Elsevier

Genomics

Volume 33, Issue 3, 1 May 1996, Pages 480-487
Genomics

Regular Article
HumanMN/CA9Gene, a Novel Member of the Carbonic Anhydrase Family: Structure and Exon to Protein Domain Relationships

https://doi.org/10.1006/geno.1996.0223Get rights and content

Abstract

We have isolated, sequenced, and characterized a humanMN/CA9gene. 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 ofMN/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 theMN/CA9gene. Sequence of the proximate 5′ end of the flanking region shows extensive homology to the long terminal repeats of HERV-K endogenous retroviruses. The putativeMN/CA9promoter 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.

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