O75899 · GABR2_HUMAN

  • Protein
    Gamma-aminobutyric acid type B receptor subunit 2
  • Gene
    GABBR2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular ComponentG protein-coupled GABA receptor complex
Cellular ComponentG protein-coupled receptor heterodimeric complex
Cellular ComponentGABA receptor complex
Cellular Componentneuron projection
Cellular Componentplasma membrane
Cellular Componentpostsynaptic membrane
Molecular FunctionG protein-coupled GABA receptor activity
Molecular Functionprotein heterodimerization activity
Molecular Functiontransmembrane signaling receptor activity
Biological Processadenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Biological Processchemical synaptic transmission
Biological ProcessG protein-coupled receptor signaling pathway
Biological Processgamma-aminobutyric acid signaling pathway
Biological Processnegative regulation of adenylate cyclase activity
Biological Processneuron-glial cell signaling
Biological Processsynaptic transmission, GABAergic

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Gamma-aminobutyric acid type B receptor subunit 2
  • Short names
    GABA-B receptor 2; GABA-B-R2; GABA-BR2; GABABR2; Gb2
  • Alternative names
    • G-protein coupled receptor 51
    • HG20

Gene names

    • Name
      GABBR2
    • Synonyms
      GPR51, GPRC3B

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    O75899
  • Secondary accessions
    • O75974
    • O75975
    • Q5VXZ2
    • Q8WX04
    • Q9P1R2

Proteomes

Organism-specific databases

Subcellular Location

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.

TypeIDPosition(s)Description
Topological domain42-483Extracellular
Transmembrane484-504Helical; Name=1
Topological domain505-522Cytoplasmic
Transmembrane523-543Helical; Name=2
Topological domain544-551Extracellular
Transmembrane552-572Helical; Name=3
Topological domain573-597Cytoplasmic
Transmembrane598-618Helical; Name=4
Topological domain619-654Extracellular
Transmembrane655-675Helical; Name=5
Topological domain676-691Cytoplasmic
Transmembrane692-712Helical; Name=6
Topological domain713-720Extracellular
Transmembrane721-741Helical; Name=7
Topological domain742-941Cytoplasmic

Keywords

Disease & Variants

Involvement in disease

Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An 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 also
    MIM:617903
Natural variants in NDPLHS
Variant IDPosition(s)ChangeDescription
VAR_079029567A>Tin 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_080572707A>Tin 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
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A 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 also
    MIM:617904
Natural variants in DEE59
Variant IDPosition(s)ChangeDescription
VAR_080569693G>Win DEE59; uncertain significance; dbSNP:rs1554689320
VAR_080570695S>Iin 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_080571705I>Nin 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.

TypeIDPosition(s)Description
Mutagenesis118Impairs interaction with GABBR1. Decreases signaling via G-proteins.
Natural variantVAR_049280163in dbSNP:rs1828312690
Natural variantVAR_079029567in 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
Natural variantVAR_010148628
Natural variantVAR_080569693in DEE59; uncertain significance; dbSNP:rs1554689320
Natural variantVAR_080570695in 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
Natural variantVAR_080571705in 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
Natural variantVAR_080572707in NDPLHS; increased basal signaling activity and only weak stimulation by GABA agonist; no effect on cell surface expression; dbSNP:rs1554689313
Natural variantVAR_010149869in dbSNP:rs10985765

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.

Go to variant viewer

Keywords

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).

