Biochemical and Biophysical Research Communications
Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors
Section snippets
Materials and methods
Gene discovery. BLAST [13] homology search with standard parameters against the GenBank and Patent databases deposited under SRS (Sequence Retrieval System, Lion Bioscience) with the known PH-αI sequence as the query identified numerous candidate sequences. These sequences underwent further manipulations including manual curation, clustering with ESTs, etc. before one of them was identified as putative novel prolyl 4-hydroxylase. Further annotations, including assignment of chromosome
Cloning and sequence analysis of PH-4
To find novel HIF-prolyl 4-hydroxylases, the PH-αI amino acid sequence was submitted as query sequence in a BLAST homology search [13]. Related overlapping EST sequences were identified and clustered to an open reading frame of 1506 bp length, which encoded a novel candidate prolyl 4-hydroxylase with a length of 502 amino acids and a relative molecular weight of 56.7 kDa, which was termed PH-4. No further putative start ATG was found upstream during analysis of the genomic sequence. The
Acknowledgements
The authors thank Stephanie Ernesti, Karin Krauss, Jaquelin Olivera, and Manuel Rauter for the excellent technical assistance and Dr. Georg Breier, Max-Planck-Institute, Bad Nauheim, for providing HIF-1α cDNA.
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