O75899 · GABR2_HUMAN
- ProteinGamma-aminobutyric acid type B receptor subunit 2
- GeneGABBR2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids941 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:9872316, PubMed:9872744).
Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688).
Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644, PubMed:10773016, PubMed:24305054).
Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:9872744).
Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:22660477, PubMed:9872744).
Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644, PubMed:22660477, PubMed:9872316, PubMed:9872744).
Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable)
Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688).
Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644, PubMed:10773016, PubMed:24305054).
Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:9872744).
Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:22660477, PubMed:9872744).
Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644, PubMed:22660477, PubMed:9872316, PubMed:9872744).
Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable)
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | G protein-coupled GABA receptor complex | |
Cellular Component | G protein-coupled receptor heterodimeric complex | |
Cellular Component | GABA receptor complex | |
Cellular Component | neuron projection | |
Cellular Component | plasma membrane | |
Cellular Component | postsynaptic membrane | |
Molecular Function | G protein-coupled GABA receptor activity | |
Molecular Function | protein heterodimerization activity | |
Molecular Function | transmembrane signaling receptor activity | |
Biological Process | adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | |
Biological Process | chemical synaptic transmission | |
Biological Process | G protein-coupled receptor signaling pathway | |
Biological Process | gamma-aminobutyric acid signaling pathway | |
Biological Process | negative regulation of adenylate cyclase activity | |
Biological Process | neuron-glial cell signaling | |
Biological Process | synaptic transmission, GABAergic |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGamma-aminobutyric acid type B receptor subunit 2
- Short namesGABA-B receptor 2; GABA-B-R2; GABA-BR2; GABABR2; Gb2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75899
- 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
Note: Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane. In contrast, GABBR2 does not depend on GABBR1 for transport to the cell membrane.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 42-483 | Extracellular | ||||
Sequence: WARGAPRPPPSSPPLSIMGLMPLTKEVAKGSIGRGVLPAVELAIEQIRNESLLRPYFLDLRLYDTECDNAKGLKAFYDAIKYGPNHLMVFGGVCPSVTSIIAESLQGWNLVQLSFAATTPVLADKKKYPYFFRTVPSDNAVNPAILKLLKHYQWKRVGTLTQDVQRFSEVRNDLTGVLYGEDIEISDTESFSNDPCTSVKKLKGNDVRIILGQFDQNMAAKVFCCAYEENMYGSKYQWIIPGWYEPSWWEQVHTEANSSRCLRKNLLAAMEGYIGVDFEPLSSKQIKTISGKTPQQYEREYNNKRSGVGPSKFHGYAYDGIWVIAKTLQRAMETLHASSRHQRIQDFNYTDHTLGRIILNAMNETNFFGVTGQVVFRNGERMGTIKFTQFQDSREVKVGEYNAVADTLEIINDTIRFQGSEPPKDKTIILEQLRKISLPLYS | ||||||
Transmembrane | 484-504 | Helical; Name=1 | ||||
Sequence: ILSALTILGMIMASAFLFFNI | ||||||
Topological domain | 505-522 | Cytoplasmic | ||||
Sequence: KNRNQKLIKMSSPYMNNL | ||||||
Transmembrane | 523-543 | Helical; Name=2 | ||||
Sequence: IILGGMLSYASIFLFGLDGSF | ||||||
Topological domain | 544-551 | Extracellular | ||||
Sequence: VSEKTFET | ||||||
Transmembrane | 552-572 | Helical; Name=3 | ||||
Sequence: LCTVRTWILTVGYTTAFGAMF | ||||||
Topological domain | 573-597 | Cytoplasmic | ||||
Sequence: AKTWRVHAIFKNVKMKKKIIKDQKL | ||||||
Transmembrane | 598-618 | Helical; Name=4 | ||||
Sequence: LVIVGGMLLIDLCILICWQAV | ||||||
Topological domain | 619-654 | Extracellular | ||||
Sequence: DPLRRTVEKYSMEPDPAGRDISIRPLLEHCENTHMT | ||||||
Transmembrane | 655-675 | Helical; Name=5 | ||||
Sequence: IWLGIVYAYKGLLMLFGCFLA | ||||||
Topological domain | 676-691 | Cytoplasmic | ||||
Sequence: WETRNVSIPALNDSKY | ||||||
Transmembrane | 692-712 | Helical; Name=6 | ||||
Sequence: IGMSVYNVGIMCIIGAAVSFL | ||||||
Topological domain | 713-720 | Extracellular | ||||
Sequence: TRDQPNVQ | ||||||
Transmembrane | 721-741 | Helical; Name=7 | ||||
Sequence: FCIVALVIIFCSTITLCLVFV | ||||||
Topological domain | 742-941 | Cytoplasmic | ||||
Sequence: PKLITLRTNPDAATQNRRFQFTQNQKKEDSKTSTSVTSVNQASTSRLEGLQSENHRLRMKITELDKDLEEVTMQLQDTPEKTTYIKQNHYQELNDILNLGNFTESTDGGKAILKNHLDQNPQLQWNTTEPSRTCKDPIEDINSPEHIQRRLSLQLPILHHAYLPSIGGVDASCVSPCVSPTASPRHRHVPPSFRVMVSGL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS)
- Note
- DescriptionAn autosomal dominant disorder characterized by psychomotor developmental stagnation or regression. NDPLHS manifest in the first years of life as loss of purposeful hand movements, loss of language, and intellectual disability.
