ACAN - Aggrecan Core Protein | Elisa - Clia - Antibody - Protein

Background

The ACAN gene encodes the protein Aggrecan, also known as cartilage-specific proteoglycan core protein or chondroitin sulfate proteoglycan 1. As a member of the lectican family, Aggrecan is a crucial component of the extracellular matrix in cartilaginous tissue, providing resistance to compression. It is a proteoglycan modified with large carbohydrates, with the human form consisting of 2316 amino acids and exhibiting multiple isoforms due to alternative splicing. Aggrecan derives its name from its ability to form large aggregates in cartilage. Mutations in this gene may lead to skeletal dysplasia and spinal degeneration. Various transcript variants encoding different protein isoforms have been identified through alternative splicing.

Protein Structure

Aggrecan has a complex structure composed of several key domains:

• Core Protein: The large central core protein is the backbone to which glycosaminoglycan (GAG) chains are attached.
• Glycosaminoglycan Chains: Aggrecan is heavily glycosylated with chondroitin sulfate and keratan sulfate chains, which are essential for its function.
• Globular Domains: Aggrecan contains three globular domains (G1, G2, G3) at the N- and C-termini, which are involved in interactions with other matrix components.
• G1 Domain: Contains binding sites for hyaluronan and link protein, facilitating the formation of large proteoglycan aggregates.
• G2 Domain: Function is less understood but believed to assist in proteoglycan aggregate formation.
• G3 Domain: Involved in the secretion and regulation of aggrecan and interacts with other matrix proteins.

Function and Biological Significance

Aggrecan plays several critical roles in cartilage and other tissues:

1. Mechanical Support: By binding water molecules, aggrecan provides cartilage with its characteristic resistance to compressive forces, essential for joint function.
2. Matrix Assembly: Aggrecan interacts with other extracellular matrix components, such as hyaluronan and link protein, to form large proteoglycan aggregates that contribute to the structural integrity of cartilage.
3. Hydration and Lubrication: The GAG chains on aggrecan attract water, which maintains tissue hydration and provides a lubricating layer that facilitates smooth joint movement.
4. Signal Modulation: Aggrecan can modulate the activity of growth factors and cytokines, influencing cell behavior and matrix remodeling.

Interactions

Aggrecan interacts with various molecules and proteins in the extracellular matrix:

1. Hyaluronan: Forms large aggregates with hyaluronan, stabilized by link protein, essential for the structural integrity of cartilage.
2. Link Protein: Stabilizes the interaction between aggrecan and hyaluronan, enhancing the formation of proteoglycan aggregates.
3. Collagen: Interacts with collagen fibers in the extracellular matrix, contributing to the tensile strength and resilience of cartilage.
4. Growth Factors and Cytokines: Aggrecan can bind and sequester growth factors and cytokines, modulating their availability and activity in the extracellular matrix.

Clinical Significance

Mutations or alterations in aggrecan expression can lead to various health issues:

1. Osteoarthritis: Degradation of aggrecan is a hallmark of osteoarthritis, leading to the breakdown of cartilage and joint pain.
2. Spondyloepiphyseal Dysplasia (SED): Mutations in the ACAN gene can cause this genetic disorder, characterized by short stature and skeletal abnormalities due to impaired cartilage function.
3. Intervertebral Disc Degeneration: Loss of aggrecan in the intervertebral discs can contribute to disc degeneration and associated back pain.
4. Familial Osteochondritis Dissecans (FOCD): Genetic variants in ACAN are associated with this condition, which affects joint cartilage and subchondral bone, leading to joint pain and dysfunction.

Summary

Aggrecan, encoded by the ACAN gene, is a vital component of cartilage that provides mechanical support, hydration, and structural integrity. Its interactions with hyaluronan, link protein, collagen, and other matrix components are crucial for maintaining healthy cartilage function. Mutations or degradation of aggrecan are linked to various skeletal disorders, including osteoarthritis, spondyloepiphyseal dysplasia, and intervertebral disc degeneration, underscoring its importance in joint health and disease.