Nomenclature: MRGPRE

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 


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
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
Database Links
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Reference Database
PharmGKB Gene
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
UniGene Hs.
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
Species:  Mouse
Technique:  Northern blot
References:  11
Species:  Mouse
Technique:  RT-PCR
References:  1
Ileum (neuronal somata, nerve fibres of tunica muscularis, lamina propria and enteric 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].
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
Gene Expression and Pathophysiology Comments
MRGPRE expression significantly downregulated in the ileum of a mouse model of Schistosoma mansoni induced intestinal schistosomiasis [1].
Biologically Significant Variants
Type:  Naturally occurring SNPs.
Species:  Human
Description:  R288Q, low frequency (<10% in all tested populations)
SNP accession: 
Type:  SNP
Species:  Human
Change:  P209L
Global MAF (%):  3
Subpopulation MAF (%):  AFR|AMR: 11|2
Minor allele count:  A=0.028/60
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  SNP
Species:  Human
Change:  G159S
Global MAF (%):  33
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 8|28|40|46
Minor allele count:  T=0.326/712
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  SNP
Species:  Human
Change:  G15S
Global MAF (%):  38
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 7|33|51|50
Minor allele count:  T=0.377/824
SNP accession: 
Validation:  1000 Genomes, Frequency
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 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0438C2A)
PathHunter® eXpress MRGPRE CHO-K1 β-Arrestin Orphan GPCR Assay (Cat no. 93-0438E2ACP1M)
more info


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 Pain4: 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. Cell106 (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. Cell139 (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. Cancer90 (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:

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: MRGPRE. Last modified on 13/03/2014. Accessed on 23/10/2014. IUPHAR database (IUPHAR-DB),

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