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Gene Review

CA6  -  carbonic anhydrase VI

Homo sapiens

Synonyms: CA-VI, Carbonate dehydratase VI, Carbonic anhydrase 6, Carbonic anhydrase VI, GUSTIN, ...
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Disease relevance of CA6

  • The metallic taste reported as a side effect after the treatment with systemic sulfonamides may be due to the inhibition of the salivary CA VI [1].
  • 5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies [2].
  • Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope") [2].
  • A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium [2].
  • CA6 is also seen along peripheral cell membranes and focally in the cytoplasm in some epithelial neoplasms [3].

High impact information on CA6


Biological context of CA6


Anatomical context of CA6


Associations of CA6 with chemical compounds


Regulatory relationships of CA6

  • In the presence of 1 mM EGTA, gustin activated cAMP PDE 5- to 6-fold, but the activating ability was completely lost after gustin was heated at 100 degrees C for 5 min [14].

Other interactions of CA6

  • The kinetic parameters for the CO(2) hydration reaction proved hCA VI to possess a k(cat) of 3.4x10(5)s(-1) and k(cat)/K(M) of 4.9x10(7)M(-1)s(-1) (at pH 7.5 and 20 degrees C). hCA VI has a significant catalytic activity for the physiological reaction, of the same order of magnitude as isoforms CA I or CA IX [13].
  • CA I, II, III and VII are cytoplasmic, CA V is mitochondrial, and CA VI is present in salivary secretions [15].
  • The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn [2].
  • Results with cultured pancreatic tumor cell, lines suggest that CA II, IV, IX, and XII are expressed in the ductal cells, and CA VI is expressed in the acinar cells [16].
  • The potential for the identification and quantification of individual branched carboxyalkyl isomeric mixtures of CA5-, CA6-, CA7-, and CA8P1EC metabolites based on corresponding dm-CA5-8P1ECs revealed the advantage of the GC-CI-MS although the detection limits in CI were clearly higher than those in EI [17].

Analytical, diagnostic and therapeutic context of CA6


  1. Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors. Nishimori, I., Minakuchi, T., Onishi, S., Vullo, D., Scozzafava, A., Supuran, C.T. J. Med. Chem. (2007) [Pubmed]
  2. Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas. Kearse, K.P., Smith, N.L., Semer, D.A., Eagles, L., Finley, J.L., Kazmierczak, S., Kovacs, C.J., Rodriguez, A.A., Kellogg-Wennerberg, A.E. Int. J. Cancer (2000) [Pubmed]
  3. Immunohistochemical distribution of tumor-associated antigen CA6 in gynecological neoplasms as detected by monoclonal antibody DS6. Smith, N.L., Halliday, B.E., Finley, J.L., Wennerberg, A.E. Int. J. Gynecol. Pathol. (2001) [Pubmed]
  4. Human carbonic anhydrases and carbonic anhydrase deficiencies. Sly, W.S., Hu, P.Y. Annu. Rev. Biochem. (1995) [Pubmed]
  5. The identification of secreted carbonic anhydrase VI as a constitutive glycoprotein of human and rat milk. Karhumaa, P., Leinonen, J., Parkkila, S., Kaunisto, K., Tapanainen, J., Rajaniemi, H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  6. The gene for human carbonic anhydrase VI(CA6) is on the tip of the short arm of chromosome 1. Sutherland, G.R., Baker, E., Fernandez, K.E., Callen, D.F., Aldred, P., Coghlan, J.P., Wright, R.D., Fernley, R.T. Cytogenet. Cell Genet. (1989) [Pubmed]
  7. Human secreted carbonic anhydrase: cDNA cloning, nucleotide sequence, and hybridization histochemistry. Aldred, P., Fu, P., Barrett, G., Penschow, J.D., Wright, R.D., Coghlan, J.P., Fernley, R.T. Biochemistry (1991) [Pubmed]
  8. Secretion of carbonic anhydrase isoenzyme VI (CA VI) from human and rat lingual serous von Ebner's glands. Leinonen, J., Parkkila, S., Kaunisto, K., Koivunen, P., Rajaniemi, H. J. Histochem. Cytochem. (2001) [Pubmed]
  9. Phenotypic characterization of a tungsten-tolerant mutant of Azotobacter vinelandii. Premakumar, R., Jacobitz, S., Ricke, S.C., Bishop, P.E. J. Bacteriol. (1996) [Pubmed]
  10. Purification and characterization of human salivary carbonic anhydrase. Murakami, H., Sly, W.S. J. Biol. Chem. (1987) [Pubmed]
  11. Salivary carbonic anhydrase isoenzyme VI. Kivela, J., Parkkila, S., Parkkila, A.K., Leinonen, J., Rajaniemi, H. J. Physiol. (Lond.) (1999) [Pubmed]
  12. Immunoelectron microscopy of carbonic anhydrase isozyme VI in human submandibular gland: comparison with isozymes I and II. Ogawa, Y., Hong, S.S., Toyosawa, S., Kuwahara, H., Shimazaki, M., Yagi, T. J. Histochem. Cytochem. (1993) [Pubmed]
  13. Carbonic anhydrase inhibitors. Inhibition studies of the human secretory isoform VI with anions. Nishimori, I., Innocenti, A., Vullo, D., Scozzafava, A., Supuran, C.T. Bioorg. Med. Chem. Lett. (2007) [Pubmed]
  14. Human salivary gustin is a potent activator of calmodulin-dependent brain phosphodiesterase. Law, J.S., Nelson, N., Watanabe, K., Henkin, R.I. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  15. The cellular physiology of carbonic anhydrases. Breton, S. JOP (2001) [Pubmed]
  16. Carbonic anhydrase in human pancreas: hypotheses for the pathophysiological roles of CA isozymes. Nishimori, I., FujikawaAdachi, K., Onishi, S., Hollingsworth, M.A. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  17. Dicarboxylic degradation products of nonylphenol polyethoxylates: synthesis and identification by gas chromatography-mass spectrometry using electron and chemical ionization modes. Hoai, P.M., Tsunoi, S., Ike, M., Inui, N., Tanaka, M., Fujita, M. Journal of chromatography. A. (2004) [Pubmed]
  18. Secretory carbonic anhydrase isoenzyme (CA VI) in human serum. Kivelä, J., Parkkila, S., Waheed, A., Parkkila, A.K., Sly, W.S., Rajaniemi, H. Clin. Chem. (1997) [Pubmed]
  19. Immunohistochemical localization of carbonic anhydrase isoenzymes VI, II, and I in human parotid and submandibular glands. Parkkila, S., Kaunisto, K., Rajaniemi, L., Kumpulainen, T., Jokinen, K., Rajaniemi, H. J. Histochem. Cytochem. (1990) [Pubmed]
  20. Salivary carbonic anhydrase isoenzyme VI is located in the human enamel pellicle. Leinonen, J., Kivelä, J., Parkkila, S., Parkkila, A.K., Rajaniemi, H. Caries Res. (1999) [Pubmed]
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