GENOMIC ORGANIZATION AND LOCALIZATION OF GENE FOR HUMAN CARBONIC ANHYDRASE-IV TO CHROMOSOME-17Q

Carbonic anhydrase IV (CA IV) is a glycosylphosphatidylinositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and on the luminal surface of proximal renal tubules. It is of interest for its functional importance in CO2 and HCO3/— transport, its ancient evolutionary status among CA isozymes, and its possible role in inherited renal abnormalities of HCO3/— transport. To determine the localization of the CA IV gene and define its genomic structure, we isolated and characterized a full-length genomic clone. The 9.5-kb gene contains eight exons and seven introns. The first exon (exon 1a) encodes the signal sequence. Exons 1b through 7 encode the remaining coding sequence. Exon 7 encodes the C terminus of the enzyme precursor, the C terminus of the mature protein and also contains the 120-bp sequence corresponding to the 3' untranslated region of the cDNA. The positions of introns 3, 4, 5, and 6 are identical with the corresponding positions of introns in the genes for the soluble CA isozymes (CA I, II, III, and VII). However, intron 1a is not found in these genes, and the positions of introns 1b and 2 in CA IV differ from the positions of the corresponding introns in genes for the soluble isozymes. The 5' upstream region of the gene (-500 to -1) is GC rich and contains 30 CpG dinucleotides. A TATA box sequence and a potential Sp1 binding site are identified upstream of the first exon. By using PCR on DNA from human/rodent somatic cell hybrids, the CA IV gene was assigned to chromosome 17. In situ hybridization confirmed this chromosome assignment and localized the gene to 17q23. CA IV is the first CA assigned to chromosome 17. © 1993 Academic Press. All rights reserved.