MRGX2_HUMAN
ID MRGX2_HUMAN Reviewed; 330 AA.
AC Q96LB1; B5B0C7; Q4QXW4; Q4QXW7; Q4QXX0; Q4QXX2; Q4QXX3; Q4QXX4; Q4QXX6;
AC Q4QXX7; W8W3L5;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Mas-related G-protein coupled receptor member X2;
GN Name=MRGPRX2; Synonyms=MRGX2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11551509; DOI=10.1016/s0092-8674(01)00483-4;
RA Dong X., Han S.-K., Zylka M.J., Simon M.I., Anderson D.J.;
RT "A diverse family of GPCRs expressed in specific subsets of nociceptive
RT sensory neurons.";
RL Cell 106:619-632(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-16; SER-62 AND LEU-78.
RX PubMed=15862286; DOI=10.1016/j.gene.2005.03.001;
RA Yang S., Liu Y., Lin A.A., Cavalli-Sforza L.L., Zhao Z., Su B.;
RT "Adaptive evolution of MRGX2, a human sensory neuron specific gene involved
RT in nociception.";
RL Gene 352:30-35(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=24583173; DOI=10.1016/j.gene.2014.02.049;
RA Premzl M.;
RT "Comparative genomic analysis of eutherian Mas-related G protein-coupled
RT receptor genes.";
RL Gene 540:16-19(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT "Genome-wide discovery and analysis of human seven transmembrane helix
RT receptor genes.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-62.
RA Martin A.L., Kaighin V.A., Aronstam R.S.;
RT "Isolation of genomic DNA coding for human MAS-related GPR, member X2
RT (MRGPRX2).";
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12044878; DOI=10.1016/s0014-5793(02)02775-8;
RA Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
RT "Identification of G protein-coupled receptor genes from the human genome
RT sequence.";
RL FEBS Lett. 520:97-101(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=12915402; DOI=10.1074/jbc.m302456200;
RA Robas N., Mead E., Fidock M.;
RT "MrgX2 is a high potency cortistatin receptor expressed in dorsal root
RT ganglion.";
RL J. Biol. Chem. 278:44400-44404(2003).
RN [10]
RP FUNCTION.
RX PubMed=15823563; DOI=10.1016/j.bbrc.2005.03.088;
RA Kamohara M., Matsuo A., Takasaki J., Kohda M., Matsumoto M., Matsumoto S.,
RA Soga T., Hiyama H., Kobori M., Katou M.;
RT "Identification of MrgX2 as a human G-protein-coupled receptor for
RT proadrenomedullin N-terminal peptides.";
RL Biochem. Biophys. Res. Commun. 330:1146-1152(2005).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=16161007; DOI=10.1002/path.1839;
RA Allia E., Tarabra E., Volante M., Cerrato M., Ghigo E., Muccioli G.,
RA Papotti M.;
RT "Expression of cortistatin and MrgX2, a specific cortistatin receptor, in
RT human neuroendocrine tissues and related tumours.";
RL J. Pathol. 207:336-345(2005).
RN [12]
RP FUNCTION.
RX PubMed=22069323; DOI=10.1074/jbc.m111.277152;
RA Subramanian H., Gupta K., Guo Q., Price R., Ali H.;
RT "Mas-related gene X2 (MrgX2) is a novel G protein-coupled receptor for the
RT antimicrobial peptide LL-37 in human mast cells: resistance to receptor
RT phosphorylation, desensitization, and internalization.";
RL J. Biol. Chem. 286:44739-44749(2011).
RN [13]
RP FUNCTION.
RX PubMed=21441599; DOI=10.1124/mol.111.071472;
RA Subramanian H., Kashem S.W., Collington S.J., Qu H., Lambris J.D., Ali H.;
RT "PMX-53 as a dual CD88 antagonist and an agonist for Mas-related gene 2
RT (MrgX2) in human mast cells.";
RL Mol. Pharmacol. 79:1005-1013(2011).
RN [14]
RP FUNCTION.
RX PubMed=23698749; DOI=10.4049/jimmunol.1300023;
RA Subramanian H., Gupta K., Lee D., Bayir A.K., Ahn H., Ali H.;
RT "beta-Defensins activate human mast cells via Mas-related gene X2.";
RL J. Immunol. 191:345-352(2013).
RN [15]
RP FUNCTION.
