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1.A.9.5.1
γ-Aminobutyric acid (GABA)-inhibited chloride channel. The major central endocannabinoid, 2-arachidonoyl glycerol (2-AG), directly acts at GABA(A) receptors. It potentiates the receptor at low GABA concentrations (Sigel et al., 2011). Hydrophobic anions potently and uncompetitively antagonize GABA (A) receptor function (Chisari et al., 2011). Regulated by neurosteroids; activated by pregnenolone and allopregnenalone (Costa et al., 2012). Different subunits contribute asymmetrically to channel conductances via residues in the extracellular domain (Moroni et al., 2011). Potentiated by general anaesthetics (Nury et al., 2011). Direct physical coupling between the GABA-A receptor and the KCC2 chloride transporter underlies ionic plasticity in cerebellar purkinje neurons in response to brain-derived neurotrophic factor (BDNF) (Huang et al. 2013).  GABA type A receptors, the brain's major inhibitory neurotransmitter receptors, are the targets for many general anesthetics, including volatile anesthetics, etomidate, propofol, and barbiturates.  Anesthetics usually bind at intersubunit sites (Chiara et al. 2013). Etomidate and propofol are potent general anesthetics that act via GABAA receptor allosteric co-agonist sites located at transmembrane beta+/alpha- inter-subunit interfaces. In heteromeric receptors, betaN265 (M2-15') on beta2 and beta3 subunits are important determinants of sensitivity to these drugs (Stewart et al. 2014). A P302L mutation in the gamma2 (γ2) subunit (Dravet syndrome in humans) of the mouse when expressed with the α1 and β3 subunits, produced a 90% decrease in conductance due to slow activation and enhance desensitization. It shifted the channel to a low-conductance state by reshaping the hour-glass-like pore cavity during transitions between closed, open, and desensitized states (Hernandez et al. 2017). Numerous postive and negative allosteric modulators have been identified (Maldifassi et al. 2016).

Accession Number:P15431
Protein Name:GAB1 aka GABRB1 aka GABRB-1
Length:474
Molecular Weight:54072.00
Species:Rattus norvegicus (Rat) [10116]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate Cl-

Cross database links:

Genevestigator: P15431
eggNOG: roNOG12839
RefSeq: NP_037088.1   
Entrez Gene ID: 25450   
Pfam: PF02931    PF02932   
KEGG: rno:25450   

Gene Ontology

GO:0030054 C:cell junction
GO:0034707 C:chloride channel complex
GO:0045211 C:postsynaptic membrane
GO:0005254 F:chloride channel activity
GO:0005230 F:extracellular ligand-gated ion channel acti...
GO:0004890 F:GABA-A receptor activity
GO:0006821 P:chloride transport
GO:0007214 P:gamma-aminobutyric acid signaling pathway

References (2)

[1] “GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs.”  Ymer S.et.al.   2548852
[2] “GABAA-receptor expressed from rat brain alpha- and beta-subunit cDNAs displays potentiation by benzodiazepine receptor ligands.”  Malherbe P.et.al.   1977069

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MWTVQNRESL GLLSFPVMVA MVCCAHSSNE PSNMSYVKET VDRLLKGYDI RLRPDFGGPP 
61:	VDVGMRIDVA SIDMVSEVNM DYTLTMYFQQ SWKDKRLSYS GIPLNLTLDN RVADQLWVPD 
121:	TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA CMMDLRRYPL DEQNCTLEIE 
181:	SYGYTTDDIE FYWNGGEGAV TGVNKIELPQ FSIVDYKMVS KKVEFTTGAY PRLSLSFRLK 
241:	RNIGYFILQT YMPSTLITIL SWVSFWINYD ASAARVALGI TTVLTMTTIS THLRETLPKI 
301:	PYVKAIDIYL MGCFVFVFLA LLEYAFVNYI FFGKGPQKKG ASKQDQSANE KNKLEMNKVQ 
361:	VDAHGNILLS TLEIRNETSG SEVLTGVSDP KATMYSYDSA SIQYRKPLSS REGFGRGLDR 
421:	HGVPGKGRIR RRASQLKVKI PDLTDVNSID KWSRMFFPIT FSLFNVVYWL YYVH