Homo sapiens MS4A1
B-lymphocyte antigen CD20 | Protein names
B-lymphocyte antigen CD20 | Alternative names
B-lymphocyte surface antigen B1, Bp35, Leukocyte surface antigen Leu-16, Membrane-spanning 4-domains subfamily A member 1 | Gene names
MS4A1 | Protein family
Belongs to the MS4A family | Function
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 (PubMed:12920111, PubMed:3925015, PubMed:7684739). Functions as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR (PubMed:12920111, PubMed:18474602, PubMed:7684739) | Subcellular location
Cell membrane, Cell membrane | Structure
Forms homotetramers (PubMed:18474602, PubMed:7684739). Interacts with the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR (PubMed:18474602) | Post-translational modification
Phosphorylated on serines and threonines in resting B-cells. Protein kinase C/PKC can use CD20 as substrate
| Involvement in disease
Immunodeficiency, common variable, 5
A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.
| Keywords
3D-structure, Alternative splicing, B-cell activation, Cell membrane, Disulfide bond, Lipoprotein, Membrane, Palmitate, Pharmaceutical, Phosphoprotein, Proteomics identification, Reference proteome, Transmembrane, Transmembrane helix | Sequence
MTTPRNSVNGTFPAEPMKGPIAMQSGPKPLFRRMSSLVGPTQSFFMRESKTLGAVQIMNG LFHIALGGLLMIPAGIYAPICVTVWYPLWGGIMYIISGSLLAATEKNSRKCLVKGKMIMN SLSLFAAISGMILSIMDILNIKISHFLKMESLNFIRAHTPYINIYNCEPANPSEKNSPST QYCYSIQSLFLGILSVMLIFAFFQELVIAGIVENEWKRTCSRPKSNIVLLSAEEKKEQTI EIKEEVVGLTETSSQPKNEEDIEIIPIQEEEEEETETNFPEPPQDQESSPIENDSSP | | UniProt accession: P11836 |
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Homo sapiens CD3E
T-cell surface glycoprotein CD3 epsilon chain | Protein names
T-cell surface glycoprotein CD3 epsilon chain | Alternative names
T-cell surface antigen T3/Leu-4 epsilon chain | Gene names
CD3E | Function
Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response (PubMed:15294938, PubMed:15546002, PubMed:2470098, PubMed:40592325, PubMed:8490660). When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD247/CD3Z (PubMed:2470098, PubMed:40592325). All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain (PubMed:2470098, PubMed:40592325). Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098, PubMed:40592325). CD3E ITAM phosphorylation creates docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (By similarity). In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development (By similarity). Also participates in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region (PubMed:10384095, PubMed:26507128). In addition to its role as a TCR coreceptor, it serves as a receptor for ITPRIPL1 (PubMed:38614099). Ligand recognition inhibits T-cell activation by promoting interaction with NCK1, which prevents CD3E-ZAP70 interaction and blocks the ERK-NFkB signaling cascade and calcium influx (PubMed:12110186, PubMed:38614099) | Subcellular location
Cell membrane | Structure
The TCR-CD3 complex is composed of a CD3D-CD3E and a CD3G-CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha-CD3E-CD3G and TCRbeta/CD3G-CD3E trimers (PubMed:15136729, PubMed:15534202, PubMed:40592325). In turn, the hexamer interacts with CD247/CD3Z homodimer to form the TCR-CD3 complex (PubMed:15136729, PubMed:15534202). Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with CD6 (PubMed:15294938). Interacts (via Proline-rich sequence) with NCK1; the interaction is ligand dependent but independent of tyrosine kinase activation (PubMed:12110186, PubMed:15972658, PubMed:38614099). Interacts with NUMB; this interaction is important for TCR-CD3 internalization and subsequent degradation (PubMed:26507128). Interacts (when tyrosine phosphorylated) with LAG3; disrupting the association between CD3E and LCK and preventing TCR activation (PubMed:15534202) | Post-translational modification
Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8
| Involvement in disease
Immunodeficiency 18
An autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18.
| Keywords
3D-structure, Adaptive immunity, Cell membrane, Disulfide bond, Immunity, Immunoglobulin domain, Membrane, Phosphoprotein, Proteomics identification, Receptor, Reference proteome, Signal, Transmembrane, Transmembrane helix | Sequence
MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQ HNDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCE NCMEMDVMSVATIVIVDICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERP PPVPNPDYEPIRKGQRDLYSGLNQRRI | | UniProt accession: P07766 |
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