MS4A1 Human
Description
Expression Profile
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Primary Sites: Expressed on B-cells from pre-B to mature stages, absent in plasma cells .
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Unexpected Localization: Detected in olfactory sensory neurons (OSNs) mediating predator odor detection .
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Cancer Context: Downregulated in colorectal carcinoma (CRC) and cervical cancer (CC), correlating with poor prognosis .
Immune System Functions
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B-Cell Development: Regulates calcium influx during B-cell receptor (BCR) activation, critical for differentiation into plasma cells .
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Therapeutic Target: Targeted by anti-CD20 monoclonal antibodies (e.g., rituximab) in B-cell malignancies .
Cancer Biology
Olfactory Function
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Sensory Role: MS4A1+ OSNs detect predator-derived odorants (e.g., trimethylamine), triggering innate avoidance behaviors in mice .
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Neuronal Specificity: Co-expressed with NeuN, distinct from canonical olfactory receptors .
Signaling Pathways
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Calcium Regulation: Functions as a store-operated calcium (SOC) channel component, amplifying BCR signaling .
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Immune Evasion: Loss in CRC tumors reduces CD8+CD20+ cytotoxic T lymphocytes (CTLs), enabling immune escape .
Experimental Data
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In Vitro Studies: Overexpression in CC cells suppresses proliferation and invasion .
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Animal Models: Ms4a1 knockout mice show defective predator odor avoidance .
Disease Associations
Therapeutic Targeting Challenges
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Resistance Mechanisms: Tumor microenvironment downregulates MS4A1, reducing CTL efficacy .
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Dual Roles: While pro-survival in B-cells, it exhibits tumor-suppressive activity in epithelial cancers .
Research Frontiers
Product Specs
MS4A1, B1, Bp35, CD20, CVID5, LEU-16, MS4A2, S7, B-lymphocyte surface antigen B1, Leukocyte surface antigen Leu-16, Membrane-spanning 4-domains subfamily A member 1.
Sf9, Insect cells.
ADPGIVENEW KRTCSRPKSN IVLLSAEEKK EQTIEIKEEV VGLTETSSQP KNEEDIEIIP IQEEEEEETE TNFPEPPQDQ ESSPIENDSS PHHHHHH.
Product Science Overview
MS4A1 is a B-lymphocyte-specific membrane protein that plays a crucial role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes . The protein contains four highly conserved transmembrane domains, flanked by N- and C-terminal cytoplasmic regions . It acts as a store-operated calcium (SOC) channel component, promoting calcium influx after activation by the B-cell receptor (BCR) .
The MS4A1 gene is localized to chromosome 11q12, among a cluster of family members . It is widely expressed during B-cell ontogeny, from early pre-B-cell developmental stages until final differentiation into plasma cells . The unique expression patterns of MS4A1 among hematopoietic cells and nonlymphoid tissues highlight its importance in the immune system .
MS4A1 is implicated in various diseases, including Common Variable Immunodeficiency (CVID) and Diffuse Large B-Cell Lymphoma (DLBCL) . The protein is a target for therapeutic antibodies, such as Rituximab, used in the treatment of B-cell malignancies . Its role in B-cell activation and calcium influx regulation makes it a critical component in immune response and a valuable target for immunotherapy .
