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

Genomics. 1996 May 1;33(3):480-7. doi: 10.1006/geno.1996.0223.


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 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' 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Blotting, Southern
  • Carbonic Anhydrases / biosynthesis*
  • Carbonic Anhydrases / genetics*
  • Cloning, Molecular
  • Conserved Sequence
  • Exons*
  • Genomic Library
  • HeLa Cells
  • Humans
  • Introns
  • Isoenzymes / biosynthesis*
  • Isoenzymes / genetics*
  • Molecular Sequence Data
  • Multigene Family*
  • Promoter Regions, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Sequence Homology, Amino Acid
  • Transcription, Genetic


  • Isoenzymes
  • Carbonic Anhydrases

Associated data

  • GENBANK/X66839
  • GENBANK/Z54349