UGT1A6 Antibodies

UDP-glucuronosyltransferase 1-6 (UGT1A6)

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.

Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity). .

Gene Information

Human
Gene Name:	UGT1A6
Uniprot:	P19224
Entrez:	54578

Family

Belongs to:
UDP-glycosyltransferase family

Alternative Names

GNT1UDPGT 1-6; HLUGP; HLUGP1; MGC29860; Phenol-metabolizing UDP-glucuronosyltransferase; UDP glucuronosyltransferase 1 family, polypeptide A6; UDP glycosyltransferase 1 family, polypeptide A6; UDP-glucuronosyltransferase 1 family polypeptide A6s; UDP-glucuronosyltransferase 1-6; UDP-glucuronosyltransferase 1A6; UDP-glucuronosyltransferase 1-F; UDPGT; UGT1; UGT1*6; UGT1.6; UGT1-06; UGT1A6S; UGT-1F; UGT1FEC 2.4.1.17

Molecular Weight

Mass (kDA):
60.751 kDA

Genomic Context

Human
Location:	2q37.1
Sequence:	2; NC_000002.12 (233691670..233773300)

Tissue Specificity

Expressed in skin. Isoforms 1 and 3 are expressed in kidney and liver. Isoform 1 but not isoform 2 is expressed in colon, esophagus and small intestine.

Subcellular Localizations

Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein.

Diseases

• Malignant Neoplasms
• Carcinoma
• Neoplasms
• Malignant Tumor Of Colon
• Liver Carcinoma
• Carcinogenesis
• Malignant Neoplasm Of Breast
• Dysequilibrium Syndrome
• Liver Neoplasms, Experimental
• Gilbert Disease (disorder)
• Colonic Neoplasms
• Adenoma
• Liver Neoplasms

• Hepatocarcinogenesis
• Colorectal Cancer
• Hyperbilirubinemia
• Colorectal Neoplasms
• Inflammation
• Mammary Neoplasms
• Adenocarcinoma

Pathways

• Conjugation
• Excretion
• Transport
• Reverse Transcription
• Sulfation
• Localization
• Xenobiotic Glucuronidation
• Intestinal Absorption
• Translation
• Cell Differentiation
• Acyl Glucuronidation
• Protein Oxidation
• Membrane Assembly

• Cell Cycle
• Drug Transport
• Metabolic Process
• Cell Proliferation
• Lactation
• Ovulation
• Bilirubin Conjugation

PTMs

• Reduction
• Hydroxylation
• Oxidation

• Phosphorylation
• Deiodination
• Carboxylation

• Bromination

Research Areas

• Cancer

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/UGT1A6

Best Uses Of The UGT1A6 Marker

In this article, we will discuss the various uses of the UGT1A6 marker and its clinical applications. In addition, we will discuss the Kurarinone inhibitor and its non-competitive inhibitory effect on UGT1A1.

Anti-UGT1A6 Marker

Anti-UGT1A6 Marker is a recombinant protein which is expressed by many human cells. It is expressed as a small ploidy protein (UGT1). This gene is expressed by the liver and is essential for cell metabolism. In addition to producing bile acids, UGT1A6 also helps digest fat. However, the protein's expression is not completely determined by the enzyme.

The company began in 1993, and its products include ELISA kits and signature antibodies. Recently, Boster Bio expanded its range to include PCR-related molecular biology products. Apart from its antibody kits and ELISA products, Boster Bio offers a wide range of services and technical resources for scientists. Moreover, the company offers free technical resources and 24 hours technical support for all customers.

The UGT1A gene cluster is located on chromosome 2q37.1 and codes for nine UGT proteins. These proteins are members of the phase II cellular detoxification system. They are important for the detoxification of aromatic amines, which are found in tobacco smoke and industrial chemicals. As such, the UGTs are involved in the protection of the bladder against bladder cancer. These functional proteins conjugate a variety of chemicals and are excreted in the urine or stool. The acidity of urine depends on body composition and diet.

This gene is expressed in the urine of humans and is expressed at a similar level in tumor and normal bladder tissue. It is not disease-specific, although the protective T allele increases the UGT1A6 gene expression. It is possible that the protective T allele of rs17863783 increases the UGT1A6 protein expression. There are two splicing variants of UGT1A6 in human cells.

The major polymorphisms of UGT1A1 and UGT2B7 contribute to variability in enzyme activity. Understanding this genetic influence on enzyme activities can allow researchers to predict in vivo effects of drugs. The UGT1A1*28 polymorphism contributes to approximately 40% of variability in the UGT1A1 enzyme. The UGT2B7*2 polymorphism contributes to less activity than the UGT1A1*28 allele.

