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CST3

Products

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

Background

Cystatin C (CST3), also known as gamma-trace, post-gamma-globulin or neuroendocrine basic polypeptide is a secreted protein of approximately 13 kDa and the most abundant extracellular cysteine protease inhibitor. CST3 is secretomed in all nucleated cells, and released into biological fluids at concentrations determined by the equilibrium between its biosynthesis and renal clearance. The serum concentration of cystatin C, unlike creatinine, does not depend upon muscle mass and is unaffected by age, sex, race and dietary protein intake; thus it reflects a better endogenous marker of GFR. The protein is freely filtered at the glomerulus and then catabolized by proximal tubular cells, with little return to the circulation. In excess of renal physiology, CST3 is particularly highly enriched in cerebrospinal fluid—its concentrations are roughly five-fold higher than plasma highlight.

Fig.1 The overview of type 2 cystatins' role including CST3. (OA Literature)Fig.1 The overview of type 2 cystatins' role on immune regulation and cancer development.1

CST3 Protein Function: A Ubiquitous Guardian of Proteolytic Homeostasis

CST3 functional portfolio is large enough to cover multiple physiological and pathological systems:

  • Cysteine Protease Inhibition: CST3 represents a potent, reversible papain-like cysteine proteases inhibitor of cathepsin B, H and L; it occludes the active site cleft of these enzymes that would otherwise be able to perform an uncontrolled active proteolysis reaction on extracellular matrix components, modulates lysosomal enzyme activity and promotes vascular wall integrity. Their inhibiting activity plays an important role in the remodeling of tissues, phagocytosis for antigen presentation and defense against pathogens.
  • Neuroprotection and Amyloid Modulation: In the brain CST3 directly binds to amyloid-β (Aβ) peptides inhibiting oligomerization and axial dimerization of fibrils. It co-localizes with amyloid plaques in senile plaque deposits and vascular deposits of cerabral vessel walls, it associates with the soluble non pathological form of Aβ in transgenic models while inhibiting plaque deposition. It is also neuroprotective against a wide range of cytotoxic insults, including protection against Aβ-induced cell death and has been reported to induce mTOR-mediated autophagy and increase clearance of aggregated proteins.
  • Vascular Integrity and Cerebral Amyloid Angiopathy: CST3 is secreted by vascular smooth muscle cells, where it protects vessel wall integrity through inhibition of proteolytic cleavage of extracellular matrix. CST3-containing amyloid-like material deposits in the walls of human cerebral vessels due to a missense mutation (L68Q) that increases the tendency for domain swapping and loss of an inhibitory activity on protease. The pathologic effects of this autosomal dominant composed mutant CST3 gene triggers a series of processes leading to cerebral amyloid angiopathy (CAA), an irreversible condition which leads to recurrent brain hemorrhage/stroke/cognitive decline. Moreover, CAA co-deposition with CST3 in sporadic cases suggests that other aggregation-prone conformations are not only responsible for vascular pathology even in the absence of germline mutations.

CST3 Protein Product

Expand your mechanistic and studies with catalog of our highly characterized recombinant CST3 protein. CST3, a typical secreted cysteine protease inhibitor rather than a membranous anchored receptor, still relies upon correct folding of disulfide bonds and protease-binding in order to produce reproducible results. Mammalian HEK293 cells and E. coli expression systems are utilized for the generation of fully active, endotoxin-free CST3 preparations that retain native cathepsin B inhibitory potency and Aβ-binding capabilities. We provide the wild-type human and mouse CST3, disease-associated L68Q variant and aggregated oligomeric forms to support studies of the pathological mechanisms. Each batch is subjected to stringent quality control such as SDS-PAGE, analytical size-exclusion chromatography, mass spectrometry and cathepsin B activity assays verifying their suitability for enzyme kinetics, ligand binding studies and antibody screening.

CST3 Protein Product

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

CST3 Stable Cell Line Product

Robust cellular models are essential for dissecting CST3-driven biology and evaluating candidates. Stable cell lines: Cell lines that express human, mouse or rat CST3 (constitutively or inducibly) and with knocked-down endogenous expression for loss-of-function studies These platforms also serve as a consistent and reproducible foundation for studies of CST3-mediated pathology and pharmacology, making them suitable for high-throughput compound screening (cathepsin activity assays), studies to inhibit Aβ aggregation, as well as GFR biomarker validation.

CST3 Stable Cell Line Product

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

CST3 Recombinant Antibody Product

CST3 High affinity recombinant antibodies targeting CST3 are included in our portfolio to support the rigorous needs of different research applications. Our recombinant CST3 antibody are more sensitive, specific, and consistent across lots compared with conventional polyclonal antibodies. Additionally, all these CST3 recombinant antibodies are validated for Western Blotting (WB), ELISA, Flow Cytometry (FCM), Immunofluorescence (IF),Immunocytochemistry(ICC) and Imunohistochemistry(IHC) etc., ensuring precise detection and quantification of CST3 in serum, plasma, cerebrospinal fluid, etc.

CST3 Recombinant Antibody Product

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

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Exceptional Lot-to-Lot Consistency: Tight lot-to-lot control for reproducible performance.
  • Customization Options: Flexible customization of tags, labels, or packaging upon request.

Custom CST3 Membrane Protein and Antibody Discovery Services

In addition to our catalog products, we have specific custom proteins and antibody discovery and development services. Drawing on our robust experience with both protease biology and neurodegenerative diseases research, we can help you with:

  • Custom CST3 Receptor Production: Tailored expression, purification, and characterization of challenging multi-domain receptor constructs.
  • Custom Antibody Development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant) for specific research applications.
  • Stable Cell Line Development: Generation of bespoke stable cell lines expressing your target of interest.
  • Functional Assay Development: Designing and executing assays to assess receptor activation and ligand.

Frequently Asked Questions (FAQ)

  1. Are you CST3 products for clinical or diagnostic use?

    No, all CST3 products and services are for research use only and not intended for human clinical diagnosis, prevention, treatment or cure.

  2. Are there available stable cell lines with inducible CST3 expression or CST3 co-expressed with cathepsin B?

    Absolutely. The cell engineering team regularly creates tetracycline-inducible systems and lines with co-expression of CST3 with cathepsin B, Aβ or autophagy reporter constructs collectively for pathway analysis. We would really appreciate ardent conversations around what the expression architecture and phenotypic needs are for this product that we can build.

  3. Are there antibodies to mature secreted CST3 dimer with little- or cross reactivity to the monomeric- and/or signal peptide-containing precursor?

    Yes, we have quaternary-structure-selective antibodies, which are designed to bind preferentially to epitopes located within the dimer interface that is formed by intermolecular disulfide linkage. These clones provide highly specific signal with an oxidized secreted dimer in western blot and immunofluorescence, but minimal recognition of the reduced monomeric species or ER-resident precursor: allowing for both detailed tracking of secretion status and extracellular accumulation.

  4. Are stable cell lines that constitutively secrete CST3 available for continuous modeling of extracellular protease inhibition, kinetics of amyloid fibril formation and cerebrovascular deposition dynamics?

    Yes, we established stable autocrine lines which secrete correctly processed CST3 into serum-free conditioned medium. In addition, each batch is qualified by quantifying the titer of secreted proteins using an ELISA and evaluated for bioactivity using a standardized cathepsin inhibition assay to maintain a continuous cellular platform for mechanistic studies over time without the need for transient transfections.

Reference
  1. Zhang, Zijun, and Fenghuang Zhan. "Type 2 cystatins and their roles in the regulation of human immune response and cancer progression." Cancers 15.22 (2023): 5363. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/cancers15225363
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