CA12 Antibodies

Structure of CA12

The CA12 gene encodes carbonic anhydrase 12, which is a transmembrane protein with a molecular weight of approximately 43-45 kDa. This enzyme belongs to the carbonic anhydrase family, and its molecular weight is highly conserved among different species. The main differences lie in the tissue-specific expression levels and post-translational modifications.

The primary structure of this protein consists of approximately 400 amino acids and folds to form a typical catalytic core of carbonic anhydrase. The characteristic of its tertiary structure is the presence of an active center zinc ion located in the extracellular domain. This zinc ion is coordinated by three histidine residues and is crucial for the catalytic reversible hydration of carbon dioxide. The region close to the cell membrane forms a hydrophobic pocket, which helps stabilize the enzyme's conformation and participate in its interaction with the substrate.

Fig. 1 High CA12 activity and Low CA12 activity.¹

Key structural properties of CA12:

• Extracellular carbonic anhydrase catalytic domain
• The active center is composed of zinc ions coordinated with three histidine residues
• Single transmembrane helical anchoring to the cell membrane
• Extracellular regions containing N-linked glycosylation sites

Functions of CA12

The core function of the protein encoded by the CA12 gene, carbonic anhydrase XII, is to catalyze the reversible hydration reaction of carbon dioxide (CO₂) (CO₂ + H₂O ⇌ HCO₃⁻+ H⁺), thereby maintaining acid-base and ion homeostasis in various tissues. The specific physiological functions are as shown in the table below:

Unlike most intracellular carbonic anhydrases, CA12, as a transmembrane protein, primarily exerts its activity outside the cell or on the cell membrane surface. This enables it to efficiently sense and regulate the acid-base balance of the local microenvironment. The reaction rate catalyzed by it is regulated by substrate concentration, pH value, and specific inhibitors. In tumor research, the inhibition of CA12's activity has been proven to reverse the acidification of the tumor microenvironment, thereby inhibiting tumor growth. This highlights its crucial pathophysiological role in the disease.

Applications of CA12 and CA12 Antibody in Literature

• Ning, Wan-Ru, et al. "Carbonic anhydrase XII mediates the survival and prometastatic functions of macrophages in human hepatocellular carcinoma." The Journal of Clinical Investigation 132.7 (2022). https://doi.org/10.1172/JCI153110

The article indicates that in hepatocellular carcinoma, tumor-associated macrophages highly express carbonic anhydrase XII (CA12). This enzyme helps cells adapt to the acidic microenvironment and promotes the secretion of CCL8, thereby enhancing tumor metastasis. Targeting CA12 can inhibit tumor growth and has a synergistic effect with immune checkpoint therapy.

• Zeng, Jiahang, et al. "The Role of the miR‐548au‐3p/CA12 Axis in Tracheal Chondrogenesis in Congenital Pulmonary Airway Malformations." Oxidative Medicine and Cellular Longevity 2023.1 (2023): 6428579. https://doi.org/10.1155/2023/6428579

The study found that the expression of miR-548au-3p was significantly upregulated in the tissues of CPAM patients. This miRNA targets and inhibits CA12, promoting the proliferation and differentiation of rat tracheal chondrocytes and affecting extracellular matrix metabolism. This provides new insights into the pathogenesis and treatment of CPAM.

• Han, Meigui, et al. "Case report: Novel CA12 homozygous variant causing isolated hyperchloridrosis in a Chinese child with hyponatremia." Frontiers in Pediatrics 10 (2022): 820707. https://doi.org/10.3389/fped.2022.820707

This study is the first to report in China a case of isolated hyperchloremic hyperchloremic hypernatremia caused by a novel homozygous missense variant c.763A>C in the CA12 gene. The patient presented with severe dehydration and hyponatremia. Oral sodium supplementation treatment was effective, and the child showed good growth and development up to the age of 3. This discovery has expanded the genetic spectrum of this disease.

• Yin, Yan, Wei Du, and Fei Li. "The construction of a hypoxia-based signature identified CA12 as a risk gene affecting uveal melanoma cell malignant phenotypes and immune checkpoint expression." Frontiers in Oncology 12 (2022): 1008770. https://doi.org/10.3389/fonc.2022.1008770

The article indicates that in uveal melanoma, the low-oxygen-related C1 subtype predicts a poor prognosis and high immune cell infiltration. The study constructed a low-oxygen risk scoring model and confirmed that targeting the gene CA12 can inhibit the epithelial-mesenchymal transition and clonogenic ability of tumor cells, and the expression of CD276 subsequently decreases. This finding provides a new target for improving the efficacy of immunotherapy.

• Deben, Christophe, et al. "Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition." Journal of Experimental & Clinical Cancer Research 43.1 (2024): 88. https://doi.org/10.1186/s13046-024-03012-z

The research has found that the anti-rheumatic drug Auranofin can selectively kill non-small cell lung cancer and pancreatic cancer cells, and a low expression of CA12 indicates higher sensitivity. Its combination with the AKT inhibitor MK2206 shows a synergistic anti-cancer effect, providing a new medication direction and biomarker for cancer treatment.

Creative Biolabs: CA12 Antibodies for Research

Creative Biolabs specializes in the production of high-quality CA12 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom CA12 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 CA12 antibodies, custom preparations, or technical support, contact us at email.