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- Table of Contents
Facts about UDP-glucuronosyltransferase 1-3.
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Human | |
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Gene Name: | UGT1A3 |
Uniprot: | P35503 |
Entrez: | 54659 |
Belongs to: |
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UDP-glycosyltransferase family |
GNT1; UDP glucuronosyltransferase 1 family, polypeptide A3; UDP glucuronosyltransferase 1A3; UDP glycosyltransferase 1 family, polypeptide A3; UDP-glucuronosyltransferase 1-3; UDP-glucuronosyltransferase 1A3; UDP-glucuronosyltransferase 1-C; UDPGT 1-3; UDPGT; UGT1; UGT1*3; UGT1.3; UGT1-03; UGT-1C; UGT1CEC 2.4.1.17
Mass (kDA):
60.338 kDA
Human | |
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Location: | 2q37.1 |
Sequence: | 2; NC_000002.12 (233729042..233773300) |
Isoform 1 and isoform 2 are expressed in liver, kidney, colon and small intestine. Isoform 1 but not isoform 2 is expressed in esophagus.
Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein.
The UGT1A3 genes encode an enzyme that regulates blood glucose. This enzyme is extremely common, but little is known about it. Steven Boster was the inventor of his first product. He earned the nickname "he who converts science into the lavatory" in 1993. Eventually, Boster's company grew to become the largest antibody catalog in China. Later, Boster created PicoKine(tm), his own proprietary ELISA platform that uses his trade secrets to deliver high sensitivity ELISA kits.
Despite its name, Boster Bio's Kurarinone is not a natural product; it is a compound found in the dried roots of Sophora flavescens Ait. This substance has many important pharmacological activities. The compound was incubated in recombinant CYP450 Supersomes to study its metabolic profile. It inhibited approximately 90% CYP and UGT enzymes. It also showed moderate permeability to pH 4.5, 7.5, indicating that kurarinone could be a CYP1A2 inhibitor.
Kurarinone is also known to inhibit CYP1A2; it interacts with CYPs 2C9-CYP2D6 as well as CYP1A2. It binds to the active site on Gln244 or Ser304, increasing their activity. It can increase the blood levels of kurarinone which can lead to adverse side effects.
4-MU was used as a probe substrate for UGT Ioforms to examine the inhibition of recombinant UGT1A1 with kurarinone. Recombinant UGTs can be found in 200mL of a mixture with kurarinone. The final concentrations for UGT1A1 & UGT1A8 were 0.125, 0.05, 0.25 and 0.2 mg/mL respectively.
PAMPA (or parallel artificial membrane permeation analysis) is an in vitro method to detect passive biomembrane penetration. Kansy, et al. first developed this method to predict passivepermeability in the gastrointestinal track. However, kurarinone's permeability has not been reported. The method allowed researchers to study the drug’s interaction with UGTs using liver macrosomes and recombinant humans supersomes.
The induction of OA/UA significantly increases the expression of UGT1A1, UGT1A3, UGT1A4, UGT1A4, as well as UGT1A9, in HepG2 cell lines. These results suggest that UGT1As are regulated by the CAR as well as the PXR. To clarify the physiological roles of CAR and PXR in regulating UGT1A1 transcription, further studies are needed.
Chemical modification is used to inhibit UGTs. Non-competitive inhibitors can be difficult to find as the enzymes have more than 1 binding site. Several UGTs enzymes have non-competitive inhibitors, including quinine and phenylbutazone. Belinostat can be used as an example of a competitive inhibitor, although its molecular mechanism is not understood.
UGT1A inhibition by OA or UA results in decreased expression in HepG2 cells. Non-competitive UGT1A1 inhibitors also have a positive affect on bilirubin metabolite. Although these inhibitors can reduce bilirubin production, they can lead to adverse drug reactions. Numerous studies have shown that UGT1A1 can be inhibited non-competitively.
Inhibiting UGT1A1 may decrease the metabolism of certain xenobiotics as well as increase their plasma concentrations in patients. This could lead to severe drug-drug interactions. Many tyrosine-kinase inhibitors have strong inhibitory effects on UGT1A1 and can cause severe drug-drug interactions. They can also cause side effects such as hyperbilirubinemia and liver function impairment.
HDACis are also known to inhibit UGT1A1. UGT1A1 inhibitors could reduce conversion of SN-38G to SN-38G. This causes more SN-38 to be produced. This causes an increase in SN-38 and other metabolites. These results demonstrate that HDACis are an effective treatment option. There are many HDAC inhibitors on market.
The UGT1A3 protein plays a critical role in a protein combination that allows antibodies to recognize different targets on different cells. This antibody is made from a rabbit polyclonal immunogen, which is extraordinarily resistant to heat. High-affinity antibodies that target the protein will have high binding affinity and cross-reactivity to many proteins.
This method is based on two methods for antibody-antigen interactions: OI-RD and Biacore. To generate binding data, the RabMAb antibody was used to capture the antigen to a solid support in duplicate. The data were fit with the 1-to-1 Langmuir model and global curve fitting analysis, which both show excellent correlation. Table 2 summarizes the results.
KD, or the equilibrium dissociation constant is what describes how strongly a particular antibody binds its target. KD values below two kD indicate higher affinity. A KD value of less than one kD is a good indicator of an antibody's affinity. The KD of a specific antigen is displayed on its product pages. It indicates its binding capacity to a target.
Antigen binding success is determined by the affinity of these primary antibody. High-affinity antibodies that use UGT1A3 markers are highly specific, and can be extremely effective in the detection a target antigen. These antibodies are made from rabbits and have a KD (7 x 10-11M) which is significantly more than that of monoclonal antibodies.
The UGT1A3 gene marker is used in biological research in many ways. It has been used to study enzymes in the liver. It can be used in drug development and screening. This marker is a product from China's Boster Bio. This company also makes high-affinity primaries. Most of these antibodies have been widely cited and validated for Western blotting and immunohistochemistry.
UGT1A3 regulates activity of several enzymes. CYP1A2 and CYP2C9 catalyze the biotransformation of kurarinone. This process involves CYP2C9, CYP2D6 and CYP2C9. CYP2D6 plays a role in metabolizing kurarinone.
The UGT1A3 gene is expressed in the liver. It is responsible to the metabolism of drugs including NSAIDs, antipsychotics, and other NSAIDs. This marker is a promising candidate for phenotypic biomarkers in many fields including drug development and association of disease states. It was discovered in late 1990s and was associated to a high risk of developing hepatitis C in adults.
It is essential to understand the role of this gene in the digestion of carbohydrates. It is well-known that it participates in glucosidation. Moreover, the UGT1A3 gene is highly conserved, with a signal peptide found only in mature protein. As such, this gene may serve as a valuable biomarker for the analysis of the metabolic functions of the body.
There are a number of ways to use this gene. It can be used by researchers to identify the metabolic pathways for drugs. It can be used to identify the metabolism for pediatric HSCT drugs. It can be used to screen drugs in patients with hepatitis C because of its high-throughput screening abilities. This enzyme plays a critical role in drug metabolism.
All tested samples show high levels of UGT1A3 gene expression. Knockdown of this gene inhibits cell viability, proliferation, migration, and invasion. It reduces tumor volume. The gene regulates neurotrophin signaling. Researchers can identify drug targets by increasing its expression. The protein could also be useful for research into neuromuscular diseases. But, it isn't known how exactly this protein works.
It is important that the UGT1A3 gene is only found in 1.2% of the population. Other genes in this locus include UGT1A8*3 as well as UGT1A9*3, whose frequencies are low. It is therefore important to carefully evaluate these variants and determine their significance. The UGT1A3 Gene is unlikely to have any impact on other genes in the body.
PMID: 1339448 by Ritter J.K., et al. A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini.
PMID: 11434514 by Gong Q.H., et al. Thirteen UDP-glucuronosyltransferase genes are encoded at the human UGT1 gene complex locus.