Recombinant Human Cytochrome P450 3A5 (CYP3A5) Protein (His)

Name: Recombinant Human Cytochrome P450 3A5 (CYP3A5) Protein (His)
Brand: Beta LifeScience
SKU: BLC-06809P
Availability: InStock

Greater than 85% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human Cytochrome P450 3A5 (CYP3A5) Protein (His) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 85% as determined by SDS-PAGE.
Uniprotkb	P20815
Target Symbol	CYP3A5
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-6His
Target Protein Sequence	MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNVLSYRQGLWKFDTECYKKYGKMWGTYEGQLPVLAITDPDVIRTVLVKECYSVFTNRRSLGPVGFMKSAISLAEDEEWKRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVRNLRREAEKGKPVTLKDIFGAYSMDVITGTSFGVNIDSLNNPQDPFVESTKKFLKFGFLDPLFLSIILFPFLTPVFEALNVSLFPKDTINFLSKSVNRMKKSRLNDKQKHRLDFLQLMIDSQNSKETESHKALSDLELAAQSIIFIFAGYETTSSVLSFTLYELATHPDVQQKLQKEIDAVLPNKAPPTYDAVVQMEYLDMVVNETLRLFPVAIRLERTCKKDVEINGVFIPKGSMVVIPTYALHHDPKYWTEPEEFRPERFSKKKDSIDPYIYTPFGTGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLDTQGLLQPEKPIVLKVDSRDGTLSGE
Expression Range	1-502aa
Protein Length	Full Length
Mol. Weight	61.2 kDa
Research Area	Cardiovascular
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.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
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 steroid hormones and vitamins. 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 hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2. Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione. Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance. Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine.
Subcellular Location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Protein Families	Cytochrome P450 family
Database References	HGNC: 2638 OMIM: 605325 KEGG: hsa:1577 STRING: 9606.ENSP00000222982 UniGene: PMID: 28094348 (1S,2S)-2-hydroxylation also correlated to T-5 N-oxidation, a CYP3A5-specific activity. PMID: 29475834 Our data support that the CYP3A53 polymorphism may be associated with increased risk of prostate cancer, particularly in African populations. Large and well-designed studies are needed to validate this association. PMID: 29970707 CYP3A5 genetic differences were not associated with the development of interstitial fibrosis, any clinical events, or the long-term function and survival of kidney grafts PMID: 29550576 Concentrations of aripiprazole, sex, CYP3A53 and CYP2D6 were involved in the development of adverse drug reations to aripiprazole PMID: 29325225 CYP3A5 genetic polymorphism had a significant influence on tacrolimus pharmacological effects in Chinese liver transplantation patients PMID: 29454235 The results obtained by CLIA, ECLIA and ACMIA were not affected by CYP3A5 polymorphism. PMID: 28891077 CYP3A5 Polymorphism is associated with drug resistance in Breast Cancer. PMID: 29479969 In summary, we explored the effects of CYP3A53, UGT2B72, and UGT2B73 variants on steady-state carbamazepine (CBZ) concentrations in 62 epileptic patients. Our study found that the UGT2B72 variant, but not the CYP3A53 and UGT2B73 variants, can affect steady-state CBZ concentrations in these patients. PMID: 30045320 Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric renal-transplant recipients PMID: 28540692 Stability of the dose-adjusted trough concentrations achieved using modified-release once-daily tacrolimus, which was clearly influenced by the CYP3A5 polymorphism, may prevent the development of rejection. PMID: 28271256 African-American kidney transplant recipients with the CYP3A51 variant require higher tacrolimus dosing. PMID: 28605053 the plasma trough concentration/dose (C/D) ratio of apixaban was used as a pharmacokinetic index and all data were stratified according to the presence of ABCB1 (ABCB1 1236C>T, 2677G>T/A, and 3435C>T), ABCG2 (ABCG2 421C>A), and CYP3A5 (CYP3A53) .These results indicate that ABCG2 421A/A and CYP3A53 genotypes and renal function are considered potential factors affecting trough concentrations of apixaban. PMID: 28678049 Patients with both CYP3A53/3 and MDR1 G2677A who underwent renal transplantation had higher blood TAC concentrations than those without those genotypes. Japanese patients should be carefully monitored for consideration of lower TAC doses, because 24% of Japanese patients have double mutations. PMID: 28736028 Donor CYP3A5 genotype, recipient age and, to a lesser extent, donor gender appear to be associated with tacrolimus disposition on day 1 after transplant PMID: 28044353 The CYP3A53 gene polymorphism was closely associated with the mRNA expression of CYP3A5, CYP3A enzyme activity and DNR plasma drug concentration, and exhibited different drug adverse reactions. PMID: 28440407 The CYP3A5 genotype had no impact on the concentrations of cyclosporine A and tacrolimus at any investigated time point PMID: 29441922 We confirmed CYP3A5 metabolic activity with the CYP3A4 selective inhibitor CYP3CIDE. PMID: 28533324 Part of the differences in tacrolimus pharmacokinetics and transplantation outcomes may relate to differences between populations in the genetics of tacrolimus-metabolizing enzymes. The best-known example is the allelic frequency of the loss-of-function CYP3A53 allele. PMID: 27790923 conclude, therefore, that there is either no association between CYP3A5 expression and blood pressure or, if there is a relationship, the strength of the association is very small in Ghanaian population. PMID: 27334520 MDR1 and CYP3A5 genetic polymorphisms significantly influence plasma trough levels and therapeutic response of imatinib in patients with chronic myeloid leukemia. Patients