ADGRG6
entrez
57211
canonical
uniprot
Q86SQ4
canonical
ensembl
ENSG00000112414
resolver
ensp
ENSP00000230173
resolver
ensp
ENSP00000296932
resolver
ensp
ENSP00000356580
resolver
ensp
ENSP00000356581
resolver
ensp
ENSP00000638577
resolver
ensp
ENSP00000712210
resolver
genesymbol
ADGRG6
resolver
genesymbol_syn
DREG
resolver
genesymbol_syn
GPR126
resolver
genesymbol_syn
VIGR
resolver
hgnc
HGNC:13841
resolver
uniprot
Q5TGN7
resolver
uniprot
Q6DHZ4
resolver
uniprot
Q6F3F5
resolver
uniprot
Q6F3F6
resolver
uniprot
Q6F3F7
resolver
uniprot
Q6F3F8
resolver
uniprot
Q6MZU7
resolver
uniprot
Q8IXA4
resolver
uniprot
Q8NC14
resolver
uniprot
Q96JW0
resolver
uniprot_entry
AGRG6_HUMAN
resolver
uniprot_sec
Q5TGN7
resolver
uniprot_sec
Q6DHZ4
resolver
uniprot_sec
Q6F3F5
resolver
uniprot_sec
Q6F3F6
resolver
uniprot_sec
Q6F3F7
resolver
uniprot_sec
Q6F3F8
resolver
uniprot_sec
Q6MZU7
resolver
uniprot_sec
Q8IXA4
resolver
uniprot_sec
Q8NC14
resolver
uniprot_sec
Q96JW0
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 (By similarity). In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation (By similarity). 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 (By similarity). The cleaved GAIN-B and N-terminal domains can then dissociate from the rest of the receptor (By similarity). {ECO:0000250|UniProtKB:Q8IZF4}.
uniprot
proteins
amino_acid_sequence
MMFRSDRMWSCHWKWKPSPLLFLFALYIMCVPHSVWGCANCRVVLSNPSGTFTSPCYPNDYPNSQACMWTLRAPTGYIIQITFNDFDIEEAPNCIYDSLSLDNGESQTKFCGATAKGLSFNSSANEMHVSFSSDFSIQKKGFNASYIRVAVSLRNQKVILPQTSDAYQVSVAKSISIPELSAFTLCFEATKVGHEDSDWTAFSYSNASFTQLLSFGKAKSGYFLSISDSKCLLNNALPVKEKEDIFAESFEQLCLVWNNSLGSIGVNFKRNYETVPCDSTISKVIPGNGKLLLGSNQNEIVSLKGDIYNFRLWNFTMNAKILSNLSCNVKGNVVDWQNDFWNIPNLALKAESNLSCGSYLIPLPAAELASCADLGTLCQATVNSPSTTPPTVTTNMPVTNRIDKQRNDGIIYRISVVIQNILRHPEVKVQSKVAEWLNSTFQNWNYTVYVVNISFHLSAGEDKIKVKRSLEDEPRLVLWALLVYNATNNTNLEGKIIQQKLLKNNESLDEGLRLHTVNVRQLGHCLAMEEPKGYYWPSIQPSEYVLPCPDKPGFSASRICFYNATNPLVTYWGPVDISNCLKEANEVANQILNLTADGQNLTSANITNIVEQVKRIVNKEENIDITLGSTLMNIFSNILSSSDSDLLESSSEALKTIDELAFKIDLNSTSHVNITTRNLALSVSSLLPGTNAISNFSIGLPSNNESYFQMDFESGQVDPLASVILPPNLLENLSPEDSVLVRRAQFTFFNKTGLFQDVGPQRKTLVSYVMACSIGNITIQNLKDPVQIKIKHTRTQEVHHPICAFWDLNKNKSFGGWNTSGCVAHRDSDASETVCLCNHFTHFGVLMDLPRSASQLDARNTKVLTFISYIGCGISAIFSAATLLTYVAFEKLRRDYPSKILMNLSTALLFLNLLFLLDGWITSFNVDGLCIAVAVLLHFFLLATFTWMGLEAIHMYIALVKVFNTYIRRYILKFCIIGWGLPALVVSVVLASRNNNEVYGKESYGKEKGDEFCWIQDPVIFYVTCAGYFGVMFFLNIAMFIVVMVQICGRNGKRSNRTLREEVLRNLRSVVSLTFLLGMTWGFAFFAWGPLNIPFMYLFSIFNSLQGLFIFIFHCAMKENVQKQWRQHLCCGRFRLADNSDWSKTATNIIKKSSDNLGKSLSSSSIGSNSTYLTSKSKSSSTTYFKRNSHTDNVSYEHSFNKSGSLRQCFHGQVLVKTGPC
uniprot
proteins
disease_involvement
DISEASE: Lethal congenital contracture syndrome 9 (LCCS9) [MIM:616503]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:26004201}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Adhesion G protein-coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP) (PubMed:35394864, PubMed:39884271). Involved in many biological processes, such as myelination, sprouting angiogenesis, placenta, ear and cartilage development (By similarity). 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:24227709, PubMed:35394864). ADGRG6 is coupled to G(i) G alpha proteins and mediates inhibition of adenylate cyclase (PubMed:24227709, PubMed:35394864). Also able to couple to G(q) G proteins (PubMed:24227709). Involved in myelination of the peripheral nervous system: required for differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:24227709). Also acts as a regulator of body length and bone mass (PubMed:18391950). Acts as a regulator of blood-brain barrier formation in the central nervous system vie its association with LRP1 and ITGB1 (By similarity). {ECO:0000250|UniProtKB:Q6F3F9, ECO:0000269|PubMed:18391950, ECO:0000269|PubMed:24227709, ECO:0000269|PubMed:35394864, ECO:0000269|PubMed:39884271}.
