Carbonic Anhydrase 2 Human (CA2), encoded by the CA2 gene on chromosome 8q22, is a zinc-containing metalloenzyme belonging to the α-carbonic anhydrase family. It catalyzes the reversible hydration of carbon dioxide (CO₂ + H₂O ⇌ HCO₃⁻ + H⁺), a reaction critical for pH regulation, ion transport, and biosynthetic processes . CA2 is ubiquitously expressed in tissues, including erythrocytes, kidneys, brain, and osteoclasts, and is implicated in both physiological homeostasis and disease pathogenesis .
Structure: Monomeric enzyme with a Zn²⁺ ion coordinated by three histidine residues (His-94, His-96, His-119) in the active site .
Catalytic Activity: Turnover frequency of ~10⁶ reactions per second, making it one of the fastest enzymes known .
CA2 maintains systemic pH by regulating bicarbonate reabsorption in renal proximal tubules and facilitating CO₂ elimination in lungs .
In osteoclasts, CA2 generates protons required for bone matrix demineralization. Loss of CA2 activity leads to impaired bone remodeling .
CA2 is expressed in oligodendrocytes, neurons (predominantly GABAergic), and choroid plexus epithelium. It contributes to cerebrospinal fluid production and cerebral calcification regulation .
CA2 modulates platelet activation and aggregation, potentially influencing cardiovascular diseases .
Anti-CA2 autoantibodies are linked to systemic lupus erythematosus (32% of patients) and Sjögren’s syndrome (21%) .
Sulfonamides (e.g., acetazolamide) are potent CA2 inhibitors used in glaucoma, epilepsy, and altitude sickness .
Recent studies developed heterobifunctional degraders (PROTACs) that induce CA2 ubiquitination and proteasomal degradation, showing potential in cancer and metabolic disorders .
Recombinant CA2 (expressed in E. coli) is utilized in biochemical assays and drug discovery .
CA2 homologs in mollusks (e.g., Haliotis discus hannai) play roles in shell biomineralization, suggesting conserved functions across species .
Mutations in the CA2 gene can lead to CA II deficiency syndrome, an autosomal recessive disorder. This syndrome is characterized by:
Recombinant human CA2 is produced using E. coli expression systems. The recombinant protein is typically purified using conventional chromatography techniques . It is available in various formulations, including those with and without carrier proteins like Bovine Serum Albumin (BSA). The carrier-free versions are recommended for applications where the presence of BSA could interfere with experimental results .
Recombinant human CA2 is widely used in research, particularly in studies related to: