Cytochrome P450 2C9

Function

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2. Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol. Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.

Classification

Family (Pfam)

PF00067 p450

InterPro

Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf, Cytochrome_P450_fam2

Functional cluster

Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 15

• 1OG2 X-ray 2.60A
• 1OG5 X-ray 2.55A
• 1R9O X-ray 2.00A
• 4NZ2 X-ray 2.45A
• 5A5I X-ray 2.00A
• 5A5J X-ray 2.90A
• 5K7K X-ray 2.30A
• 5W0C X-ray 2.00A
• 5X23 X-ray 2.00A
• 5X24 X-ray 2.48A
• 5XXI X-ray 2.30A
• 6VLT X-ray 3.12A
• … and 3 more

A predicted model is available from AlphaFold.

Gene Ontology · 31

• GO:0005737 cytoplasm
• GO:0005789 endoplasmic reticulum membrane
• GO:0043231 intracellular membrane-bounded organelle
• GO:0052741 (R)-limonene 6-monooxygenase activity
• GO:0018675 (S)-limonene 6-monooxygenase activity
• GO:0018676 (S)-limonene 7-monooxygenase activity
• GO:0008405 arachidonate 11,12-epoxygenase activity
• GO:0008404 arachidonate 14,15-epoxygenase activity
• GO:0008392 arachidonate epoxygenase activity
• GO:0034875 caffeine oxidase activity
• GO:0101021 estrogen 2-hydroxylase activity
• GO:0020037 heme binding
• GO:0005506 iron ion binding
• GO:0004497 monooxygenase activity
• GO:0016491 oxidoreductase activity
• GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
• GO:0008395 steroid hydroxylase activity
• GO:0008203 cholesterol metabolic process
• GO:0019373 epoxygenase P450 pathway
• GO:0008210 estrogen metabolic process
• GO:0046456 icosanoid biosynthetic process
• GO:0042759 long-chain fatty acid biosynthetic process
• GO:0032787 monocarboxylic acid metabolic process
• GO:0016098 monoterpenoid metabolic process
• GO:0097267 omega-hydroxylase P450 pathway
• GO:0090346 organofluorine metabolic process
• GO:0070989 oxidative demethylation
• GO:0008202 steroid metabolic process
• GO:0019627 urea metabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0006805 xenobiotic metabolic process

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Cytochrome P450 2C19 0.99
• Cytochrome P450 2C29 0.99
• Cytochrome P450 2C6 0.99
• Cytochrome P450 2C39 0.98
• Cytochrome P450 2C38 0.98
• Cytochrome P450 2C18 0.98
• Cytochrome P450 2C14 0.98
• Cytochrome P450 2C11 0.98
• Cytochrome P450 2C27 0.98
• Cytochrome P450 2C26 0.98
• Cytochrome P450 2C2 0.98
• Cytochrome P450 2C25 0.98

Co-cited proteins · studied together in the literature

• Cytochrome P450 2C8 6 shared papers
• Cytochrome P450 3A4 6 shared papers
• Cytochrome P450 2C19 3 shared papers
• Cytochrome P450 1A2 5 shared papers
• Cytochrome P450 2D6 3 shared papers
• Cytochrome P450 2C23 1 shared papers
• Cytochrome P450 2C11 1 shared papers
• Cytochrome P450 2B6 2 shared papers
• Cytochrome P450 1A1 3 shared papers
• Cytochrome P450 2J2 1 shared papers
• Cytochrome P450 3A5 2 shared papers
• Cytochrome P450 3A7 1 shared papers

Literature · 34 cited papers

• Identification and Functional Assessment of a New CYP2C9 Allelic Variant CYP2C9*59. Drug Metab. Dispos. · 2015
• Warfarin dose requirements in a patient with the CYP2C9*14 allele. Pharmacogenomics · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Implication of novel CYP2C9*57 (p.Asn204His) variant in coumarin hypersensitivity. Thromb. Res. · 2013
• Cholesterol 25-hydroxylation activity of CYP3A. J. Lipid Res. · 2011
• Characterization of a novel CYP2C9 gene mutation and structural bioinformatic protein analysis in a warfarin hypersensitive patient. Pharmacogenet. Genomics · 2011
• Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. · 2010
• Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily. Biochem. Biophys. Res. Commun. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics · 2004
• The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• … and 22 more in the literature graph