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The CD33 gene is located in the 19q13.41 region of the human chromosome and encodes the CD33 molecule (CD33), also known as sialic acid-binding Ig-like lectin 3 (SIGLEC-3), a member of the CD33-related SIGLEC family within the immunoglobulin superfamily. CD33 is a type I transmembrane glycoprotein, with two extracellular immunoglobulin-like domains (an N-terminal V-set domain and a C2-set domain), a single transmembrane region, and a cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Its native molecular weight is approximately 67 kDa due to extensive glycosylation, and it is predominantly expressed on myeloid lineage cells including monocytes, macrophages, granulocytes, and microglia, with expression levels decreasing during myeloid maturation. As an inhibitory receptor involved in immune regulation, CD33 recognizes α2,6- and α2,3-linked sialic acid-containing glycans on cell surfaces, and upon ligand engagement, its ITIMs are phosphorylated by Src-family kinases, leading to recruitment of the tyrosine phosphatases SHP-1 and SHP-2, which dephosphorylate downstream signaling molecules and attenuate cellular activation. These processes play important roles in maintaining immune homeostasis, modulating phagocytic activity, and regulating inflammatory responses. This gene produces two major isoforms through alternative splicing: full-length CD33M, which localizes to the plasma membrane, and CD33m, which lacks the sialic acid-binding V-set domain and is predominantly retained in intracellular compartments. Genetic polymorphisms in the CD33 locus, particularly in the promoter region and exon 2, influence the relative abundance of these isoforms. Therefore, CD33 is regarded as an important molecular target for studying immune inhibitory signaling and myeloid cell regulation. Its functional analysis provides valuable tools for understanding the molecular mechanisms of immune checkpoint control and cell-cell recognition mediated by the sialic acid-SIGLEC axis.
Fig. 1 Model for CD33 inhibition in NK cells.1
The functional spectrum of CD33 encompasses multiple layers of immune regulatory activity and is being actively investigated:
Creative Biolabs offers a comprehensive series of high-quality CD33 membrane protein products designed to support structural and functional investigations of sialic acid recognition and inhibitory signaling. Built upon the independently developed MemDX™ recombinant membrane protein technology platform, CD33 proteins can be prepared through multiple expression systems, including virus-like particles (VLP) and in vitro prokaryotic expression systems, among others. These rigorously characterized protein products, which include MemDX™ recombinant human CD33 membrane protein (as virus-like particles) and human CD33 proteins derived from diverse expression systems, are suitable for ELISA, antibody screening and identification, binding experiments, and functional research, equipping investigators with dependable reagents for analyzing CD33-mediated sialic acid recognition and immune inhibitory signaling mechanisms.
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Constructing a robust cell model is crucial for investigating CD33 function in immune inhibitory signaling. As a plasma membrane inhibitory receptor that recruits SHP-1 and SHP-2 phosphatases via its ITIM motifs, the expression level and ligand-binding capacity of CD33 directly affect the threshold of myeloid cell activation and downstream signaling responses. Alterations in CD33 expression or changes in the relative abundance of its isoforms may lead to significant differences in cellular activation states. Creative Biolabs offers customized CD33 membrane protein stable transfection cell models, covering wild-type and various isoform-specific forms. These models stably express the target protein on the plasma membrane, and are suitable for studies on sialic acid ligand binding, ITIM phosphorylation dynamics, phagocytosis assays, and quantitative assessment of inhibitory signaling output, providing a reliable and reproducible platform for exploring the molecular mechanism, structure-function relationship, and regulatory role of CD33 in immune cell homeostasis. Our technology ensures correct protein localization and plasma membrane integrity, facilitating your research.
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Creative Biolabs offers highly specific recombinant antibodies targeting CD33, produced using advanced recombinant antibody technology. Compared to traditional antibodies, these recombinant antibodies demonstrate superior performance in terms of specificity, sensitivity, and batch-to-batch consistency. They can also be modified and labeled in various ways. Our CD33 recombinant antibodies support a wide range of applications, including Western Blot, ELISA, flow cytometry, immunofluorescence, immunocytochemistry, immunohistochemistry, and immunoprecipitation, and can be used to detect differences in CD33 expression levels in various tissues or cell sources, analyze its plasma membrane localization and isoform distribution, and conduct related research such as sialic acid ligand binding analysis and ITIM signaling pathway investigation. These antibodies provide reliable detection tools for the structural analysis, functional study of CD33, and the investigation of its role in immune inhibitory signaling and myeloid cell regulation.
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In addition to the standard products, Creative Biolabs also offers professional customized services for CD33. CD33 exists as two major isoforms with distinct subcellular distributions and functional properties. These isoforms have specific requirements in aspects such as membrane protein expression, antigen design, and functional characterization. Leveraging our technology platform, we can assist you in completing the following customized projects:
CD33 functions as an inhibitory receptor on the surface of myeloid lineage cells, recognizing sialic acid-containing glycans through its N-terminal V-set immunoglobulin-like domain. Upon ligand engagement, its cytoplasmic ITIM motifs are phosphorylated, recruiting the tyrosine phosphatases SHP-1 and SHP-2 to dephosphorylate downstream signaling molecules, thereby attenuating cellular activation, phagocytosis, and inflammatory cytokine production. CD33 serves as an important model for studying immune inhibitory signaling and glycan-dependent immune regulation.
CD33 exists as two major isoforms with distinct subcellular localizations and functional properties, providing a valuable system for studying alternative splicing-mediated regulation of immune receptor function. Investigating CD33 is helpful for understanding the molecular mechanisms of ITIM-mediated inhibitory signaling, the role of sialic acid recognition in immune homeostasis, and how genetic variation modulates immune receptor activity. CD33 also represents an important model for studying the CD33-related SIGLEC family, which plays broad roles in immune regulation.
Not applicable. All CD33 products and services provided by Creative Biolabs are for research purposes only and cannot be used for any clinical diagnosis, prevention, treatment or cure of any disease.
We offer a variety of product types, including recombinant CD33 membrane proteins, stable cell models expressing CD33, high-quality recombinant CD33 antibodies, as well as comprehensive customized services.