cDna cloning and expression of CYP4F12, a novel human cytochrome P450.
cDNA of a novel human cytochrome P450 was cloned from human liver by reverse transcription-polymerase chain reaction and designated CYP4F12. The open reading frame coded for 524 amino acids, and the sequence could be aligned with 78-83% amino acid identity to the four human CYP4F enzymes (CYP4F2, CYP4F3, CYP4F8 and CYP4F11). Northern blot analysis suggested three major transcripts of CYP4F12, which were detected in liver, kidney, colon, small intestine and heart. The CYP4F12 gene contained 13 exons and was located at chromosome 19p13.1. CYP4F12, expressed in yeast, oxidized arachidonic acid to 18-hydroxyarachidonic acid, and the omega-side chain of two stable prostaglandin (PG) H(2) analogs (11,9-epoxymethano-PGH(2) and 9,11-diazo-15-deoxy-PGH(2)). CYP4F12 oxidized the omega-side chain of leukotriene B(4), PGE(2), PGF(2 alpha), PGH(2), and 9,11-epoxymethano-PGH(2) poorly. Several CYP4F enzymes are important omega 1- and omega 2-hydroxylases of eicosanoids. The physiological function of CYP4F12 merits further investigation.
Bylund
J
J
Department of Pharmaceutical Biosciences, BMC, SE-751 24 Uppsala, Sweden. Johan.Bylund@farmbio.uu.se
Bylund
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Oliw
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D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007438:Introns; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D017931:DNA Primers; D018076:DNA, Complementary; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C422180:CYP4F12 protein, human