TypeIDPosition(s)SourceDescription
Signal1-41UniProt
ChainPRO_000001295242-941UniProtGamma-aminobutyric acid type B receptor subunit 2
Glycosylation90UniProtN-linked (GlcNAc...) asparagine
Disulfide bond108↔135UniProt
Disulfide bond237↔266UniProt
Disulfide bond265↔302UniProt
Glycosylation298UniProtN-linked (GlcNAc...) asparagine
Glycosylation389UniProtN-linked (GlcNAc...) asparagine
Glycosylation404UniProtN-linked (GlcNAc...) asparagine
Glycosylation453UniProtN-linked (GlcNAc...) asparagine
Modified residue776UniProtPhosphoserine
Modified residue779UniProtPhosphoserine
Modified residue (large scale data)779PRIDEPhosphoserine
Modified residue (large scale data)793PRIDEPhosphoserine
Modified residue819UniProtPhosphothreonine
Modified residue (large scale data)819PRIDEPhosphothreonine
Modified residue884UniProtPhosphoserine
Modified residue (large scale data)884PRIDEPhosphoserine
Modified residue893UniProtPhosphoserine
Modified residue913UniProtPhosphoserine
Modified residue916UniProtPhosphoserine
Modified residue920UniProtPhosphoserine
Modified residue924UniProtPhosphoserine

Keywords

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).

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).

Binary interactions

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, coiled coil.

TypeIDPosition(s)Description
Region763-790Disordered
Coiled coil781-819

Domain

Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR1.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Protein family/group databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    941
  • Mass (Da)
    105,821
  • Last updated
    1998-11-01 v1
  • Checksum
    09F1773DB0673C5D
MASPRSSGQPGPPPPPPPPPARLLLLLLLPLLLPLAPGAWGWARGAPRPPPSSPPLSIMGLMPLTKEVAKGSIGRGVLPAVELAIEQIRNESLLRPYFLDLRLYDTECDNAKGLKAFYDAIKYGPNHLMVFGGVCPSVTSIIAESLQGWNLVQLSFAATTPVLADKKKYPYFFRTVPSDNAVNPAILKLLKHYQWKRVGTLTQDVQRFSEVRNDLTGVLYGEDIEISDTESFSNDPCTSVKKLKGNDVRIILGQFDQNMAAKVFCCAYEENMYGSKYQWIIPGWYEPSWWEQVHTEANSSRCLRKNLLAAMEGYIGVDFEPLSSKQIKTISGKTPQQYEREYNNKRSGVGPSKFHGYAYDGIWVIAKTLQRAMETLHASSRHQRIQDFNYTDHTLGRIILNAMNETNFFGVTGQVVFRNGERMGTIKFTQFQDSREVKVGEYNAVADTLEIINDTIRFQGSEPPKDKTIILEQLRKISLPLYSILSALTILGMIMASAFLFFNIKNRNQKLIKMSSPYMNNLIILGGMLSYASIFLFGLDGSFVSEKTFETLCTVRTWILTVGYTTAFGAMFAKTWRVHAIFKNVKMKKKIIKDQKLLVIVGGMLLIDLCILICWQAVDPLRRTVEKYSMEPDPAGRDISIRPLLEHCENTHMTIWLGIVYAYKGLLMLFGCFLAWETRNVSIPALNDSKYIGMSVYNVGIMCIIGAAVSFLTRDQPNVQFCIVALVIIFCSTITLCLVFVPKLITLRTNPDAATQNRRFQFTQNQKKEDSKTSTSVTSVNQASTSRLEGLQSENHRLRMKITELDKDLEEVTMQLQDTPEKTTYIKQNHYQELNDILNLGNFTESTDGGKAILKNHLDQNPQLQWNTTEPSRTCKDPIEDINSPEHIQRRLSLQLPILHHAYLPSIGGVDASCVSPCVSPTASPRHRHVPPSFRVMVSGL

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0U1RR59A0A0U1RR59_HUMANGABBR2183
A0A1B0GW60A0A1B0GW60_HUMANGABBR277

Sequence caution

The sequence AAH35071.2 differs from that shown. Reason: Erroneous initiation

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict6in Ref. 2; AAC99345
Sequence conflict12in Ref. 2; AAC99345
Sequence conflict424in Ref. 5; AAD30389
Sequence conflict797in Ref. 8; AAH35071

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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