Recombinant Human Cytochrome P450 2C9 (CYP2C9) Protein (His&Myc)

Name: Recombinant Human Cytochrome P450 2C9 (CYP2C9) Protein (His&Myc)
Brand: Beta LifeScience
SKU: BLC-04902P
Availability: InStock

Greater than 85% as determined by SDS-PAGE.

Collections: All products, High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Description	Recombinant Human Cytochrome P450 2C9 (CYP2C9) Protein (His&Myc) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 85% as determined by SDS-PAGE.
Uniprotkb	P11712
Target Symbol	CYP2C9
Synonyms	(R)-limonene 6-monooxygenase; (S)-limonene 6-monooxygenase; (S)-limonene 7-monooxygenase; CP2C9_HUMAN; CPC9; CYP2C; CYP2C10; CYP2C9; CYPIIC9; cytochrome P-450 S-mephenytoin 4-hydroxylase; Cytochrome P-450MP; Cytochrome P450 2C9; Cytochrome P450 MP-4; Cytochrome P450 MP-8; Cytochrome P450 PB-1; Cytochrome P450; family 2; subfamily C; polypeptide 9; Cytochrome p4502C9; flavoprotein-linked monooxygenase; MGC149605; MGC88320; microsomal monooxygenase; OTTHUMP00000020135; P450 MP; P450 PB 1; P450 PB1; P450IIC9; P450MP; S mephenytoin 4 hydroxylase; S-mephenytoin 4-hydroxylase; xenobiotic monooxygenase
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-10His&C-Myc
Target Protein Sequence	MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKGG
Expression Range	1-162aa
Protein Length	Full Length of Isoform 2
Mol. Weight	25.4 kDa
Research Area	Others
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target 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.
Subcellular Location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Protein Families	Cytochrome P450 family
Database References	HGNC: 2623 OMIM: 601130 KEGG: hsa:1559 STRING: 9606.ENSP00000260682 UniGene: PMID: 29746595 Lower expression of CYP2C9 was associated with better overall survival and disease-free survival in Hepatocellular carcinoma tumor samples. PMID: 29974848 A significant association between CYP2C93 and phenytoin-induced Stevens-Johnson syndrome was identified, especially in a Thai population (Meta-Analysis) PMID: 29274302 In this study, we showed that patients with VKORC1-1639GA and CYP2C91/1 alleles have lower sensitivity for warfarin than those with VKORC1-1639AA and CYP2C91/1 alleles. PMID: 29781049 Enzyme phenotyping with correlation analysis confirmed the predominant role of CYP2C9 in the biotransformation of siponimod and demonstrated the functional consequence of CYP2C9 genetic polymorphisms and fluconazole on siponimod metabolism. PMID: 29273968 Comparisons of pharmacokinetics of 25 substrates CYP2C9, CYP2C19, or CYP2D6 in healthy Chinese and European subjects (classified with same enzyme activity) suggest that, for most substrates, limited interethnic pharmacokinetic differences exist (according to the databases used in this study). (CYP2C19 = cytochrome P450 family 2 subfamily C member 19; CYP2D6 = cytochrome P450 family 2 subfamily D member 6) PMID: 29181698 genetic association studies in population in Scotland: data suggest, in type 2 diabetes treated with sulfonylureas, 2 SNPs in CYP2C9 (CYP2C92, R144C, rs1799853; CYP2C93, I359L, rs1057910) are associated with drug-induced hypoglycemia; an SNP in POR (POR28, A503V, rs1057868) is associated with better response to sulfonylureas. (CYP2C9 = cytochrome P450 family 2 subfamily C member 9; POR = cytochrome p450 oxidoreductase) PMID: 28656666 The plasma S-warfarin (Cp(S)) time courses following the genotype-based dosing algorithms simulated using the PPK estimates showed African Americans with CYP2C91/1 and any of the VKORC1 genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than in Asians and whites. PMID: 27503578 The final regression models for White and Black patients (Fig. 1) included age, weight, prosthetic valves, amiodarone use, CYP2C93, and VKORC1 3673 G>A genotypes as covariates, whereas possession of CYP2C92 and simvastatin use were retained in the final model for White, but not Black patients. PMID: 28263279 Our results further support a minor contribution of CYP2C9 genetic variability toward steady-state endoxifen concentrations. Integration of clinician and genetic variables into