EFR3A, an Intriguing Gene, and Protein with a Scaffolding Function.

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Eighty-Five Requiring 3 (EFR3) proteins are eukaryotic peripheral plasma membrane proteins belonging to the armadillo-like superfamily.
• Two paralog genes, EFR3A and EFR3B, exist in higher vertebrates, each producing multiple protein isoforms.
• EFR3 proteins are implicated in diverse physiological processes, including phototransduction, G protein-coupled receptors (GPCRs), and insulin receptor signaling.

Purpose of the Study:

• To review the current understanding of EFR3 proteins, with a focus on EFR3A.
• To explore the structural characteristics and known molecular functions of EFR3 proteins.
• To discuss the implications of EFR3A in human disorders and its potential roles in cellular processes.

Main Methods:

• This review synthesizes information from existing literature.
• Structural data analysis reveals EFR3's superhelical rod-like structure with armadillo (ARM) repeats and a triple helical motif.
• Functional analysis is based on reported interactions and physiological roles.

Main Results:

• EFR3 proteins anchor the phosphatidylinositol 4-kinase A complex to the plasma membrane, vital for cell signaling.
• EFR3A's interaction with flotillin-2 suggests a role in membrane raft domain organization.
• Mutations in EFR3A are associated with neurological disorders, cardiovascular diseases, and various cancers.

Conclusions:

• EFR3 proteins, particularly EFR3A, play critical roles in fundamental cellular processes and human health.
• EFR3A's function in anchoring key signaling complexes and its involvement in membrane organization highlight its significance.
• Further research into EFR3A is warranted due to its association with disease and its intriguing molecular functions.