GABBR1

Protein identityUniProt · HPA

UniProt accession

Q9UBS5

Gene

GABBR1

Ensembl

ENSG00000204681

Chromosome

6

Canonical length

961 aa

Protein class

FDA approved drug targets, G-protein coupled receptors, Plasma proteins, Predicted membrane proteins

Subcellular location

Basal body,Cytosol

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

Canonical amino-acid sequenceUniProt

961 residues, UniProt reviewed canonical sequence.

>Q9UBS5|GABBR1
     1  MLLLLLLAPL FLRPPGAGGA QTPNATSEGC QIIHPPWEGG IRYRGLTRDQ VKAINFLPVD
    61  YEIEYVCRGE REVVGPKVRK CLANGSWTDM DTPSRCVRIC SKSYLTLENG KVFLTGGDLP
   121  ALDGARVDFR CDPDFHLVGS SRSICSQGQW STPKPHCQVN RTPHSERRAV YIGALFPMSG
   181  GWPGGQACQP AVEMALEDVN SRRDILPDYE LKLIHHDSKC DPGQATKYLY ELLYNDPIKI
   241  ILMPGCSSVS TLVAEAARMW NLIVLSYGSS SPALSNRQRF PTFFRTHPSA TLHNPTRVKL
   301  FEKWGWKKIA TIQQTTEVFT STLDDLEERV KEAGIEITFR QSFFSDPAVP VKNLKRQDAR
   361  IIVGLFYETE ARKVFCEVYK ERLFGKKYVW FLIGWYADNW FKIYDPSINC TVDEMTEAVE
   421  GHITTEIVML NPANTRSISN MTSQEFVEKL TKRLKRHPEE TGGFQEAPLA YDAIWALALA
   481  LNKTSGGGGR SGVRLEDFNY NNQTITDQIY RAMNSSSFEG VSGHVVFDAS GSRMAWTLIE
   541  QLQGGSYKKI GYYDSTKDDL SWSKTDKWIG GSPPADQTLV IKTFRFLSQK LFISVSVLSS
   601  LGIVLAVVCL SFNIYNSHVR YIQNSQPNLN NLTAVGCSLA LAAVFPLGLD GYHIGRNQFP
   661  FVCQARLWLL GLGFSLGYGS MFTKIWWVHT VFTKKEEKKE WRKTLEPWKL YATVGLLVGM
   721  DVLTLAIWQI VDPLHRTIET FAKEEPKEDI DVSILPQLEH CSSRKMNTWL GIFYGYKGLL
   781  LLLGIFLAYE TKSVSTEKIN DHRAVGMAIY NVAVLCLITA PVTMILSSQQ DAAFAFASLA
   841  IVFSSYITLV VLFVPKMRRL ITRGEWQSEA QDTMKTGSST NNNEEEKSRL LEKENRELEK
   901  IIAEKEERVS ELRHQLQSRQ QLRSRRHPPT PPEPSGGLPR GPPEPPDRLS CDGSRVHLLY
   961  K

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GABBR1 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)

0.31

Highest tissue expression

224 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GABBR1.

Disease | AllUniProt

Conditions GABBR1 is implicated in, by any mechanism.

• Neurodevelopmental disorder with language delay and variable cognitive abnormalities (NEDLC) MIM:620502

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 190 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with language delay and variable cognitive abnormalities
• Intellectual disability
• Global developmental delay
• Delayed speech and language development
• Atypical behavior

Disease | AutoantibodyPubMed

Conditions in which antibodies against GABBR1 are reported. Each links to that disease's full target list.

• Encephalitis 18
• Limbic Encephalitis 12
• Hashimoto Disease 10
• Lung Neoplasms 9
• Seizures 5
• Adenocarcinoma 3
• Paraneoplastic Syndromes, Nervous System 3

Showing 7 of 9 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for GABBR1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.22

gnomAD pLI

1

gnomAD missense Z

4.82

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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
• gamma-aminobutyric acid signaling pathway
• negative regulation of cell population proliferation
• negative regulation of dopamine secretion
• negative regulation of epinephrine secretion
• negative regulation of gamma-aminobutyric acid secretion
• negative regulation of synaptic transmission
• neuron-glial cell signaling
• osteoblast differentiation
• positive regulation of glutamate secretion
• positive regulation of growth hormone secretion
• response to ethanol
• response to nicotine
• synaptic transmission, GABAergic

Molecular functions

• extracellular matrix protein binding
• G protein-coupled GABA receptor activity
• G protein-coupled neurotransmitter receptor activity involved in regulation of postsynaptic membrane potential
• G protein-coupled neurotransmitter receptor activity involved in regulation of presynaptic membrane potential
• protein heterodimerization activity

Cellular components

• axolemma
• dendritic shaft
• dendritic spine
• endoplasmic reticulum membrane
• extracellular space
• G protein-coupled GABA receptor complex
• G protein-coupled receptor heterodimeric complex
• GABA-ergic synapse
• glutamatergic synapse
• mitochondrial membrane
• neuronal cell body
• plasma membrane
• postsynaptic membrane
• presynaptic membrane
• Schaffer collateral - CA1 synapse
• synaptic vesicle

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Receptor, ligand binding region
• GPCR family 3, GABA-B receptor
• GPCR family 3, C-terminal
• Periplasmic binding protein-like I
• Sushi/SCR/CCP superfamily
• 7 transmembrane sweet-taste receptor of 3 GCPR
• Sushi repeat (SCR repeat)
• Receptor family ligand binding region
• GPCR family 3, gamma-aminobutyric acid receptor, type B1

KeywordsUniProt

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

InteractionsUniProt · HPA

Protein binding partners of GABBR1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• JAKMIP1
• GABBR2
• GPR37