individualized tamoxifen dosing algorithms would marginally improve their accuracy and potentially enhance tamoxifen treatment outcomes. PMID: 28877533 CYP2C9 genetic variation was associated with long-term overall mortality and non-major bleeding in elderly patients treated with vitamin K antagonists. PMID: 28834238 Until the age of 19, weight has a far greater effect on Vitamin K antagonist dosing variation than VKORC1 and CYP2C9 polymorphisms. During the age of 20-40years, VKORC1 and CYP2C9 polymorphisms play a significant role. PMID: 28284562 CYP2C93 did show significant effect on warfarin dose requirement PMID: 27313202 Two SNPs in CYP2C9, rs2153628 and rs1799853 are associated with response to indomethacin for the treatment patent ductus arteriosus. PMID: 28609430 the carriership of individual C and T alleles in the case of CYP2C92 gene, as well as A and C for CYP2C93 is not a predictor of antiretroviral drug-induced liver injury. PMID: 29787666 Genetic polymorphisms in CYP2C9 cause significant interindividual variability in the metabolism of its substrates. This study estimated the coefficient of variation (CV) for the intrinsic hepatic clearance of tolbutamide by CYP2C9 for each CYP2C9 genotype using previously reported area under the blood concentration curve (AUC) and oral clearance (CLoral) values in a Monte Carlo simulation with a dispersion model. PMID: 28435143 These results suggest that genetic polymorphisms of CYP2C9 enzymes result in the production of varying levels of biologically active JWH-018 metabolites in some individuals, offering a mechanistic explanation for the diverse clinical toxicity often observed following JWH-018 abuse. PMID: 29522717 Studied the association of CYP2C92 (430C/T), 3 (1075A/C) and VKORC1 (-1639G/A) polymorphisms on warfarin dose requirements in patients post cardiac valve surgery. Found age and presence of CYP2C9 2 allele significantly affect the daily dosage of warfarin during initiation of warfarin therapy after cardiac valve replacement surgery. PMID: 29182754 CYP2C9 mutations had a significant impact on 2-propyl-4-pentenoic acid concentration PMID: 28315807 Angiotensin II receptor blockers exhibit different degrees of inhibition of the metabolism of arachidonic acid by recombinant CYP2C9, CYP2J2 and liver microsomes. PMID: 28374982 analysis of VKORC1 AA-CYP2C911 genotypes reveals dosing algorithms for vitamin K antagonists PMID: 28063245 To investigate whether the CYP2C92 and 3 variants modify benzodiazepine-related fall risk. CYP2C92 and 3 allele variants modify benzodiazepine-related fall risk. Those using benzodiazepines and having reduced CYP2C9 enzyme activity based on their genotype are at increased fall risk. PMID: 27889507 In an Indian population of children with epilepsy on phenytoin monotherapy, CYP2C91, 2 & 3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C93 allelic group showed significantly higher serum phenytoin levels compared to the wild variants. PMID: 27179628 The genotype distributions of the CYP2C93, CYP2D610, and CYP3A53 genetic polymorphisms were associated with the warfarin maintenance dose. PMID: 28872889 CYP2C92 and CYP2C93 genetic polymorphisms are associated with reduced S-warfarin oral clearance in healthy subjects PMID: 27878474 Case Report: time course of CYP2C9 deinduction appeared to be delayed compared to CYP3A after discontinuation of rifampicin therapy. PMID: 28157069 Data suggest that SNPs in CYP2C9 (3, I359L; 30, A477T) that reduce catalytic activity of CYP2C9 also alter interaction with antihypertensive drug losartan; I359L substitution located far from active site remarkably alters residue side chains near active site and access channel, whereas the T477 substitution illustrates hydrogen-bonding interaction with reoriented side chain of Q214. PMID: 28972767 SNP rs4918758 of CYP2C9 showed a suggestive association with decreased risk of coronary heart disease. PMID: 28687336 CYP2C931075AC genotype with combined alcohol and nevirapine usage indicated a risk for development of antiretroviral-associated hepatotoxicity PMID: 28370504 CYP2C9 polymorphisms showed