- See alsoMIM:617903
Natural variants in NDPLHS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_079029 | 567 | A>T | in NDPLHS; increased basal signaling activity and only weak stimulation by GABA agonist; when injected into Xenopus tadpoles, causes abnormal swimming patterns and increased frequencies of seizure-like behavior compared to wild-type-injected animals; no effect on cell surface expression; dbSNP:rs922847767 | |
VAR_080572 | 707 | A>T | in NDPLHS; increased basal signaling activity and only weak stimulation by GABA agonist; no effect on cell surface expression; dbSNP:rs1554689313 |
Developmental and epileptic encephalopathy 59 (DEE59)
- Note
- DescriptionA form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE59 is an autosomal dominant condition characterized by onset of refractory seizures in early infancy.
- See alsoMIM:617904
Natural variants in DEE59
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_080569 | 693 | G>W | in DEE59; uncertain significance; dbSNP:rs1554689320 | |
VAR_080570 | 695 | S>I | in DEE59; full signaling activity in the absence of GABA agonist; when injected into Xenopus tadpoles, causes abnormal swimming patterns and increased frequencies of seizure-like behavior compared to wild-type-injected animals; no effect on cell surface expression; dbSNP:rs1554689319 | |
VAR_080571 | 705 | I>N | in DEE59; increased basal signaling activity and no stimulation by GABA agonist; when injected into Xenopus tadpoles, causes abnormal swimming patterns and increased frequencies of seizure-like behavior compared to wild-type-injected animals; no effect on cell surface expression; dbSNP:rs1554689315 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 118 | Impairs interaction with GABBR1. Decreases signaling via G-proteins. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_049280 | 163 | in dbSNP:rs1828312690 | |||
Sequence: L → P | ||||||
Natural variant | VAR_079029 | 567 | in NDPLHS; increased basal signaling activity and only weak stimulation by GABA agonist; when injected into Xenopus tadpoles, causes abnormal swimming patterns and increased frequencies of seizure-like behavior compared to wild-type-injected animals; no effect on cell surface expression; dbSNP:rs922847767 | |||
Sequence: A → T | ||||||
Natural variant | VAR_010148 | 628 | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_080569 | 693 | in DEE59; uncertain significance; dbSNP:rs1554689320 | |||
Sequence: G → W | ||||||
Natural variant | VAR_080570 | 695 | in DEE59; full signaling activity in the absence of GABA agonist; when injected into Xenopus tadpoles, causes abnormal swimming patterns and increased frequencies of seizure-like behavior compared to wild-type-injected animals; no effect on cell surface expression; dbSNP:rs1554689319 | |||
Sequence: S → I | ||||||
Natural variant | VAR_080571 | 705 | in DEE59; increased basal signaling activity and no stimulation by GABA agonist; when injected into Xenopus tadpoles, causes abnormal swimming patterns and increased frequencies of seizure-like behavior compared to wild-type-injected animals; no effect on cell surface expression; dbSNP:rs1554689315 | |||
Sequence: I → N | ||||||
Natural variant | VAR_080572 | 707 | in NDPLHS; increased basal signaling activity and only weak stimulation by GABA agonist; no effect on cell surface expression; dbSNP:rs1554689313 | |||
Sequence: A → T | ||||||
Natural variant | VAR_010149 | 869 | in dbSNP:rs10985765 | |||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 792 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-41 | UniProt | |||||
Sequence: MASPRSSGQPGPPPPPPPPPARLLLLLLLPLLLPLAPGAWG | |||||||
Chain | PRO_0000012952 | 42-941 | UniProt | Gamma-aminobutyric acid type B receptor subunit 2 | |||
Sequence: WARGAPRPPPSSPPLSIMGLMPLTKEVAKGSIGRGVLPAVELAIEQIRNESLLRPYFLDLRLYDTECDNAKGLKAFYDAIKYGPNHLMVFGGVCPSVTSIIAESLQGWNLVQLSFAATTPVLADKKKYPYFFRTVPSDNAVNPAILKLLKHYQWKRVGTLTQDVQRFSEVRNDLTGVLYGEDIEISDTESFSNDPCTSVKKLKGNDVRIILGQFDQNMAAKVFCCAYEENMYGSKYQWIIPGWYEPSWWEQVHTEANSSRCLRKNLLAAMEGYIGVDFEPLSSKQIKTISGKTPQQYEREYNNKRSGVGPSKFHGYAYDGIWVIAKTLQRAMETLHASSRHQRIQDFNYTDHTLGRIILNAMNETNFFGVTGQVVFRNGERMGTIKFTQFQDSREVKVGEYNAVADTLEIINDTIRFQGSEPPKDKTIILEQLRKISLPLYSILSALTILGMIMASAFLFFNIKNRNQKLIKMSSPYMNNLIILGGMLSYASIFLFGLDGSFVSEKTFETLCTVRTWILTVGYTTAFGAMFAKTWRVHAIFKNVKMKKKIIKDQKLLVIVGGMLLIDLCILICWQAVDPLRRTVEKYSMEPDPAGRDISIRPLLEHCENTHMTIWLGIVYAYKGLLMLFGCFLAWETRNVSIPALNDSKYIGMSVYNVGIMCIIGAAVSFLTRDQPNVQFCIVALVIIFCSTITLCLVFVPKLITLRTNPDAATQNRRFQFTQNQKKEDSKTSTSVTSVNQASTSRLEGLQSENHRLRMKITELDKDLEEVTMQLQDTPEKTTYIKQNHYQELNDILNLGNFTESTDGGKAILKNHLDQNPQLQWNTTEPSRTCKDPIEDINSPEHIQRRLSLQLPILHHAYLPSIGGVDASCVSPCVSPTASPRHRHVPPSFRVMVSGL | |||||||
