Nucleotide Structure and Characterization of the Murine Gene Encoding Anticoagulant Protein C

Louise R. Jalbert; Elliot D. Rosen; Ann Lissens; Peter Carmeliet; Désiré Collen; Francis J. Castellino

doi:10.1055/s-0037-1615006

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(02): 310-316
DOI: 10.1055/s-0037-1615006

Scientific and Standardization Committee Communication

Schattauer GmbH

Nucleotide Structure and Characterization of the Murine Gene Encoding Anticoagulant Protein C

Authors

Louise R. Jalbert

¹Department of Chemistry and Biochemistry and the Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA
Elliot D. Rosen

¹Department of Chemistry and Biochemistry and the Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA
Ann Lissens

²Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium
Peter Carmeliet

²Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium
Désiré Collen

²Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Belgium
Francis J. Castellino

¹Department of Chemistry and Biochemistry and the Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana, USA

Abstract

Summary

The 15,160 bp murine gene encoding anticoagulation protein C (PC) was cloned and sequenced, including 414 bp upstream of exon 1 and 80 bp downstream of the translation stop codon. Nine exons and eight introns were identified. The first exon was untranslated and contained the major transcriptional start site, the surrounding nucleotide sequence of which matched reasonably well with the consensus eukaryotic Cap element sequence. The translational initiator methio-nine residue was located in exon 2. The other introns were positioned as splices between the major domain units of the protein. The 5’ untranslated region contained two possible CCAAT sequences and GC boxes, but no TATA box was obvious within the optimal range of distances from the transcription start site. The 3’-flanking nucleotides included a probable polyadenylation site (ATTAAA), beginning 80 nucleotides downstream of the translation stop codon, and a downstream consensus sequence (AGTGTTTC) required for the efficient formation of a 3’ terminus of mRNA. Several high probability transcription factor recognition sequences, including proteins that are enriched in, or specific to, the liver, such as C/EBP, C/EBP, HNF1, and HNF3, have been located in the 5’ region of the gene. These results indicate that all elements are present for liver-based transcription of the gene for murine PC.

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References

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