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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; Q96LB2; HS. 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 FT ligand-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 //