Glycosylation | 90 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 108↔135 | UniProt | |||||
Sequence: CDNAKGLKAFYDAIKYGPNHLMVFGGVC | |||||||
Disulfide bond | 237↔266 | UniProt | |||||
Sequence: CTSVKKLKGNDVRIILGQFDQNMAAKVFCC | |||||||
Disulfide bond | 265↔302 | UniProt | |||||
Sequence: CCAYEENMYGSKYQWIIPGWYEPSWWEQVHTEANSSRC | |||||||
Glycosylation | 298 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 389 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 404 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 453 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 776 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 779 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 779 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 793 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 819 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 819 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 884 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 884 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 893 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 913 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 916 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 920 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 924 | UniProt | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in brain, especially in cerebral cortex, thalamus, hippocampus, frontal, occipital and temporal lobe, occipital pole and cerebellum, followed by corpus callosum, caudate nucleus, spinal cord, amygdala and medulla (PubMed:10087195, PubMed:10328880, PubMed:10727622, PubMed:9872744).
Weakly expressed in heart, testis and skeletal muscle (PubMed:10087195, PubMed:10727622).
Weakly expressed in heart, testis and skeletal muscle (PubMed:10087195, PubMed:10727622).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Heterodimer of GABBR1 and GABBR2 (PubMed:10773016, PubMed:10906333, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:9872316, PubMed:9872744).
Homodimers may form, but are inactive (PubMed:15617512).
Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity).
Homodimers may form, but are inactive (PubMed:15617512).
Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O75899 | GABBR1 Q9UBS5 | 4 | EBI-715469, EBI-724156 | |
BINARY | O75899 | GABBR1 Q9UBS5-2 | 6 | EBI-715469, EBI-16084001 | |
BINARY | O75899 | NSF P46459 | 4 | EBI-715469, EBI-712251 | |
BINARY | O75899 | RIMS1 Q86UR5 | 2 | EBI-715469, EBI-1043236 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 763-790 | Disordered | ||||
Sequence: TQNQKKEDSKTSTSVTSVNQASTSRLEG | ||||||
Coiled coil | 781-819 | |||||
Sequence: NQASTSRLEGLQSENHRLRMKITELDKDLEEVTMQLQDT |
Domain
Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR1.
Sequence similarities
Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
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.
- Length941
- Mass (Da)105,821
- Last updated1998-11-01 v1
- Checksum09F1773DB0673C5D
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0U1RR59 | A0A0U1RR59_HUMAN | GABBR2 | 183 | ||
A0A1B0GW60 | A0A1B0GW60_HUMAN | GABBR2 | 77 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 6 | in Ref. 2; AAC99345 | ||||
Sequence: S → R | ||||||
Sequence conflict | 12 | in Ref. 2; AAC99345 | ||||
Sequence: P → R | ||||||
Sequence conflict | 424 | in Ref. 5; AAD30389 | ||||
Sequence: G → E | ||||||
Sequence conflict | 797 | in Ref. 8; AAH35071 | ||||
Sequence: R → H |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ012188 EMBL· GenBank· DDBJ | CAA09942.1 EMBL· GenBank· DDBJ | mRNA | ||
AF069755 EMBL· GenBank· DDBJ | AAC99345.1 EMBL· GenBank· DDBJ | mRNA | ||
AF099033 EMBL· GenBank· DDBJ | AAD45867.1 EMBL· GenBank· DDBJ | mRNA | ||
AF056085 EMBL· GenBank· DDBJ | AAC63228.1 EMBL· GenBank· DDBJ | mRNA | ||
AF095784 EMBL· GenBank· DDBJ | AAD30389.1 EMBL· GenBank· DDBJ | mRNA | ||
AF074483 EMBL· GenBank· DDBJ | AAD03336.1 EMBL· GenBank· DDBJ | mRNA | ||
AL445495 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL353782 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL356282 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL591502 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC035071 EMBL· GenBank· DDBJ | AAH35071.2 EMBL· GenBank· DDBJ | mRNA | Different initiation |