Carbonic Anhydrase IX/CA9 Products

Description

Carbonic anhydrase alpha, isozyme IX, belongs to a family of zinc-containing metalloproteins which hydrate carbon dioxide to generate bicarbonate ions and protons (1). This main catalytic function allows carbonic anhydrase IX to participate in cellular pH regulation. The large family of carbonic anhydrase metalloproteins includes three major classes which have been identified based on sequence and structure analysis. The alpha class is a monomer found in mammals. The beta class may occur as a dimer, tetramer, hexamer or octamer and is found in plants, algae, and bacteria. Lastly, the gamma class is a trimer found in bacteria and represents the most ancient carbonic anhydrase. These three classes of carbonic anhydrase enzymes lack sequence or structural similarities, but all share a conserved active site zinc atom (1).

Carbonic anhydrase IX (theoretical molecular weight 50kDa) belongs to the monomeric alpha class and is a single pass-transmembrane protein with two extracellular domains which serve catalytic and cell adhesion functions (2, 3). By cooperating with sodium bicarbonate cotransporters (NBC), lactate and proton exporting monocarboxylic acid transporters (MCT), and a sodium/hydrogen exchanger (NHE), carbonic anhydrase IX is involved in pH regulation across the cell membrane. This functional property protects cancer cells from intracellular acidification and partly explains the role of carbonic anhydrase IX in cancer cell survival and proliferation. In contrast, the pH regulating activity of carbonic anhydrase IX induces extracellular acidification, which has been implicated in epithelial to mesenchymal transition (EMT) and promoting cancer invasion. Carbonic anhydrase IX is frequently overexpressed in cancer cells (e.g., colorectal-, breast-, lung-carcinoma and brain tumors), an effect promoted by hypoxia within the tumor microenvironment (4). An exception are tumors carrying pVHL inactivating mutations, such as clear cell renal cell carcinoma (ccRCC), where HIF-alpha is stabilized due to dysfunctional proteasomal targeting and can induce HRE (Hypoxia Response Element) containing genes even under physiological normoxia (5). Carbonic anhydrase IX may be detected by immunostaining in tumors, which is found in association with necrotic tissue and metastatic cells. Because the expression of carbonic anhydrase IX correlates with both tumor grade and stage, analysis of its expression in tumors serves as a prognostic factor (4, 6).

References

1. Tripp, B. C., Smith, K., & Ferry, J. G. (2001). Carbonic Anhydrase: New Insights for an Ancient Enzyme. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.R100045200

2. Nishimori, I., & Onishi, S. (2001). Carbonic anhydrase isozymes in the human pancreas. Digestive and Liver Disease. https://doi.org/10.1016/s1590-8658(01)80138-9

3. Zavadova, Z., & Zavada, J. (2005). Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment. Oncology Reports. https://doi.org/10.3892/or.13.5.977

4. Pastorekova, S., & Gillies, R. J. (2019). The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer and Metastasis Reviews. https://doi.org/10.1007/s10555-019-09799-0

5. Haase, V. (2009). The VHL Tumor Suppressor: Master Regulator of HIF. Current Pharmaceutical Design. https://doi.org/10.2174/138161209789649394

6. Young, J. R., Coy, H., Kim, H. J., Douek, M., Sisk, A., Pantuck, A. J., & Raman, S. S. (2018). Association of the gross appearance of intratumoral vascularity at MDCT with the carbonic anhydrase IX score in clear cell renal cell carcinoma. American Journal of Roentgenology. https://doi.org/10.2214/AJR.18.19725

Bioinformatics

Entrez	230099 Mouse 768 Human
Uniprot	NM_001216 Human Q16790 Human Q8VHB5 Mouse
Product By Gene ID	768
Alternate Names	CAIX CA-IX Carbonate dehydratase IX carbonic anhydrase 9 carbonic anhydrase IX carbonic dehydratase EC 4.2.1.1 G250 Membrane antigen MN MN P54/58N PMW1 RCC-associated antigen G250 RCC-associated protein G250 Renal cell carcinoma-associated antigen G250

Research Areas for Carbonic Anhydrase IX/CA9

Find related products by research area and learn more about each of the different research areas below.

Cancer
Cellular Markers
HIF Target Genes
Hypoxia
Lipid and Metabolism
Phospho-Specific
Signal Transduction
Vision

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