GABBR1 Membrane Protein Introduction

Introduction of GABBR1

GABBR1 is encoded by the GABBR1 gene. The GABBR1 gene is located in humans at 6p21.3. It contains 22 exons and its mRNA is 4.4 kb in length. It is a G-protein coupled receptor subunit, inhibition of adenylyl cyclase activity, stimulation of phospholipase A2, activation of potassium channels, inactivation of voltage-dependent calcium channels, and modulation of inositol phospholipid hydrolysis of G-proteins mediate their activity. GABBR1 plays a key role in the fine-tuning of inhibitory synaptic transmission.

Function of GABBR1 Membrane Protein

The GABA heterodimeric G protein-coupled receptors formed by GABBR1 and GABBR2 are within the heterodimeric GABA receptor, GABBR1 binding agonists, and GABBR2 mediates the coupling of G proteins. When the ligand binds to it, it causes a conformational change, and the regulation of the activity of the downstream effector is accomplished by triggering signal transduction by a guanine nucleotide binding protein (G protein), which eventually inhibits adenylyl cyclase, stimulating phospholipase A2, which activates potassium channels, inactivates voltage-dependent calcium channels and regulates the hydrolysis of inositol phospholipids. Presynaptic GABA receptors down-regulate high voltage-activated calcium channels to inhibit neurotransmitter release. Moreover, postsynaptic GABA receptors reduce neuronal excitability by activating prominent inward rectifier potassium (Kir) conductance as late inhibitory synapses post-potential basis.

Fig.1 Structure of GABA receptors subunit composition. (Eduardo, 2012)

Application of GABBR1 Membrane Protein in Literature

1. Enoch M.A., et al. GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations. Alcohol Clin Exp Res. 2016, 40(1): 93-101. PubMed ID: 26727527
   
   

   The article shows that with both GABBR1 and SLC6A1, the minor genotypes/alleles are protective against risk for alcoholism. Finally, GABBR1 rs29220 might predict treatment response/adverse effects for baclofen, a GABAB receptor agonist.

2. Vangeel E.B., et al. Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1. Clin Epigenetics. 2017, 9: 107. PubMed ID: 29026448
   
   

   This article reveals that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. The findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.

3. Longqiu Y., et al. A miRNAs panel promotes the proliferation and invasion of colorectal cancer cells by targeting GABBR1. Cancer Med. 2016, 5(8): 2022-31. PubMed ID: 27230463
   
   

   The article demonstrates that miR-106a/b, miR-20a/b and miR-17 promote the proliferation and invasion of colorectal cancer by targeting their common target gene GABBR1, and play a key role in the proliferation and invasion of colorectal cancer.

4. Wang R., et al. Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus. Circ Heart Fail. 2016, 9(1): e002261. PubMed ID: 26699387
   
   

   This article indicates that there is an ANG II/AT1R/HoxD10/miR-7b/GABBR1 pathway in the PVN that contributes to sympathoexcitation and deterioration of cardiac function in CHF.

5. Gumerov V., et al. MicroRNA-derived network analysis of differentially methylated genes in schizophrenia, implicating GABA receptor B1 [GABBR1] and protein kinase B [AKT1]. Biol Direct. 2015, 10: 59. PubMed ID: 26450699
   
   

   This article shows that GABBR1 is of central importance to schizophrenia, even if there was no direct causal relationship at that time. In addition to being the center of microRNA-derived regulatory pathways and protein-protein interactions, its centrality is also supported by a large number of cis-regulatory elements and transcription factor binding sites that regulate its transcription.

GABBR1 Preparation Options

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Reference

1. Eduardo E. (2012). GABAB receptors: Structure, functions, and clinical implication. Neurology. 78, 578.

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