Nomenclature: MRGPRX1

Family: Class A Orphans

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

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 322 11p15.1 MRGPRX1 MAS-related GPR, member X1
Previous and Unofficial Names
Mas-related G-protein coupled receptor member X1
Sensory neuron-specific G-protein coupled receptor 1
Mrgc
Mrgprc
Mrgprc11
Snsr
Snsr1
MRGX1
SNSR3
Mrgprb2
SNSR4
MRGPRX1
G protein-coupled receptor MRGX1
G protein-coupled receptor SNSR3
MAS-related GPR, member X1
MrgX1
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
BAM8-22 {Sp: Human}
Comments: Proposed ligand, two publications
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
BAM8-22 {Sp: Human} Hs Full agonist 7.99 pKd 6
pKd 7.99 (Kd 1.02x10-8 M) [6]
BAM8-22 {Sp: Human} Hs Full agonist 7.68 pKi 6
pKi 7.68 (Ki 2.1x10-8 M) [6]
BAM8-22 {Sp: Human} Hs Full agonist 5.3 – 7.8 pEC50 2,6,9
pEC50 5.3 – 7.8 [2,6,9]
chloroquine Hs Agonist 3.53 pEC50 7
pEC50 3.53 (EC50 2.97x10-4 M) [7]
Agonist Comments
Reports that BAM(8-22) was the most potent of a series of proenkephalin A–derived peptides as an agonist of MRGPRX1 in assays of calcium mobilisation and radioligand binding [6] were replicated in an independent study using a β-arrestin recruitment assay [9].
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  Stimulates inositol trisphosphate mediated Ca2+ release from intracellular stores. Coupling specificity examined in HEK 293 cells [4].
References:  4
Tissue Distribution
Dorsal root ganglia
Species:  Human
Technique:  RT-PCR
References:  6,11
Functional Assays
BAM8-22 produces itch and nociceptive sensation in a histamine-independent manner via MRGPRX1
Species:  Human
Tissue:  Volar forearm
Response measured:  Itch and nociceptive sensation
References:  8
Biologically Significant Variants
Type:  SNP
Species:  Human
Change:  F273L
Global MAF (%):  2
Subpopulation MAF (%):  AMR|EUR: 6|3
Minor allele count:  G=0.022/49
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  SNP
Species:  Human
Change:  R55L
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 5
Minor allele count:  A=0.012/26
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  SNP
Species:  Human
Change:  A46T
Global MAF (%):  17
Subpopulation MAF (%):  AFR|AMR|EUR: 17|21|18|15
Minor allele count:  T=0.174/380
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  SNP
Species:  Human
Change:  I36V
Global MAF (%):  4
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 13|2|1
Minor allele count:  C=0.036/78
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
General Comments
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 [3]. Certain rodent MRGs have been reported to respond to adenine [1] and to RF-amide peptides including neuropeptide FF [4-5] 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 MRGPRX1 β-Arrestin Cell Line (Cat no. 93-0919C2) more info

REFERENCES

1. 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]

2. Chen H, Ikeda SR. (2004) Modulation of ion channels and synaptic transmission by a human sensory neuron-specific G-protein-coupled receptor, SNSR4/mrgX1, heterologously expressed in cultured rat neurons. J Neurosci24: 5044-5053. [PMID:15163697]

3. 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]

4. 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]

5. 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]

6. Lembo PM, Grazzini E, Groblewski T, O'Donnell D, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M et al.. (2002) Proenkephalin A gene products activate a new family of sensory neuron--specific GPCRs. Nat. Neurosci.5 (3): 201-9. [PMID:11850634]

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. Sikand P, Dong X, LaMotte RH. (2011) BAM8-22 peptide produces itch and nociceptive sensations in humans independent of histamine release. J. Neurosci.31 (20): 7563-7. [PMID:21593341]

9. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen18 (5): 599-609. [PMID:23396314]

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. Zylka MJ, Dong X, Southwell AL, Anderson DJ. (2003) Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc. Natl. Acad. Sci. U.S.A.100 (17): 10043-8. [PMID:12909716]

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: MRGPRX1. Last modified on 09/08/2013. Accessed on 23/08/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=156.

Contact us | Print | Back to top | Help
Copyright © 2014 IUPHAR