caa a22 4500 397557639 CHVBK 20180308164807.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/oxfordjournals.jbchem.a021331 doi (NATIONALLICENCE)oxford-10.1093/oxfordjournals.jbchem.a021331 Sterol 14-Demethylase P450 (P45014DM*) Is One of the Most Ancient and Conserved P450 Species [Elektronische Daten] [Yuri Aoyama, Mitsuhide Noshiro, Osamu Gotoh, Susumu Imaoka, Yoshihiko Funae, Norio Kurosawa, Tadao Horiuchi, Yuzo Yoshida] To determine the orthology of sterol 14-demethylase (P45014DM), the only known P450 enzyme distributed widely in eukaryotes with a conserved metabolic role, the full-length amino acid sequences of rat and human P45014DMs were determined from the cloned cDNA sequences, and compared with those of the corresponding fungal proteins (CYP51). The amino acid identity value between given pairs of P45014DMs ranged from 93% (human/rat) to 39% (human or rat/Saccharomyces cerevisiae;). All the P45014DMs formed a single cluster in a phylogenetic tree constructed from representative P450 protein sequences currently available. The nearest neighbors to the P45014DM cluster in the phylogenetic tree were CYP7 (cholesterol 7α-hydroxylase) and CYP8 (prostacyclin synthase), and the divergence point of fungal and mammalian P45014DMs was clearly more recent than that of P45014DM and CYP7/CYP8. These lines of evidence show that fungal and mammalian P45014DMs are really orthologous. This is the first example of orthologous P450s occurring in distinct kingdoms. P45014DM may be an ancient P450 which arose before the divergence of major eukaryotic branches and has been conserved throughout evolution. The amino acid identity value (93%) between human and rat P45014DMs was comparable to those observed for some housekeeping enzymes. In addition, a processed pseudogene of P45014DM was found in a rat genomic DNA library, suggesting the expression of P45014DM in germ line cells. These facts suggest that P45014DM may be a housekeeping enzyme essential for the viability of mammals. © by the Journal of Biochemistry Regular Papers nationallicence molecular evolution nationallicence orthologous gene nationallicence P450 nationallicence processed pseudogene nationallicence sterol 14- demethy lase nationallicence Aoyama Yuri Department of Bioengineering, Faculty of Engineering, Soka University Hachioji, Tokyo 192 aut Noshiro Mitsuhide Department of Biochemistry, Hiroshima University School of Dentistry Hiroshima 734 aut Gotoh Osamu Department of Biochemistry, Saitama Cancer Center Research Institute Saitama 362 aut Imaoka Susumu Department of Chemistry, Osaka City University School of Medicine Osaka 545 aut Funae Yoshihiko Department of Chemistry, Osaka City University School of Medicine Osaka 545 aut Kurosawa Norio Department of Bioengineering, Faculty of Engineering, Soka University Hachioji, Tokyo 192 aut Horiuchi Tadao Department of Bioengineering, Faculty of Engineering, Soka University Hachioji, Tokyo 192 aut Yoshida Yuzo School of Pharmaceutical Sciences, Mukogawa Women's University 11-68 Koshien-Kyubancho, Nishinomiya 663 aut The Journal of Biochemistry Oxford University Press 119/5(1996-05), 926-933 0021-924X 119:5<926 1996 119 jbchem https://doi.org/10.1093/oxfordjournals.jbchem.a021331 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/oxfordjournals.jbchem.a021331 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Aoyama Yuri Department of Bioengineering, Faculty of Engineering, Soka University Hachioji, Tokyo 192 aut NATIONALLICENCE 700 1- Noshiro Mitsuhide Department of Biochemistry, Hiroshima University School of Dentistry Hiroshima 734 aut NATIONALLICENCE 700 1- Gotoh Osamu Department of Biochemistry, Saitama Cancer Center Research Institute Saitama 362 aut NATIONALLICENCE 700 1- Imaoka Susumu Department of Chemistry, Osaka City University School of Medicine Osaka 545 aut NATIONALLICENCE 700 1- Funae Yoshihiko Department of Chemistry, Osaka City University School of Medicine Osaka 545 aut NATIONALLICENCE 700 1- Kurosawa Norio Department of Bioengineering, Faculty of Engineering, Soka University Hachioji, Tokyo 192 aut NATIONALLICENCE 700 1- Horiuchi Tadao Department of Bioengineering, Faculty of Engineering, Soka University Hachioji, Tokyo 192 aut NATIONALLICENCE 700 1- Yoshida Yuzo School of Pharmaceutical Sciences, Mukogawa Women's University 11-68 Koshien-Kyubancho, Nishinomiya 663 aut NATIONALLICENCE 773 0- The Journal of Biochemistry Oxford University Press 119/5(1996-05), 926-933 0021-924X 119:5<926 1996 119 jbchem Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford