Recombinant Human Cholesterol 24-hydroxylase (CYP46A1), partial

Code CSB-YP897584HU
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Source Yeast
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Code CSB-EP897584HU
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Source E.coli
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Code CSB-EP897584HU-B
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Source E.coli
Conjugate Avi-tag Biotinylated
E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code CSB-BP897584HU
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Source Baculovirus
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Code CSB-MP897584HU
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Source Mammalian cell
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Product Details

Purity
>85% (SDS-PAGE)
Target Names
CYP46A1
Uniprot No.
Alternative Names
CYP46A1; CYP46Cholesterol 24-hydroxylase; CH24H; EC 1.14.14.25; Cholesterol 24-monooxygenase; Cholesterol 24S-hydroxylase; Cytochrome P450 46A1
Species
Homo sapiens (Human)
Protein Length
Partial
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Form
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer before Lyophilization
Tris/PBS-based buffer, 6% Trehalose, pH 8.0
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet
Please contact us to get it.

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Target Background

Function
P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation. By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning. Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis. Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain. May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole.
Gene References into Functions
  1. the APOEepsilon4 alleles were significantly higher in patients with Alzheimer's disease (AD) and there was a potential synergistic interaction between the CYP46A1 C allele and APOEepsilon4 allele in AD. PMID: 29516283
  2. Data suggest that CYP46A1, the enzyme responsible for the majority of cholesterol elimination from the brain, exhibits activation by neurotransmitters, L-glutamate, L-aspartate, gamma-aminobutyric acid, and acetylcholine; L-glutamate-induced CYP46A1 activation may be of physiological relevance. PMID: 28642370
  3. CYP46A1 rs4900442 genetic polymorphism was associated with increased risk of Alzheimer disease in the Chinese population, but no evidences were detected in Caucasian population. PMID: 27026489
  4. Findings of this study suggest that CYP46A1 gene and PPARgamma2 gene polymorphisms can be a predictive marker for early identification of population at risk of primary open angle glaucoma (POAG). PMID: 27162448
  5. hippocampal CYP46A1 protein and 24S-hydroxycholesterol levels were reduced in a mouse model of Alzheimer's Disease-like Tau neuropathology PMID: 26358780
  6. under conditions of membrane cholesterol reduction by increased CYP46A1 expression, neurons increase isoprenoid synthesis and sGTPase prenylation. This leads to a reduction in liver X receptor activity PMID: 25084760
  7. Human CYP46A1 oxidizes 7-dehydrocholesterol to 24-hydroxy-7-dehydrocholesterol and 25-hydroxy-7-dehydrocholesterol. PMID: 25017465
  8. While there were no differences in cognitive performance between participants with and those without metabolic syndrome, ApoE and CYP46 genotypes did correlate with mental manipulation scores. PMID: 24924840
  9. results of meta-analysis suggested that CYP46A1 rs754203 is a minor risk factor for Alzheimer's disease PMID: 23792195
  10. An meta-analysis has successfully proved that CC genotype of the CYP46A1 T/C polymorphism could increase the risk of Alzheimer's disease. PMID: 23070465
  11. A meta-analysis indicates that the CYP46 gene SNP rs754203 is not significantly associated with sporadic Alzheimer's disease susceptibility in Chinese Han populations. PMID: 23167762
  12. To identify the determinants of tight azole binding to CYP46A1. PMID: 23604141
  13. analysis of binding of the cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1 PMID: 23288837
  14. The intronic polymorphism in CYP46A1 is associated with Alzheimer disease in a Chinese Han population, and the CYP46A1 T allele might be a risk factor. PMID: 22528464
  15. The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative age-related macular degeneration in patients who carry no risk alleles in the CFH and LOC387715 genes. PMID: 22977134
  16. Differentiated Ntera2/clone D1 (NT2) cells express the key genes involved in brain cholesterol homeostasis including CYP46A1. PMID: 22185844
