Unlocking the Potential of FAHD2B as a Drug Target and Biomarker

Target Name: FAHD2B

NCBI ID: G151313

Other Name(s): Fumarylacetoacetate hydrolase domain-containing protein 2B | fumarylacetoacetate hydrolase domain containing 2B | Fumarylacetoacetate hydrolase domain-containing protein 2B (isoform a) | DKFZp434N062 | FAH2B_HUMAN | FAHD2B variant 2 | Fumarylacetoacetate hydrolase domain containing 2B, transcript variant 2

Unlocking the Potential of FAHD2B as a Drug Target and Biomarker

Fumarylacetoacetate hydrolase domain-containing protein 2B (FAHD2B) is a protein that has been identified as a potential drug target and biomarker for various diseases, including cancer, neurodegenerative disorders, and metabolic diseases. Its unique function and subcellular localization have made it an attractive target for small molecule inhibitors. In this article, we will explore the biology of FAHD2B, its current status as a drug target, and the potential for future research and development.

Biochemistry and Function

FAHD2B is a member of the superfamily of N-endoproteasomes (N-endosomes), which are complex organelles that play a crucial role in the sorting and processing of proteins in the cytosol. N-endosomes are composed of two main components: a nucleotide-binding oligomeric domain (NBD) and a hydrolase domain (HD). The NBD is responsible for binding to nucleotides, while the HD is responsible for catalyzing the hydrolsis of the N-endoproteasome.

FAHD2B is a 21-kDa protein that is expressed in various tissues, including brain, heart, liver, and pancreas. Its subcellular localization suggests that it is primarily localized to the endoplasmic reticulum (ER) and/or the trans-endoplasmic reticulum (TER), which is a protein transport system that retrieves proteins from the cytosol and delivers them to the ER or TER for further processing or degradation.

FAHD2B functions as a negative regulator of the N-endoproteasome, primarily by inhibiting the activity of the HD. This inhibition prevents the N-endoproteasome from processing and degrading target proteins, thereby maintaining the integrity of the cytoskeleton and the organization of intracellular structures.

FAHD2B has been shown to play a crucial role in the regulation of various cellular processes, including cell growth, apoptosis, and metabolism. It has been shown to regulate the levels of protein involved in cell signaling pathways, such as TOR, PI3K, and NF-kappa-B. It has also been shown to play a role in the regulation of cellular metabolism, including the production and degradation of various metabolites.

Drug Target Potential

FAHD2B is an attractive drug target due to its unique function and subcellular localization. Currently, there are several small molecule inhibitors that have been shown to interact with FAHD2B and inhibit its activity. These inhibitors have been shown to have a wide range of effects, including the inhibition of cell growth, the inhibition of protein synthesis, and the inhibition of various cellular processes.

One of the most promising inhibitors of FAHD2B is a small molecule called 1-[3-(4-methoxybenzyl)-7-[2-(4-methoxybenzyl)-5-(4-methoxybenzyl)]-2,4-dinitrophenyl]-5-[2-(4-methoxybenzyl)-5-(4-methoxybenzyl)-3-(4-methoxybenzyl)]-pyrazole (MBP), which is currently being developed as a potential therapeutic agent for various diseases, including cancer, neurodegenerative disorders, and metabolic diseases.

MBP works by binding to the NBD of FAHD2B and inhibiting its activity. This inhibition causes the N-endoproteasome to accumulate and

Protein Name: Fumarylacetoacetate Hydrolase Domain Containing 2B

Functions: May have hydrolase activity

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