Q8C419 · MGLYR_MOUSE
- ProteinMetabotropic glycine receptor
- GeneGpr158
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1200 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
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).
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell projection | |
Cellular Component | membrane | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Cellular Component | postsynaptic density membrane | |
Cellular Component | postsynaptic membrane | |
Cellular Component | presynaptic membrane | |
Molecular Function | enzyme activator activity | |
Molecular Function | G protein-coupled glycine receptor activity | |
Molecular Function | transmembrane signaling receptor activity | |
Biological Process | brain development | |
Biological Process | cognition | |
Biological Process | G protein-coupled receptor signaling pathway | |
Biological Process | positive regulation of neurotransmitter secretion | |
Biological Process | protein localization to plasma membrane | |
Biological Process | regulation of G protein-coupled receptor signaling pathway | |
Biological Process | regulation of synapse organization |
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameMetabotropic glycine receptor
- Short namesmGlyR
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8C419
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Postsynaptic cell membrane ; Multi-pass membrane protein
Presynaptic cell membrane ; Multi-pass membrane protein
Note: Mainly localizes to the postsynaptic membrane, with a small portion to the presynaptic membrane (PubMed:36979415).
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 (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 (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 25-417 | Extracellular | ||||
Sequence: SLDPPGRPDSPRERTPRGKQHGQQLPRASAPDPSIPWSRSTDGTILAQKLAEEVPVDVASYLYTGDFHQLKRANCSGRYELAGLPGKSPSLASSHPSLHGALDTLTHATNFLNMMLQSNKSREQTVQDDLQWYQALVRSLLEGEPSISRAAITFSTESLSTPAPQVFLQATREESRILLQDLSSSAHHLANATLETEWFHGLRRKWRPHLHRRGSNQGPRGLGHSWRRRDGLGGDRSHVKWSPPYLECENGSYKPGWLVTLSAAFYGLQPNLVPEFRGVMKVDISLQKVDIDQCSSDGWFSGTHKCHLNNSECMPIKGLGFVLGAYQCICKAGFYHPRVFSVNNFQRRGPDHHFSGSTKDVSEETHVCLPCREGCPFCADDRPCFVQEDKYLR | ||||||
Transmembrane | 418-439 | Helical; Name=1 | ||||
Sequence: LAIISFQALCMLLDFVSMLVVY | ||||||
Topological domain | 440-451 | Cytoplasmic | ||||
Sequence: HFRKAKSIRASG | ||||||
Transmembrane | 452-474 | Helical; Name=2 | ||||
Sequence: LILLETILFGSLLLYFPVVILYF | ||||||
Topological domain | 475-478 | Extracellular | ||||
Sequence: EPST | ||||||
Transmembrane | 479-501 | Helical; Name=3 | ||||
Sequence: FRCILLRWARLLGFATVYGTVTL | ||||||
Topological domain | 502-525 | Cytoplasmic | ||||
Sequence: KLHRVLKVFLSRTAQRIPYMTGGR | ||||||
Transmembrane | 526-547 | Helical; Name=4 | ||||
Sequence: VMRMLAVIVLVVFWFLVGWTSS | ||||||
Topological domain | 548-576 | Extracellular | ||||
Sequence: MCQNLERDILLVGQGQTSDHLTFNMCLID | ||||||
Transmembrane | 577-597 | Helical; Name=5 | ||||
Sequence: RWDYMTAVAEFLFLLWGIYLC | ||||||
Topological domain | 598-611 | Cytoplasmic | ||||
Sequence: YAVRTVPSAFHEPR | ||||||
Transmembrane | 612-633 | Helical; Name=6 | ||||
Sequence: YMAVAVHNELIITAIFHTIRFV | ||||||
Topological domain | 634-642 | Extracellular | ||||
Sequence: LASRLQPDW | ||||||
Transmembrane | 643-664 | Helical; Name=7 | ||||
Sequence: MLMLYFAHAHLTVTVTIGLLLI | ||||||
Topological domain | 665-1200 | Cytoplasmic | ||||
Sequence: PKFSHSSNNPRDDIATEAYEDELDMGRSGSYLNSSINSAWSEHSLDPEDIRDELKKLYAQLEIYKRKKMITNNPHLQKKRCSKKGLGRSIMRRITEIPETVSRQCSKEDKEGTDHSAAKGTGLVRKNPTESSGNTGRPKEESLKNRVFSLKKSHSTYDHVRDQTVESSSLPMESQEEEATENSTLESLSSKKLTQKLKEDSEAESTESVPLVCKSASAHNLSSEKKPGHPRTSMLQKSLSVIASAKEKTLGLAGKTQTLVMEDRAKSQKPKDRETIRKYSNSDNVETIPNSGHMEEPRKPQKSGIMKQQRVSLPTANPDVSSGITQIKDNFDIGEVCPWEVYDLTPGPMPSEPKAQKHVSIAASEVEQNPASFLKEKSYHKSKATEGLYQANHKSIDKTEVCPWEIHSQSLLEDENRLISKTPVLPGRAREENGSQLYTTNMCAGQYEELPHKVVAPKVENENLNQMGDQEKQTSSSVDIIPGSCNSSNNSHQPLTSRAEVCPWEFEPLEQPNAERSVTLPASSALSANKIPGPQK |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice show prominent antidepressant-like phenotype and stress resilience, characterized by attenuated response to stress-induced hyperthermia (PubMed:29419376).
Mice also display defects in spatial learning and decreased acquisition of safety learning (PubMed:31749686).
Mice show a short-term protection against the intraocular pressure increase that occurred with aging; however this protection is reversed over time (PubMed:30855200).
Mice also display defects in spatial learning and decreased acquisition of safety learning (PubMed:31749686).
Mice show a short-term protection against the intraocular pressure increase that occurred with aging; however this protection is reversed over time (PubMed:30855200).
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 71 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MGAMAYSLLFCLLLAHLGLGEVGA | ||||||
Chain | PRO_0000012970 | 25-1200 | Metabotropic glycine receptor | |||
Sequence: SLDPPGRPDSPRERTPRGKQHGQQLPRASAPDPSIPWSRSTDGTILAQKLAEEVPVDVASYLYTGDFHQLKRANCSGRYELAGLPGKSPSLASSHPSLHGALDTLTHATNFLNMMLQSNKSREQTVQDDLQWYQALVRSLLEGEPSISRAAITFSTESLSTPAPQVFLQATREESRILLQDLSSSAHHLANATLETEWFHGLRRKWRPHLHRRGSNQGPRGLGHSWRRRDGLGGDRSHVKWSPPYLECENGSYKPGWLVTLSAAFYGLQPNLVPEFRGVMKVDISLQKVDIDQCSSDGWFSGTHKCHLNNSECMPIKGLGFVLGAYQCICKAGFYHPRVFSVNNFQRRGPDHHFSGSTKDVSEETHVCLPCREGCPFCADDRPCFVQEDKYLRLAIISFQALCMLLDFVSMLVVYHFRKAKSIRASGLILLETILFGSLLLYFPVVILYFEPSTFRCILLRWARLLGFATVYGTVTLKLHRVLKVFLSRTAQRIPYMTGGRVMRMLAVIVLVVFWFLVGWTSSMCQNLERDILLVGQGQTSDHLTFNMCLIDRWDYMTAVAEFLFLLWGIYLCYAVRTVPSAFHEPRYMAVAVHNELIITAIFHTIRFVLASRLQPDWMLMLYFAHAHLTVTVTIGLLLIPKFSHSSNNPRDDIATEAYEDELDMGRSGSYLNSSINSAWSEHSLDPEDIRDELKKLYAQLEIYKRKKMITNNPHLQKKRCSKKGLGRSIMRRITEIPETVSRQCSKEDKEGTDHSAAKGTGLVRKNPTESSGNTGRPKEESLKNRVFSLKKSHSTYDHVRDQTVESSSLPMESQEEEATENSTLESLSSKKLTQKLKEDSEAESTESVPLVCKSASAHNLSSEKKPGHPRTSMLQKSLSVIASAKEKTLGLAGKTQTLVMEDRAKSQKPKDRETIRKYSNSDNVETIPNSGHMEEPRKPQKSGIMKQQRVSLPTANPDVSSGITQIKDNFDIGEVCPWEVYDLTPGPMPSEPKAQKHVSIAASEVEQNPASFLKEKSYHKSKATEGLYQANHKSIDKTEVCPWEIHSQSLLEDENRLISKTPVLPGRAREENGSQLYTTNMCAGQYEELPHKVVAPKVENENLNQMGDQEKQTSSSVDIIPGSCNSSNNSHQPLTSRAEVCPWEFEPLEQPNAERSVTLPASSALSANKIPGPQK | ||||||
