MS4A1

What is MS4A1 protein?

MS4A1 (membrane spanning 4-domains A1) gene is a protein coding gene which situated on the long arm of chromosome 11 at locus 11q12. This gene encodes a member of the membrane-spanning 4A gene family. Members of this nascent protein family are characterized by common structural features and similar intron/exon splice boundaries and display unique expression patterns among hematopoietic cells and nonlymphoid tissues. This gene encodes a B-lymphocyte surface molecule which plays a role in the development and differentiation of B-cells into plasma cells. The MS4A1 protein is consisted of 297 amino acids and its molecular mass is approximately 33.1 kDa.

What is the function of MS4A1 protein?

MS4A1 is a b-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes. It also acts as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR.

MS4A1 Related Signaling Pathway

The MS4A1 protein is a cell membrane protein that is involved in a variety of signaling pathways and biological processes. The following are some of the signaling pathways associated with MS4A1 protein: MS4A1 protein is widely expressed in immune cells, including lymphocytes, dendritic cells, etc. It is involved in a variety of immunomodulatory processes, regulating the function of immune cells and immune responses by interacting with other signaling molecules. The MS4A1 protein is expressed in several cell types, including tumor cells and nerve cells. It plays an important role in cell proliferation and survival through PI3K-Akt signaling pathway, MAPK signaling pathway and so on.

MS4A1 Related Diseases

MS4A1, also known as CD20, protein plays an important role in the activation and differentiation of T cells, so its abnormal function may lead to immune deficiency diseases, such as congenital immune deficiency syndrome (CIDS). Its abnormal function may lead to the occurrence of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus and so on. MS4A1 protein is abnormally expressed in many cancers, such as breast cancer, colon cancer, lung cancer and Non-Hodgkin's lymphoma, etc.

Fig1. A higher power view (Patient 1) shows epidermotropic lymphocytes (A), with expression of CD3 (B, D) and CD20 (C, D). Co-expression of CD3 and CD20 is confirmed on a dual CD3/CD20 immunohistochemical study (D; CD3 in red, CD20 in brown). (Kelly L Harms, 2014)

Bioapplications of MS4A1

Using the specific expression of MS4A1, researchers are exploring the possibility of wrapping drugs in specific vectors for targeted delivery by binding to MS4A1. Drugs that interact with MS4A1 are being developed for use in tumor therapy.

Case study 1: Martijn Vlaming, 2021

The presence of T cells that are dimly positive for the B cell marker CD20 is well-established in autoimmunity and correlates with disease severity in various diseases. CD20-positive T cells were previously identified as IFN-gamma producing, low proliferative, CD8 cytotoxic T cells with an effector memory (EM) differentiation state. However, the exact phenotype and relevance of CD20-positive T cells remains unclear.

To gain insight into potential functional properties of CD20 expression in T cells, CD20 was ectopically expressed on healthy human T cells and phenotypic, functional, migratory and adhesive properties were determined in vitro and in vivo. Together, these assays revealed a reduced transmigration and an enhanced adhesive profile combined with an enhanced activation status for CD20-positive T cells.

Fig1. 1.0 × 10^6 primary T cells were transduced with the CD20 or SFCMM-3 retroviral vector (mean of 50% CD20 + or 50% NGFR-positive) and the influence of CD20 expression on the viability of cells was investigated by Annexin-V and PI staining at 7 days post transduction.

Fig2. Immunohistochemical evaluation was performed in mice injected with T cells ectopically expressing CD20.

Case study 2: Veronika Kozlova, 2020

Surface protein CD20 serves as the critical target of immunotherapy in various B-cell malignancies for decades, however its biological function and regulation remain largely elusive. Using CRISPR/Cas9 technique, the researchers have abrogated CD20 expression in five different malignant B-cell lines. The findings show that CD20 deletion has no effect upon B-cell receptor signaling or calcium flux. Also B-cell survival and proliferation is unaffected in the absence of CD20. Mechanistically, we could identify a reduction in chemokine-triggered PYK2 activation, a calcium-activated signaling protein involved in activation of MAP kinases and cytoskeleton regulation. These cellular defects in consequence result in a severely disturbed homing of B cells in vivo.

Fig3. Ramos control and CD20 knockout cells were stimulated with Rituximab (RTX) or anti-IgM antibodies for indicated times (minutes).

Fig4. Defective chemokine signaling in the absence of CD20. Ramos (left panels) and MEC1 (right panels) control and CD20-knockout cells were stimulated with chemokines SDF1α or CCL19, respectively, for indicated times (minutes).

MS4A1 has several biochemical functions, for example, MHC class II protein complex binding,epidermal growth factor receptor binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by MS4A1 itself. We selected most functions MS4A1 had, and list some proteins which have the same functions with MS4A1. You can find most of the proteins on our site.

MS4A1 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 MS4A1 here. Most of them are supplied by our site. Hope this information will be useful for your research of MS4A1.

CCDC155;IGHM;IGHD;CREB3;xthA;tyrS