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Characterization of CA XIII, a novel member of the carbonic anhydrase isozyme family
Lehtonen J,et al .
The carbonic anhydrase (CA) gene family has been reported to consist of at least 11 enzymatically active members and a few inactive homologous proteins. Recent analyses of human and mouse databases provided evidence that human and mouse genomes contain genes for still another novel CA isozyme hereby named CA XIII. In the present study, we modeled the structure of human CA XIII. This model revealed a globular molecule with high structural similarity to cytosolic isozymes, CA I, II and III. Recombinant mouse CA XIII showed catalytic activity similar to those of mitochondrial CA V and cytosolic CA I, with kcat/KM of 4.3 x 107 M-1s-1, and kcat of 8.3 x 104 s-1. It is very susceptible to inhibition by sulfonamide and anionic inhibitors, with inhibition constants of 17 nM for acetazolamide, a clinically used sulfonamide, and of 0.25 mM, for cyanate, respectively. Using panels of cDNAs we evaluated human and mouse CA13 gene expression in a number of different tissues. In human tissues, positive signals were identified in the thymus, small intestine, spleen, prostate, ovary, colon, and testis. In mouse, positive tissues included the spleen, lung, kidney, heart, brain, skeletal muscle, and testis. We also investigated the cellular and subcellular localization of CA XIII in human and mouse tissues using an antibody raised against a polypeptide of 14 amino acids common for both human and mouse orthologues. Immunohistochemical staining showed a unique and widespread distribution pattern for CA XIII compared to the other cytosolic CA isozymes. In conclusion, the predicted amino acid sequence, structural model, distribution and activity data suggest that CA XIII represents a novel enzyme, which may play important physiological roles in several organs.
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NCBI Summary:
Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA XII is predicted to be a type I membrane protein and is most closely related to the other transmembrane CA isoform, CA IX. However, unlike CA IX, which is expressed in clear-cell renal cell carcinoma, but not in normal kidney or most other normal tissues, CA XII is highly expressed in normal tissues, such as kidney, colon and pancreas.
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