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ADAM17

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

ADAM metallopeptidase domain 17 (ADAM17) is a type-I transmembrane zinc metalloprotease composed of an 824-amino-acid polypeptide. ADAM17 is broadly expressed in all human tissues but with elevated levels particularly in immune cells, endothelial and epithelial cells, as well as neurons. To put it simply, the pathological significance of these germination processes is equally general. In inflammation, ADAM17 mediates the release of soluble TNF-α and IL-6R which triggers and augments innate immune responses. In cancer, shedding of EGFR ligands by ADAM17 drives proliferation of tumor cells, whereas its cleavage on natural killer (NK) cells prevents antibody-dependent cellular cytotoxicity through processing of the NK cell receptor CD16A. In the cardiovascular disease domain, ADAM17 is involved in atherosclerosis and heart failure via shedding of adhesive molecules and growth factors. In neurodegeneration, it cleaves neuregulins and amyloid precursor protein, its role in synaptic dysfunction and Alzheimer's disease. After SARS-CoV-2 infection ADAM17, being release from numerous cell types, cleaves ACE2 and disrupts the protective signaling of ACE2 thus contributing to the cytokine storm. The scale of these associations — along with the technical obstacles in drug discovery that involve targeting them — has made ADAM17 one of the most sought-after but difficult to crack pharmacological targets.

Fig.1 Role of ADAM17-mediated shedding on inflammatory cytokines and renin-angiotensin system (RAS). (OA Literature)Fig.1 Role of ADAM17-mediated shedding on inflammatory cytokines and renin-angiotensin system (RAS) in hypertension.1

ADAM17 Protease Function: A Master Regulator of Membrane Protein Fate

ADAM17 has a functional scope encompassing virtually all domains of physiology and pathology:

  • Cytokine and Growth Factor Shedding: ADAM17 is the main mediator of shedding soluble TNF-α from its membrane-bound precursor, as well as for cleavaging IL-6Rα to produce the soluble form of the IL-6 receptor that promotes trans-signaling. Lastly, it also provides EGFR ligands propagating autocrine and paracrine growth factor loops.
  • Receptor Processing and Immune Modulation: ADAM17 promotes accessibility of cytokine receptors (TNFR1, TNFR2) and Fc receptor (CD16A) on immune cells via shedding. It can either decrease inflammation (by producing soluble receptors) or counter anti-tumor immunity.
  • Notch Signaling and Development: ADAM17 performs the S2 cleavage of Notch receptors in ligand-independent settings, producing the membrane-bound intermediate that is later processed by γ-secretase to produce NICD release and transcriptional programs governing cell fate.

ADAM17 Membrane Protein Product

Structural and pharmacological studies of ADAM17 are particularly challenging due to the multidomain structure of the protease, its maturation being dependent on removal of a prodomain, regulation mediated by iRhoms, and sensitivity to auto-activation upon heterologous expression. To tackle these obstacles, Creative Biolabs has developed a unique ADAM17 protein design platform yielding conformationally intact protease preparations for structural biology, inhibitor screening and therapeutic antibody drug development. Using cryo-EM–guided structural insights—including the recent structure of an iRhom2–ADAM17 complex, codon-optimized gene synthesis, with proprietary expression protocols—our engineering team identifies constructs generating maximal yield while retaining the catalytic zinc site; iRhom-binding interface; and substrate recognition pocket. Our process starts with a deep technical consultation to ensure the protein architecture is aligned with your application of interest, be it for crystallography, substrate profiling or high-throughput inhibitor screening.

ADAM17 Protein Product

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

ADAM17 Stable Cell Line Product

Cellular models expressing functional, mature ADAM17 at the plasma membrane, along with catabolism-dependent shedding maintain both regulated shedding activity—robust properties that necessarily makes them indispensable in substrate profiling, inhibitor screening and targeting studies. Engineered custom ADAM17 stable cell lines for Creative Biolabs using optimized transduction and selection protocols to produce homogeneous, sustained protease expression. The methodology we are using includes lentiviral delivery, transposon-mediated integration and targeted knock-in technology for precise genetic control by our cell engineering platform. All lines are monoclonally selected and phenotypically characterized to validate surface protease density as well as functional TNF-α shedding and EGFR ligand release upon stimulation.

ADAM17 Stable Cell Line Product

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

ADAM17 Recombinant Antibody Product

Sequence-defined, high affinity anti-ADAM17 antibodies are needed to detect the protease in tissue biopsies, map its surface distribution during activation, block substrate shedding for therapeutic purposes and distinguish ADAM17 from its closely related family member ADAM10. End-to-End recombinant antibody discovery programs targeting extracellular, catalytic, and conformational ADAM17 epitopes Creative Biolabs The antibody development pipeline involves immunogen design, multi-platform selection and downstream engineering to provide binders with the specificity, affinity, and developability profiles needed for research. Utilizing recombinant expression and clonal sequencing, you get a renewable, fully characterized reagent with no batch-to-batch variability.

ADAM17 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 ADAM17 Membrane Protein and Antibody Discovery Services

Creative Biolabs goes beyond typical catalog solutions by providing innovative discovery services covering the entire range of ADAM17 study needs. These advanced capabilities are intended for investigators who seek mechanistic insights that require custom-designed reagents, complex assay architectures, or multi-component integrated workflows:

  • Custom ADAM17 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 your recombinant ADAM17 proteins suitable for infusion into humans and can they be used to modulate inflammatory cytokine shedding or epidermal growth factor receptor ligand release?

    No—our ADAM17 products, including recombinant proteins, stable cell lines,nand antibody reagents are made for research use only. It has not been subjected to the safety, sterility, or regulatory scrutiny required to be considered safe for human administration.

  2. Do you provide antibodies that can support studies of mature or activated ADAM17?

    We can discuss antibody development targeting extracellular or catalytic-domain epitopes of ADAM17 according to specific research requirements. The suitability of individual antibodies for distinguishing mature or activated ADAM17 from precursor forms can be evaluated using appropriate assay formats and experimental controls.

  3. Do you offer stable cell lines that co-express ADAM17 with pro-TNF-α or pro-amphiregulin for continuous modeling of ectodomain shedding kinetics and paracrine signaling release?

    Yes, we have established dual-stable lines constitutively expressing full-length both ADAM17 and selected substrates of our choice from independent loci. They are released in batches with documentation of the shedding efficiency stimulated by a phorbol ester, measured using ELISA of shed ectodomains, providing a uniform and consistent cellular platform for continuous mechanistic and pharmacology studies without needing to perform transient transfection multiple times.

  4. Are your anti-ADAM17 antibodies suitable for immunofluorescence staining of paraformaldehyde-fixed cells to differentiate plasma membrane–resident enzyme from the intracellular recycling pool in perinuclear endosomes?

    Yes, selected clones have been validated on antagonised and permeabilised cells with clear plasma membrane and perinuclear staining patterns. Confirmed by co-localization with established early endosome and recycling compartment markers as part of antibody qualification to ensure appropriate subcellular distribution and trafficking itinerary.

Reference
  1. De Queiroz, Thyago M., Navya Lakkappa, and Eric Lazartigues. "ADAM17-mediated shedding of inflammatory cytokines in hypertension." Frontiers in Pharmacology 11 (2020): 1154. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fphar.2020.01154
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