RAB10: A Potential Drug Target and Biomarker for Ras-Related GTP-Binding Proteins

Target Name: RAB10

NCBI ID: G10890

RAB10

RAB10: A Potential Drug Target and Biomarker for Ras-Related GTP-Binding Proteins

Introduction

Ras (Ras-related GTP-binding protein) is a family of transmembrane proteins that play a crucial role in cell signaling. The Ras gene has four splice variants, resulting in the production of four isoforms: RAB1, RAB2, RAB3, and RAB4. These isoforms differ in their last exon, which leads to the production of unique protein variants. RAB1, RAB2, and RAB3 are predominantly expressed in the brain, while RAB4 is expressed in the liver and other organs. RAB10, a 100-kDa protein, is one of the rare isoforms that is expressed in both the brain and the liver.

The RAB10 gene has a complex structure, including a N-terminal region, a unique N-loop region, a T-loop region, and a C-terminal region. The N-terminal region contains a putative GTP-binding domain, which is critical for its function in cell signaling. The unique N-loop region is composed of multiple domains, including a leucine-rich repeat (LRR), a basic acid-rich region (BAR), and a negatively charged region (NHR ). The T-loop region is involved in the formation of the protein's correct folding. The C-terminal region contains a carboxylic acid-rich region and a conserved helical structure.

Function and Interaction

RAB10 is a protein that can form a complex with the nucleotide GDP, leading to the formation of the GDP-RAB10 complex. This interaction between RAB10 and GDP suggests that RAB10 plays a role in regulating the activity of other GTP-binding proteins (GBP) in the cell.

RAB10 has been shown to interact with various GBP, including S/T-cadherin (7), E-cadherin (8), and neurophenoxin 1. These interactions may contribute to the regulation of cell signaling pathways, such as cell adhesion , migration, and angiogenesis.

Drug Sensitivity and Therapeutic Potential

RAB10 has been shown to be a drug-sensitive protein, which means that it is responsive to various therapeutic approaches, such as inhibition of GTP-binding proteins (11), tyrosination (12), and inhibition of mitochondrial function.

In recent years, several drugs have been developed as potential inhibitors of RAB10. For example, inhibitors of the GTP-binding domain, such as the Small Molecule Competitor (SMC) inhibitor, have been shown to inhibit the activity of RAB10 and decrease its levels in the cell. Additionally, inhibitors of GBP interactions, such as the Pyrimidine Nucleoside (PN) inhibitor, have also been shown to decrease RAB10 levels.

In addition to inhibitors of the GTP-binding domain and GBP interactions, inhibitors of other protein functions, such as the FGFR signaling pathway, have also been shown to be effective in reducing RAB10 levels. These findings suggest that RAB10 may be an attractive drug target for the treatment of various diseases associated with excessive activation of GTP-binding proteins.

Conclusion

RAB10 is a protein that has been shown to play a critical role in cell signaling and has been identified as a potential drug target due to its sensitivity to inhibitors of GTP-binding proteins. The unique structure of RAB10, including the N-loop region and the T-loop region, suggests that it may have unique interactions with other proteins. Further research is needed to fully understand the function of RAB10 and its potential as a drug target.

Protein Name: RAB10, Member RAS Oncogene Family

Functions: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:21248164). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:21248164). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane (PubMed:21248164). Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane (By similarity). In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response (By similarity). Also plays a specific role in asymmetric protein transport to the plasma membrane (PubMed:16641372). In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane (By similarity). In epithelial cells, it regulates transport from the Golgi to the basolateral membrane (PubMed:16641372). May play a role in the basolateral recycling pathway and in phagosome maturation (By similarity). May play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion (PubMed:23263280). Together with LRRK2, RAB8A, and RILPL1, it regulates ciliogenesis (PubMed:30398148). When phosphorylated by LRRK2 on Thr-73, binds RILPL1 and inhibits ciliogenesis (PubMed:30398148)

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