with GG genotype for CYP3A5-A6986G (P=0.016) and TT genotype for MDR1-C3435T (P=0.013) polymorphisms had significantly higher trough levels of imatinib. PMID: 28330783 The CYP3A5 gene may be associated with the risk of hypertension in the Chinese Han population, and this effect may be exacerbated by drinking. PMID: 28448186 The study demonstrated no correlation between CYP3A5 genotype and the development of vincristine neurotoxicity in childhood malignancies. PMID: 28697165 The A/G genotypes, G/G genotypes, and G allele of CYP3A53 in the LEDVT group were observed with increased frequency compared with the control group. The genotype distributions of the CYP2C93, CYP2D610, and CYP3A53 genetic polymorphisms were associated with the warfarin maintenance dose. PMID: 28872889 Steroid resistance during acute renal allograft rejection is associated with donor genotype and intragraft expression levels of CYP3A5. PMID: 27926596 A significant association of CYP3A5 genotypes was found with tacrolimus daily dose in kidney transplant recipients. PMID: 27977332 The authors found a correlation between genetic SNP variations in CYP3A5 enzyme and tacrolimus blood levels in this Jordanian kidney transplant recipients. PMID: 27225724 In patients with ulcerative colitis treated with tacrolimus, the incidence of nephrotoxicity was significantly higher in CYP3A5 expressers compared to non-expressers. PMID: 27717793 The present study evaluated the ability of a Saccharomyces cerevisiae expression system to predict the pharmacokinetic (PK) activity of a calcium channel blocker in patients with distinct cytochrome P450 3A5 (CYP3A5) polymorphisms. PMID: 28259948 In the CYP3A53/3 group, the concentration of tacrolimus was significantly higher in men than in women in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients. PMID: 28324194 There are no significant differences in serum creatinine, haematocrit and albumin values between CYP3A5 expressers and non-expressers. PMID: 27885697 population pharmacokinetic analysis identified that the combined genotype of CYP3A5-POR was the only covariant for the apparent clearance of tacrolimus PMID: 26227094 The GG and TT genotypes in CYP3A53 and ABCB1 C3435T, respectively, were linked with higher TPC. PMID: 27426203 CYP3A5 single nucleotide polymorphisms are associated with Clopidogrel Resistance in Acute Ischemic Stroke. PMID: 26961113 There was no significant correlation between CYP3A5 rs776746 polymorphism and major adverse events of clopidogrel therapy. [Meta-Analysis] PMID: 27649539 pharmacokinetics of once-daily tacrolimus formulation in relation to polymorphisms of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene and recipient adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1) gene in 80 consecutive living-donor liver transplant recipients PMID: 27503662 CYP3A5 (6986A > G) genotype, rather than MDR-1 (2677G > A/T) variant, has an impact on tacrolimus pharmacokinetics PMID: 26856709 study to determine the impact of CYP3A5 genetic polymorphisms on paclitaxel/carboplatin-induced myelosuppression and neurotoxicity in patients with epithelial ovarian cancer; found that CYP3A533 was associated with a lower risk of paclitaxel/carboplatin-induced myelosuppression compared with other CYP3A5 genotypes PMID: 26179145 Liver transplant patients with CYP3A5 polymorphisms required significantly higher doses of tacrolimus to achieve target blood concentrations. PMID: 27320564 CYP3A5 genetic polymorphisms in Uyghur population. PMID: 26739429 The results suggest that early post-transplantation bioavailability differences in time to reach tacrolimus therapeutic levels are due to CYP3A5 genotype. This also appears to affect graft rejection and survival. PMID: 27110018 CYP3A5 and MDR1 polymorphisms may be the main explanation for the differences observed in RUP pharmacokinetics. PMID: 25427746 that there was association between CYP3A5 FNx01 3 polymorphism and the altered risk of acute lymphoblastic leukemia in children, especially in Caucasian populations PMID: 25673168 Cyclosporin A-based maintenance therapy is safe for Chinese de novo kidney transplant recipients who are CYP3A5 expressers. PMID: 26177348 CYP3A5 and ABCB1-1236 genotyping, in addition to recipient age, are necessary for establishing a more accurate TAC dosage regimen in paediatric liver recipients. PMID: 26176181 Patients with CYP3A511 genotypes require higher doses of tacrolimus to achieve the target concentration and may be at risk of acute rejection soon after transplant because of inadequate immunosuppression. PMID: 26177012 We herein discuss all published data on the contribution of CYP3A5 and its polymorphisms to the metabolism of antipsychotics and antidepressants that are known to be metabolized by CYP3A enzymes, as well as of carbamazepine, an antiepileptic drug used as mood stabilizer PMID: 26651976 Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on biopsy-proven acute rejection was not observed in this study PMID: 26635230 The requirement for daily maintenance dose was higher in those with CYP3A51/1 variants in both tacrolimus formulations in the Malaysian Renal Transplant patients. Furthermore, those with CYP3A53/3 demonstrated significantly higher dose-adjusted within-patient variability trough levels with Advograf. PMID: 26915847 Loss-of-function variants in CYP3A5 is associated with tacrolimus trough concentrations in African American kidney allograft recipients. PMID: 26485092

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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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