MRGPRX4
entrez
117196
canonical
uniprot
Q96LA9
canonical
ensembl
ENSG00000179817
resolver
ensp
ENSP00000314042
resolver
enst
ENST00000314254
resolver
genesymbol
MRGPRX4
resolver
genesymbol_syn
MRGX4
resolver
genesymbol_syn
SNSR5
resolver
genesymbol_syn
SNSR6
resolver
hgnc
HGNC:17617
resolver
uniprot
Q3KNU3
resolver
uniprot
Q3KNU4
resolver
uniprot
Q502W0
resolver
uniprot
Q8TDD6
resolver
uniprot
Q8TDD7
resolver
uniprot_entry
MRGX4_HUMAN
resolver
uniprot_sec
Q3KNU3
resolver
uniprot_sec
Q3KNU4
resolver
uniprot_sec
Q502W0
resolver
uniprot_sec
Q8TDD6
resolver
uniprot_sec
Q8TDD7
resolver
activity_regulation
ACTIVITY REGULATION: Bilirubin IXalpha facilites activation by acting as a positive allosteric modulator (PubMed:31500698). Activated by nateglinide drug, a FDA approved drug for the treatment of diabetes, eliciting chronic itching (pruritus), a well-known side effect of nateglinide (PubMed:30768591, PubMed:31500698). Specifically activated by MS47134, a nateglinide analog (PubMed:34789874). Activated by fospropofol, a sedative-hypnotic drug, eliciting chronic itching (pruritus), a well-known side effect of fospropofol (PubMed:38718132). Menthol hampers activation by acting as a negative modulator (PubMed:30768591). {ECO:0000269|PubMed:30768591, ECO:0000269|PubMed:31500698, ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:38718132}.
uniprot
proteins
amino_acid_sequence
MDPTVPVFGTKLTPINGREETPCYNQTLSFTVLTCIISLVGLTGNAVVLWLLGYRMRRNAVSIYILNLAAADFLFLSFQIIRLPLRLINISHLIRKILVSVMTFPYFTGLSMLSAISTERCLSVLWPIWYRCRRPTHLSAVVCVLLWGLSLLFSMLEWRFCDFLFSGADSSWCETSDFIPVAWLIFLCVVLCVSSLVLLVRILCGSRKMPLTRLYVTILLTVLVFLLCGLPFGILGALIYRMHLNLEVLYCHVYLVCMSLSSLNSSANPIIYFFVGSFRQRQNRQNLKLVLQRALQDKPEVDKGEGQLPEESLELSGSRLGP
uniprot
proteins
disease_involvement
DISEASE: Note=MRGPRX4 activation by high blood levels of bile salts in individuals with cholestasis is involved in the pathogenesis of chronic itch experienced by these patients. {ECO:0000269|PubMed:30657454, ECO:0000269|PubMed:31068464, ECO:0000269|PubMed:31500698, ECO:0000269|PubMed:39476841}.
uniprot
proteins
function
FUNCTION: G protein-coupled receptor for bile acids, which is specifically expressed in sensory neurons of dorsal root ganglion and is involved in itch perception (PubMed:31068464, PubMed:31500698, PubMed:34789874, PubMed:38718132, PubMed:39476841). Activated by bile acids, such as deoxycholate, chenodeoxycholate, taurocholate, taurodeoxycholate and taurodeoxycholate (PubMed:31068464, PubMed:31500698, PubMed:39476841). Has a preference for 3-sulfated bile acids, such as deoxycholate 3-sulfate, glycoursodeoxycholate 3-sulfate and tauroursodeoxycholate 3-sulfate, which are present at high level in cholestatic patients with itch symptoms (PubMed:39476841). Bile acid-binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:30768591, PubMed:31068464, PubMed:31500698, PubMed:34789874, PubMed:38718132, PubMed:39476841). MRGPRX4 is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca2+ ions from intracellular stores, respectively (PubMed:30768591, PubMed:31068464, PubMed:31500698, PubMed:34789874, PubMed:38718132, PubMed:39476841). {ECO:0000269|PubMed:30768591, ECO:0000269|PubMed:31068464, ECO:0000269|PubMed:31500698, ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:38718132, ECO:0000269|PubMed:39476841}.
