ID MRGX1_HUMAN Reviewed; 322 AA.
AC Q96LB2; Q4V9L2; Q8TDD8; Q8TDD9;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 27-MAR-2024, entry version 166.
DE RecName: Full=Mas-related G-protein coupled receptor member X1;
DE AltName: Full=Sensory neuron-specific G-protein coupled receptor 3/4;
GN Name=MRGPRX1; Synonyms=MRGX1, SNSR3, SNSR4;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11850634; DOI=10.1038/nn815;
RA Lembo P.M.C., Grazzini E., Groblewski T., O'Donnell D., Roy M.-O.,
RA Zhang J., Hoffert C., Cao J., Schmidt R., Pelletier M., Labarre M.,
RA Gosselin M., Fortin Y., Banville D., Shen S., Stroem P., Payza K., Dray A.,
RA Walker P., Ahmad S.;
RT "Proenkephalin A gene products activate a new family of sensory neuron-
RT specific GPCRs.";
RL Nat. Neurosci. 5:201-209(2002).
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP FUNCTION AS ITCH RECEPTOR.
RX PubMed=20004959; DOI=10.1016/j.cell.2009.11.034;
RA Liu Q., Tang Z., Surdenikova L., Kim S., Patel K.N., Kim A., Ru F.,
RA Guan Y., Weng H.J., Geng Y., Undem B.J., Kollarik M., Chen Z.F.,
RA Anderson D.J., Dong X.;
RT "Sensory neuron-specific GPCR Mrgprs are itch receptors mediating
RT chloroquine-induced pruritus.";
RL Cell 139:1353-1365(2009).
RN [8]
RP VARIANTS VAL-36; THR-46; LEU-55; SER-131; ARG-133; ARG-137 AND LEU-273,
RP CHARACTERIZATION OF VARIANTS VAL-36; THR-46; LEU-55; SER-131; ARG-133;
RP ARG-137 AND LEU-273, AND FUNCTION.
RX PubMed=26582731; DOI=10.1124/jpet.115.227058;
RA Heller D., Doyle J.R., Raman V.S., Beinborn M., Kumar K., Kopin A.S.;
RT "Novel probes establish mas-related G protein-coupled receptor X1 variants
RT as receptors with loss or gain of function.";
RL J. Pharmacol. Exp. Ther. 356:276-283(2016).
CC -!- FUNCTION: Orphan receptor. Probably involved in the function of
CC nociceptive neurons. May regulate nociceptor function and/or
CC development, including the sensation or modulation of pain. Potently
CC activated by enkephalins including BAM22 (bovine adrenal medulla
CC peptide 22) and BAM (8-22)(PubMed:26582731). BAM22 is the most potent
CC compound and evoked a large and dose-dependent release of intracellular
CC calcium in stably transfected cells. G(alpha)q proteins are involved in
CC the calcium-signaling pathway. Activated by the antimalarial drug,
CC chloroquine. May mediate chloroquine-induced itch, in a histamine-
CC independent manner. {ECO:0000269|PubMed:11850634,
CC ECO:0000269|PubMed:20004959, ECO:0000269|PubMed:26582731}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Uniquely localized in a subset of small dorsal root
CC and trigeminal sensory neurons. {ECO:0000269|PubMed:11850634}.
CC -!- MISCELLANEOUS: Activation of this receptor requires concentrations that
CC exceed the chloroquine concentrations observed in plasma of patients
CC undergoing chloroquine treatment. However, chloroquine accumulates at
CC much higher level in the skin where the receptor is located.
CC Chloroquine-induced itch is very common among black Africans (up to
CC 70%) but less common in other populations.
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; AY042213; AAK91804.1; -; Genomic_DNA.
DR EMBL; AF474989; AAL86880.2; -; Genomic_DNA.
DR EMBL; AF474990; AAL86881.1; -; Genomic_DNA.