RX PubMed=24930830; DOI=10.1016/j.bmcl.2014.05.060;
RA Johnson T., Siegel D.;
RT "Complanadine A, a selective agonist for the Mas-related G protein-coupled
RT receptor X2.";
RL Bioorg. Med. Chem. Lett. 24:3512-3515(2014).
RN [16]
RP FUNCTION.
RX PubMed=25517090; DOI=10.1038/nature14022;
RA McNeil B.D., Pundir P., Meeker S., Han L., Undem B.J., Kulka M., Dong X.;
RT "Identification of a mast-cell-specific receptor crucial for pseudo-
RT allergic drug reactions.";
RL Nature 519:237-241(2015).
CC -!- FUNCTION: Mast cell-specific receptor for basic secretagogues, i.e.
CC cationic amphiphilic drugs, as well as endo- or exogenous peptides,
CC consisting of a basic head group and a hydrophobic core
CC (PubMed:25517090). Recognizes and binds small molecules containing a
CC cyclized tetrahydroisoquinoline (THIQ), such as non-steroidal
CC neuromuscular blocking drugs (NMBDs), including tubocurarine and
CC atracurium. In response to these compounds, mediates pseudo-allergic
CC reactions characterized by histamine release, inflammation and airway
CC contraction (By similarity). Acts as a receptor for a number of other
CC ligands, including peptides and alkaloids, such as cortistatin-14,
CC proadrenomedullin N-terminal peptides PAMP-12 and, at lower extent,
CC PAMP-20, antibacterial protein LL-37, PMX-53 peptide, beta-defensins,
CC and complanadine A. {ECO:0000250|UniProtKB:Q3KNA1,
CC ECO:0000269|PubMed:15823563, ECO:0000269|PubMed:21441599,
CC ECO:0000269|PubMed:22069323, ECO:0000269|PubMed:23698749,
CC ECO:0000269|PubMed:24930830, ECO:0000269|PubMed:25517090,
CC ECO:0000305|PubMed:12915402}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in mast cells. Has a limited
CC expression profile, both peripheral and within the central nervous
CC system, with highest levels in dorsal root ganglion (PubMed:12915402).
CC Detected in blood vessels, scattered lymphocytes, and gastrointestinal
CC ganglia (at protein level) (PubMed:16161007).
CC {ECO:0000269|PubMed:12915402, ECO:0000269|PubMed:16161007}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. Mas
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AY042214; AAK91805.1; -; Genomic_DNA.
DR EMBL; HG426071; CDG86189.1; -; Genomic_DNA.
DR EMBL; AY651130; AAW70043.1; -; Genomic_DNA.
DR EMBL; AY651131; AAW70044.1; -; Genomic_DNA.
DR EMBL; AY651132; AAW70045.1; -; Genomic_DNA.
DR EMBL; AY651133; AAW70046.1; -; Genomic_DNA.
DR EMBL; AY651134; AAW70047.1; -; Genomic_DNA.
DR EMBL; AY651135; AAW70048.1; -; Genomic_DNA.
DR EMBL; AY651136; AAW70049.1; -; Genomic_DNA.
DR EMBL; AY651137; AAW70050.1; -; Genomic_DNA.
DR EMBL; AY651138; AAW70051.1; -; Genomic_DNA.
DR EMBL; AY651139; AAW70052.1; -; Genomic_DNA.
DR EMBL; AY651140; AAW70053.1; -; Genomic_DNA.
DR EMBL; AY651141; AAW70054.1; -; Genomic_DNA.
DR EMBL; AY651142; AAW70055.1; -; Genomic_DNA.
DR EMBL; AY651143; AAW70056.1; -; Genomic_DNA.
DR EMBL; AY651144; AAW70057.1; -; Genomic_DNA.
DR EMBL; AY651145; AAW70058.1; -; Genomic_DNA.
DR EMBL; AY651146; AAW70059.1; -; Genomic_DNA.
DR EMBL; AY651147; AAW70060.1; -; Genomic_DNA.
DR EMBL; AY651148; AAW70061.1; -; Genomic_DNA.
DR EMBL; AY651149; AAW70062.1; -; Genomic_DNA.
DR EMBL; AY651150; AAW70063.1; -; Genomic_DNA.
DR EMBL; AY651151; AAW70064.1; -; Genomic_DNA.
DR EMBL; AY651152; AAW70065.1; -; Genomic_DNA.
DR EMBL; AY651153; AAW70066.1; -; Genomic_DNA.
