Human MN/CA9 gene, a novel member of the carbonic anhydrase family: Structure and exon to protein domain relationships

René Opavský, Silvia Pastoreková, Vladimír Zelník, Adriana Gibadulinová, Eric J. Stanbridge, Jan Závada, Richard Kettmann, Jaromír Pastorek

Research output: Contribution to journalArticlepeer-review

307 Scopus citations

Abstract

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'-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 α-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 MTV/CA9 gene. Sequence of the proximate 5' end of the flanking region 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 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.

Original languageEnglish (US)
Pages (from-to)480-487
Number of pages8
JournalGenomics
Volume33
Issue number3
DOIs
StatePublished - May 1 1996

ASJC Scopus subject areas

  • Genetics

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