ADGRD1
entrez
283383
canonical
uniprot
Q6QNK2
canonical
ensembl
ENSG00000111452
resolver
ensp
ENSP00000261654
resolver
ensp
ENSP00000444425
resolver
ensp
ENSP00000551119
resolver
ensp
ENSP00000551120
resolver
ensp
ENSP00000551121
resolver
ensp
ENSP00000793819
resolver
ensp
ENSP00000793820
resolver
genesymbol
ADGRD1
resolver
genesymbol_syn
GPR133
resolver
genesymbol_syn
PGR25
resolver
hgnc
HGNC:19893
resolver
uniprot
B2CKK9
resolver
uniprot
B7ZLF7
resolver
uniprot
Q2M1L3
resolver
uniprot
Q6ZMQ1
resolver
uniprot
Q7Z7M2
resolver
uniprot
Q86SM4
resolver
uniprot_entry
AGRD1_HUMAN
resolver
uniprot_sec
B2CKK9
resolver
uniprot_sec
B7ZLF7
resolver
uniprot_sec
Q2M1L3
resolver
uniprot_sec
Q6ZMQ1
resolver
uniprot_sec
Q7Z7M2
resolver
uniprot_sec
Q86SM4
resolver
activity_regulation
ACTIVITY REGULATION: Forms a heterodimer of 2 chains generated by proteolytic processing that remain associated through non-covalent interactions mediated by the GAIN-B domain (PubMed:34022221, PubMed:35418678). In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation (PubMed:35418678, PubMed:35418679). On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling (PubMed:35418678, PubMed:35418679). The cleaved GAIN-B and N-terminal domains can then dissociate from the rest of the receptor (PubMed:35418678, PubMed:35418679). Interaction with ESYT1 in absence of cytosolic calcium inhibits the G protein-coupled receptor activity; interaction and inhibition is relieved when cytosolic calcium increases (PubMed:38758649). Activated by AP503, a small molecule that activates ADGRD1 without activating androgen nuclear receptors: AP503 enhances muscle strength without eliciting androgenic adverse effects (PubMed:39884271). Activated by the 8E3E8 antibody that targets the N-terminus (PubMed:35447113). {ECO:0000269|PubMed:34022221, ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0000269|PubMed:35447113, ECO:0000269|PubMed:38758649, ECO:0000269|PubMed:39884271}.
uniprot
proteins
amino_acid_sequence
MEKLLRLCCWYSWLLLFYYNFQVRGVYSRSQDHPGFQVLASASHYWPLENVDGIHELQDTTGDIVEGKVNKGIYLKEEKGVTLLYYGRYNSSCISKPEQCGPEGVTFSFFWKTQGEQSRPIPSAYGGQVISNGFKVCSSGGRGSVELYTRDNSMTWEASFSPPGPYWTHVLFTWKSKEGLKVYVNGTLSTSDPSGKVSRDYGESNVNLVIGSEQDQAKCYENGAFDEFIIWERALTPDEIAMYFTAAIGKHALLSSTLPSLFMTSTASPVMPTDAYHPIITNLTEERKTFQSPGVILSYLQNVSLSLPSKSLSEQTALNLTKTFLKAVGEILLLPGWIALSEDSAVVLSLIDTIDTVMGHVSSNLHGSTPQVTVEGSSAMAEFSVAKILPKTVNSSHYRFPAHGQSFIQIPHEAFHRHAWSTVVGLLYHSMHYYLNNIWPAHTKIAEAMHHQDCLLFATSHLISLEVSPPPTLSQNLSGSPLITVHLKHRLTRKQHSEATNSSNRVFVYCAFLDFSSGEGVWSNHGCALTRGNLTYSVCRCTHLTNFAILMQVVPLELARGHQVALSSISYVGCSLSVLCLVATLVTFAVLSSVSTIRNQRYHIHANLSFAVLVAQVLLLISFRLEPGTTPCQVMAVLLHYFFLSAFAWMLVEGLHLYSMVIKVFGSEDSKHRYYYGMGWGFPLLICIISLSFAMDSYGTSNNCWLSLASGAIWAFVAPALFVIVVNIGILIAVTRVISQISADNYKIHGDPSAFKLTAKAVAVLLPILGTSWVFGVLAVNGCAVVFQYMFATLNSLQGLFIFLFHCLLNSEVRAAFKHKTKVWSLTSSSARTSNAKPFHSDLMNGTRPGMASTKLSPWDKSSHSAHRVDLSAV
uniprot
proteins
function
FUNCTION: Adhesion G protein-coupled receptor (aGPCR) for androgen hormone 5alpha-dihydrotestosterone (5alpha-DHT), also named 17beta-hydroxy-5alpha-androstan-3-one, the most potent hormone among androgens (PubMed:39884271). Also activated by methenolone drug (PubMed:39884271). 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:39884271). ADGRD1 is coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (PubMed:22025619, PubMed:22575658, PubMed:35447113, PubMed:39884271). Acts as a 5alpha-DHT receptor in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength (PubMed:39884271). {ECO:0000269|PubMed:22025619, ECO:0000269|PubMed:22575658, ECO:0000269|PubMed:35447113, ECO:0000269|PubMed:39884271}.