Clinical applications

The UGT1A6 gene is unique in its expression, and the four common exons were also studied. A study by Gong et al. characterized the complex and provided further information on the UGT1A gene. The UGT1A6 gene, in turn, has a large number of clinical applications, including in cancer diagnosis. In the study described here, UGT1A6 was associated with a significantly reduced risk of gastrointestinal cancers in Caucasian Dukes' stage B2 and C colon cancer patients.

Kurarinone inhibitor

The glucuronidation of kurarinone is a crucial step in the metabolism of proteins. In this study, we used rUGTs to identify the UGTs involved in glucuronidation. The enzymes UGT1A1, UGT1A2, UGT1A3, and UGT2B8 showed the highest kurarinone glucuronidation activity. The other UGTs had no glucuronidation activity on M4.

In this study, the kurarinone inhibitor inhibited CYP1A2 and UGT1A6, and it exhibited non-competitive inhibition of CYP1A2. We observed a significant difference in the kinetics and bioavailability of kurarinone with CYP1A2. The metabolite exhibited a moderate toxicity at pH 7.4.

The recombinant glucuronidase enzyme was also inhibited. This enzyme is responsible for glucuronidation of bilirubin, estrogens, and flavanoids. The polymorphism of UGT1A1 is a potential toxicity factor for drugs. As a result, regulatory agencies recommend that DDI packages include a UGT inhibitor assessment. The kurarinone inhibitor assay from Cyprotex measures the reduction of a UGT-specific metabolite and its formation. Ki determination was also performed for IC50.

Inhibition of kurarinone requires interaction with CYP1A2, CYP2D6, and CYP2C9 enzymes. This interaction has been verified through docking studies in which kurarinone bound to the binding pockets of each enzyme. The kurarinone inhibitor inhibited the formation of P1 and exhibited typical Michaelis-Menten kinetics. The Eadie-Hofstee plots were used to calculate the kinetic parameters of the kurarinone inhibitor.

This inhibitor inhibits glucuronidation of 17b-estradiol 3-glucuronidation but has no effect on UGT1A6-mediated glucuronidation of naphthol. This drug also inhibits UGT1A4 and UGT1A9 glucuronidation. Thus, it inhibits these UGT enzymes in several types of cancer.

The uridine diphosphate, kurarinone, is an UGT1A6 marker. This is because it inhibits the activity of both CYP enzymes and UGT1A6. Moreover, this inhibitor inhibits CYPs and UGT1A6 in vitro. However, permeability in this assay was not measured. The inhibitor showed moderate permeability at pH 4.0 and 7.

Another promising anti-cancer drug is belinostat, a kinase inhibitor. Belinostat inhibits glucuronidation of SN-38 in three types of pooled HLMs: wild-type homozygote, UGT1A1*1*28 homozygote, and heterozygote for TA6TAA. In addition, this inhibitor is also known to inhibit UGT1A1 as a marker in human liver cancer.

Non-competitive inhibition against UGT1A1

Inhibitors of the enzyme, including emodin and citreorosein, are able to inhibit the enzyme via interactions with amino acid residues at the cytosolic end. The amino acid residues involved in these interactions are rhein, PRO258 and physcion. Furthermore, inhibitors of this enzyme are able to interact with two regions of the protein, PHE283 and MET265 (site C).

The pharmacological activity of dianthrones was investigated by docking compounds into the two most active sites (C and F) of the enzyme. Various compounds showed a competitive and mixed-competitive inhibition. However, compounds with uncompetitive inhibition exhibited increased enzymatic activity and decreased enzymatic activity. This suggests that emodin is a good candidate for non-competitive inhibition of UGT1A1.

However, despite these benefits, the clinical toxicity of ketoconazole should not be underestimated. It inhibits UGT1A1 enzymomically, thereby reducing the risk of liver toxicity. However, ketoconazole can interact with other anti-cancer agents and may result in treatment-related toxicity. This makes it necessary to carefully monitor the interactions between irinotecan and ketoconazole before they are used together.

The non-competitive inhibitors of UGT1A1 have been developed by two Canadian and one American companies. BD Gentest and Toronto Research Chemicals have produced human recombinant UGT1A1 enzymes. These inhibitors are effective against both human and rat UGT1A1 enzymes and the allelic variants of UGT1A1 and the corresponding phospholipase A.

TKIs are effective against various types of cancers and can induce serious drug-drug interactions. While many of them are potent inhibitors of UGT1A1, they have been associated with severe liver toxicity. Hence, the FDA recommends that patients receive careful monitoring of TKIs while using them. Aside from toxicity, the TKIs may cause hyperbilirubinemia, hepatotoxicity, and other side effects.

The IC50 values of TKIs against different UGTs were estimated by incubating the inhibitors with the substrate and the glucuronide metabolite. The IC50 values of these inhibitors were estimated using nonlinear regression analysis in Graphpad Prism 6.0. Once the IC50 values were determined, they were compared to the IC50 values obtained from the inhibition of UGT1A1.