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Gene and Protein Information  |
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| 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 |
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| Mrgc | Mrgprb2 | Mrgprc | Mrgprc11 | MRGX1 | Sensory neuron-specific G-protein coupled receptor 4 | SNSR4 [6] | |
| Database Links |
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| 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 |
| 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 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||
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| Primary Transduction Mechanisms
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| 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
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| Functional Assays
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| Biologically Significant Variants
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| 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]. |
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]
