MRGPRX1

Target id: 156

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.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for MRGPRX1 in GtoImmuPdb

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 family member X1
Previous and Unofficial Names
Mrgc | Mrgprb2 | Mrgprc | Mrgprc11 | MRGX1 | Sensory neuron-specific G-protein coupled receptor 4 | SNSR4 [6]
Database Links
Specialist databases
GPCRDB mrgx1_human (Hs)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
bovine adrenal medulla peptide 8-22 {Sp: Human} Hs Full agonist 8.0 pKd 6
pKd 8.0 (Kd 1.02x10-8 M) [6]
bovine adrenal medulla peptide 8-22 {Sp: Human} Hs Full agonist 7.7 pKi 6
pKi 7.7 (Ki 2.1x10-8 M) [6]
bovine adrenal medulla peptide 8-22 {Sp: Human} Hs Full agonist 5.3 – 7.8 pEC50 2,6,9
pEC50 5.3 – 7.8 [2,6,9]
chloroquine Hs Agonist 3.5 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 [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:  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: 
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: 
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: 
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: 
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 [7,10].

References

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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]

Contributors

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How to cite this page

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 11/01/2016. Accessed on 20/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=156.