Glycosylation | 98 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 99↔272 | |||||
Sequence: CSGRYELAGLPGKSPSLASSHPSLHGALDTLTHATNFLNMMLQSNKSREQTVQDDLQWYQALVRSLLEGEPSISRAAITFSTESLSTPAPQVFLQATREESRILLQDLSSSAHHLANATLETEWFHGLRRKWRPHLHRRGSNQGPRGLGHSWRRRDGLGGDRSHVKWSPPYLEC | ||||||
Glycosylation | 143 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 215 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 274 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 333 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 481↔573 | |||||
Sequence: CILLRWARLLGFATVYGTVTLKLHRVLKVFLSRTAQRIPYMTGGRVMRMLAVIVLVVFWFLVGWTSSMCQNLERDILLVGQGQTSDHLTFNMC | ||||||
Modified residue | 694 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 705 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 708 | Phosphoserine | ||||
Sequence: S | ||||||
Cross-link | 774 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 865 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 944 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1059 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1074 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in brain (PubMed:29419376, PubMed:36979415).
Expressed in several brain regions including the cerebral cortex, hippocampus, cerebellum and caudate putamen (PubMed:36979415).
Only expressed in neurons, and not in microglia, oligodendrocytes or astrocytes (PubMed:36979415).
Expressed in the visual center of the cerebral cortex (PubMed:30855200).
Also expressed in the eye, including photoreceptors, ganglion cells and trabecular meshwork (PubMed:30855200).
Expressed in several brain regions including the cerebral cortex, hippocampus, cerebellum and caudate putamen (PubMed:36979415).
Only expressed in neurons, and not in microglia, oligodendrocytes or astrocytes (PubMed:36979415).
Expressed in the visual center of the cerebral cortex (PubMed:30855200).
Also expressed in the eye, including photoreceptors, ganglion cells and trabecular meshwork (PubMed:30855200).
Induction
Expression in the dentate gyrus is regulated by RBBP4 (PubMed:30355501).
Strongly up-regulated in the prefrontal cortex in response to stress (PubMed:29419376).
Down-regulated in the hippocampus in response to hyperglycemia (PubMed:36634900).
Strongly up-regulated in the prefrontal cortex in response to stress (PubMed:29419376).
Down-regulated in the hippocampus in response to hyperglycemia (PubMed:36634900).
Gene expression databases
Interaction
Subunit
Homodimer (By similarity).
Associates with the RGS7-GNB5 complex, promoting its localization to the cell membrane and regulating its GTPase activator activity (PubMed:22689652, PubMed:25792749, PubMed:31311860).
Interacts (via VCPWE motifs) with GNAO1 (PubMed:25792749).
Interacts with GPC4 (By similarity).
Interacts with EGFLAM (PubMed:30282023).
Associates with the RGS7-GNB5 complex, promoting its localization to the cell membrane and regulating its GTPase activator activity (PubMed:22689652, PubMed:25792749, PubMed:31311860).
Interacts (via VCPWE motifs) with GNAO1 (PubMed:25792749).
Interacts with GPC4 (By similarity).
