Recombinant Human NR1I2, N-His

Description of Recombinant Human NR1I2, N-His

Introduction to Recombinant Human NR1I2

Recombinant human NR1I2, also known as the nuclear receptor subfamily 1 group I member 2, is a protein that plays a crucial role in the regulation of drug metabolism and disposition. It belongs to the nuclear receptor superfamily, which consists of transcription factors that control gene expression in response to various stimuli. NR1I2 is highly expressed in the liver, intestine, and kidney, and is involved in the metabolism of endogenous compounds, such as steroids, as well as exogenous substances, including drugs and environmental toxins.

Structure of Recombinant Human NR1I2

NR1I2 is a 434 amino acid protein with a molecular weight of approximately 49 kDa. It has a modular structure consisting of five domains: the N-terminal A/B domain, the DNA binding domain (DBD), the hinge region, the ligand binding domain (LBD), and the C-terminal F domain. The DBD and LBD are the most conserved regions of NR1I2 and are responsible for its DNA and ligand binding activities, respectively.

The DBD contains two zinc fingers that are crucial for DNA binding. These zinc fingers interact with specific DNA sequences called response elements, which are located in the promoter regions of target genes. The LBD, on the other hand, has a hydrophobic pocket that can accommodate various ligands, including endogenous hormones and xenobiotics. Upon ligand binding, NR1I2 undergoes a conformational change, allowing it to interact with co-regulator proteins and initiate gene transcription.

Activity of Recombinant Human NR1I2

NR1I2 is a ligand-activated transcription factor that regulates the expression of genes involved in drug metabolism and disposition. Its activity is tightly regulated by ligands, co-regulator proteins, and post-translational modifications. When activated by a ligand, NR1I2 forms a complex with co-regulator proteins, such as co-activators or co-repressors, which modulate its transcriptional activity. This complex then binds to response elements in the DNA, leading to the upregulation or downregulation of target gene expression.

NR1I2 is also subject to post-translational modifications, such as phosphorylation and acetylation, which can affect its activity. For example, phosphorylation of specific serine residues in the LBD can enhance the transcriptional activity of NR1I2, while acetylation of the DBD can inhibit its DNA binding ability. These modifications provide an additional level of regulation for NR1I2 activity.

Application of Recombinant Human NR1I2

Due to its crucial role in drug metabolism and disposition, NR1I2 has become an important drug target for the treatment of various diseases. It is involved in the metabolism of many drugs, including chemotherapeutic agents, antihypertensives, and antibiotics. Therefore, targeting NR1I2 can potentially improve the efficacy and safety of these drugs.

One of the most well-known applications of NR1I2 is in the treatment of cancer. Many chemotherapeutic agents are metabolized by NR1I2, and their efficacy can be affected by the activity of this protein. By targeting NR1I2, researchers aim to modulate the metabolism of these drugs and enhance their anti-cancer effects. Additionally, NR1I2 has been linked to drug resistance in some cancers, making it a potential target for overcoming resistance and improving treatment outcomes.

NR1I2 is also being studied as a potential target for the treatment of other diseases, such as cardiovascular diseases, diabetes, and viral infections. By targeting NR1I2, researchers hope to improve the efficacy and safety of current treatments and develop new therapies for these diseases.