LRBA - LPS responsive beige-like anchor protein | Elisa - Clia - Antibody - Protein

Background

LRBA (LPS-responsive beige-like anchor protein) is a gene encoding a protein that plays a crucial role in the immune system. This protein is primarily involved in the regulation of vesicular trafficking, autophagy, and immune responses. The LRBA gene is located on chromosome 4q31.3 and has been linked to various immunodeficiency disorders when mutated. This protein is expressed in a variety of tissues, with significant expression in immune cells such as B and T lymphocytes. The understanding of LRBA's function has expanded significantly in recent years, particularly due to its association with autoimmune diseases and immune dysregulation syndromes.

Protein Structure

• Size and Composition: The LRBA protein is approximately 285 kDa and consists of 2,863 amino acids.
• Domain Structure:
• PH (Pleckstrin Homology) Domain: Involved in binding phosphoinositides and membrane association.
• WD40 Repeats: Facilitate protein-protein interactions.
• Beach Domain: Associated with vesicle trafficking.
• Coiled-coil Region: Important for protein dimerization and interaction.
• C-terminal Region: Involved in anchoring LRBA to membranes and possibly in protein-protein interactions.

Classification and Subtypes

• LRBA belongs to the BEACH (Beige and Chediak-Higashi) domain family of proteins.
• There are no subtypes of LRBA; however, it is related to other BEACH domain-containing proteins, such as LYST and NBEA.

Function and Biological Significance

• Vesicular Trafficking: LRBA is crucial for the regulation of vesicle formation and trafficking, particularly in immune cells.
• Autophagy: It plays a significant role in the autophagic process, which is essential for cellular homeostasis and the removal of damaged organelles and proteins.
• Immune Regulation: LRBA is vital for the normal functioning of B and T cells. It regulates the expression and recycling of immune receptors and is involved in cytokine signaling.
• Protection Against Apoptosis: LRBA can protect cells from apoptosis, contributing to cell survival during immune responses.

Clinical Issues

• Primary Immunodeficiency: Mutations in LRBA cause LRBA deficiency, leading to immune dysregulation, autoimmunity, and primary immunodeficiency. Symptoms include recurrent infections, autoimmunity, enteropathy, and lymphoproliferation.
• Autoimmune Disorders: Patients with LRBA mutations often exhibit autoimmune symptoms such as type 1 diabetes, autoimmune hemolytic anemia, and inflammatory bowel disease.
• Therapeutic Target: LRBA deficiency can be treated with immunosuppressive therapies and hematopoietic stem cell transplantation. Targeting LRBA pathways is also being investigated for therapeutic purposes in autoimmune diseases.

Summary

LRBA is an essential protein involved in the regulation of immune cell function and vesicular trafficking. Its role in autophagy and receptor recycling is crucial for maintaining immune homeostasis. Mutations in LRBA can lead to significant clinical issues, primarily immunodeficiency and autoimmune diseases. Understanding the molecular mechanisms of LRBA and its pathways opens avenues for targeted therapies to manage associated disorders.