no effect on PC doses. Similar findings were observed in the initiation phase of PC therapy. High complications rates under PC therapy were observed particularly at the beginning. PMID: 26984978 Genetic variants of CYP2C9/VKORC1 and age are significant determinants of the maintenance dose of warfarin in patients with atrial fibrillation/valve replacement. PMID: 27117036 CYP2C93 polymorphism genotype and allele frequency were not statistically different between the case and control Ankylosing Spondylitis groups (P>0.05). the efficacy of NSAID in treatment of AS and COX-2 gene -1290A/G and -1195G/A polymorphism were associated (all P<0.05), but it is not associated with CYP2C9 3 polymorphism (all P>0.05). PMID: 28403136 polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol PMID: 27826892 Possession of CYP2C92 and/or CYP2C93 allele variants is associated with lower time of international normalized ratio (INR) in the therapeutic range (TTR) values and warfarin dose variations in aortic valve replacement patients, the latter affected also by VKORC1 c.-1693G>A polymorphism PMID: 27511999 Three SNPs (CYP2C9 2, 3 and VKORC1 c.-1639G > A) were genotyped by electrochemical detection using a sandwich-type format that included a 3' short thiol capture probe and a 5' ferrocene-labeled signal probe. PMID: 28083852 Two subjects with CYP2C9PM genotype both showed markedly higher AUC, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypesTwo subjects with CYP2C9PM genotype both showed markedly higher AUC0-infinity, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes PMID: 27864660 CYP2C9 IVS8-109 T carriers showed significantly higher dose-corrected phenoytoin blood concentrations and this allele was found in a higher frequency in epileptic patients with supratherapeutic phenytoin levels. PMID: 26122019 Med25, a variable member of the Mediator complex, is a coactivator of ligand-activated ERalpha that interacts with ERalpha through its C-terminal LXXLL motif after BPA exposure, and is functionally involved in BPA-induced transcriptional regulation of CYP2C9 expression and enzyme activity. PMID: 27273787 Our results show that anticoagulated patients have a high risk of adverse events if they are carriers of 1 or more genetic polymorphisms in the VKORC1 (rs9923231) and CYP2C9 (rs1799853 and rs1057910) genes. PMID: 28033245 Review/Meta-analysis: CYP2C9 gene polymorphism was significantly associated with decreased warfarin maintenance dose requirements in pediatric patients. PMID: 27661060 The intrinsic clearance (Vmax/Km) values of all variants, with the exception of CYP2C92, CYP2C911, CYP2C923, CYP2C929, CYP2C934, CYP2C938, CYP2C944, CYP2C946 and CYP2C948, were significantly different from CYP2C91. CYP2C927, 40, 41, 47, 49, 51, 53, 54, 56 and N418T variant exhibited markedly larger values than CYP2C91. PMID: 27163851 Report roles for CYP3A4 and CYP2C9 in sequential two-step bioactivation of diclofenac to reactive p-benzoquinone imines. PMID: 27130197 CYP2C92 and 3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians. PMID: 27938396 Cyp2C9 genetic polymorphisms significantly affected the plasma concentrations of zafirlukast. PMID: 27377818 The high frequency of CYP2C93 and the absence of CYP2C92 in Jahais suggest that genetic drift may be occurring in this ethnic group. PMID: 26402341 VKORC1-CYP2C9 interaction can affect warfarin stable dosage. PMID: 25187307 Results show a statistically significant association between CYP2C93 polymorphism and phenytoin-related Stevens-Johnson syndrome. PMID: 26928377 P450 (Cytochrome) Oxidoreductase Gene (POR) Common Variant (POR28) Significantly Alters CYP2C9 Activity in Swedish, But Not in Korean Healthy Subjects PMID: 26669712 VKORC1S1639 GG and the wild type CYP2C911 genotypes are associated with the high-dose requirement for warfarin therapy. PMID: 24978953 Patients with variant CYP2C9 are at increased risk for cyclophosphamide-induced leukopenia but may have a better chance to respond to treatment. PMID: 26894931

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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