uniprot
proteins
mass_dalton
36461
uniprot
proteins
mutagenesis
MUTAGEN 82; /note="R->A: Decreased binding to 3-sulfated bile acids. Decreased activation by phosphate-modified drugs, such as fospropofol. Decreased activation by agonists."; /evidence="ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:38718132, ECO:0000269|PubMed:39476841"; MUTAGEN 86; /note="R->A: Decreased binding to 3-sulfated bile acids. Decreased activation by phosphate-modified drugs, such as fospropofol."; /evidence="ECO:0000269|PubMed:38718132, ECO:0000269|PubMed:39476841"; MUTAGEN 95; /note="R->A: Decreased binding to 3-sulfated bile acids. Decreased activation by phosphate-modified drugs, such as fospropofol. Decreased activation by agonists."; /evidence="ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:38718132, ECO:0000269|PubMed:39476841"; MUTAGEN 96; /note="K->A: Decreased binding to 3-sulfated bile acids. Decreased activation by agonists."; /evidence="ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:39476841"; MUTAGEN 99; /note="V->A: Decreased binding to 3-sulfated bile acids."; /evidence="ECO:0000269|PubMed:39476841"; MUTAGEN 158; /note="W->A: Decreased activation by phosphate-modified drugs, such as fospropofol. Decreased activation by agonists."; /evidence="ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:38718132"; MUTAGEN 159; /note="R->A: Reduced affinity for deoxycholate ligand."; /evidence="ECO:0000269|PubMed:31500698"; MUTAGEN 180; /note="P->A: Reduced affinity for deoxycholate ligand. Increased localization to the plasma membrane."; /evidence="ECO:0000269|PubMed:31500698"; MUTAGEN 232; /note="F->A: Decreased binding to 3-sulfated bile acids."; /evidence="ECO:0000269|PubMed:39476841"; MUTAGEN 235; /note="L->A: Reduced affinity for deoxycholate and 3-sulfated bile acids."; /evidence="ECO:0000269|PubMed:31500698, ECO:0000269|PubMed:39476841"; MUTAGEN 240; /note="Y->A: Decreased binding to 3-sulfated bile acids. Decreased activation by agonists."; /evidence="ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:39476841"; MUTAGEN 241; /note="R->A: Decreased binding to 3-sulfated bile acids."; /evidence="ECO:0000269|PubMed:39476841"; MUTAGEN 250; /note="Y->A: Decreased activation by phosphate-modified drugs, such as fospropofol."; /evidence="ECO:0000269|PubMed:38718132"; MUTAGEN 254; /note="Y->A: Decreased activation by phosphate-modified drugs, such as fospropofol."; /evidence="ECO:0000269|PubMed:38718132
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
15489334
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
30657454
uniprot
proteins
pubmed
30768591
uniprot
proteins
pubmed
31068464
uniprot
proteins
pubmed
31500698
uniprot
proteins
pubmed
34789874
uniprot
proteins
pubmed
38718132
uniprot
proteins
pubmed
39476841
uniprot
proteins
sequence_length
322
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31500698}; Multi-pass membrane protein {ECO:0000269|PubMed:34789874, ECO:0000269|PubMed:38718132, ECO:0000269|PubMed:39476841}.
uniprot
proteins
transmembrane_region
TRANSMEM 28..46; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P"; TRANSMEM 63..87; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P"; TRANSMEM 94..122; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P"; TRANSMEM 138..156; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P"; TRANSMEM 176..201; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P"; TRANSMEM 214..238; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P"; TRANSMEM 250..272; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:34789874, ECO:0007744|PDB:7S8P
uniprot
proteins