MRGPRX4

Target id: 159

Nomenclature: MRGPRX4

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 MRGPRX4 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 MRGPRX4 MAS related GPR family member X4
Previous and Unofficial Names
SNSR6 [6] | MAS-related GPR, member X4 | Sensory neuron-specific G-protein coupled receptor 6
Database Links
Specialist databases
GPCRDB mrgx4_human (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  2
Tissue Distribution
Dorsal root ganglion
Species:  Human
Technique:  RT-PCR
References:  6
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  F8L
Global MAF (%):  34
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 23|33|48|32
Minor allele count:  G=0.343/750
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  N245S
Global MAF (%):  2
Subpopulation MAF (%):  AFR|AMR: 10|1
Minor allele count:  G=0.023/51
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  V142M
Global MAF (%):  3
Subpopulation MAF (%):  AFR|AMR: 12|1
Minor allele count:  A=0.029/64
SNP accession: 
Validation:  1000 Genomes, Frequency, Cluster
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  A182V
Global MAF (%):  14
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 6|17|3|27
Minor allele count:  T=0.141/307
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  L83S
Global MAF (%):  3
Subpopulation MAF (%):  AFR|AMR: 13|1
Minor allele count:  T=0.031/67
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  Y54C
Global MAF (%):  38
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 37|34|48|32
Minor allele count:  G=0.377/823
SNP accession: 
Validation:  1000 Genomes, Frequency, Cluster
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  S150F
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  N25K
SNP accession: 
General Comments
MRGPRX4 is a member of the sensory neuron-specific G protein-coupled receptors, which are uniquely expressed in small nociceptive sensory neurons [6].

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 [7-8].

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. Burstein ES, Ott TR, Feddock M, Ma JN, Fuhs S, Wong S, Schiffer HH, Brann MR, Nash NR. (2006) Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors. Br. J. Pharmacol.147 (1): 73-82. [PMID:16284629]

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. 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]

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: MRGPRX4. Last modified on 11/01/2016. Accessed on 21/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=159.