DR EMBL; AY651154; AAW70067.1; -; Genomic_DNA.
DR EMBL; AY651155; AAW70068.1; -; Genomic_DNA.
DR EMBL; AY651156; AAW70069.1; -; Genomic_DNA.
DR EMBL; AY651157; AAW70070.1; -; Genomic_DNA.
DR EMBL; AY651158; AAW70071.1; -; Genomic_DNA.
DR EMBL; AY651159; AAW70072.1; -; Genomic_DNA.
DR EMBL; AY651160; AAW70073.1; -; Genomic_DNA.
DR EMBL; AY651161; AAW70074.1; -; Genomic_DNA.
DR EMBL; AY845175; AAW70082.1; -; Genomic_DNA.
DR EMBL; AY845176; AAW70083.1; -; Genomic_DNA.
DR EMBL; EU883579; ACG60653.1; -; Genomic_DNA.
DR EMBL; AB083626; BAB89339.1; -; Genomic_DNA.
DR EMBL; AB065811; BAC06030.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68359.1; -; Genomic_DNA.
DR EMBL; BC063450; AAH63450.1; -; mRNA.
DR CCDS; CCDS7847.1; -.
DR RefSeq; NP_001290544.1; NM_001303615.1.
DR RefSeq; NP_473371.1; NM_054030.3.
DR PDB; 7S8L; EM; 2.45 A; R=2-330.
DR PDB; 7S8M; EM; 2.54 A; R=2-330.
DR PDB; 7S8N; EM; 2.90 A; R=2-330.
DR PDB; 7S8O; EM; 2.58 A; R=2-330.
DR PDB; 7VDH; EM; 2.90 A; R=1-330.
DR PDB; 7VDL; EM; 3.22 A; R=1-330.
DR PDB; 7VDM; EM; 2.98 A; R=1-330.
DR PDB; 7VUY; EM; 2.84 A; R=1-330.
DR PDB; 7VUZ; EM; 2.89 A; R=1-330.
DR PDB; 7VV0; EM; 3.50 A; R=1-330.
DR PDB; 7VV3; EM; 2.97 A; R=1-330.
DR PDB; 7VV4; EM; 2.97 A; R=1-330.
DR PDB; 7VV5; EM; 2.76 A; R=1-330.
DR PDB; 7VV6; EM; 3.30 A; R=1-330.
DR PDBsum; 7S8L; -.
DR PDBsum; 7S8M; -.
DR PDBsum; 7S8N; -.
DR PDBsum; 7S8O; -.
DR PDBsum; 7VDH; -.
DR PDBsum; 7VDL; -.
DR PDBsum; 7VDM; -.
DR PDBsum; 7VUY; -.
DR PDBsum; 7VUZ; -.
DR PDBsum; 7VV0; -.
DR PDBsum; 7VV3; -.
DR PDBsum; 7VV4; -.
DR PDBsum; 7VV5; -.
DR PDBsum; 7VV6; -.
DR AlphaFoldDB; Q96LB1; -.
DR SMR; Q96LB1; -.
DR IntAct; Q96LB1; 1.
DR STRING; 9606.ENSP00000333800; -.
DR BindingDB; Q96LB1; -.
DR ChEMBL; CHEMBL5849; -.
DR GuidetoPHARMACOLOGY; 157; -.
DR BioMuta; MRGPRX2; -.
DR DMDM; 50401127; -.
DR MassIVE; Q96LB1; -.
DR PaxDb; Q96LB1; -.
DR PeptideAtlas; Q96LB1; -.
DR PRIDE; Q96LB1; -.
DR Antibodypedia; 12419; 279 antibodies from 30 providers.
DR DNASU; 117194; -.
DR Ensembl; ENST00000329773.3; ENSP00000333800.2; ENSG00000183695.3.
DR GeneID; 117194; -.
DR KEGG; hsa:117194; -.
DR MANE-Select; ENST00000329773.3; ENSP00000333800.2; NM_054030.4; NP_473371.1.
DR UCSC; uc001mph.4; human.
DR CTD; 117194; -.
DR DisGeNET; 117194; -.
DR GeneCards; MRGPRX2; -.
DR HGNC; HGNC:17983; MRGPRX2.
DR HPA; ENSG00000183695; Tissue enhanced (skin).
DR MIM; 607228; gene.
DR neXtProt; NX_Q96LB1; -.
