The P450 Superfamily: Update on New Sequences, Gene Mapping, and Recommended Nomenclature

Abstract

We provide here a list of 154 P450 genes and seven putative pseudogenes that have been characterized as of October 20, 1990. These genes have been described in a total of 23 eukaryotes (including nine mammalian and one plant species) and six prokaryotes. Of 27 gene families so far described, 10 exist in all mammals. These 10 families comprise 18 subfamilies, of which 16 and 14 have been mapped in the human and mouse genomes, respectively; to date, each subfamily appears to represent a cluster of tightly linked genes. We propose here a modest revision of the initially proposed (Nebert et al., DNA 6, 1-11, 1987) and updated (Nebert et al., DNA 8, 1-13, 1989) nomenclature system based on evolution of the superfamily. For the gene we recommend that the italicized root symbol CYP for human (Cyp for mouse), representing cytochrome P450, be followed by an Arabic number denoting the family, a letter designating the subfamily (when two or more exist), and an Arabic numeral representing the individual gene within the subfamily. A hyphen should precede the final number in mouse genes. We suggest that the human nomenclature system be used for other species. This system is consistent with our earlier proposed nomenclature for P450 of all eukaryotes and prokaryotes, except that we are discouraging the future use of cumbersome Roman numerals.

Genetics of Congenital Adrenal Hyperplasia

“…3 CYP21A2 (previously called P450c21B, CYP21B or CYP21) encodes 21-hydroxylase, a cytochrome P450 type II enzyme of 495 amino acids. 7,8 The CYP21A2 gene and its duplicated pseudogene (CYP21A1P), a nonfunctional by-product of the functional gene that was formed from selective pressure during evolution, are located 30kb apart in the human leukocyte antigen (HLA) class III region in the major histocompatibility (MHC) locus on the short arm of chromosome 6 (band 6p21.3), and share approximately 98% sequence homology (Figure 1 and 2). 9 The CYP21A1P gene is inactive due to the presence of approximately 11 deleterious mutations in its coding region (Figure 2).…”

Sterol 14α-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms

“…The enzyme catalyzing this reaction was first purified from yeast in 1984 (Sacharomyces cerevisiea [8]), and following determination of its primary structure [9] the cytochrome P450 sterol 14α-demethylases were placed into the CYP51 family, a number reserved for fungal sequences [10]. In 1986 the orthologous mammalian P450 was purified from rat liver microsomes [11], in 1996 the first sterol 14α-demethylase was found in plants (Sorghum bicolor [12]), and in 2000 the orthologous nature of a CYP51-like gene [13] from Mycobacterium tuberculosis to eukaryotic CYP51s was confirmed [14].…”

CYP2E1 and oxidative liver injury by alcohol

“…Many different enzymes belong to this P450 family; P450s are present in virtually all living organisms. A systematic nomenclature system was developed for the P450 family which is based on the sequence identity of the different P450 enzymes (2,3). The enzymes are named CYP for cytochrome P450, followed by an Arabic number denoting the family (more than 40% identity on the amino acid sequence level), a letter designating the subfamily (more than 55% identity) and finally an Arabic numeral representing the individual gene in the subfamily.…”