA; Bifolck-Fisher, A; Liu, Q; Patel, KN; Dong, X; Bautista, DM. (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat. Neurosci., 14 (5): 595-602. [PMID:21460831]

11. Zhang, L; Taylor, N; Xie, Y; Ford, R; Johnson, J; Paulsen, JE; Bates, B. (2005) Cloning and expression of MRG receptors in macaque, mouse, and human. Brain Res. Mol. Brain Res., 133 (2): 187-97. [PMID:15710235]

To cite this database page, please use the following:

Amy E. Monaghan.
Class A Orphans: MRGPRE. Last modified on 05/11/2012. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=153.


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