GPR158
Domain
The Cache-like region shares similarity with the Cache domain, a well-known receptor for amino acids (PubMed:34793198). It acts as a ligand-binding module that recognizes and binds glycine and taurine (PubMed:36996198).
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).
Sequence Similarities
Belongs to the G-protein coupled receptor 3 family.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Postsynaptic cell membrane
- Multi-pass membrane protein
- Presynaptic cell membrane
- Multi-pass membrane protein
- Nucleus
- 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).
Alternative names
KIAA1136, GPR158, Metabotropic glycine receptor, mGlyR, G-protein coupled receptor 158