Cytochrome P450 2C9 (CYP2C9)

CYP2C10; P450IIC9; Cytochrome P450,Subfamily IIC(Mephenytoin 4-Hydroxylase)Polypeptide 9; S-mephenytoin 4-hydroxylase

SPN	J999
HGNC	2623
PubMed	23863877
UniProt	P11712
Wiki	CYP2C9

CYP2C9 encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin.The binding mode of warfarin suggests that CYP2C9 may undergo an allosteric mechanism during its function.

The newly discovered binding pocket also suggests that CYP2C9 may simultaneously accommodate multiple ligands during its biologic function, and provides a possible molecular basis for understanding complex drug-drug interactions.

Reference

"Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10."
Am. J. Hum. Genet. 42:26-37(1988) [PubMed] [Europe PMC] [Abstract]

"cDNA and amino acid sequences of two members of the human P450IIC gene subfamily."
Nucleic Acids Res. 15:10053-10054(1987) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 10."
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Nucleotide sequence of a human liver cytochrome P-450 related to the rat male specific form."
J. Biochem. 102:1075-1082(1987) [PubMed] [Europe PMC] [Abstract]

"Cloning and sequence determination of a complementary DNA related to human liver microsomal cytochrome P-450 S-mephenytoin 4-hydroxylase."
Biochemistry 26:1094-1099(1987) [PubMed] [Europe PMC] [Abstract]

"Characterization of cDNAs, mRNAs, and proteins related to human liver microsomal cytochrome P-450 (S)-mephenytoin 4'-hydroxylase."
Biochemistry 27:6929-6940(1988) [PubMed] [Europe PMC] [Abstract]

"Six-base deletion occurring in messages of human cytochrome P-450 in the CYP2C subfamily results in reduction of tolbutamide hydroxylase activity."
Biochem. Int. 27:1073-1081(1992) [PubMed] [Europe PMC] [Abstract]

"Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism. Purification and characterization of two similar forms involved in the reaction."
J. Biol. Chem. 261:909-921(1986) [PubMed] [Europe PMC] [Abstract]

"Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization."
J. Biochem. 104:912-916(1988) [PubMed] [Europe PMC] [Abstract]

"Separation of human liver microsomal tolbutamide hydroxylase and (S)-mephenytoin 4'-hydroxylase cytochrome P-450 enzymes."
Mol. Pharmacol. 40:69-79(1991) [PubMed] [Europe PMC] [Abstract]

"Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms."
Arch. Biochem. Biophys. 333:447-458(1996) [PubMed] [Europe PMC] [Abstract]

"Expression of modified cytochrome P450 2C10 (2C9) in Escherichia coli, purification, and reconstitution of catalytic activity."
Arch. Biochem. Biophys. 306:443-450(1993) [PubMed] [Europe PMC] [Abstract]

"Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes."
Drug Metab. Dispos. 30:602-607(2002) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of human cytochrome P450 2C9 with bound warfarin."
Nature 424:464-468(2003) [PubMed] [Europe PMC] [Abstract]

"Genetic analysis of the human cytochrome P450 CYP2C9 locus."
Pharmacogenetics 6:429-439(1996) [PubMed] [Europe PMC] [Abstract]

"Allelic and functional variability of cytochrome P4502C9."
Pharmacogenetics 7:51-58(1997) [PubMed] [Europe PMC] [Abstract]

"Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus."
Pharmacogenetics 10:85-89(2000) [PubMed] [Europe PMC] [Abstract]

"Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans."
Mol. Pharmacol. 60:382-387(2001) [PubMed] [Europe PMC] [Abstract]

"Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy."
JAMA 287:1690-1698(2002) [PubMed] [Europe PMC] [Abstract]

"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population."
Pharmacogenomics 5:895-931(2004) [PubMed] [Europe PMC] [Abstract]