uniprot
proteins
mass_dalton
96530
uniprot
proteins
mutagenesis
MUTAGEN 543; /note="H->D: Increased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 543; /note="H->R: Does not affect membrane trafficking and basal activity. Abolished autoproteolytic cleavage."; /evidence="ECO:0000269|PubMed:22025619, ECO:0000269|PubMed:34022221, ECO:0000269|PubMed:35447113"; MUTAGEN 544; /note="L->N: Increased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 545; /note="T->A: Decreased autoproteolytic cleavage and decreased G protein-coupled receptor activity; does not affect subcellular location."; /evidence="ECO:0000269|PubMed:25533341, ECO:0000269|PubMed:35418678"; MUTAGEN 546; /note="N->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 547; /note="F->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 549; /note="I->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 550; /note="L->A: Abolishes G protein-coupled receptor activity; does not affect subcellular location."; /evidence="ECO:0000269|PubMed:25533341, ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 551; /note="M->A: Abolishes G protein-coupled receptor activity; does not affect subcellular location."; /evidence="ECO:0000269|PubMed:25533341, ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 553; /note="V->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 554; /note="V->A: Abolishes G protein-coupled receptor activity; does not affect subcellular location."; /evidence="ECO:0000269|PubMed:25533341, ECO:0000269|PubMed:35418679"; MUTAGEN 563; /note="Q->A: Decreased activation by 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 605; /note="H->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 619; /note="L->A: Decreased activation by 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 623; /note="F->A: Decreased activation by 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 640; /note="H->A: Increased affinity to 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 643; /note="F->A: Decreased activation by 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 647; /note="F->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 650; /note="M->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 653; /note="E->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 656; /note="H->A,D: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 657; /note="L->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 658; /note="Y->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 705; /note="W->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 713; /note="I->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 714; /note="W->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 716; /note="F->A: Increased affinity to 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 720; /note="A->G: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 724; /note="I->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 727; /note="N->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 730; /note="I->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 734; /note="V->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 765; /note="L->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 767; /note="P->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 768; /note="I->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 769; /note="L->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 770; /note="G->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 773; /note="W->A: Decreased activation by 5alpha-dihydrotestosterone. Strongly decreased G protein-coupled receptor signaling. Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0000269|PubMed:39884271"; MUTAGEN 791; /note="F->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 795; /note="N->L: Decreased activation by 5alpha-dihydrotestosterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 798; /note="Q->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679"; MUTAGEN 799; /note="G->A: Strongly decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418679"; MUTAGEN 805; /note="F->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 806; /note="H->A: Decreased G protein-coupled receptor signaling."; /evidence="ECO:0000269|PubMed:35418678"; MUTAGEN 808; /note="L->T: Does not affect membrane trafficking. Abolishes receptor activity."; /evidence="ECO:0000269|PubMed:22025619
uniprot
proteins
post_translational_modification
PTM: Autoproteolytically processed at the GPS region of the GAIN-B domain; this cleavage modulates receptor activity (By similarity) (PubMed:34022221, PubMed:35418678, PubMed:35447113). Cleavage takes place early in the secretory pathway before N-glycosylation (PubMed:35418678). {ECO:0000255|PROSITE-ProRule:PRU00098, ECO:0000269|PubMed:34022221, ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35447113}.
uniprot
proteins
protein_family
Adhesion G protein-coupled receptor (ADGR) subfamily
uniprot
proteins
protein_family
G protein-coupled receptor 2 family
uniprot
proteins
pubmed
12679517
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15203201
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
22025619
uniprot
proteins
pubmed
22575658
uniprot
proteins
pubmed
25533341
uniprot
proteins
pubmed
25713288
uniprot
proteins
pubmed
27516204
uniprot
proteins
pubmed
27775701
uniprot
proteins
pubmed
34022221
uniprot
proteins
pubmed
35418678
uniprot
proteins
pubmed
35418679
uniprot
proteins
pubmed
35447113
uniprot
proteins
pubmed
38758649
uniprot
proteins
pubmed
39884271
uniprot
proteins
sequence_length
874
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22025619, ECO:0000269|PubMed:25533341, ECO:0000269|PubMed:34022221}; Multi-pass membrane protein {ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679}.
uniprot
proteins
transmembrane_region
TRANSMEM 568..590; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2"; TRANSMEM 602..623; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2"; TRANSMEM 633..655; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2"; TRANSMEM 674..695; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2"; TRANSMEM 711..732; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2"; TRANSMEM 758..780; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2"; TRANSMEM 784..810; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:35418678, ECO:0000269|PubMed:35418679, ECO:0007744|PDB:7EPT, ECO:0007744|PDB:7WU2
uniprot
proteins