Top ▲

MRGPRX1

Click here for help

Target id: 156

Nomenclature: MRGPRX1

Family: Class A Orphans

Contents:

Gene and Protein Information Click here for help
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 family member X1
Previous and Unofficial Names Click here for help
Mrgc | Mrgprb2 | Mrgprc | Mrgprc11 | MRGX1 | Sensory neuron-specific G-protein coupled receptor 4 | SNSR4 [6]
Database Links Click here for help
Specialist databases
GPCRdb mrgx1_human (Hs)
Other databases
Alphafold Q96LB2 (Hs)
ChEMBL Target CHEMBL5850 (Hs)
Ensembl Gene ENSG00000170255 (Hs)
Entrez Gene 259249 (Hs)
Human Protein Atlas ENSG00000170255 (Hs)
KEGG Gene hsa:259249 (Hs)
OMIM 607227 (Hs)
Pharos Q96LB2 (Hs)
RefSeq Nucleotide NM_147199 (Hs)
RefSeq Protein NP_671732 (Hs)
UniProtKB Q96LB2 (Hs)
Wikipedia MRGPRX1 (Hs)
Natural/Endogenous Ligands Click here for help
bovine adrenal medulla peptide 8-22 {Sp: Human}
Comments: Proposed ligand, two publications

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
bovine adrenal medulla peptide 8-22 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 8.0 pKd 6
⤷ pKd 8.0 (Kd 1.02x10-8 M) [6]
bovine adrenal medulla peptide 8-22 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 7.7 pKi 6
⤷ pKi 7.7 (Ki 2.1x10-8 M) [6]
compound 16 [PMID: 31498617] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.3 pEC50 8
⤷ pEC50 7.3 (EC50 5x10-8 M) [8]
Description: Agonist activity at human MRGPRX1 stably expressed in HEK293 cells by FLIPR claciun mobilisation assay.
bovine adrenal medulla peptide 8-22 {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 5.3 – 7.8 pEC50 2,6,10
⤷ pEC50 5.3 – 7.8 [2,6,10]
GPR15L {Sp: Human} Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 4.7 pEC50 11
⤷ pEC50 4.7 (EC50 1.81x10-5 M) [11]
Description: Determined in a FLIPR calcium imaging assay using HEK cells heterologously expressing hMRGPRX1
chloroquine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Guide to Malaria Pharmacology Ligand Hs Agonist 3.5 pEC50 7
⤷ pEC50 3.5 (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 an arrestin recruitment assay [10].
Immuno Process Associations
Immuno Process:  Inflammation
Primary Transduction Mechanisms Click here for help
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 Click here for help
Dorsal root ganglia
Species:  Human
Technique:  RT-PCR
References:  6,13
Functional Assays Click here for help
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:  9
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid 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:  rs138263314
Validation:  1000 Genomes, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  I36V
Global MAF (%):  4
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 13|2|1
Minor allele count:  C=0.036/78
SNP accession:  rs11024885
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  A46T
Global MAF (%):  17
Subpopulation MAF (%):  AFR|AMR|EUR: 17|21|18|15
Minor allele count:  T=0.174/380
SNP accession:  rs78179510
Validation:  1000 Genomes, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid 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:  rs55954376
Validation:  1000 Genomes, 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 [7,12].

References

Show »

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 USA, 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 Neurosci, 24 (21): 5044-53. [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. Cell, 106 (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 USA, 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. Cell, 139 (7): 1353-65. [PMID:20004959]

8. Prchalová E, Hin N, Thomas AG, Veeravalli V, Ng J, Alt J, Rais R, Rojas C, Li Z, Hihara H et al.. (2019) Discovery of Benzamidine- and 1-Aminoisoquinoline-Based Human MAS-Related G-Protein-Coupled Receptor X1 (MRGPRX1) Agonists. J Med Chem, 62 (18): 8631-8641. [PMID:31498617]

9. 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]

10. 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 Screen, 18 (5): 599-609. [PMID:23396314]

11. Tseng PY, Hoon MA. (2022) GPR15L is an epithelial inflammation-derived pruritogen. Sci Adv, 8 (24): eabm7342. DOI: 10.1126/sciadv.abm7342 [PMID:35704588]

12. 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]

13. 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 USA, 100 (17): 10043-8. [PMID:12909716]

Contributors

Show »

How to cite this page