MRGPRX1
entrez
259249
canonical
uniprot
Q96LB2
canonical
ensembl
ENSG00000170255
resolver
ensp
ENSP00000305766
resolver
ensp
ENSP00000499076
resolver
enst
ENST00000302797
resolver
enst
ENST00000526914
resolver
genesymbol
MRGPRX1
resolver
genesymbol_syn
MRGX1
resolver
genesymbol_syn
SNSR3
resolver
genesymbol_syn
SNSR4
resolver
hgnc
HGNC:17962
resolver
uniprot
Q4V9L2
resolver
uniprot
Q8TDD8
resolver
uniprot
Q8TDD9
resolver
uniprot_entry
MRGX1_HUMAN
resolver
uniprot_sec
Q4V9L2
resolver
uniprot_sec
Q8TDD8
resolver
uniprot_sec
Q8TDD9
resolver
activity_regulation
ACTIVITY REGULATION: Activated by the positive allosteric modulator ML382 (2-(cyclopropanesulfonamido)-N-(2-ethoxyphenyl)benzamide) (PubMed:25209672, PubMed:36302898). Activated by the synthetic small-molecule agonist compound-16 (N-(2-(1-aminoisoquinolin-6-yloxy)-4-methylphenyl)-2-methoxybenzenesulfonamide) (PubMed:31498617, PubMed:36302898, PubMed:37347749). {ECO:0000269|PubMed:25209672, ECO:0000269|PubMed:31498617, ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749}.
uniprot
proteins
amino_acid_sequence
MDPTISTLDTELTPINGTEETLCYKQTLSLTVLTCIVSLVGLTGNAVVLWLLGCRMRRNAFSIYILNLAAADFLFLSGRLIYSLLSFISIPHTISKILYPVMMFSYFAGLSFLSAVSTERCLSVLWPIWYRCHRPTHLSAVVCVLLWALSLLRSILEWMLCGFLFSGADSAWCQTSDFITVAWLIFLCVVLCGSSLVLLIRILCGSRKIPLTRLYVTILLTVLVFLLCGLPFGIQFFLFLWIHVDREVLFCHVHLVSIFLSALNSSANPIIYFFVGSFRQRQNRQNLKLVLQRALQDASEVDEGGGQLPEEILELSGSRLEQ
uniprot
proteins
function
FUNCTION: G protein-coupled receptor specifically expressed in sensory neurons of dorsal root ganglion, and which is involved in itch perception and pain transmission (PubMed:11850634, PubMed:20004959, PubMed:26582731, PubMed:33358893, PubMed:36302898, PubMed:37347749, PubMed:37591889, PubMed:39725036). Specifically activated by a variety of enkephalin (PENK) neuropeptides, such as BAM22 and BAM8-22, which induce itch in a histamine-independent manner (PubMed:11850634, PubMed:36302898, PubMed:37591889, PubMed:39725036). Activated by some tick defensins, such as I.persulcatus Def1 and I.ricinus Def2, evoking itch (PubMed:33358893). Also activated by conotoxin CNF-Tx2, inducing itch sensation (PubMed:30243794, PubMed:37591889). Activated by the antimalarial drug chloroquine; however, activation requires concentrations that exceed the chloroquine concentrations observed in plasma of patients undergoing chloroquine treatment (PubMed:20004959). Also activated following cleavage by the dust mite cysteine protease Der p1 (PubMed:28768771). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:36302898, PubMed:37591889). MRGPRX1 is both coupled to G(q) and G(i) G proteins: G(q) coupling activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers, leading to sensitize TRPV1 in pruriceptors, while G(i) coupling mediates inhibition of adenylate cyclase activity (PubMed:23074220, PubMed:36302898, PubMed:37347749, PubMed:37591889). Activation of MRGPRX1 in the peripheral nervous system elicits itch, evoking scratching (PubMed:28223516). MRGPRX1 activation in sensory neurons of the nasal mucosa mediates sneezing responses to irritants or influenza-virus (By similarity). Activation in the central nervous system dampens chronic pain: BAM8-22-binding at the central terminals prevents pain signals passing to spinal cord neurons, attenuating spinal nociceptive transmission (PubMed:28223516). Activation by CXCL17 induces chemotactic movement (PubMed:41167449). {ECO:0000250|UniProtKB:Q8CIP3, ECO:0000269|PubMed:11850634, ECO:0000269|PubMed:20004959, ECO:0000269|PubMed:23074220, ECO:0000269|PubMed:26582731, ECO:0000269|PubMed:28223516, ECO:0000269|PubMed:28768771, ECO:0000269|PubMed:30243794, ECO:0000269|PubMed:33358893, ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0000269|PubMed:39725036, ECO:0000269|PubMed:41167449}.
