CD63

What is CD63 Protein?

CD63 gene (CD63 molecule) is a protein coding gene which situated on the long arm of chromosome 12 at locus 12q13. The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. The encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. The CD63 protein is consisted of 238 amino acids and CD63 molecular weight is approximately 25.6 kDa.

What is the Function of CD63 Protein?

CD63 can interact with a variety of molecules such as integrin, CD81, CD9, etc., and participate in the regulation of cell morphology, movement, signal transduction and plasma membrane dynamics. CD63 is involved in the sorting and transport of proteins within the cell, especially in endosomal and lysosomal pathways, contributing to the stability and protection of proteins and preventing their degradation. CD63 is involved in the transport and storage of cholesterol in the endosomes and its distribution through exosomes, and is essential for maintaining intracellular cholesterol balance. By activating integrin signaling, CD63 promotes cell adhesion, diffusion, and migration, affecting cell survival and cytoskeletal recombination. CD63 plays a role in VEGFA signaling by regulating the internalization of KDR/VEGFR2, affecting the angiogenesis process. CD63 is involved in white blood cell adhesion to endothelial cells by regulating SELE protein transport.

Fig1. Schematic overview showing the occurrence of CD63 in intermediates of the biosynthetic- and endosomal pathways. (Maaike S Pols, 2009)

CD63 Related Signaling Pathway

CD63 is a key component of small extracellular vesicles, sorting cholesterol into intracavicular vesicles (ILVs), forming a library that can be mobilized by NPC1/2 complexes and exported to recipient cells via exosomes, affecting intercellular communication. CD63 acts as a lipid sorting mechanism in the endosome and is involved in the transport and distribution of cholesterol. When CD63 is absent, cholesterol is recovered from the endosome via actin-dependent vesicle transport. CD63 and cholesterol play a central role in endointimal inward and outward bud balance. CD63, through its endosomal and lysosomal localization, participates in extracellular vesicle-mediated signaling, affecting intercellular communication and substance exchange. CD63 can quench cKIT tyrosine kinase function and cKIT phosphorylation of Y721, regulate cKIT signaling, affect erythroblastic stem cell factor response, and may play a role in the pathogenesis of diseases such as polycythemia true.

CD63 Related Diseases

CD63 is a cell surface protein that is mainly expressed on immune cells such as monocytes, macrophages and dendritic cells. CD63 is associated with a variety of diseases, including autoimmune diseases, infectious diseases, and tumors. For example, CD63 is up-regulated in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, suggesting that CD63 may be involved in the pathogenesis of these diseases. In addition, CD63 also plays an important role in infectious diseases such as viral infections and bacterial infections, and may affect the progression of diseases by regulating immune responses and inflammatory responses. Finally, CD63 also plays an important role in the occurrence and development of tumors, and may affect the prognosis of tumors by regulating the proliferation, invasion and metastasis of tumor cells.

Bioapplications of CD63

As an important cell surface protein, CD63 has a wide range of applications in immunology and disease diagnosis. For example, CD63 can be used as a marker to distinguish different types of immune cells and to study the function of the immune system and the mechanism of disease occurrence. In addition, CD63 can also be used as a marker for the diagnosis of certain diseases, such as rheumatoid arthritis, systemic lupus erythematosus and other autoimmune diseases. In oncology, CD63 can be used to evaluate the prognosis of tumors and predict the effect of treatment. Therefore, the study of CD63 is of great significance for the in-depth understanding of the function of the immune system and the mechanism of disease occurrence, as well as the development of new diagnostic and therapeutic methods.

Case Study 1: Bart E C G de Goeij, 2016

For many cell surface proteins and carbohydrate structures on tumor cells, however, the magnitude of these processes is insufficient to allow for an effective antibody-drug conjugates (ADC) approach. Researchers hypothesized that we could overcome this limitation by enhancing lysosomal ADC delivery via a bispecific antibody (bsAb) approach, in which one binding domain would provide tumor specificity, whereas the other binding domain would facilitate targeting to the lysosomal compartment. Therefore a bsAb was designed in which one binding arm specifically targeted CD63, a protein that is described to shuttle between the plasma membrane and intracellular compartments, and combined it in a bsAb with a HER2 binding arm, which was selected as model antigen for tumor-specific binding. The resulting bsHER2xCD63his demonstrated strong binding, internalization and lysosomal accumulation in HER2-positive tumor cells, and minimal internalization into HER2-negative cells.

Fig1. Lysosomes were stained with mouse anti-human LAMP1-APC (red), and CD63 antibodies were stained with goat anti-human IgG1-FITC (green).

Fig2. Efficacy of bsHER2xCD63his-Duo3, bsHER2xb12-Duo3, bsCD63hisxb12-Duo3, IgG1 b12-Duo3, and IgG1-b12 in a SK-OV-3 xenograft model.

Case Study 2: Antonella Lupia, 2014

The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. Researchers employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. They used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth.

Fig3. Immunoblot analysis of CD63 expression level in A375, M21, and SSM2c cells.

Fig4. Correlation between CD63 expression levels and migration.

CD63 has several biochemical functions, for example, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CD63 itself. We selected most functions CD63 had, and list some proteins which have the same functions with CD63. You can find most of the proteins on our site.

CD63 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CD63 here. Most of them are supplied by our site. Hope this information will be useful for your research of CD63.

env;TIMP1;LMP1;ITGB1;SRC;Ptpra;Enam;Ambn;q6krg0_bacan;Amelx