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Human MN/CA9 gene, a novel member of the carbonic anhydrase family: Structure and exon to protein domain relationships
Author(s): Opavsky R, Pastorekova S, Zelnik V, Gibadulinova A, Stanbridge EJ, Zavada J, Kettmann R, Pastorek J
Source: GENOMICS    Volume: 33    Issue: 3    Pages: 480-487    Published: MAY 1 1996  
Times Cited: 173     References: 36     
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 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 hn 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. (C) 1996 Academic Press, Inc.
Document Type: Article
Language: English
Addresses:
1. SLOVAK ACAD SCI, INST VIROL, BRATISLAVA 84246, SLOVAKIA
2. UNIV CALIF IRVINE, COLL MED, DEPT MICROBIOL & MOLEC GENET, IRVINE, CA 92717 USA
3. FAC AGR SCI, DEPT BIOL MOLEC, GEMBLOUX, BELGIUM
4. ACAD SCI CZECH REPUBL, INST MOLEC GENET, PRAGUE, CZECH REPUBLIC
Publisher: ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495
Subject Category: Biotechnology & Applied Microbiology; Genetics & Heredity
IDS Number: UK511
ISSN: 0888-7543
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