Actin-related Protein hARP-M2: A Potential Drug Target and Biomarker

Target Name: ACTRT2

NCBI ID: G140625

Actin-related Protein hARP-M2: A Potential Drug Target and Biomarker

Actin-related protein (hARP) M2 is a key regulator of actin dynamics and organization in various cellular processes. It plays a crucial role in the regulation of cell division, cytoskeletal organization, and intracellular transport. The hARP family consists of six isoforms, hARP1-6, each with distinct nuclear localization and cytoplasmic localization patterns. In this article, we focus on hARP-M2, a potential drug target and biomarker.

HARP-M2: Structure and Function

HARP-M2 is a 21-kDa protein that consists of 192 amino acid residues. It has a distinct N-terminal region that includes a putative nuclear localization domain and a C-terminal region that is involved in protein-protein interactions. The hARP-M2 protein is predominantly cytoplasmic and has a limited nuclear localization, as demonstrated by its nuclear localization assays.

HARP-M2 functions as a negative regulator of the actin filament, which is composed of two beta-tubules and an alpha-tubulin protein. It interacts with the alpha-tubulin protein and prevents it from polymerizing into the filament. This interaction between hARP-M2 and alpha-tubulin inhibits the formation of the actin filament, which results in a disorganized actin structure and reduced cytoskeletal stability.

hARP-M2's function in actin regulation has important implications for the study of actin-related diseases, such as actin-based diseases, where misregulation of actin dynamics can contribute to the pathogenesis. Additionally, hARP-M2's role in regulating actin dynamics may be a potential drug target for new therapeutic approaches.

Drug Target Potential

hARP-M2's unique structure and function make it an attractive drug target. The N-terminal region of hARP-M2 contains a putative nuclear localization domain that can be targeted by small molecules. Additionally, hARP-M2's cytoplasmic localization and limited nuclear localization in the cell can be leveraged to deliver small molecules to the cytoplasm without affecting the protein's function in the cell.

Several small molecules have been shown to interact with hARP-M2 and inhibit its activity. One such compound, KIAA-0992, is a specific inhibitor of hARP-M2 that has been shown to disrupt the protein's interaction with alpha-tubulin and inhibit actin polymerization. KIAA-0992 has been shown to be effective in animal models of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

Biomarker Potential

hARP-M2's role in actin regulation is also an attractive biomarker for various diseases. hARP-M2's inhibition of actin polymerization is a potential therapeutic approach for diseases where actin dysfunction plays a significant role in the pathogenesis. For example, hARP-M2's inhibition of actin polymerization could be a potential therapeutic approach for neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease.

In addition to its potential therapeutic applications, hARP-M2 may also be used as a biomarker for various diseases. The inhibition of hARP-M2's activity by small molecules can be used as a readout for the efficacy of potential therapeutic compounds. Additionally, hARP-M2's interaction with alpha-tubulin can be used as a biomarker for the presence of certain diseases, such as neurofibrillary tangles in Alzheimer's disease.

Conclusion

hARP-M2 is a unique protein that plays a crucial role in regulating actin dynamics in various cellular processes. Its inhibition of actin polymerization and limited nuclear localization make it an attractive drug target and biomarker for various diseases. The unique structure and function of hARP-M2 make it an attractive target for new therapeutic approaches, and its potential as a biomarker for various diseases make it a valuable tool in the study of these diseases.

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Protein Name: Actin Related Protein T2

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