Isolation and sequence analysis of three cloned cDNAs for rabbit liver proteins that are related to rabbit cytochrome P-450 (form 2), the major phenobarbital-inducible form

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Abstract
Three cDNA clones of 1400-1800 base pairs that hybridize selectively to RNA from animals treated with phenobarbital were isolated from rabbit liver. The nucleotide sequences of the cDNA were determined. In the protein coding region the nucleotide sequences of 2 of the cDNA are 88% homologous and the 3rd cDNA is .apprx. 72-74% homologous to the other 2. All 3 are 55-60% homologous to rat liver cytochrome P-450b cDNA. The amino acid sequences derived from the cDNA sequences are .apprx. 50% homologous to those of rat liver cytochrome P-450b and rabbit liver cytochrome P-450 (form 2). The degree of homology differs substantially in different regions of the protein. The hydrophobicity profiles of these 5 mammalian cytochromes P-450 are very similar and contain up to 8 regions of hydrophobicity that are long enough to span a membrane. These 3 cDNA code for rabbit liver cytochromes P-450 which are different from any rabbit liver cytochrome P-450 for which amino acid sequence information is published. These cDNA are part of a family of genes that are related to rabbit liver cytochrome P-450 (form 2) and rat liver cytochrome P-450b which are the major phenobarbital-inducible forms. The divergence of amino acid sequence between the rat and rabbit forms and the divergence of nucleotide sequences of silent sites in the 2 most closely related rabbit forms suggest that cytochromes P-450 have a relatively high rate of amino acid divergence compared to many other vertebrate proteins.