Human Gene GABBR2 (ENST00000259455.4)
  Description: Homo sapiens gamma-aminobutyric acid type B receptor subunit 2 (GABBR2), mRNA. (from RefSeq NM_005458)
RefSeq Summary (NM_005458): The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010].
Gencode Transcript: ENST00000259455.4
Gencode Gene: ENSG00000136928.7
Transcript (Including UTRs)
   Position: hg38 chr9:98,288,109-98,708,935 Size: 420,827 Total Exon Count: 19 Strand: -
Coding Region
   Position: hg38 chr9:98,290,584-98,708,737 Size: 418,154 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:98,288,109-98,708,935)mRNA (may differ from genome)Protein (941 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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HPRDLynxMGIneXtProtOMIMPubMed
ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: GABR2_HUMAN
DESCRIPTION: RecName: Full=Gamma-aminobutyric acid type B receptor subunit 2; Short=GABA-B receptor 2; Short=GABA-B-R2; Short=GABA-BR2; Short=GABABR2; Short=Gb2; AltName: Full=G-protein coupled receptor 51; AltName: Full=HG20; Flags: Precursor;
FUNCTION: Receptor for GABA. The activity of this receptor is mediated by G-proteins that inhibit adenylyl cyclase activity, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipids hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA-B-R inhibit neurotransmitter release by down-regulating high- voltage activated calcium channels, whereas postsynaptic GABA-B-R decrease neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.
SUBUNIT: Heterodimer of GABA-B-R1 and GABA-B-R2. Neither of which is effective on its own and homodimeric assembly does not seem to happen. Interacts with ATF4 via its C-terminal region.
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Note=Moreover coexpression of GABA-B-R1 and GABA-B-R2 appears to be a prerequisite for maturation and transport of GABA-B-R1 to the plasma membrane.
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. Weakly expressed in heart, testis and skeletal muscle.
DOMAIN: Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABA-B receptor 1.
SIMILARITY: Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
SEQUENCE CAUTION: Sequence=AAH35071.2; Type=Erroneous initiation;

-  MalaCards Disease Associations
  MalaCards Gene Search: GABBR2
Diseases sorted by gene-association score: nicotine dependence, protection against* (581), sensory neuropathy type 1 (13), temporal lobe epilepsy (8), patent ductus arteriosus (5), cleft lip/palate (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001418 Baclofen
  • C040029 gabapentin
  • D005680 gamma-Aminobutyric Acid
  • C015068 1-(3-chlorophenyl)piperazine
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C029790 2,2',3',4,4',5-hexachlorobiphenyl
  • C014024 2,4,5,2',4',5'-hexachlorobiphenyl
  • C438607 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol
  • C030370 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone
  • D015104 3,4-Methylenedioxyamphetamine
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 48.34 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 239.80 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -117.30198-0.592 Picture PostScript Text
3' UTR -792.422475-0.320 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001828 - ANF_lig-bd_rcpt
IPR000337 - GPCR_3
IPR017978 - GPCR_3_C
IPR017979 - GPCR_3_CS
IPR002455 - GPCR_3_GABA_rcpt_B
IPR002457 - GPCR_3_GABA_rcpt_B2

Pfam Domains:
PF00003 - 7 transmembrane sweet-taste receptor of 3 GCPR
PF01094 - Receptor family ligand binding region

Protein Data Bank (PDB) 3-D Structure
MuPIT help

4F11
- X-ray MuPIT

4F12
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O75899
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsemblWormBase 
Protein SequenceProtein Sequence Protein SequenceProtein Sequence 
AlignmentAlignment AlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004871 signal transducer activity
GO:0004930 G-protein coupled receptor activity
GO:0004965 G-protein coupled GABA receptor activity
GO:0005515 protein binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007194 negative regulation of adenylate cyclase activity
GO:0007214 gamma-aminobutyric acid signaling pathway
GO:0007268 chemical synaptic transmission

Cellular Component:
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030054 cell junction
GO:0038039 G-protein coupled receptor heterodimeric complex
GO:0043005 neuron projection
GO:0045202 synapse
GO:0045211 postsynaptic membrane
GO:1902710 GABA receptor complex


