Alternative titles; symbols
HGNC Approved Gene Symbol: MRGPRX2
Cytogenetic location: 11p15.1 Genomic coordinates (GRCh38): 11:19,054,455-19,060,717 (from NCBI)
MRGPRX2 is a member of the MAS (MAS1; 165180)-related G protein-coupled receptor (GPCR) family that is expressed primarily in human dorsal root ganglia and mast cells. It serves as a receptor for the antimicrobial peptide LL37 (CAMP; 600474) (Subramanian et al., 2011).
Dong et al. (2001) identified, in the mouse and human genomes, a family of GPCRs related to the MAS1 oncogene, including MRGX2. Several pseudogenes were also identified. The predicted MRG proteins contain transmembrane, extracellular, and cytoplasmic domains. A subset of MRGs was expressed in specific subpopulations of sensory neurons that detect painful stimuli. The expression patterns of these genes thus revealed an unexpected degree of molecular diversity among nociceptive neurons. Some MRGs could be specifically activated in heterologous cells by RFamide neuropeptides such as NPFF and NPAF (see 604643), which are analgesic in vivo. The authors concluded that MRGs may regulate nociceptor function and/or development, including the sensation or modulation of pain.
Subramanian et al. (2011) reported that a human mast cell line expressing MRGX2, as well as mast cells derived from pluripotent stem cells, responded to LL37 (CAMP; 600474) for sustained Ca(2+) mobilization and degranulation. In contrast, an immature mast cell line lacking MRGX2 and a mast cell line treated with short hairpin RNA (shRNA) against MRGX2 did not respond to LL37. Mast cell lines stably expressing MRGX2 responded to LL37 by chemotaxis, degranulation, and CCL4 (182284) production. MRGX2 resisted LL37-induced phosphorylation, desensitization, and internalization. Knockdown of GPCR kinase-2 (GRK2, or ADRBK1; 109635) and GRK3 (ADRBK2; 109636) via shRNA had no effect on mast cell degranulation induced by LL37. Subramanian et al. (2011) concluded that MRGX2 is a novel GPCR for LL37 that differs from other GPCRs in that it is resistant to agonist-induced receptor phosphorylation, desensitization, and internalization.
By genomic sequence analysis, Dong et al. (2001) mapped the MRGX2 gene to chromosome 11. Gross (2012) mapped the MRGPRX2 gene to chromosome 11p15.1 based on an alignment of the MRGPRX2 sequence (GenBank AY042214) with the genomic sequence (GRCh37).
Dong, X., Han, S., Zylka, M. J., Simon, M. I., Anderson, D. J. A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106: 619-632, 2001. [PubMed: 11551509] [Full Text: https://doi.org/10.1016/s0092-8674(01)00483-4]
Gross, M. B. Personal Communication. Baltimore, Md. 5/4/2012.
Subramanian, H., Gupta, K., Guo, Q., Price, R., Ali, H. Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the antimicrobial peptide LL-37 in human mast cells: resistance to receptor phosphorylation, desensitization, and internalization. J. Biol. Chem. 286: 44739-44749, 2011. [PubMed: 22069323] [Full Text: https://doi.org/10.1074/jbc.M111.277152]