CD93 - CD93 molecule |Elisa - Clia - Antibody - Protein

Background

CD93, also known as C1q receptor-like protein or complement component C1q receptor, is a transmembrane glycoprotein primarily expressed on cells involved in the immune system, including endothelial cells, monocytes, and certain leukocytes. CD93 has key functions in inflammation, immune responses, and tissue remodeling and has been studied for its role in angiogenesis, cell adhesion, and clearance of apoptotic cells. It is also recognized as a receptor involved in the regulation of phagocytosis and the inflammatory response. Due to its role in these vital cellular processes, CD93 has drawn significant interest in studies related to cancer, cardiovascular diseases, and immune disorders.

Encoded by the CD93 gene located on chromosome 20, the protein structure of CD93 enables interaction with a variety of ligands, allowing it to participate in different cellular and molecular pathways. This includes roles in immune cell adhesion and transmigration, particularly in inflammatory environments where endothelial cell function and integrity are critical. Research on CD93 continues to clarify its functional versatility, identifying its significance in modulating immune responses, cellular survival, and repair mechanisms in tissues.

Protein Structure

The CD93 protein is a transmembrane glycoprotein approximately 652 amino acids long and includes several structural domains that enable it to interact with a range of ligands and signaling molecules. These domains include:

C-Type Lectin Domain:

• At the N-terminal, CD93 features a C-type lectin-like domain that enables it to bind carbohydrates, facilitating interactions with glycosylated ligands. This domain is involved in pathogen recognition and immune response initiation, as C-type lectins are common in immune receptors responsible for recognizing pathogen-associated molecular patterns.

EGF-Like Repeats:

• CD93 contains five epidermal growth factor (EGF)-like repeats, which are crucial for protein-protein interactions. EGF-like repeats are known for their role in cell adhesion and signaling, which supports CD93’s involvement in immune cell adhesion and migration.
• These repeats also contribute to structural stability, allowing CD93 to maintain its functional conformation across different cell types.

Mucin-Like Domain:

• CD93 features a mucin-like domain rich in serine and threonine residues, which undergo extensive O-glycosylation. This domain allows CD93 to function in a hydrated and flexible state on the cell surface, aiding in cell-cell interactions, especially under inflammatory conditions where cell adhesion and migration are critical.
• The mucin-like domain provides a highly glycosylated structure that can be involved in creating a protective environment on the cell surface, limiting unwanted interactions or damage from pathogens or other environmental stressors.

Single-Transmembrane Helix:

• The protein has a single-pass transmembrane domain that anchors it within the cell membrane, stabilizing it and orienting the extracellular domains appropriately to interact with extracellular ligands. This region is key to maintaining CD93’s structural stability within the plasma membrane.

Cytoplasmic Tail:

• CD93 possesses a short cytoplasmic tail that is involved in intracellular signaling. This domain interacts with signaling molecules within the cell, allowing CD93 to mediate immune and inflammatory responses effectively.
• Specific phosphorylation sites in the cytoplasmic tail allow for signal transduction and downstream effects, impacting cellular processes such as phagocytosis and immune cell migration.

Classification and Subtypes

CD93 is classified as part of the C-type lectin-like superfamily due to its N-terminal lectin domain. However, it is distinct from other classical lectins because it also includes mucin-like and EGF-like domains, which broaden its functional repertoire. CD93 has no identified subtypes, but it is structurally and functionally related to CD141, which also participates in immune cell functions and inflammation regulation. CD93 is a unique molecule within its family due to its multifunctional domains, which allow it to engage in various immune pathways and cellular adhesion processes.

Function and Biological Significance

CD93 is multifunctional, participating in numerous critical biological processes:

Immune Response and Phagocytosis:

• CD93 plays an essential role in the immune system, particularly in phagocytosis. It has been shown to facilitate the clearance of apoptotic cells by phagocytes, an essential process for tissue homeostasis and preventing autoimmunity.
• Through interactions with ligands such as C1q, CD93 activates phagocytic cells to recognize and engulf apoptotic cells or pathogens, thus aiding in the resolution of inflammation.

Endothelial Function and Angiogenesis:

• CD93 is highly expressed on endothelial cells and is involved in vascular remodeling and angiogenesis. It facilitates cell adhesion and migration of endothelial cells, which are vital for new blood vessel formation.
• Angiogenesis promoted by CD93 is essential for wound healing and tissue repair and is a target of interest in tumor biology, as tumors rely on angiogenesis for nutrient supply.

Inflammatory Response:

• In inflammatory settings, CD93 expression increases, which supports leukocyte adhesion and transmigration across the endothelium to reach inflamed tissues. CD93 assists immune cells, particularly monocytes, in attaching to and migrating through endothelial layers.
• This function is critical in conditions requiring rapid immune cell mobilization, such as during infections or inflammatory diseases.

Role in Cell Adhesion and Signaling:

• CD93 participates in cell-cell adhesion through its mucin-like and EGF-like domains, which facilitate interactions with other cellular receptors and extracellular matrix components. This enhances cellular adhesion under inflammatory conditions, ensuring efficient immune surveillance.
• By engaging in signaling pathways through its cytoplasmic domain, CD93 modulates various intracellular cascades that regulate cell survival, proliferation, and immune responses.

Cancer and Tissue Remodeling:

• CD93 is implicated in tissue remodeling and is highly expressed in several cancer types, where it plays a role in cancer cell adhesion, migration, and angiogenesis. In cancer, CD93’s role in cell adhesion and angiogenesis is exploited to promote tumor growth and metastasis.

Clinical Issues

Cardiovascular Diseases:

• CD93 has been associated with vascular inflammation and endothelial dysfunction, factors that contribute to atherosclerosis and cardiovascular diseases. Variants in the CD93 gene have been linked to increased susceptibility to vascular diseases and poor outcomes in individuals with cardiovascular conditions.

Cancer:

• CD93’s role in promoting angiogenesis and cell adhesion has made it a target of interest in cancer therapy. Its expression on tumor-associated endothelial cells facilitates tumor growth and metastasis by enhancing blood vessel formation.
• Therapeutic strategies targeting CD93 or blocking its signaling pathways have been explored in cancers, such as glioblastoma, where inhibiting CD93 may restrict tumor angiogenesis and reduce tumor aggressiveness.

Inflammatory and Autoimmune Disorders:

• CD93 dysregulation is associated with autoimmune and inflammatory conditions. For example, increased expression of CD93 has been observed in rheumatoid arthritis, where it contributes to immune cell migration to the affected joints.
• Variants in the CD93 gene have been investigated in the context of autoimmune diseases, where CD93’s role in phagocytosis and apoptotic cell clearance may influence disease progression.

Infectious Diseases:

• CD93 expression is upregulated in infectious conditions, facilitating immune cell migration to infection sites. However, its role in viral infections, such as hepatitis or HIV, remains an area of active research, where CD93’s function in immune modulation could affect infection outcomes.

Summary

CD93 is a transmembrane glycoprotein with a complex structure that includes a C-type lectin domain, EGF-like repeats, and a mucin-like domain, all of which contribute to its roles in immune response, cell adhesion, and inflammation regulation. Primarily expressed on endothelial cells and immune cells, CD93 facilitates phagocytosis, enhances endothelial cell function, and promotes immune cell migration, especially under inflammatory conditions. Clinically, CD93 is involved in various disease states, including cardiovascular diseases, cancer, and autoimmune disorders, and its role in these contexts makes it a promising therapeutic target. Understanding CD93’s molecular function and interactions continues to reveal its potential in disease treatment, particularly in targeting inflammation, angiogenesis, and immune cell regulation.