CD53 - CD53 molecule |Elisa - Clia - Antibody - Protein

Background

CD53 is a cell surface glycoprotein and a member of the tetraspanin superfamily, which plays a critical role in immune cell function. It is expressed primarily on hematopoietic cells, including leukocytes such as T cells, B cells, monocytes, neutrophils, and natural killer (NK) cells. CD53 is involved in immune cell signaling, adhesion, and trafficking, making it an important molecule for maintaining immune system integrity and function. CD53's role in facilitating interactions between immune cells and in transducing signals that promote activation and differentiation makes it a key participant in the regulation of immune responses.

The tetraspanins, of which CD53 is a member, are integral membrane proteins that form complexes with other membrane proteins, including integrins, growth factor receptors, and immune receptors. CD53 is known to associate with other tetraspanins and create specialized membrane domains called tetraspanin-enriched microdomains (TEMs), which function in organizing membrane proteins and coordinating signaling pathways. The protein has been implicated in the immune system’s defense against pathogens and in the activation and function of leukocytes.

Protein Structure

CD53 belongs to the tetraspanin superfamily, which is characterized by the presence of four transmembrane domains. The molecular weight of CD53 is approximately 32 to 35 kDa, and the protein is heavily glycosylated. The structural features of CD53 are typical of tetraspanins, and they include the following components:

Four Transmembrane Domains:

• CD53 spans the plasma membrane four times, creating four transmembrane helices. These helices are essential for anchoring the protein in the cell membrane and are involved in the interactions of CD53 with other proteins, especially other tetraspanins and integrins.
• The transmembrane regions also mediate the clustering of tetraspanins into TEMs, which are critical for organizing membrane microdomains involved in cell signaling.

Two Extracellular Loops:

• CD53 has two extracellular loops: a small first extracellular loop (SEL) and a larger second extracellular loop (LEL). The LEL is the most functionally significant region of the protein and contains several conserved cysteine residues that form disulfide bonds, contributing to the protein’s stability and function.
• The LEL plays a critical role in interacting with other membrane proteins and in mediating cell adhesion and signaling. It is also the site where the protein undergoes post-translational modifications, including N-glycosylation, which influences the protein’s ability to mediate cell interactions and immune responses.

Short N- and C-terminal Cytoplasmic Domains:

• Both the N- and C-termini of CD53 are located within the cytoplasm and contain regions essential for signal transduction. These domains interact with cytoskeletal proteins and signaling molecules, allowing CD53 to influence cell motility and immune activation.

Glycosylation:

• CD53 is glycosylated on its extracellular domain, particularly within the LEL. This glycosylation influences the protein's structural conformation and can affect how CD53 interacts with other tetraspanins or receptors on the cell surface.

Tetraspanin Enriched Microdomains (TEMs):

• CD53, like other tetraspanins, plays a pivotal role in the formation of TEMs. These are specialized membrane areas where tetraspanins cluster with other molecules such as integrins, growth factor receptors, and immune receptors. TEMs serve as signaling platforms that coordinate various cellular processes, such as cell adhesion, migration, and immune cell activation.

Classification and Subtypes

CD53 is classified as a member of the tetraspanin family of proteins. This family is characterized by a conserved structure featuring four transmembrane domains and two extracellular loops. Tetraspanins, including CD53, are not known to have distinct subtypes, but they do engage in highly specific interactions with other tetraspanins and membrane proteins. These interactions allow tetraspanins to modulate the activity of their partner proteins, impacting various cellular processes.

CD53 is closely related to other members of the tetraspanin family, such as CD9, CD37, CD63, and CD81, all of which are involved in forming TEMs. These proteins often interact with one another to regulate cell adhesion, migration, and immune signaling. CD53's functional importance is particularly notable in cells of the immune system, where it participates in the coordination of responses to external stimuli.