uniprot
proteins
mass_dalton
136695
uniprot
proteins
mutagenesis
MUTAGEN 468; /note="R->A: Abolished cleavage by furin like-convertase without affecting localization to the cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 469; /note="S->A: No effect on cleavage."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 803; /note="C->S: No cleavage and not detected at the cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 813; /note="S->A: No effect on G protein-mediated cAMP release."; /evidence="ECO:0000269|PubMed:25533341"; MUTAGEN 815; /note="G->A: Abolishes G protein-mediated cAMP release."; /evidence="ECO:0000269|PubMed:25533341"; MUTAGEN 818; /note="N->A: Abolishes G protein-mediated cAMP release."; /evidence="ECO:0000269|PubMed:25533341"; MUTAGEN 819; /note="T->A: Abolishes G protein-mediated cAMP release."; /evidence="ECO:0000269|PubMed:25533341"; MUTAGEN 822; /note="C->S: No cleavage and not detected at the cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 835; /note="C->S: No cleavage and not detected at the cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 837; /note="C->S: No cleavage and not detected at the cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 841; /note="T->A: No cleavage but detected at cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 841; /note="T->P: No cleavage and not detected at the cell surface."; /evidence="ECO:0000269|PubMed:15189448"; MUTAGEN 915; /note="F->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864, ECO:0000269|PubMed:39884271"; MUTAGEN 916; /note="L->A: Does not impair G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 937; /note="L->A: Does not impair G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 941; /note="L->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864, ECO:0000269|PubMed:39884271"; MUTAGEN 1001; /note="K->A: Impaired conformational change in response to 17alpha-hydroxyprogesterone (17OHP) without affecting response to progesterone."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 1012; /note="F->A: Impaired conformational change in response to 17alpha-hydroxyprogesterone (17OHP) without affecting response to progesterone."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 1014; /note="W->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 1081; /note="W->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864, ECO:0000269|PubMed:39884271"; MUTAGEN 1085; /note="F->A: Impaired response to progesterone, but not to17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 1091; /note="L->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 1099; /note="F->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864"; MUTAGEN 1099; /note="F->L: Decreased activation by 17alpha-hydroxyprogesterone."; /evidence="ECO:0000269|PubMed:39884271"; MUTAGEN 1103; /note="N->A: Strongly decreased G protein-coupled receptor activity in response to 17alpha-hydroxyprogesterone (17OHP)."; /evidence="ECO:0000269|PubMed:35394864, ECO:0000269|PubMed:39884271
uniprot
proteins
post_translational_modification
PTM: Proteolytically cleaved into 2 conserved sites: one in the GPS region of the GAIN-B domain (S1 site) and the other in the middle of the extracellular domain (S2 site) (PubMed:15189448). The proteolytic cleavage at S1 site generates an extracellular subunit and a seven-transmembrane subunit (PubMed:15189448, PubMed:26004201). Furin is involved in the cleavage of the S2 site generating a soluble fragment (PubMed:15189448). Processing at the GPS region occurred independent of and probably prior to the cleavage at the S2 site (PubMed:15189448). Proteolytic cleavage is required for activation of the receptor (PubMed:15189448, PubMed:26004201). {ECO:0000269|PubMed:15189448, ECO:0000269|PubMed:26004201}.; PTM: Highly glycosylated. {ECO:0000269|PubMed:15225624}.
uniprot
proteins
protein_family
Adhesion G protein-coupled receptor (ADGR) subfamily
uniprot
proteins
protein_family
G protein-coupled receptor 2 family
uniprot
proteins
pubmed
12565841
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15084671
uniprot
proteins
pubmed
15189448
uniprot
proteins
pubmed
15225624
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16335952
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18391950
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
24227709
uniprot
proteins
pubmed
25533341
uniprot
proteins
pubmed
26004201
uniprot
proteins
pubmed
27509131
uniprot
proteins
pubmed
31924782
uniprot
proteins
pubmed
35394864
uniprot
proteins
pubmed
39884271
uniprot
proteins
sequence_length
1221
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15189448, ECO:0000269|PubMed:15225624, ECO:0000269|PubMed:24227709, ECO:0000269|PubMed:31924782}; Multi-pass membrane protein {ECO:0000255}. Note=Detected on the cell surface of activated but not resting umbilical vein. {ECO:0000269|PubMed:15225624}.
uniprot
proteins
transmembrane_region
TRANSMEM 863..883; /note="Helical; Name=1"; /evidence="ECO:0000255"; TRANSMEM 904..924; /note="Helical; Name=2"; /evidence="ECO:0000255"; TRANSMEM 930..950; /note="Helical; Name=3"; /evidence="ECO:0000255"; TRANSMEM 971..991; /note="Helical; Name=4"; /evidence="ECO:0000255"; TRANSMEM 1025..1045; /note="Helical; Name=5"; /evidence="ECO:0000255"; TRANSMEM 1070..1090; /note="Helical; Name=6"; /evidence="ECO:0000255"; TRANSMEM 1093..1113; /note="Helical; Name=7"; /evidence="ECO:0000255
uniprot
proteins