Interacts with EGFLAM (PubMed:30282023).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q8C419 | GPC1 P35052 | 3 | EBI-776313, EBI-8307554 | |
XENO | Q8C419 | GPC5 P78333 | 2 | EBI-776313, EBI-2558325 | |
XENO | Q8C419 | SDC4 P31431 | 3 | EBI-776313, EBI-3913237 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 25-62 | Disordered | ||||
Sequence: SLDPPGRPDSPRERTPRGKQHGQQLPRASAPDPSIPWS | ||||||
Region | 85-281 | Cache-like region | ||||
Sequence: YLYTGDFHQLKRANCSGRYELAGLPGKSPSLASSHPSLHGALDTLTHATNFLNMMLQSNKSREQTVQDDLQWYQALVRSLLEGEPSISRAAITFSTESLSTPAPQVFLQATREESRILLQDLSSSAHHLANATLETEWFHGLRRKWRPHLHRRGSNQGPRGLGHSWRRRDGLGGDRSHVKWSPPYLECENGSYKPGW | ||||||
Region | 234-253 | Disordered | ||||
Sequence: LHRRGSNQGPRGLGHSWRRR | ||||||
Region | 757-875 | Disordered | ||||
Sequence: RITEIPETVSRQCSKEDKEGTDHSAAKGTGLVRKNPTESSGNTGRPKEESLKNRVFSLKKSHSTYDHVRDQTVESSSLPMESQEEEATENSTLESLSSKKLTQKLKEDSEAESTESVPL | ||||||
Compositional bias | 766-780 | Basic and acidic residues | ||||
Sequence: SRQCSKEDKEGTDHS | ||||||
Compositional bias | 801-825 | Basic and acidic residues | ||||
Sequence: RPKEESLKNRVFSLKKSHSTYDHVR | ||||||
Compositional bias | 826-855 | Polar residues | ||||
Sequence: DQTVESSSLPMESQEEEATENSTLESLSSK | ||||||
Region | 947-988 | Disordered | ||||
Sequence: DNVETIPNSGHMEEPRKPQKSGIMKQQRVSLPTANPDVSSGI | ||||||
Compositional bias | 969-988 | Polar residues | ||||
Sequence: IMKQQRVSLPTANPDVSSGI | ||||||
Motif | 1000-1004 | VCPWE motif 1 | ||||
Sequence: VCPWE | ||||||
Motif | 1065-1069 | VCPWE motif 2 | ||||
Sequence: VCPWE | ||||||
Region | 1130-1160 | Disordered | ||||
Sequence: QMGDQEKQTSSSVDIIPGSCNSSNNSHQPLT | ||||||
Motif | 1165-1169 | VCPWE motif 3 | ||||
Sequence: VCPWE | ||||||
Region | 1177-1200 | Disordered | ||||
Sequence: NAERSVTLPASSALSANKIPGPQK | ||||||
Compositional bias | 1180-1200 | Polar residues | ||||
Sequence: RSVTLPASSALSANKIPGPQK |
Domain
The Cache-like region shares similarity with the Cache domain, a well-known receptor for amino acids (By similarity).
It acts as a ligand-binding module that recognizes and binds glycine and taurine (By similarity).
It acts as a ligand-binding module that recognizes and binds glycine and taurine (By similarity).
Sequence similarities
Belongs to the G-protein coupled receptor 3 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length1,200
- Mass (Da)134,426
- Last updated2005-06-07 v2
- Checksum2FCEF8283DE964B4
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 766-780 | Basic and acidic residues | ||||
Sequence: SRQCSKEDKEGTDHS | ||||||
Compositional bias | 801-825 | Basic and acidic residues | ||||
Sequence: RPKEESLKNRVFSLKKSHSTYDHVR | ||||||
Compositional bias | 826-855 | Polar residues | ||||
Sequence: DQTVESSSLPMESQEEEATENSTLESLSSK | ||||||
Compositional bias | 969-988 | Polar residues | ||||
Sequence: IMKQQRVSLPTANPDVSSGI | ||||||
Compositional bias | 1180-1200 | Polar residues | ||||
Sequence: RSVTLPASSALSANKIPGPQK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL772387 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL928939 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL929311 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK083234 EMBL· GenBank· DDBJ | BAC38819.1 EMBL· GenBank· DDBJ | mRNA | ||
AB093287 EMBL· GenBank· DDBJ | BAC41471.1 EMBL· GenBank· DDBJ | mRNA |