Characterization of CA XV, a new GPI-anchored form of carbonic anhydrase

Mika Hilvo (Corresponding Author), M. Tolvanen, A. Clark, B. Shen, G.N. Shah, A. Waheed, P. Halmi, M. Hänninen, J.M. Hämäläinen, M. Vihinen, W.S. Sly, S. Parkkila

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145 Citations (Scopus)

Abstract

The main function of CAs (carbonic anhydrases) is to participate in the regulation of acid–base balance. Although 12 active isoenzymes of this family had already been described, analyses of genomic databases suggested that there still exists another isoenzyme, CA XV. Sequence analyses were performed to identify those species that are likely to have an active form of this enzyme. Eight species had genomic sequences encoding CA XV, in which all the amino acid residues critical for CA activity are present. However, based on the sequence data, it was apparent that CA XV has become a non-processed pseudogene in humans and chimpanzees. RT-PCR (reverse transcriptase PCR) confirmed that humans do not express CA XV. In contrast, RT-PCR and in situ hybridization performed in mice showed positive expression in the kidney, brain and testis. A prediction of the mouse CA XV structure was performed. Phylogenetic analysis showed that mouse CA XV is related to CA IV. Therefore both of these enzymes were expressed in COS-7 cells and studied in parallel experiments. The results showed that CA XV shares several properties with CA IV, i.e. it is a glycosylated glycosylphosphatidylinositol-anchored membrane protein, and it binds CA inhibitor. The catalytic activity of CA XV is low, and the correct formation of disulphide bridges is important for the activity. Both specific and non-specific chaperones increase the production of active enzyme. The results suggest that CA XV is the first member of the α-CA gene family that is expressed in several species, but not in humans and chimpanzees.
Original languageEnglish
Pages (from-to)83-92
JournalBiochemical Journal
Volume392
Issue number1
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

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