Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2XA799)

DOT Name	Mas-related G-protein coupled receptor member X2 (MRGPRX2)
Gene Name	MRGPRX2
UniProt ID	MRGX2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	7S8L; 7S8M; 7S8N; 7S8O; 7VDH; 7VDL; 7VDM; 7VUY; 7VUZ; 7VV0; 7VV3; 7VV4; 7VV5; 7VV6
Pfam ID	PF00001
Sequence	MDPTTPAWGTESTTVNGNDQALLLLCGKETLIPVFLILFIALVGLVGNGFVLWLLGFRMR RNAFSVYVLSLAGADFLFLCFQIINCLVYLSNFFCSISINFPSFFTTVMTCAYLAGLSML STVSTERCLSVLWPIWYRCRRPRHLSAVVCVLLWALSLLLSILEGKFCGFLFSDGDSGWC QTFDFITAAWLIFLFMVLCGSSLALLVRILCGSRGLPLTRLYLTILLTVLVFLLCGLPFG IQWFLILWIWKDSDVLFCHIHPVSVVLSSLNSSANPIIYFFVGSFRKQWRLQQPILKLAL QRALQDIAEVDHSEGCFRQGTPEMSRSSLV
Function	Mast cell-specific receptor for basic secretagogues, i.e. cationic amphiphilic drugs, as well as endo- or exogenous peptides, consisting of a basic head group and a hydrophobic core. Recognizes and binds small molecules containing a cyclized tetrahydroisoquinoline (THIQ), such as non-steroidal neuromuscular blocking drugs (NMBDs), including tubocurarine and atracurium. In response to these compounds, mediates pseudo-allergic reactions characterized by histamine release, inflammation and airway contraction. Acts as a receptor for a number of other ligands, including peptides and alkaloids, such as cortistatin-14, proadrenomedullin N-terminal peptides PAMP-12 and, at lower extent, PAMP-20, antibacterial protein LL-37, PMX-53 peptide, beta-defensins, and complanadine A.
Tissue Specificity	Mainly expressed in mast cells. Has a limited expression profile, both peripheral and within the central nervous system, with highest levels in dorsal root ganglion . Detected in blood vessels, scattered lymphocytes, and gastrointestinal ganglia (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mas-related G-protein coupled receptor member X2 (MRGPRX2).	[1]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Mas-related G-protein coupled receptor member X2 (MRGPRX2).	[2]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dextromethorphan	DMUDJZM	Approved	Dextromethorphan affects the binding of Mas-related G-protein coupled receptor member X2 (MRGPRX2).	[3]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mas-related G-protein coupled receptor member X2 (MRGPRX2).	[4]
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References

1	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
2	The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
3	Dextromethorphan - A widely-used cough suppressant - Induces local anaphylaxis via MRGPRX2 on mast cells. Chem Biol Interact. 2020 Oct 1;330:109248. doi: 10.1016/j.cbi.2020.109248. Epub 2020 Aug 29.
4	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.