DR OpenTargets; ENSG00000183695; -.
DR PharmGKB; PA142671335; -.
DR VEuPathDB; HostDB:ENSG00000183695; -.
DR eggNOG; ENOG502RTWA; Eukaryota.
DR GeneTree; ENSGT01030000234639; -.
DR HOGENOM; CLU_009579_4_1_1; -.
DR InParanoid; Q96LB1; -.
DR OMA; WFLAIRI; -.
DR OrthoDB; 1123658at2759; -.
DR PhylomeDB; Q96LB1; -.
DR TreeFam; TF336336; -.
DR PathwayCommons; Q96LB1; -.
DR SignaLink; Q96LB1; -.
DR SIGNOR; Q96LB1; -.
DR BioGRID-ORCS; 117194; 8 hits in 1066 CRISPR screens.
DR GeneWiki; MRGPRX2; -.
DR GenomeRNAi; 117194; -.
DR Pharos; Q96LB1; Tchem.
DR PRO; PR:Q96LB1; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96LB1; protein.
DR Bgee; ENSG00000183695; Expressed in skin of abdomen and 48 other tissues.
DR Genevisible; Q96LB1; HS.
DR GO; GO:0016021; C:integral component of membrane; IC:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:1990595; F:mast cell secretagogue receptor activity; ISS:UniProtKB.
DR GO; GO:0042923; F:neuropeptide binding; IPI:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0045576; P:mast cell activation; IDA:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; IDA:UniProtKB.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0019233; P:sensory perception of pain; NAS:UniProtKB.
DR GO; GO:0030431; P:sleep; NAS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR026234; MRGPCRFAMILY.
DR InterPro; IPR027338; MRGPCRX1/MRGPCRX2.
DR PANTHER; PTHR11334; PTHR11334; 1.
DR PANTHER; PTHR11334:SF22; PTHR11334:SF22; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR02108; MRGPCRFAMILY.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; G-protein coupled receptor; Membrane;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..330
FT /note="Mas-related G-protein coupled receptor member X2"
FT /id="PRO_0000069775"
FT TOPO_DOM 1..33
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..63
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..84
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 85..96
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 145..165
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 166..184
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 16
FT /note="N -> H (in dbSNP:rs11024970)"
FT /evidence="ECO:0000269|PubMed:15862286"
FT /id="VAR_024739"
FT VARIANT 43
FT /note="V -> I (in dbSNP:rs11823569)"
FT /id="VAR_049418"
FT VARIANT 62
FT /note="N -> S (in dbSNP:rs10833049)"
FT /evidence="ECO:0000269|PubMed:15862286, ECO:0000269|Ref.5"
FT /id="VAR_019433"
FT VARIANT 78
FT /note="F -> L (in dbSNP:rs79763999)"
FT /evidence="ECO:0000269|PubMed:15862286"
FT /id="VAR_024740"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:7VV5"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:7VV5"
FT HELIX 31..56
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 65..94
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 104..132
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 145..166
FT /evidence="ECO:0007829|PDB:7S8L"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:7S8L"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 178..210
FT /evidence="ECO:0007829|PDB:7S8L"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:7VDH"
FT HELIX 219..244
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 246..249
FT /evidence="ECO:0007829|PDB:7S8L"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:7VDH"
FT HELIX 257..279
FT /evidence="ECO:0007829|PDB:7S8L"
FT TURN 280..283
FT /evidence="ECO:0007829|PDB:7S8L"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:7VV5"
SQ SEQUENCE 330 AA; 37099 MW; 0B328FD78B1DF6BE CRC64;
MDPTTPAWGT ESTTVNGNDQ ALLLLCGKET LIPVFLILFI ALVGLVGNGF VLWLLGFRMR
RNAFSVYVLS LAGADFLFLC FQIINCLVYL SNFFCSISIN FPSFFTTVMT CAYLAGLSML
STVSTERCLS VLWPIWYRCR RPRHLSAVVC VLLWALSLLL SILEGKFCGF LFSDGDSGWC
QTFDFITAAW LIFLFMVLCG SSLALLVRIL CGSRGLPLTR LYLTILLTVL VFLLCGLPFG
IQWFLILWIW KDSDVLFCHI HPVSVVLSSL NSSANPIIYF FVGSFRKQWR LQQPILKLAL
QRALQDIAEV DHSEGCFRQG TPEMSRSSLV
