UniprotKB/SwissProt ID: Q8C419 (Q8C419)
Gene Name:
Gpr158
Organism: Mus musculus (Mouse)
Function: Metabotropic receptor for glycine that controls synapse formation and function in the brain (PubMed:29419376, PubMed:31311860, PubMed:31749686, PubMed:36996198). Acts as an atypical G-protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins (PubMed:22689652, PubMed:25792749, PubMed:30546127, PubMed:31311860). 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 (By similarity). 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 (By similarity). Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity (By similarity). Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (PubMed:31311860, 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 (PubMed:28851741, PubMed:29419376, PubMed:30546127, PubMed:31311860, PubMed:31749686). Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability (PubMed:31749686). 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 (PubMed:30290982). In addition to glycine, may also act as a receptor for osteocalcin (Bglap or Bglap2) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (PubMed:28851741, PubMed:30355501)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Cell membrane. Postsynaptic cell membrane. Presynaptic cell membrane. Nucleus
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