Function and Biological Significance

CD53 plays several critical roles in the immune system, primarily by modulating leukocyte activity and facilitating immune cell communication. Key functions of CD53 include:

Immune Cell Signaling:

• CD53 participates in signaling pathways that are essential for immune cell activation and function. For instance, CD53 has been implicated in the signal transduction pathways of T cells and B cells, where it helps regulate processes like cell proliferation, differentiation, and survival. It does this by associating with other tetraspanins and forming TEMs, which act as platforms for initiating signaling cascades in response to external stimuli.
• CD53 has also been linked to the activation of mitogen-activated protein kinases (MAPKs), which are involved in mediating immune responses and inflammation.

Cell Adhesion and Migration:

• CD53 is involved in regulating cell adhesion and motility, particularly in leukocytes. It helps control the migration of immune cells to sites of infection or inflammation by interacting with integrins and other adhesion molecules. This ability to regulate cell motility is crucial for immune surveillance and the initiation of immune responses.
• By forming complexes with integrins, CD53 enhances the ability of immune cells to adhere to endothelial cells and move across the vascular endothelium, a process known as transendothelial migration. This is particularly important during the immune response, when leukocytes must leave the bloodstream to reach infected or damaged tissues.

Protection Against Apoptosis:

• CD53 has been implicated in protecting immune cells from apoptosis (programmed cell death). This function is vital for ensuring the survival of leukocytes, particularly during an immune response. The anti-apoptotic role of CD53 is thought to be linked to its interactions with other proteins within TEMs, where it influences signaling pathways that regulate cell survival.

Immune Regulation:

• CD53 plays a role in regulating immune homeostasis, ensuring that immune responses are properly controlled and that immune cells do not become over-activated. Dysregulation of CD53 function can lead to impaired immune responses or contribute to autoimmune diseases.

Role in Inflammatory Responses:

• CD53 also appears to be involved in regulating inflammatory responses. It has been shown to participate in the activation of neutrophils and monocytes during inflammation, helping to modulate their responses to pro-inflammatory signals. This includes the production of cytokines and other inflammatory mediators.

Clinical Issues

Immunodeficiencies:

• Mutations or deficiencies in CD53 are associated with immunodeficiency syndromes, where patients exhibit compromised immune responses. For example, individuals with CD53 deficiency may suffer from recurrent infections due to impaired leukocyte function. The inability of immune cells to effectively migrate, adhere, or signal properly can lead to a weakened immune system and increased susceptibility to infections.

Role in Cancer:

• CD53 expression has been linked to certain types of lymphomas and leukemias, where its overexpression or altered function may contribute to the survival and proliferation of cancerous immune cells. Studies suggest that CD53 may play a role in the regulation of B-cell lymphomas, and its expression could be used as a marker for disease progression in some cases.

Autoimmune Diseases:

• Altered CD53 function has been observed in autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). In these diseases, immune cells become overactive and attack the body’s own tissues. Dysfunctional CD53-mediated signaling may contribute to the dysregulation of immune responses that leads to autoimmunity.

Therapeutic Targeting:

• Given its role in immune cell function, CD53 is being explored as a therapeutic target. Modulating CD53 activity could be beneficial in treating immune-related conditions, including cancers and autoimmune diseases. For instance, targeting CD53 in immune cells might help to enhance immune responses in cancer or reduce immune overactivity in autoimmunity.

Summary

CD53 is a tetraspanin glycoprotein that plays a crucial role in immune cell signaling, adhesion, and survival. Its structure, characterized by four transmembrane domains and two extracellular loops, allows it to interact with other membrane proteins and form tetraspanin-enriched microdomains (TEMs), which serve as hubs for immune signaling. CD53 is predominantly expressed in hematopoietic cells, where it regulates leukocyte activity, migration, and protection against apoptosis. Clinically, CD53 is associated with immunodeficiency disorders, certain cancers, and autoimmune diseases, making it a potential therapeutic target for treating immune-related conditions. Its ability to modulate immune responses highlights its importance in maintaining immune homeostasis and defending against pathogens. Further research into CD53 could provide insights into new treatments for cancer, autoimmune disorders, and immunodeficiencies.