GPR158
entrez
57512
canonical
uniprot
Q5T848
canonical
ensembl
ENSG00000151025
resolver
ensp
ENSP00000365529
resolver
enst
ENST00000376351
resolver
genesymbol
GPR158
resolver
genesymbol_syn
KIAA1136
resolver
hgnc
HGNC:23689
resolver
uniprot
Q6QR81
resolver
uniprot
Q9ULT3
resolver
uniprot_entry
MGLYR_HUMAN
resolver
uniprot_sec
Q6QR81
resolver
uniprot_sec
Q9ULT3
resolver
amino_acid_sequence
MGAMAYPLLLCLLLAQLGLGAVGASRDPQGRPDSPRERTPKGKPHAQQPGRASASDSSAPWSRSTDGTILAQKLAEEVPMDVASYLYTGDSHQLKRANCSGRYELAGLPGKWPALASAHPSLHRALDTLTHATNFLNVMLQSNKSREQNLQDDLDWYQALVWSLLEGEPSISRAAITFSTDSLSAPAPQVFLQATREESRILLQDLSSSAPHLANATLETEWFHGLRRKWRPHLHRRGPNQGPRGLGHSWRRKDGLGGDKSHFKWSPPYLECENGSYKPGWLVTLSSAIYGLQPNLVPEFRGVMKVDINLQKVDIDQCSSDGWFSGTHKCHLNNSECMPIKGLGFVLGAYECICKAGFYHPGVLPVNNFRRRGPDQHISGSTKDVSEEAYVCLPCREGCPFCADDSPCFVQEDKYLRLAIISFQALCMLLDFVSMLVVYHFRKAKSIRASGLILLETILFGSLLLYFPVVILYFEPSTFRCILLRWARLLGFATVYGTVTLKLHRVLKVFLSRTAQRIPYMTGGRVMRMLAVILLVVFWFLIGWTSSVCQNLEKQISLIGQGKTSDHLIFNMCLIDRWDYMTAVAEFLFLLWGVYLCYAVRTVPSAFHEPRYMAVAVHNELIISAIFHTIRFVLASRLQSDWMLMLYFAHTHLTVTVTIGLLLIPKFSHSSNNPRDDIATEAYEDELDMGRSGSYLNSSINSAWSEHSLDPEDIRDELKKLYAQLEIYKRKKMITNNPHLQKKRCSKKGLGRSIMRRITEIPETVSRQCSKEDKEGADHGTAKGTALIRKNPPESSGNTGKSKEETLKNRVFSLKKSHSTYDHVRDQTEESSSLPTESQEEETTENSTLESLSGKKLTQKLKEDSEAESTESVPLVCKSASAHNLSSEKKTGHPRTSMLQKSLSVIASAKEKTLGLAGKTQTAGVEERTKSQKPLPKDKETNRNHSNSDNTETKDPAPQNSNPAEEPRKPQKSGIMKQQRVNPTTANSDLNPGTTQMKDNFDIGEVCPWEVYDLTPGPVPSESKVQKHVSIVASEMEKNPTFSLKEKSHHKPKAAEVCQQSNQKRIDKAEVCLWESQGQSILEDEKLLISKTPVLPERAKEENGGQPRAANVCAGQSEELPPKAVASKTENENLNQIGHQEKKTSSSEENVRGSYNSSNNFQQPLTSRAEVCPWEFETPAQPNAGRSVALPASSALSANKIAGPRKEEIWDSFKV
uniprot
proteins
function
FUNCTION: Metabotropic receptor for glycine that controls synapse formation and function in the brain (PubMed:36996198). Acts as an atypical G protein-coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins (PubMed:31189666, PubMed:36996198). In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:36996198). Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels (PubMed:36996198). Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity (PubMed:36996198). Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (PubMed:36996198). Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (By similarity). Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability (By similarity). Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4 (By similarity). In addition to glycine, may also act as a receptor for osteocalcin (BGLAP) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (By similarity). {ECO:0000250|UniProtKB:Q8C419, ECO:0000269|PubMed:31189666, ECO:0000269|PubMed:36996198}.
