Alternative titles; symbols
HGNC Approved Gene Symbol: CA6
Cytogenetic location: 1p36.23 Genomic coordinates (GRCh38): 1:8,945,868-8,975,092 (from NCBI)
Carbonic anhydrases (CAs) are a family of zinc metalloenzymes. For background information on the CA family, see 114800.
CA VI is a 42-kD secreted isozyme found in salivary glands and saliva (Murakami and Sly, 1987). By using biochemical and immunohistochemical techniques, Karhumaa et al. (2001) demonstrated that CA VI is also an elementary component of milk.
Aldred et al. (1991) isolated and sequenced cDNA clones coding for CA6. The clones identified a 1.45-kb mRNA that was present in high levels in parotid submandibular salivary glands but absent in other tissues such as sublingual gland, kidney, liver, and prostate. The cDNA encoded a protein of 308 amino acids that included a 17-amino acid leader sequence typical of secreted proteins. The mature CA VI protein has 291 amino acids, compared to the 259 or 260 residues of the cytoplasmic isozymes; most of the extra amino acids present are in the carboxyl terminal region. CA VI has diverged significantly in its structure from the cytoplasmic isozymes, including CA I (114800), CA II (611492), and CA III (114750), which are closely related to one another. The CA VI protein has 35% sequence identity with human CA II, while residues involved in the active site of the enzymes have been conserved. Southern analysis of human DNA indicated that there is only 1 gene coding for CA VI.
Thatcher et al. (1998) identified gustin as CA6. Gustin contains 2 potential N-linked glycosylation sites. By RP-HPLC and SDS-PAGE, gustin purified from human saliva had a molecular mass of 37 kD before deglycosylation and 33 kD after.
Karhumaa et al. (2001) showed that the 42-kD CA VI glycopolypeptide purified from human milk shares 100% homology with salivary CA VI in protein sequence. They found that its concentration is approximately 8 times higher in human colostrum than in mature milk, the latter corresponding to the levels previously detected in human saliva. The high concentration in colostrum, in particular its functional and structural stability in an acidic milieu, and its growth-supporting role in the taste buds suggest that milk CA VI is an essential factor in normal growth and development of the infant alimentary tract.
By means of Southern analysis of a somatic cell hybrid panel and by in situ hybridization, Sutherland et al. (1989) mapped the CA6 gene to 1p36.33-p36.22. White et al. (1998) reported physical mapping of the CA6, ENO1 (172430), and SLC2A5 (138230) genes to 1p36 by study of yeast- and P1-artificial chromosome (YAC and PAC) contigs. PACs from the contig were mapped to 1p36.2 by fluorescence in situ hybridization.
Aldred, P., Fu, P., Barrett, G., Penschow, J. D., Wright, R. D., Coghlan, J. P., Fernley, R. T. Human secreted carbonic anhydrase: cDNA cloning, nucleotide sequence, and hybridization histochemistry. Biochemistry 30: 569-575, 1991. [PubMed: 1899030] [Full Text: https://doi.org/10.1021/bi00216a035]
Karhumaa, P., Leinonen, J., Parkkila, S., Kaunisto, K., Tapanainen, J., Rajaniemi, H. The identification of secreted carbonic anhydrase VI as a constitutive glycoprotein of human and rat milk. Proc. Nat. Acad. Sci. 98: 11604-11608, 2001. [PubMed: 11553764] [Full Text: https://doi.org/10.1073/pnas.121172598]
Murakami, H., Sly, W. S. Purification and characterization of human salivary carbonic anhydrase. J. Biol. Chem. 262: 1382-1388, 1987. [PubMed: 2433278]
Sutherland, G. R., Baker, E., Fernandez, K. E. W., Callen, D. F., Aldred, P., Coghlan, J. P., Wright, R. D., Fernley, R. T. The gene for human carbonic anhydrase VI (CA6) is on the tip of the short arm of chromosome 1. Cytogenet. Cell Genet. 50: 149-150, 1989. [PubMed: 2505973] [Full Text: https://doi.org/10.1159/000132746]
Thatcher, B. J., Doherty, A. E., Orvisky, E., Martin, B. M., Henkin, R. I. Gustin from human parotid saliva is carbonic anhydrase VI. Biochem. Biophys. Res. Commun. 250: 635-641, 1998. [PubMed: 9784398] [Full Text: https://doi.org/10.1006/bbrc.1998.9356]
White, P. S., Jensen, S. J., Rajalingam, V., Stairs, D., Sulman, E. P., Maris, J. M., Biegel, J. A., Wooster, R., Brodeur, G. M. Physical mapping of the CA6, ENO1, and SLC2A5 (GLUT5) genes and reassignment of SLC2A5 to 1p36.2. Cytogenet. Cell Genet. 81: 60-64, 1998. [PubMed: 9691177] [Full Text: https://doi.org/10.1159/000014989]