MRGPRD
entrez
116512
canonical
uniprot
Q8TDS7
canonical
ensembl
ENSG00000172938
resolver
ensp
ENSP00000310631
resolver
enst
ENST00000309106
resolver
genesymbol
MRGPRD
resolver
genesymbol_syn
MRGD
resolver
hgnc
HGNC:29626
resolver
uniprot
Q8NGK7
resolver
uniprot_entry
MRGRD_HUMAN
resolver
uniprot_sec
Q8NGK7
resolver
activity_regulation
ACTIVITY REGULATION: Activated by diethylstilbestrol, a synthetic estrogen hormone. {ECO:0000269|PubMed:23091359}.
uniprot
proteins
amino_acid_sequence
MNQTLNSSGTVESALNYSRGSTVHTAYLVLSSLAMFTCLCGMAGNSMVIWLLGFRMHRNPFCIYILNLAAADLLFLFSMASTLSLETQPLVNTTDKVHELMKRLMYFAYTVGLSLLTAISTQRCLSVLFPIWFKCHRPRHLSAWVCGLLWTLCLLMNGLTSSFCSKFLKFNEDRCFRVDMVQAALIMGVLTPVMTLSSLTLFVWVRRSSQQWRRQPTRLFVVVLASVLVFLICSLPLSIYWFVLYWLSLPPEMQVLCFSLSRLSSSVSSSANPVIYFLVGSRRSHRLPTRSLGTVLQQALREEPELEGGETPTVGTNEMGA
uniprot
proteins
function
FUNCTION: G protein-coupled receptor that acts as a mediator of peripheral pain and itch sensations (PubMed:15037633, PubMed:23091359, PubMed:35840655, PubMed:39580805). Activated by various ligands, such as beta-alanine, beta-aminoisobutyrate, angiotensin 1-7, alamandine and allantoin, causing a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:15037633, PubMed:23091359, PubMed:35840655, PubMed:39580805). MRGPRD 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, while G(i) coupling mediates inhibition of adenylate cyclase activity (PubMed:15037633, PubMed:23091359, PubMed:35840655, PubMed:39580805). MRGPRD is specifically expressed in neurons that innervate the epidermis and acts as a key mediator of skin stimuli, such as itch, pain and mechanical stimuli (By similarity). Required to maintain skin homeostasis in response to irritant dermatitis by initiating a signaling that promotes glutamate release, inhibiting mast cell hyperresponsiveness and skin inflammation (By similarity). Required to prevent cardiomyocyte hypertrophy following activation by alamandine, a decarboxylation product of angiotensin 1-7 (By similarity). Acts as a receptor for allantoin in dorsal root ganglion neurons, eliciting chronic itch (pruritus) (By similarity). {ECO:0000250|UniProtKB:Q91ZB8, ECO:0000269|PubMed:15037633, ECO:0000269|PubMed:23091359, ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805}.
uniprot
proteins
mass_dalton
36118
uniprot
proteins
mutagenesis
MUTAGEN 102; /note="K->A: Does not affect G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39580805"; MUTAGEN 103; /note="R->A: Abolished G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805"; MUTAGEN 106; /note="Y->A: Decreased G(i)- and G(q)-mediated signaling."; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805"; MUTAGEN 109; /note="Y->A: Decreased G(i)-mediated signaling."; /evidence="ECO:0000269|PubMed:35840655"; MUTAGEN 157; /note="N->A: Slightly increased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39580805"; MUTAGEN 179; /note="D->A: Abolished G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805"; MUTAGEN 182; /note="Q->A: Slightly increased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:39580805"; MUTAGEN 234; /note="S->A: Decreased G(i)-mediated signaling."; /evidence="ECO:0000269|PubMed:35840655"; MUTAGEN 237; /note="L->A: Decreased G(i)-mediated signaling."; /evidence="ECO:0000269|PubMed:35840655"; MUTAGEN 241; /note="W->A: Abolished G protein-coupled receptor signaling. Abolished G(i)- and G(q)-mediated signaling."; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805"; MUTAGEN 242; /note="F->A: Abolished G(i)- and G(q)-mediated signaling."; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805"; MUTAGEN 245; /note="Y->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805"; MUTAGEN 246; /note="W->A: Abolished G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35840655
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
protein_family
Mas subfamily
uniprot
proteins
pubmed
12044878
uniprot
proteins
pubmed
12909716
uniprot
proteins
pubmed
15037633
uniprot
proteins
pubmed
23091359
uniprot
proteins
pubmed
35840655
uniprot
proteins
pubmed
39580805
uniprot
proteins
sequence_length
321
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15037633}; Multi-pass membrane protein {ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805}. Note=Localized at the plasma membrane but internalized into the cytoplasm after treatment with beta-alanine. {ECO:0000269|PubMed:15037633}.
uniprot
proteins
transmembrane_region
TRANSMEM 25..50; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ"; TRANSMEM 62..88; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ"; TRANSMEM 96..125; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ"; TRANSMEM 141..165; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ"; TRANSMEM 177..203; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ"; TRANSMEM 220..244; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ"; TRANSMEM 255..279; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:35840655, ECO:0000269|PubMed:39580805, ECO:0007744|PDB:7Y12, ECO:0007744|PDB:7Y13, ECO:0007744|PDB:7Y14, ECO:0007744|PDB:7Y15, ECO:0007744|PDB:9DQH, ECO:0007744|PDB:9DQJ
uniprot
proteins