GAD2 Antibodies

Structure of GAD2

The molecular weight of the glutamic acid decarboxylase 2 protein encoded by the GAD2 gene is approximately 65-67 kDa. There are minor differences among different species, mainly due to slight changes in their amino acid sequences.

This protein is composed of approximately 585 amino acids and folds into two main domains, forming a functional homodimer. Its active center contains a pyridoxal phosphate (a derivative of vitamin B6) binding site, which is the key to catalyzing the decarboxylation of glutamic acid to γ -aminobutyric acid (GABA). Its three-dimensional structure, through a specific combination of α -helices and β -folds, forms a hydrophobic channel that guides the substrate into and stabilizes the reaction intermediate. A key lysine residue covalently binds to the coenzyme, while the conserved aspartic acid and histidine residues located in the active pocket work in synergy to precisely regulate the progress of the decarboxylation reaction.

Fig. 1 SNP map of the GAD2 gene.¹

Key structural properties of GAD2:

• Homodimer structure
• Pyridoxal phosphate (PLP) -dependent active centers
• Substrate channels and binding pockets

Functions of GAD2

The core function of the protein encoded by the GAD2 gene (glutamic acid decarboxylase 2) is to catalyze the conversion of glutamic acid into γ -aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the central nervous system. Its specific functions are as follows:

Unlike GAD1 (GAD67), which is mainly distributed in synaptic vesicles and is responsible for the rapid response of GABA synthesis, the enzymatic activity of GAD2 (GAD65) is highly sensitive to the availability of the coenzyme pyridoxal phosphate (PLP), which enables its activity to be rapidly regulated to adapt to the instantaneous changes in neuronal activity, playing the role of an "adjustable reserve".

Applications of GAD2 and GAD2 Antibody in Literature

1. Boutin, Philippe, et al. "GAD2 on chromosome 10p12 is a candidate gene for human obesity." PLoS biology 1.3 (2003): e68. https://doi.org/10.1371/journal.pbio.0000068

The article indicates that the GAD2 gene is associated with morbid obesity. Its -243A>G variation can enhance promoter activity, increase hunger, and affect insulin secretion. Haplotype analysis suggests that specific allele combinations have protective effects, supporting the role of the GABAergic system in regulating eating and the occurrence of obesity.

2. Davis, Kasey N., et al. "GAD2 alternative transcripts in the human prefrontal cortex, and in schizophrenia and affective disorders." PLoS One 11.2 (2016): e0148558. https://doi.org/10.1371/journal.pone.0148558

The article indicates that the GAD2 gene is abnormally expressed in the prefrontal cortex of patients with schizophrenia and mood disorders. The expression of full-length transcripts decreased, while the truncated variants changed in opposite directions in different diseases. Its expression level is affected by suicidal behavior and nicotine exposure.

3. Boutin, Philippe, et al. "GAD2 on chromosome 10p12 is a candidate gene for human obesity." PLoS biology 1.3 (2003): e68. https://doi.org/10.1371/journal.pbio.0000068

The article indicates that GAD2 gene variations affect the risk of morbid obesity. Its -243A>G variation enhances promoter activity and is associated with higher hunger. The +61450C>A and +83897T>A haplotypes have protective effects and are associated with lower insulin secretion.

4. Swarbrick, Michael M., et al. "Lack of support for the association between GAD2 polymorphisms and severe human obesity." PLoS biology 3.9 (2005): e315. https://doi.org/10.1371/journal.pbio.0030315

The article indicates that in the expanded sample study, the association between GAD2 gene polymorphisms (including -243 A>G) and severe obesity was not repeatedly verified. Neither meta-analysis nor functional studies supported the pathological role of this genetic variation in this type of obesity.

5. Liu, Dan, et al. "Sugar beverage habitation relieves chronic stress-induced anxiety-like behavior but elicits compulsive eating phenotype via vLSGAD2 neurons." International Journal of Molecular Sciences 24.1 (2022): 661. https://doi.org/10.3390/ijms24010661

Studies have shown that under chronic stress, excessive intake of sucrose can relieve anxiety, but it can induce binge eating and compulsive eating behaviors in mice and lead to weight gain. Activating GABAergic neurons in the ventrolateral septum of the brain can simulate this compulsive eating phenotype, suggesting it as a potential intervention target.

Creative Biolabs: GAD2 Antibodies for Research

Creative Biolabs specializes in the production of high-quality GAD2 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom GAD2 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our GAD2 antibodies, custom preparations, or technical support, contact us at email.