-  Descriptions from all associated GenBank mRNAs
  AF056085 - Homo sapiens GABA-B receptor mRNA, complete cds.
AF099033 - Homo sapiens gamma-aminobutyric acid type B receptor 2 (GABABR2) mRNA, complete cds.
BC035071 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 2, mRNA (cDNA clone MGC:43091 IMAGE:5260138), complete cds.
AF095784 - Homo sapiens GABA-B receptor R2 (GABBR2) mRNA, complete cds.
AF069755 - Homo sapiens orphan G protein-coupled receptor HG20 (HG20) mRNA, complete cds.
AF074483 - Homo sapiens GABA-B receptor 2 mRNA, complete cds.
AJ012188 - Homo sapiens mRNA for GABAB receptor, subunit 2.
JQ308173 - Homo sapiens gamma-aminobutyric acid B receptor 2 mRNA, complete cds.
DQ891731 - Synthetic construct clone IMAGE:100004361; FLH179488.01X; RZPDo839H01130D gamma-aminobutyric acid (GABA) B receptor, 2 (GABBR2) gene, encodes complete protein.
KJ901996 - Synthetic construct Homo sapiens clone ccsbBroadEn_11390 GABBR2 gene, encodes complete protein.
AK308139 - Homo sapiens cDNA, FLJ98087.
DQ894908 - Synthetic construct Homo sapiens clone IMAGE:100009368; FLH179484.01L; RZPDo839H01129D gamma-aminobutyric acid (GABA) B receptor, 2 (GABBR2) gene, encodes complete protein.
AB384741 - Synthetic construct DNA, clone: pF1KB3078, Homo sapiens GABBR2 gene for gamma-aminobutyric-acid type B receptor, subunit 2 precursor, complete cds, without stop codon, in Flexi system.
CU690042 - Synthetic construct Homo sapiens gateway clone IMAGE:100017829 5' read GABBR2 mRNA.
BC055425 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 2, mRNA (cDNA clone IMAGE:5263781).
BC031317 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 2, mRNA (cDNA clone IMAGE:5277497).
AB015334 - Homo sapiens HRIHFB2099 mRNA, partial cds.
JD470336 - Sequence 451360 from Patent EP1572962.
JD477488 - Sequence 458512 from Patent EP1572962.
JD458477 - Sequence 439501 from Patent EP1572962.
JD056235 - Sequence 37259 from Patent EP1572962.
JD458584 - Sequence 439608 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04080 - Neuroactive ligand-receptor interaction

Reactome (by CSHL, EBI, and GO)

Protein O75899 (Reactome details) participates in the following event(s):

R-HSA-420688 GABAB heterodimeric receptor binds GABA
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-1013020 Activation of GIRK/Kir3 Channels
R-HSA-420499 Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-977444 GABA B receptor activation
R-HSA-418594 G alpha (i) signalling events
R-HSA-500792 GPCR ligand binding
R-HSA-977443 GABA receptor activation
R-HSA-388396 GPCR downstream signalling
R-HSA-372790 Signaling by GPCR
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-162582 Signal Transduction
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-997272 Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
R-HSA-1296041 Activation of G protein gated Potassium channels
R-HSA-112316 Neuronal System
R-HSA-991365 Activation of GABAB receptors
R-HSA-1296059 G protein gated Potassium channels
R-HSA-1296065 Inwardly rectifying K+ channels
R-HSA-1296071 Potassium Channels

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000259455.1, ENST00000259455.2, ENST00000259455.3, GABR2_HUMAN, GPR51, GPRC3B, NM_005458, O75899, O75974, O75975, Q5VXZ2, Q8WX04, Q9P1R2, Q9UNR1, Q9UNS9, uc004ays.1, uc004ays.2, uc004ays.3, uc004ays.4, uc004ays.5, uc004ays.6
UCSC ID: ENST00000259455.4
RefSeq Accession: NM_005458
Protein: O75899 (aka GABR2_HUMAN or GBR2_HUMAN)
CCDS: CCDS6736.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.