DR EMBL; AB065846; BAC06064.1; -; Genomic_DNA.
DR EMBL; AB083628; BAB89341.1; -; Genomic_DNA.
DR EMBL; AC023078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096835; AAH96835.1; -; mRNA.
DR CCDS; CCDS7846.1; -.
DR RefSeq; NP_671732.3; NM_147199.3.
DR PDB; 8DWC; EM; 2.87 A; R=2-322.
DR PDB; 8DWG; EM; 2.71 A; R=2-322.
DR PDB; 8DWH; EM; 3.25 A; R=2-322.
DR PDB; 8HJ5; EM; 3.00 A; F=1-322.
DR PDBsum; 8DWC; -.
DR PDBsum; 8DWG; -.
DR PDBsum; 8DWH; -.
DR PDBsum; 8HJ5; -.
DR AlphaFoldDB; Q96LB2; -.
DR EMDB; EMD-27752; -.
DR EMDB; EMD-27753; -.
DR EMDB; EMD-27754; -.
DR SMR; Q96LB2; -.
DR BioGRID; 129233; 4.
DR STRING; 9606.ENSP00000305766; -.
DR BindingDB; Q96LB2; -.
DR ChEMBL; CHEMBL5850; -.
DR GuidetoPHARMACOLOGY; 156; -.
DR GlyCosmos; Q96LB2; 1 site, No reported glycans.
DR GlyGen; Q96LB2; 1 site.
DR iPTMnet; Q96LB2; -.
DR PhosphoSitePlus; Q96LB2; -.
DR BioMuta; MRGPRX1; -.
DR DMDM; 50401128; -.
DR MassIVE; Q96LB2; -.
DR PaxDb; 9606-ENSP00000305766; -.
DR PeptideAtlas; Q96LB2; -.
DR Antibodypedia; 25195; 157 antibodies from 26 providers.
DR DNASU; 259249; -.
DR Ensembl; ENST00000302797.4; ENSP00000305766.3; ENSG00000170255.8.
DR Ensembl; ENST00000526914.2; ENSP00000499076.2; ENSG00000170255.8.
DR GeneID; 259249; -.
DR KEGG; hsa:259249; -.
DR MANE-Select; ENST00000526914.2; ENSP00000499076.2; NM_001393578.1; NP_001380507.1.
DR AGR; HGNC:17962; -.
DR CTD; 259249; -.
DR DisGeNET; 259249; -.
DR GeneCards; MRGPRX1; -.
DR HGNC; HGNC:17962; MRGPRX1.
DR HPA; ENSG00000170255; Not detected.
DR MIM; 607227; gene.
DR neXtProt; NX_Q96LB2; -.
DR OpenTargets; ENSG00000170255; -.
DR PharmGKB; PA142671334; -.
DR VEuPathDB; HostDB:ENSG00000170255; -.
DR eggNOG; ENOG502RTWA; Eukaryota.
DR GeneTree; ENSGT01030000234639; -.
DR HOGENOM; CLU_009579_4_1_1; -.
DR InParanoid; Q96LB2; -.
DR OMA; ITAGWVM; -.
DR OrthoDB; 4338913at2759; -.
DR PhylomeDB; Q96LB2; -.
DR TreeFam; TF336336; -.
DR PathwayCommons; Q96LB2; -.
DR SignaLink; Q96LB2; -.
DR SIGNOR; Q96LB2; -.
DR BioGRID-ORCS; 259249; 13 hits in 1131 CRISPR screens.
DR GeneWiki; MRGPRX1; -.
DR GenomeRNAi; 259249; -.
DR Pharos; Q96LB2; Tchem.
DR PRO; PR:Q96LB2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96LB2; Protein.
DR Bgee; ENSG00000170255; Expressed in primordial germ cell in gonad and 6 other cell types or tissues.
DR ExpressionAtlas; Q96LB2; baseline and differential.
DR Genevisible; Q96LB2; HS.
