GABBR2

Protein identityUniProt · HPA

UniProt accession

O75899

Gene

GABBR2

Ensembl

ENSG00000136928

Chromosome

9

Canonical length

941 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

941 residues, UniProt reviewed canonical sequence.

>O75899|GABBR2
     1  MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG
    61  LMPLTKEVAK GSIGRGVLPA VELAIEQIRN ESLLRPYFLD LRLYDTECDN AKGLKAFYDA
   121  IKYGPNHLMV FGGVCPSVTS IIAESLQGWN LVQLSFAATT PVLADKKKYP YFFRTVPSDN
   181  AVNPAILKLL KHYQWKRVGT LTQDVQRFSE VRNDLTGVLY GEDIEISDTE SFSNDPCTSV
   241  KKLKGNDVRI ILGQFDQNMA AKVFCCAYEE NMYGSKYQWI IPGWYEPSWW EQVHTEANSS
   301  RCLRKNLLAA MEGYIGVDFE PLSSKQIKTI SGKTPQQYER EYNNKRSGVG PSKFHGYAYD
   361  GIWVIAKTLQ RAMETLHASS RHQRIQDFNY TDHTLGRIIL NAMNETNFFG VTGQVVFRNG
   421  ERMGTIKFTQ FQDSREVKVG EYNAVADTLE IINDTIRFQG SEPPKDKTII LEQLRKISLP
   481  LYSILSALTI LGMIMASAFL FFNIKNRNQK LIKMSSPYMN NLIILGGMLS YASIFLFGLD
   541  GSFVSEKTFE TLCTVRTWIL TVGYTTAFGA MFAKTWRVHA IFKNVKMKKK IIKDQKLLVI
   601  VGGMLLIDLC ILICWQAVDP LRRTVEKYSM EPDPAGRDIS IRPLLEHCEN THMTIWLGIV
   661  YAYKGLLMLF GCFLAWETRN VSIPALNDSK YIGMSVYNVG IMCIIGAAVS FLTRDQPNVQ
   721  FCIVALVIIF CSTITLCLVF VPKLITLRTN PDAATQNRRF QFTQNQKKED SKTSTSVTSV
   781  NQASTSRLEG LQSENHRLRM KITELDKDLE EVTMQLQDTP EKTTYIKQNH YQELNDILNL
   841  GNFTESTDGG KAILKNHLDQ NPQLQWNTTE PSRTCKDPIE DINSPEHIQR RLSLQLPILH
   901  HAYLPSIGGV DASCVSPCVS PTASPRHRHV PPSFRVMVSG L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GABBR2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

62 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GABBR2.

Disease | AllUniProt

Conditions GABBR2 is implicated in, by any mechanism.

• Neurodevelopmental disorder with poor language and loss of hand skills (NDPLHS) MIM:617903
• Developmental and epileptic encephalopathy 59 (DEE59) MIM:617904

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 1,171 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy, 59
• Neurodevelopmental disorder with poor language and loss of hand skills
• Epileptic encephalopathy
• Inborn genetic diseases
• Rett syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.17

gnomAD pLI

1

gnomAD missense Z

4.63

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• chemical synaptic transmission
• G protein-coupled receptor signaling pathway
• gamma-aminobutyric acid signaling pathway
• negative regulation of adenylate cyclase activity
• neuron-glial cell signaling
• synaptic transmission, GABAergic

Molecular functions

• G protein-coupled GABA receptor activity
• protein heterodimerization activity
• transmembrane signaling receptor activity

Cellular components

• cytoplasm
• G protein-coupled GABA receptor complex
• G protein-coupled receptor heterodimeric complex
• GABA receptor complex
• neuron projection
• plasma membrane
• postsynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• GPCR, family 3
• Receptor, ligand binding region
• GPCR family 3, GABA-B receptor
• GPCR family 3, C-terminal
• GPCR, family 3, conserved site
• Periplasmic binding protein-like I
• 7 transmembrane sweet-taste receptor of 3 GCPR
• Receptor family ligand binding region
• GPCR family 3, gamma-aminobutyric acid receptor, type B2
• Gamma-aminobutyric acid type B receptor subunit 2, coiled-coil domain
• Gamma-aminobutyric acid type B receptor subunit 2 coiled-coil domain

KeywordsUniProt

• Cell membrane
• Coiled coil
• Disulfide bond
• Epilepsy
• G-protein coupled receptor
• Glycoprotein
• Intellectual disability
• Membrane
• Phosphoprotein
• Postsynaptic cell membrane
• Receptor
• Signal
• Synapse
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GABBR2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GABBR1