TY - JOUR
T1 - Human MN/CA9 gene, a novel member of the carbonic anhydrase family
T2 - Structure and exon to protein domain relationships
AU - Opavský, René
AU - Pastoreková, Silvia
AU - Zelník, Vladimír
AU - Gibadulinová, Adriana
AU - Stanbridge, Eric J.
AU - Závada, Jan
AU - Kettmann, Richard
AU - Pastorek, Jaromír
N1 - Funding Information:
We are very grateful to Dr. David Hewett-Emmett for the computer analysis of intron distribution, for critical comments on the manu- script, and for communicating results prior to publication. We also thank J. BesedicÏova and K. TaraÂbkova for technical assistance and N. Dokoupil for photodocumentation. This work was supported by Ciba Corning Diagnostic Corp., USA, and in part by research Grant 2/1246/94 from the Slovak Grant Agency, Grant 301/93/0308 from the Czech Grant Agency, and a grant from the Belgian SSTC (PAI 15). R.K. is a Research Director from the Belgian FNRS.
PY - 1996/5/1
Y1 - 1996/5/1
N2 - 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.
AB - 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.
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U2 - 10.1006/geno.1996.0223
DO - 10.1006/geno.1996.0223
M3 - Article
C2 - 8661007
AN - SCOPUS:0029975564
VL - 33
SP - 480
EP - 487
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 3
ER -