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CD33

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

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 CD33-mediated NK cell inhibition: a model. (OA Literature)Fig. 1 Model for CD33 inhibition in NK cells.1

Function of CD33 Protein: A Key Inhibitory Receptor Regulating Myeloid Cell Signaling

The functional spectrum of CD33 encompasses multiple layers of immune regulatory activity and is being actively investigated:

  • Sialic acid recognition and ligand binding: CD33 functions as a sialic acid-binding lectin, with its N-terminal V-set immunoglobulin-like domain preferentially recognizing α2,6- and α2,3-linked sialic acid residues presented on glycoproteins and glycolipids of neighboring cells. This glycan-dependent recognition mediates cell-cell interactions and serves as a mechanism for discriminating self from non-self.
  • ITIM-mediated inhibitory signaling: The cytoplasmic tail of CD33 contains two conserved ITIM sequences at Tyr-340 and Tyr-358. Upon ligand binding, these motifs are phosphorylated by Src-family kinases such as LCK, creating docking sites for the SH2 domain-containing phosphatases SHP-1 and SHP-2. These phosphatases dephosphorylate key signaling intermediates, leading to suppression of calcium mobilization and attenuation of downstream activation cascades.
  • Regulation of myeloid cell activation and phagocytosis: Through its inhibitory signaling capacity, CD33 negatively regulates myeloid cell functions including pro-inflammatory cytokine production, oxidative burst, and phagocytic activity. Engagement of CD33 dampens cellular activation thresholds, contributing to the maintenance of immune quiescence under homeostatic conditions.
  • Isoform diversity and functional modulation: The two major CD33 isoforms exhibit distinct subcellular distributions: full-length CD33M localizes to the plasma membrane and functions as a canonical inhibitory receptor, while the shorter CD33m isoform, lacking the V-set domain, is predominantly retained in intracellular compartments. The relative expression ratio of these isoforms, influenced by genetic variation in the CD33 locus, modulates the net inhibitory tone on myeloid cells and represents an important determinant of CD33-mediated immune regulation.

CD33 Membrane Protein Product

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.

CD33 Protein Product

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CD33 Stable Cell Line Product

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.

CD33 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

CD33 Recombinant Antibody Product

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.

CD33 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • Multiple expression platforms: Recombinant proteins can be produced through several expression systems (encompassing virus-like particles and both prokaryotic and eukaryotic hosts), addressing the requirements of diverse experimental settings.
  • Broad experimental compatibility: The products are suitable for use in ELISA, antibody screening, binding assays, Western Blot, immunofluorescence, immunohistochemistry, and related applications.
  • Consistent quality across batches: Strict quality control measures maintain product uniformity between batches, ensuring experimental results remain reproducible and dependable.
  • Tailored customization services: Personalized services are available for specific protein forms, labeling approaches, or preferred expression platforms.

Custom CD33 Membrane Protein and Antibody Discovery Services

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:

  • Customized production of plasma membrane proteins: Tailored expression (using multiple expression systems), purification, and characterization for full-length CD33 and its individual extracellular domains.
  • Customized antibody development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant antibodies), supporting isoform-specific detection or common epitope recognition.
  • Construction of stable cell models: Generate stable cell models expressing wild-type or isoform-specific CD33, suitable for ligand binding and signaling studies.
  • Development of functional detection systems: Design and execute experimental protocols such as sialic acid binding assays, ITIM phosphorylation analysis, and quantitative assessment of inhibitory signaling activity.

Frequently Asked Questions (FAQ)

  1. What is the main function of the CD33 protein?

    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.

  2. Why is CD33 an important research target?

    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.

  3. Is the CD33 product of Creative Biolabs suitable for clinical applications?

    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.

  4. What types of CD33 products does Creative Biolabs offer?

    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.

Reference
  1. Hernández-Caselles, Trinidad, et al. "CD33 (Siglec‐3) inhibitory function: role in the NKG2D/DAP10 activating pathway." Journal of immunology research 2019.1 (2019): 6032141. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.1155/2019/6032141
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