GPR161
entrez
23432
canonical
uniprot
Q8N6U8
canonical
ensembl
ENSG00000143147
resolver
ensp
ENSP00000271357
resolver
ensp
ENSP00000356809
resolver
ensp
ENSP00000356810
resolver
ensp
ENSP00000356812
resolver
ensp
ENSP00000437576
resolver
ensp
ENSP00000441039
resolver
ensp
ENSP00000444348
resolver
ensp
ENSP00000506967
resolver
ensp
ENSP00000537385
resolver
ensp
ENSP00000537387
resolver
ensp
ENSP00000537391
resolver
ensp
ENSP00000537392
resolver
ensp
ENSP00000537393
resolver
ensp
ENSP00000537397
resolver
enst
ENST00000271357
resolver
genesymbol
GPR161
resolver
hgnc
HGNC:23694
resolver
uniprot
A0A0A0MQW8
resolver
uniprot
B3KV34
resolver
uniprot
B7Z5D7
resolver
uniprot
B7Z5E8
resolver
uniprot
B7Z5Z6
resolver
uniprot
F5GXD6
resolver
uniprot
F5H6J7
resolver
uniprot
O75963
resolver
uniprot
Q5TGK0
resolver
uniprot
Q5TGK1
resolver
uniprot
Q5TGK2
resolver
uniprot_entry
A0A0A0MQW8_HUMAN
resolver
uniprot_entry
GP161_HUMAN
resolver
uniprot_sec
B3KV34
resolver
uniprot_sec
B7Z5D7
resolver
uniprot_sec
B7Z5E8
resolver
uniprot_sec
B7Z5Z6
resolver
uniprot_sec
F5GXD6
resolver
uniprot_sec
F5H6J7
resolver
uniprot_sec
O75963
resolver
uniprot_sec
Q5TGK0
resolver
uniprot_sec
Q5TGK1
resolver
uniprot_sec
Q5TGK2
resolver
activity_regulation
ACTIVITY REGULATION: In contrast to the majority of G protein-coupled receptors, it is not activated by a ligand and it either acts as a constitutively active receptor or as a mechanosensitive receptor (PubMed:38326651). Cholesterol promotes coupling to G(s)/GNAS and G protein-coupled receptor activity (PubMed:38326651). {ECO:0000269|PubMed:38326651}.
uniprot
proteins
amino_acid_sequence
MSLNSSLSCRKELSNLTEEEGGEGGVIITQFIAIIVITIFVCLGNLVIVVTLYKKSYLLTLSNKFVFSLTLSNFLLSVLVLPFVVTSSIRREWIFGVVWCNFSALLYLLISSASMLTLGVIAIDRYYAVLYPMVYPMKITGNRAVMALVYIWLHSLIGCLPPLFGWSSVEFDEFKWMCVAAWHREPGYTAFWQIWCALFPFLVMLVCYGFIFRVARVKARKVHCGTVVIVEEDAQRTGRKNSSTSTSSSGSRRNAFQGVVYSANQCKALITILVVLGAFMVTWGPYMVVIASEALWGKSSVSPSLETWATWLSFASAVCHPLIYGLWNKTVRKELLGMCFGDRYYREPFVQRQRTSRLFSISNRITDLGLSPHLTALMAGGQPLGHSSSTGDTGFSCSQDSGTDMMLLEDYTSDDNPPSHCTCPPKRRSSVTFEDEVEQIKEAAKNSILHVKAEVHKSLDSYAASLAKAIEAEAKINLFGEEALPGVLVTARTVPGGGFGGRRGSRTLVSQRLQLQSIEEGDVLAAEQR
uniprot
proteins
disease_involvement
DISEASE: Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. {ECO:0000269|PubMed:31609649}. Note=Disease susceptibility may be associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: G protein-coupled receptor that acts as a key inhibitor of the smoothened signaling pathway in primary cilia (PubMed:38326651). Inhibits the smoothened signaling pathway in absence of hedgehog (DHH, IHH or SHH) by promoting formation of the transcription repressor form of GLI2 and GLI3 transcription factors (PubMed:38326651). GPR161 activation triggers signaling via guanine nucleotide-binding protein G(s)/GNAS, mediating activation of adenylate cyclase activity and production of cAMP (PubMed:38326651). Increased cAMP levels activate PKA, promoting PKA-dependent processing of GLI2 and GLI3 transcription factors, leading to formation of transcription repressor GLI2R and GLI3R, which repress expression of target genes (PubMed:38326651). GPR161 also activates PKA by acting as a PKA-anchoring protein, which directly associates with type I PKA regulatory subunits (PRKAR1A and/or PRKAR1B), recruiting PKA followed by PKA-dependent processing of GLI2 and GLI3 transcription factors (PubMed:38326651). In presence of hedgehog, GPR161 is removed from primary cilia by smoothened (SMO), preventing its activity and allowing activation of the smoothened signaling (By similarity). In contrast to the majority of G protein-coupled receptors, it is not activated by a ligand and it either acts as a constitutively active receptor or as a mechanosensitive receptor (PubMed:38326651). Involved in regulation of the smoothened signaling pathway during early neural tube development, forelimb formation, skeletal development, embryonic cerebellar development and forebrain development (By similarity). Involved in the saltatory migration of neurons during brain development by acting as a mechanosensitive receptor that senses mechanical forces generated by fluid shear stress (By similarity). {ECO:0000250|UniProtKB:B2RPY5, ECO:0000269|PubMed:38326651}.
uniprot
proteins
mass_dalton
58559
uniprot
proteins
mutagenesis
MUTAGEN 177; /note="M->R,A: Abolished constitutive G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:38326651"; MUTAGEN 179; /note="V->A: Reduced constitutive G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:38326651"; MUTAGEN 179; /note="V->R: Abolished constitutive G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:38326651"; MUTAGEN 182; /note="W->R,A: Abolished constitutive G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:38326651"; MUTAGEN 323..332; /note="IYGLWNKTVR->AYGLWAKTVA: Abolished binding to cholesterol."; /evidence="ECO:0000269|PubMed:38326651
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by GRK2 in presence of smoothened (SMO), promoting association with beta-arrestin (ARRB1 or ARRB2), and export from primary cilia by the BBSome and IFT-B complexes. {ECO:0000269|PubMed:40384633}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
20889716
uniprot
proteins
pubmed
31609649
uniprot
proteins
pubmed
38326651
uniprot
proteins
pubmed
40384633
uniprot
proteins
pubmed
9932290
uniprot
proteins
sequence_length
529
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell projection, cilium membrane {ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:40384633}; Multi-pass membrane protein {ECO:0000269|PubMed:38326651}. Cell membrane {ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:40384633}; Multi-pass membrane protein {ECO:0000269|PubMed:38326651}. Note=Recruited to primary cilium in a TULP3 and IFT-A complex-dependent manner (PubMed:20889716). In presence of smoothened (SMO), it is removed from primary cilia and is internalized into recycling endosomes and is apparently not degraded (PubMed:40384633). Export from primary cilia is mediated via a beta-arrestin, BBSome and IFT-B complex-dependent mechanism (PubMed:40384633). {ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:40384633}.
uniprot
proteins
transmembrane_region
TRANSMEM 32..55; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV"; TRANSMEM 59..81; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV"; TRANSMEM 106..126; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV"; TRANSMEM 140..158; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV"; TRANSMEM 192..212; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV"; TRANSMEM 268..287; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV"; TRANSMEM 308..327; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:38326651, ECO:0007744|PDB:8SMV
uniprot
proteins