GABRG3 Membrane Protein Introduction

Introduction of GABRG3

Gamma-aminobutyric acid receptor subunit gamma-3 (GABRG3), also known as GABA(A) receptor subunit gamma-3, is a protein that in humans is encoded by the GABRG3 gene. It is a subunit of the GABAA receptor for the neurotransmitter gamma-Aminobutyric acid (GABA).

Basic Information of GABRG3
Protein Name	Gamma-aminobutyric acid receptor subunit gamma-3
Gene Name	GABRG3
Aliases	GABA(B) receptor subunit gamma-3
Organism	Homo sapiens (Human)
UniProt ID	Q99928
Transmembrane Times	4
Length (aa)	467
Sequence	MAPKLLLLLCLFSGLHARSRKVEEDEYEDSSSNQKWVLAPKSQDTDVTLILNKLLREYDKKLRPDIGIKPTVIDVDIYVNSIGPVSSINMEYQIDIFFAQTWTDSRLRFNSTMKILTLNSNMVGLIWIPDTIFRNSKTAEAHWITTPNQLLRIWNDGKILYTLRLTINAECQLQLHNFPMDEHSCPLIFSSYGYPKEEMIYRWRKNSVEAADQKSWRLYQFDFMGLRNTTEIVTTSAGDYVVMTIYFELSRRMGYFTIQTYIPCILTVVLSWVSFWIKKDATPARTALGITTVLTMTTLSTIARKSLPRVSYVTAMDLFVTVCFLFVFAALMEYATLNYYSSCRKPTTTKKTTSLLHPDSSRWIPERISLQAPSNYSLLDMRPPPTAMITLNNSVYWQEFEDTCVYECLDGKDCQSFFCCYEECKSGSWRKGRIHIDILELDSYSRVFFPTSFLLFNLVYWVGYLYL

Function of GABRG3 Membrane Protein

GABA is the major inhibitory neurotransmitter in the human central nervous system and involved in many of the neurochemical pathways that affect alcohol use and related disorders. Studies have shown that GABA produces its effect on target cells by interacting with two major classes of receptor, namely ionotropic type GABAA receptors, and metabotropic type GABAB receptors. It has been reported that GABA is associated with several of the behavioral effects of alcohol, including motor incoordination, anxiolysis, sedation, withdrawal signs, and ethanol preference. Generally, GABAA receptors are composed of multiple subunits that can be grouped according to sequence similarity into alpha (alpha 1-6), beta (beta 1-4), gamma (gamma 1-3), and delta (delta 1-2). As a member of the GABA receptors, GABRG3 shares 64% amino acid sequence identical with that of GABRG2. Furthermore, GABRG3 contributes to the formation of the benzodiazepine-binding site that is located at the interface between the γ2 and 3 subunits.

Fig.1 Organization of the γ-aminobutyric acid type A (GABAA) receptor. (Akk, 2011)

Application GABRG3 of Membrane Protein in Literature

Dick D.M., et al. Association of GABRG3 with alcohol dependence. Alcoholism: Clinical and Experimental Research. 2004, 28(1):4-9. PubMed ID: 14745296

This article finds that GABRG3 may be involved in the risk for alcohol dependence, which supports the theory that the predisposition to alcoholism may be inherited as a general state of central nervous system disinhibition/hyperexcitability that results from an altered responsiveness to GABA.
Greger V., et al. The γ-aminobutyric acid receptor γ3 subunit gene (GABRG3) is tightly linked to the α5 subunit gene (GABRA5) on human chromosome 15q11–q13 and is transcribed in the same orientation. Genomics. 1995, 26(2):258-64. PubMed ID: 7601451

This article shows that lambda and P1 phage clones surrounding both ends of GABRG3 are isolated, the clones derived from the 5' end of GABRG3 are linked to an existing phage contig spanning the 3' end of GABRA5. The two genes are located within 35 kb of each other and are transcribed in the same orientation.
Knoflach F., et al. The γ3-subunit of the GABAA-receptor confers sensitivity to benzodiazepine receptor ligands. FEBS letters. 1991, 293(1-2):191-4. PubMed ID: 1660002

This article indicates that gamma 3-subunit has the potential to functionally replace the gamma 2-subunit with regard to the bi-directional allosteric drug modulation.

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Reference

Akk, et al. (2011). Structural studies of the actions of anesthetic drugs on the γ-aminobutyric acid type A receptor. Anesthesiology: The Journal of the American Society of Anesthesiologists. 115(6), 1338-1348.

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