COL4A3 - Collagen Type IV Alpha 3 Chain | Elisa - Clia - Antibody - Protein

Background

Collagen Type IV Alpha 3 Chain (COL4A3) is one of the six alpha chains that make up type IV collagen, a crucial component of basement membranes in various tissues. The COL4A3 gene, located on chromosome 2 (2q36-q37), encodes this alpha chain. Type IV collagen provides structural support and plays a vital role in the filtration function of the glomerular basement membrane in the kidneys. COL4A3 is specifically important in the structural integrity and function of the glomerular basement membrane, alveolar membrane in the lungs, and the lens capsule in the eyes. Mutations in the COL4A3 gene are associated with Alport syndrome, a genetic disorder characterized by progressive kidney disease, hearing loss, and eye abnormalities.

Protein Structure

COL4A3 is a protein composed of several important regions:

• Triple Helix Domain: The central part of the protein forms a triple helix, which is a characteristic feature of collagen molecules. This helical structure provides tensile strength and stability to basement membranes.
• NC1 Domain (Non-Collagenous 1): Located at the C-terminal end, this domain is involved in the formation of the collagen network through interactions with other collagen IV chains.
• Gly-X-Y Repeats: The triple helix domain consists of repeating Glycine-X-Y sequences, where X and Y are frequently proline and hydroxyproline, essential for the stability of the helix.

Classification and Subtypes

COL4A3 is classified within the type IV collagen family, which includes six different alpha chains (α1-α6). These chains form heterotrimers, most commonly composed of α1, α2, and either α3, α4, or α5 chains. Specifically, COL4A3 often pairs with COL4A4 and COL4A5 to form the collagen IV network in basement membranes.

Function and Biological Significance

COL4A3 plays several key roles in the body:

• Basement Membrane Structure: It contributes to the structure and function of basement membranes in various tissues, providing mechanical support and filtration capabilities.
• Filtration Barrier: In the kidneys, COL4A3 is essential for the function of the glomerular basement membrane, which acts as a filtration barrier.
• Cell Adhesion and Migration: It facilitates cell adhesion and migration, which are important for tissue repair and maintenance.
• Interaction with Other Molecules: The NC1 domain interacts with other collagen IV chains and matrix molecules, contributing to the overall network formation and stability.

Clinical Issues

• Alport Syndrome: Mutations in the COL4A3 gene cause Alport syndrome, leading to progressive renal disease, hearing loss, and ocular abnormalities. This condition can be inherited in an autosomal recessive or autosomal dominant manner.
• Thin Basement Membrane Nephropathy: Also associated with mutations in COL4A3, this condition is characterized by thinning of the glomerular basement membrane, resulting in benign familial hematuria.
• Other Diseases: Dysregulation or mutation of COL4A3 may also contribute to other diseases affecting basement membranes, such as certain forms of focal segmental glomerulosclerosis (FSGS).

Summary

Collagen Type IV Alpha 3 Chain (COL4A3) is a crucial protein for the structural integrity and function of basement membranes in various tissues. Its role in the formation of the triple helical structure and the NC1 domain interactions are essential for maintaining the mechanical support and filtration functions of these membranes. Mutations in COL4A3 are primarily associated with Alport syndrome and thin basement membrane nephropathy, highlighting its importance in kidney function and overall basement membrane stability. Understanding the molecular mechanisms and clinical implications of COL4A3 can aid in diagnosing and treating related genetic disorders.