MS4A1
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Official Full Name
membrane-spanning 4-domains, subfamily A, member 1
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Overview
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. This family member is localized to 11q12, among a cluster of family members. Alternative splicing of this gene results in two transcript variants which encode the same protein. [provided by RefSeq, Jul 2008] -
Synonyms
MS4A1; membrane-spanning 4-domains, subfamily A, member 1; B1; S7; Bp35; CD20; CVID5; MS4A2; LEU-16; B-lymphocyte antigen CD20; CD20 antigen; CD20 receptor; leukocyte surface antigen Leu-16; B-lymphocyte cell-surface antigen B1;
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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.
High Purity
Fig1. SDS-PAGE (MS4A1-3928H) (PROTOCOL for western blot)
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Fig2. Activity Data. (MS4A1-3928H)
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.
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).
MS4A1 involved in several pathways and played different roles in them. We selected most pathways MS4A1 participated on our site, such as Hematopoietic cell lineage, which may be useful for your reference. Also, other proteins which involved in the same pathway with MS4A1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
| Pathway Name | Pathway Related Protein |
|---|---|
| Hematopoietic cell lineage | GM2002;FCGR1;FCER2;IL5RA;ANPEP;CD7;TFRC;IL6R;IL1A |
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.
| Function | Related Protein |
|---|---|
| MHC class II protein complex binding | PKM2;HLA-DMB;MS4A1;HLA-DMA;HLA-DRA;HSPA8;YWHAE;CD74;ANXA11 |
| epidermal growth factor receptor binding | CBLC;VAV2;PLSCR1;SNX1;VAV3;MS4A1;EFEMP1;LINGO1B;BTC |
| protein binding | CBL;LDB3;HSFX1;ITGA6;EFHA1;OLIG3;CDK13;C9orf43;NFASC |
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
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Q&As (7)
Ask a questionMS4A1 expression is tightly regulated during different stages of B-cell development. It is absent in early B-cell progenitors and gradually increases during maturation. MS4A1 expression is upregulated upon B-cell activation and can be influenced by various cytokines and signaling pathways. This tightly controlled expression pattern ensures proper B-cell development, while aberrant regulation may contribute to B-cell disorders or malignancies.
MS4A1 expression levels have been explored as potential diagnostic or prognostic markers for certain B-cell disorders. Quantification of CD20 expression by immunohistochemistry or flow cytometry can aid in the diagnosis and classification of B-cell malignancies. Additionally, low CD20 expression levels have been associated with resistance to CD20-targeted therapies, serving as a prognostic indicator in B-cell lymphomas.
While CD20-targeted antibodies have revolutionized the treatment of B-cell malignancies, further therapeutic strategies are being explored. These include enhancing CD20 internalization, using antibody-drug conjugates, and developing novel targeted therapies based on the signaling pathways associated with MS4A1. Investigating these approaches may provide alternative treatments and improve outcomes for patients with B-cell disorders.
MS4A1 helps maintain immune tolerance by preventing the production of autoreactive B cells. It contributes to the elimination of self-reactive B cell clones through mechanisms such as antibody-dependent cellular cytotoxicity and antibody-mediated phagocytosis. MS4A1 dysregulation, however, can lead to the production of autoantibodies and the development of autoimmune diseases. Understanding the fine-tuned regulation of MS4A1's functions is essential for maintaining immune homeostasis and preventing autoimmunity.
MS4A1 interacts with multiple proteins, such as tetraspanins, Src-family kinases, and lipid rafts, which form a complex network involved in B-cell signaling. Upon ligand binding, MS4A1 activates intracellular signaling pathways, including PI3K/Akt and MAPK/ERK, which regulate B-cell survival, proliferation, and differentiation. Understanding these pathways and their crosstalk with MS4A1 can provide insights into B-cell activation and potential therapeutic targets.
The MS4A1 protein, also known as CD20, is a tetraspanin membrane protein found predominantly in B cells. It plays a crucial role in B-cell development, activation, and antibody production. Structurally, CD20 consists of four transmembrane domains and a large extracellular loop. Functionally, it regulates B-cell signaling by promoting calcium influx upon B-cell receptor activation, modulating cell cycle progression, and facilitating antibody-mediated cytotoxicity.
MS4A1 dysregulation has been implicated in B-cell malignancies, including non-Hodgkin lymphomas and leukemia. Increased expression or altered signaling of MS4A1 may promote survival and proliferation of malignant B cells. CD20-targeted therapies, such as monoclonal antibodies, have been successfully employed in treating B-cell malignancies, highlighting the significance of MS4A1 as a therapeutic target in these diseases.
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