uniprot
proteins
mass_dalton
36250
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="D->H: Does not affect activation by the dust mite cysteine protease Der p1."; /evidence="ECO:0000269|PubMed:28768771"; MUTAGEN 11; /note="E->H: Abolished activation by the dust mite cysteine protease Der p1."; /evidence="ECO:0000269|PubMed:28768771"; MUTAGEN 22; /note="L->H: Abolished activation by the dust mite cysteine protease Der p1."; /evidence="ECO:0000269|PubMed:28768771"; MUTAGEN 33; /note="L->P: Abolished G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:39725036"; MUTAGEN 59; /note="N->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 61; /note="F->A: Decreased G(i) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 82; /note="Y->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898"; MUTAGEN 96; /note="K->A: Strongly reduced G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37347749"; MUTAGEN 99; /note="Y->A: Strongly reduced activation by the synthetic small-molecule agonist compound-16. Strongly reduced activation by conotoxin CNF-Tx2. Strongly reduced G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889"; MUTAGEN 106; /note="Y->A: Strongly reduced activation by the synthetic small-molecule agonist compound-16."; /evidence="ECO:0000269|PubMed:37347749"; MUTAGEN 119; /note="E->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 124; /note="V->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 130; /note="Y->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 131; /note="R->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 132; /note="C->A: Decreased G(i) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 134; /note="R->A: Decreased G(i) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 157; /note="E->A: Strongly reduced G protein-coupled receptor signaling in response to CNF-Tx2- and BAM8-22-binding. Strongly reduced activation by the synthetic small-molecule agonist compound-16."; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889"; MUTAGEN 160; /note="L->A: Strongly reduced activation by conotoxin CNF-Tx2."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 161; /note="C->A: Abolished G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37347749"; MUTAGEN 173; /note="C->A: Abolished G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37347749"; MUTAGEN 177; /note="D->A: Abolished G protein-coupled receptor signaling in response to BAM8-22-binding. Strongly reduced activation by the synthetic small-molecule agonist compound-16."; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749"; MUTAGEN 198; /note="L->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 213; /note="R->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 214; /note="L->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 217; /note="T->A: Decreased G(q) G protein-mediated signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 229; /note="G->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 231; /note="P->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 232; /note="F->A: Decreased G protein-coupled receptor signaling. Strongly reduced activation by the synthetic small-molecule agonist compound-16."; /evidence="ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889"; MUTAGEN 233; /note="G->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:37591889"; MUTAGEN 236; /note="F->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37591889"; MUTAGEN 237; /note="F->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding. Strongly reduced activation by the synthetic small-molecule agonist compound-16."; /evidence="ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889"; MUTAGEN 240; /note="L->A: Strongly reduced G protein-coupled receptor signaling in response to CNF-Tx2- and BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37591889"; MUTAGEN 241; /note="W->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898"; MUTAGEN 249; /note="L->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898"; MUTAGEN 250; /note="F->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898"; MUTAGEN 254; /note="H->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898"; MUTAGEN 258; /note="I->A: Strongly reduced G protein-coupled receptor signaling in response to BAM8-22-binding."; /evidence="ECO:0000269|PubMed:36302898
uniprot
proteins
post_translational_modification
PTM: Cleavage by D.pteronyssinus cysteine protease Der p1 leads to activation. {ECO:0000269|PubMed:28768771}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
protein_family
Mas subfamily
uniprot
proteins
pubmed
11551509
uniprot
proteins
pubmed
11850634
uniprot
proteins
pubmed
12044878
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
20004959
uniprot
proteins
pubmed
23074220
uniprot
proteins
pubmed
25209672
uniprot
proteins
pubmed
26582731
uniprot
proteins
pubmed
28223516
uniprot
proteins
pubmed
28768771
uniprot
proteins
pubmed
30243794
uniprot
proteins
pubmed
31498617
uniprot
proteins
pubmed
33358893
uniprot
proteins
pubmed
36302898
uniprot
proteins
pubmed
37347749
uniprot
proteins
pubmed
37591889
uniprot
proteins
pubmed
39725036
uniprot
proteins
pubmed
41167449
uniprot
proteins
sequence_length
322
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:36302898}; Multi-pass membrane protein {ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889}.
uniprot
proteins
transmembrane_region
TRANSMEM 25..53; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG"; TRANSMEM 61..87; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG"; TRANSMEM 94..122; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG"; TRANSMEM 138..165; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG"; TRANSMEM 172..200; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG"; TRANSMEM 214..240; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG"; TRANSMEM 251..275; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:36302898, ECO:0000269|PubMed:37347749, ECO:0000269|PubMed:37591889, ECO:0007744|PDB:8DWC, ECO:0007744|PDB:8DWG, ECO:0007744|PDB:8DWH, ECO:0007744|PDB:8HJ5, ECO:0007744|PDB:8JGB, ECO:0007744|PDB:8JGF, ECO:0007744|PDB:8JGG
uniprot
proteins