DR GO; GO:0009986; C:cell surface; IC:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IMP:UniProtKB.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:1902349; P:response to chloroquine; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR CDD; cd15106; 7tmA_MrgprX-like; 1.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR026234; MRGPCRFAMILY.
DR PANTHER; PTHR11334; MAS-RELATED G-PROTEIN COUPLED RECEPTOR; 1.
DR PANTHER; PTHR11334:SF22; MAS-RELATED G-PROTEIN COUPLED RECEPTOR MEMBER X1; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR02108; MRGPCRFAMILY.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
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; Acute phase; Cell membrane; G-protein coupled receptor;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..322
FT /note="Mas-related G-protein coupled receptor member X1"
FT /id="PRO_0000069772"
FT TOPO_DOM 1..31
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..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..177
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..254
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 255..275
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 276..322
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 16
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 36
FT /note="I -> V (no alteration in ligand-mediated receptor
FT activity; dbSNP:rs11024885)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_019432"
FT VARIANT 46
FT /note="A -> T (no alteration in ligand-mediated receptor
FT activity; dbSNP:rs78179510)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_075462"
FT VARIANT 55
FT /note="R -> L (no alteration in ligand-mediated receptor
FT activity; dbSNP:rs55954376)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_075463"
FT VARIANT 131
FT /note="R -> S (decrease in ligand-mediated and ligand-
FT independent receptor activity; dbSNP:rs111448117)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_075464"
FT VARIANT 133
FT /note="H -> R (increase in ligand-mediated receptor
FT activity; dbSNP:rs140351170)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_075465"
FT VARIANT 137
FT /note="H -> R (no alteration in ligand-mediated receptor
FT activity; dbSNP:rs143702818)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_075466"
FT VARIANT 273
FT /note="F -> L (no alteration in ligand-mediated receptor
FT activity; dbSNP:rs137866403)"
FT /evidence="ECO:0000269|PubMed:26582731"
FT /id="VAR_075467"
FT CONFLICT 5
FT /note="I -> V (in Ref. 2; AAL86880)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="F -> L (in Ref. 2; AAL86880)"
FT /evidence="ECO:0000305"
FT CONFLICT 298..299
FT /note="AS -> TP (in Ref. 2; AAL86880)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="Q -> W (in Ref. 2; AAL86880)"
FT /evidence="ECO:0000305"
FT CONFLICT 310..312
FT /note="EEI -> QET (in Ref. 2; AAL86880)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="E -> D (in Ref. 6; AAH96835)"
FT /evidence="ECO:0000305"
FT HELIX 24..52
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 60..87
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 93..97
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 99..125
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 127..132
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 138..160
FT /evidence="ECO:0007829|PDB:8DWG"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:8DWG"
FT TURN 164..168
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 171..203
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 212..228
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 231..238
FT /evidence="ECO:0007829|PDB:8DWG"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 246..265
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 268..272
FT /evidence="ECO:0007829|PDB:8DWG"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:8DWC"
SQ SEQUENCE 322 AA; 36250 MW; C7F3A9F4418E8AD1 CRC64;
MDPTISTLDT ELTPINGTEE TLCYKQTLSL TVLTCIVSLV GLTGNAVVLW LLGCRMRRNA
FSIYILNLAA ADFLFLSGRL IYSLLSFISI PHTISKILYP VMMFSYFAGL SFLSAVSTER
CLSVLWPIWY RCHRPTHLSA VVCVLLWALS LLRSILEWML CGFLFSGADS AWCQTSDFIT
VAWLIFLCVV LCGSSLVLLI RILCGSRKIP LTRLYVTILL TVLVFLLCGL PFGIQFFLFL
WIHVDREVLF CHVHLVSIFL SALNSSANPI IYFFVGSFRQ RQNRQNLKLV LQRALQDASE
VDEGGGQLPE EILELSGSRL EQ
//