uniprot
proteins
mass_dalton
135489
uniprot
proteins
mutagenesis
MUTAGEN 135; /note="F->A: Does not affect ability to regulate cAMP levels; when associated with A-540 and A-578."; /evidence="ECO:0000269|PubMed:34815401"; MUTAGEN 173; /note="R->A: Nearly abolished glycine-binding and ability to inhibit the GTPase activator activity of RGS7."; /evidence="ECO:0000269|PubMed:36996198"; MUTAGEN 266; /note="S->A: Nearly abolished ability to inhibit the GTPase activator activity of RGS7 without affecting glycine-binding."; /evidence="ECO:0000269|PubMed:36996198"; MUTAGEN 269; /note="Y->A: Nearly abolished glycine-binding and ability to inhibit the GTPase activator activity of RGS7."; /evidence="ECO:0000269|PubMed:36996198"; MUTAGEN 271; /note="E->A: Nearly abolished glycine-binding and ability to inhibit the GTPase activator activity of RGS7."; /evidence="ECO:0000269|PubMed:36996198"; MUTAGEN 502; /note="K->E: Does not affect G protein alpha subunit activation."; /evidence="ECO:0000269|PubMed:31189666"; MUTAGEN 505; /note="R->E: Does not affect G protein alpha subunit activation."; /evidence="ECO:0000269|PubMed:31189666"; MUTAGEN 540; /note="F->A: Does not affect ability to regulate cAMP levels; when associated with A-135 and A-578."; /evidence="ECO:0000269|PubMed:34815401"; MUTAGEN 578; /note="W->A: Does not affect ability to regulate cAMP levels; when associated with A-135 and A-540."; /evidence="ECO:0000269|PubMed:34815401"; MUTAGEN 609; /note="E->H: Induces an increase of cAMP levels."; /evidence="ECO:0000269|PubMed:34815401"; MUTAGEN 719..720; /note="KK->QQ: In M1 mutant; decreased localization to the nucleus."; /evidence="ECO:0000269|PubMed:23451275"; MUTAGEN 731..732; /note="KK->QQ: In M2 mutant; decreased localization to the nucleus."; /evidence="ECO:0000269|PubMed:23451275"; MUTAGEN 1007..1009; /note="CPW->AAA: In Mut1; decreased interaction with GNAO1."; /evidence="ECO:0000269|PubMed:31189666"; MUTAGEN 1072..1074; /note="CLW->AAA: In Mut2; does not affect interaction with GNAO1."; /evidence="ECO:0000269|PubMed:31189666"; MUTAGEN 1172..1174; /note="CPW->AAA: In Mut3; decreased interaction with GNAO1."; /evidence="ECO:0000269|PubMed:31189666"; MUTAGEN 1172..1174; /note="CPW->AAA: In Mut4; does not affect interaction with GNAO1."; /evidence="ECO:0000269|PubMed:31189666
uniprot
proteins
protein_family
G protein-coupled receptor 3 family
uniprot
proteins
pubmed
10574461
uniprot
proteins
pubmed
12168954
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
18655026
uniprot
proteins
pubmed
23451275
uniprot
proteins
pubmed
30855200
uniprot
proteins
pubmed
31189666
uniprot
proteins
pubmed
34793198
uniprot
proteins
pubmed
34815401
uniprot
proteins
pubmed
36996198
uniprot
proteins
sequence_length
1215
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23451275, ECO:0000269|PubMed:30855200, ECO:0000269|PubMed:31189666}; Multi-pass membrane protein {ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401}. Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q8C419}; Multi-pass membrane protein {ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401}. Presynaptic cell membrane {ECO:0000250|UniProtKB:Q8C419}; Multi-pass membrane protein {ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401}. Nucleus {ECO:0000269|PubMed:23451275, ECO:0000269|PubMed:30855200}. Note=Mainly localizes to the postsynaptic membrane, with a small portion to the presynaptic membrane (By similarity). Trafficks between the nucleus and the cell membrane; it is unclear how a multi-pass membrane protein can traffick between the nucleus and the cell membrane (PubMed:23451275). {ECO:0000250|UniProtKB:Q8C419, ECO:0000269|PubMed:23451275}.
uniprot
proteins
transmembrane_region
TRANSMEM 418..439; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF"; TRANSMEM 452..474; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF"; TRANSMEM 479..501; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF"; TRANSMEM 526..547; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF"; TRANSMEM 577..597; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF"; TRANSMEM 612..633; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF"; TRANSMEM 643..664; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:34793198, ECO:0000269|PubMed:34815401, ECO:0007744|PDB:7EWL, ECO:0007744|PDB:7EWP, ECO:0007744|PDB:7EWR, ECO:0007744|PDB:7SHE, ECO:0007744|PDB:7SHF
uniprot
proteins