Human MN/CA9 gene, a novel member of the carbonic anhydrase family: Structure and exon to protein domain relationships
- Institute of Virology, Bratislava (Slovakia); and others
We have isolated, sequenced, and characterized a human MN/CA9 gene. This gene is a novel member of the carbonic anhydrase (CA) family, which codes for widely distributed catalysts of the reversible conversion of carbon dioxide to carbonic acid. So far, MN/CA IX is the only tumor-associated CA isoenzyme. The entire genomic sequence of MN/CA9, including the 5{prime}-flanking region, encompasses 10.9 kb. The coding sequence is divided into 11 exons, whose organization and relationships to predicted protein domains suggest that the gene arose by exon shuffling. Exon 1 encodes a signal peptide and a proteoglycan-related region. Exons 2-8 code for a CA domain with a highly conserved active site. The exon/intron pattern of the CA coding region is similar but not identical to other described animal kingdom {alpha}-CA genes. Exons 10 and 11 encode a transmembrane anchor and an intracytoplasmic tail, respectively. We have also determined the transcription initiation and termination sites by RNase protection assay and analyzed the 3.5-kb region upstream of the MN/CA9 gene. Sequence of the proximate 5{prime} end of the flanking regions shows extensive homology to the long terminal repeats of HERV-K endogenous retroviruses. The putative MN/CA9 promoter immediately preceding the transcription start site does not possess a TATA box, but contains consensus sequences for the AP1, AP2, p53, and Inr transcription start site does not possess a TATA box, but contains consensus sequences for the AP1, AP2, p53, and Inr transcription factors. This study will allow further investigations of the molecular events regulating expression of MN/CA IX as well as elucidation of its biological function. 36 refs., 6 figs., 1 tab.
- OSTI ID:
- 466664
- Journal Information:
- Genomics, Journal Name: Genomics Journal Issue: 3 Vol. 33; ISSN 0888-7543; ISSN GNMCEP
- Country of Publication:
- United States
- Language:
- English
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