ID:CP2CJ_HUMAN DESCRIPTION: RecName: Full=Cytochrome P450 2C19; EC=1.14.13.-; AltName: Full=(R)-limonene 6-monooxygenase; EC=1.14.13.80; AltName: Full=(S)-limonene 6-monooxygenase; EC=1.14.13.48; AltName: Full=(S)-limonene 7-monooxygenase; EC=1.14.13.49; AltName: Full=CYPIIC17; AltName: Full=CYPIIC19; AltName: Full=Cytochrome P450-11A; AltName: Full=Cytochrome P450-254C; AltName: Full=Mephenytoin 4-hydroxylase; FUNCTION: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. CATALYTIC ACTIVITY: (+)-(R)-limonene + NADPH + O(2) = (+)-trans- carveol + NADP(+) + H(2)O. CATALYTIC ACTIVITY: (-)-(S)-limonene + NADPH + O(2) = (-)-trans- carveol + NADP(+) + H(2)O. CATALYTIC ACTIVITY: (-)-(S)-limonene + NADPH + O(2) = (-)-perillyl alcohol + NADP(+) + H(2)O. COFACTOR: Heme group (By similarity). SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. INDUCTION: P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. POLYMORPHISM: Genetic variation in CYP2C19 is responsible for poor drug metabolism [MIM:609535]. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM). The PM phenotype is inherited in an autosomal recessive manner, with the EM phenotype comprising both homozygous dominant and heteroyzgote genotypes. There are marked interracial differences in the frequency of this polymorphism. Poor metabolizers represent 2-5% of Caucasians, 13-23% of Asian populations, and as many as 38-79% of individuals of some of the islands of Polynesia and Micronesia. Different alleles of CYP2C19 are known: CYP2C19*1A CYP2C19*1B, CYP2C19*1C, CYP2C19*2A (CYP2C19m1 or CYP2C19m1A), CYP2C19*2B (CYP2C19m1B), CYP2C19*2C (CYP2C19*21), CYP2C19*3A (CYP2C19m2), CYP2C19*3B (CYP2C19*20), CYP2C19*4 (CYP2C19m3), CYP2C19*5A (CYP2C19m4), CYP2C19*5B, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9, CYP2C19*10, CYP2C19*11 CYP2C19*12, CYP2C19*13, CYP2C19*14 CYP2C19*15, CYP2C19*16, CYP2C19*18, CYP2C19*19. Defective CYP2C19*2 and CYP2C19*3 alleles are characterized by a splice mutation and a stop codon, respectively, and account for most of the PM alleles. The sequence shown is that of allele CYP2C19*1B. SIMILARITY: Belongs to the cytochrome P450 family. CAUTION: P450-254C was originally listed as a separate gene (CYP2C17). Resequencing demonstrated that it is not a separate gene, but a chimera. The 5'-portion corresponds to a partial 2C18 clone, and the 3'-portion corresponds to a partial 2C19 clone. WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; Note=CYP2C19 alleles; URL="http://www.cypalleles.ki.se/cyp2c19.htm"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cyp2c19/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P33261
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004497 monooxygenase activity GO:0005506 iron ion binding GO:0008392 arachidonic acid epoxygenase activity GO:0008395 steroid hydroxylase activity GO:0016491 oxidoreductase activity GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0019825 oxygen binding GO:0019899 enzyme binding GO:0020037 heme binding GO:0046872 metal ion binding
Biological Process: GO:0006805 xenobiotic metabolic process GO:0008202 steroid metabolic process GO:0016098 monoterpenoid metabolic process GO:0017144 drug metabolic process GO:0019373 epoxygenase P450 pathway GO:0042738 exogenous drug catabolic process GO:0046483 heterocycle metabolic process GO:0055114 oxidation-reduction process GO:0097267 omega-hydroxylase P450 pathway
M61858 - Human cytochrome P4502C17 (CYP2C17) mRNA, clone 254c. L07093 - Human cytochrome P4502C18 and P4502C19 splice variant or composite clone mRNA. X65962 - H.sapiens mRNA for cytochrome P-450. M61854 - Human cytochrome P4502C19 (CYP2C19) mRNA, clone 11a. AB463557 - Synthetic construct DNA, clone: pF1KB7196, Homo sapiens CYP2C19 gene for cytochrome P450, family 2, subfamily C, polypeptide 19, without stop codon, in Flexi system. BC111846 - Synthetic construct Homo sapiens clone IMAGE:40080839, MGC:133393 CYP2C19 protein (CYP2C19) mRNA, encodes complete protein. E10866 - cDNA encoding human cytochrome P450. JD337675 - Sequence 318699 from Patent EP1572962. JD463216 - Sequence 444240 from Patent EP1572962. JD413788 - Sequence 394812 from Patent EP1572962. JD115397 - Sequence 96421 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCyc Knowledge Library PWY-6398 - melatonin degradation I PWY-6402 - superpathway of melatonin degradation PWY66-401 - superpathway of L-tryptophan utilization
Reactome (by CSHL, EBI, and GO)
Protein P33261 (Reactome details) participates in the following event(s):
R-HSA-2161814 Arachidonic acid is hydroxylated to 19-HETE by CYP(2) R-HSA-2161899 Arachidonic acid is epoxidated to 8,9/11,12/14,15-EET by CYP(5) R-HSA-211929 CYP2C19 5-hydroxylates omeprazole R-HSA-76354 Vinyl chloride is oxidized to 2-Chloroethylene oxide R-HSA-76397 Acetaminophen oxidised to N-acetylbenzoquinoneimine (NAPQI) R-HSA-76416 Benzene is hydroxylated to phenol R-HSA-76434 Dehalogenation of carbon tetrachloride to form a free radical R-HSA-76475 Dehalogenation of the poly-halogenated hydrocarbon Halothane to form the acylhalide Trifluoroacetlychloride and hydrogen bromide R-HSA-143468 MEOS oxidizes ethanol to acetaldehyde R-HSA-211910 CYP2C8 inactivates paclitaxel by 6alpha-hydroxylation R-HSA-76456 O-atom dealkylation of dextromethorphan R-HSA-211966 CYP2D6 4-hydroxylates debrisoquine R-HSA-211988 CYP2C9 inactivates tolbutamide by 4methyl-hydroxylation R-HSA-211991 Cyclophosphamide is 4-hydroxylated by CYP2B6 R-HSA-212005 CYP2F1 dehydrogenates 3-methylindole R-HSA-212004 CYP2C18 initiates bioactivation of phenytoin by 4-hydroxylation R-HSA-211881 Coumarin is 7-hydroxylated by CYP2A13 R-HSA-2142816 Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) R-HSA-2142670 Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET) R-HSA-211981 Xenobiotics R-HSA-211999 CYP2E1 reactions R-HSA-2142753 Arachidonic acid metabolism R-HSA-211897 Cytochrome P450 - arranged by substrate type R-HSA-8978868 Fatty acid metabolism R-HSA-211945 Phase I - Functionalization of compounds R-HSA-556833 Metabolism of lipids R-HSA-211859 Biological oxidations R-HSA-1430728 Metabolism
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