  17. There was no association between the CYP46 genotype and measures of cognitive event-related potentials. PMID: 21729100
  18. Study of two independent Chinese data sets indicates individuals with CYP46A1 promoter bearing the CG haplotype are genetically more susceptible to Alzheimer's disease than those with TA haplotype. PMID: 20693622
  19. The data of this study suggested that CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects. PMID: 19647891
  20. The rs754203 polymorphism itself is unlikely a genetic risk factor for primary open angle glaucoma in Caucasian individuals. PMID: 21386929
  21. The average P450 concentrations/mg of total tissue protein were 345 fmol of CYP46A1 and 110 fmol of CYP27A1 in the temporal lobe, and 60 fmol of CYP46A1 and 490 fmol of CYP27A1 in the retina. PMID: 21049985
  22. Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain. PMID: 20667828
  23. Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons PMID: 19212968
  24. These results suggest that a disturbance of cholesterol metabolism may contribute to loss of EAAT2 in AD. PMID: 20193040
  25. In addition to its involvement in cholesterol homeostasis in the brain, CYP46A1 has a broad substrate specificity and is able to metabolize neurosteroids and drugs that can cross the blood-brain barrier and are targeted to the central nervous system. PMID: 14640697
  26. Polymorphisms in the CYP46 gene are found not to be risk factors for Alzheimer's disease nor are they associated with parenchymal or vascular accumulation of amyloid-beta protein. PMID: 15106838
  27. The distribution of CYP46 genotypes was significantly different in AD compared to controls and the CYP46 and ApoE polymorphisms synergically increase the risk for AD development. PMID: 15165699
  28. In contrast to two previous reports but in accordance with one other, we were unable to detect an association between an intron 2 polymorphism of CYP46 and Alzheimer disease. PMID: 15172102
  29. the polymorphism of CYP46 intron 2 is implicated in the susceptibility to late-onset Alzheimer's disease and a strong synergistic interaction between CYP46 TT homozoygots PMID: 15450677
  30. The GG genotype of the known rs754203 polymorphic site might be a risk factor for AD, especially in APOE varepsilon4 carriers. Interestingly, in AD patients the rs754203 G allele was more frequent in males than in females. PMID: 15936520
  31. Based on the results of genome-wide screens, along with biological studies, we selected three genes as candidates for AD risk factors: ATP-binding cassette transporter A1 (ABCA1), cholesterol 25-hydroxylase (CH25H) and cholesterol 24-hydroxylase (CH24H). PMID: 16157450
  32. Polymorphism was associated with the risk of Alzheimer disease(AD) but subjects homozygous for the C alleles were protected from AD with an adjusted odds ratio. PMID: 16734927
  33. here was no significant difference in the genotype or allele frequencies for CYP46 gene between AD patients and controls. PMID: 17335784
  34. substantial substrate-induced conformational changes in CYP46A1 suggest that structurally distinct compounds could bind in the enzyme active site PMID: 18621681
  35. The expression of CYP46A1, as well as other cytochrome P450s involved in cholesterol homeostasis, are potently regulated by histone acetylation status. PMID: 19059217
  36. the substrate, cholesterol, enters CYP46A1 from the membrane PMID: 19161969
  37. From the logistic regression ananlsis of this stidy showed that the highest risk for was found for Alzheimer's disease individuals who co-inherited APOE epsilon4 allele, PRNP codon 129 homozygosity, PRND codon 174 Thr allele, and CYP46 rs754203 g allele. PMID: 19363267
  38. The rs754203 SNP in CYP46A1 was associated with a risk for POAG. This polymorphism was not associated with changes in plasma 24S-hydroxycholesterol. PMID: 19553612

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Subcellular Location
Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass membrane protein. Cell junction, synapse, postsynapse. Cell junction, synapse, presynapse. Cell projection, dendrite.
Protein Families
Cytochrome P450 family
Tissue Specificity
Expressed in brain. The mRNA was broadly distributed with higher levels in gray matter zones and lower levels in regions rich in white matter. Not detected in fetal sample but its expression increases linearly with age.
Database Links

HGNC: 2641

OMIM: 604087

KEGG: hsa:10858

STRING: 9606.ENSP00000261835

UniGene: Hs.25121

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