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Functional ADAM17 (human) Antibody, mAb (recombinant) (blocking) (preservative free)
- SPECIFICATION
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- PROTOCOLS
- BACKGROUND
| Primary Accession | P78536 |
|---|---|
| Reactivity | Human |
| Clonality | Monoclonal |
| Isotype | Human IgG1 |
| Gene Source | Human |
| Endotoxin | <0.001EU/ µg |
| Application Note | ,FUNC (Blocking), Inhibits ADAM17 activity at 15 µg/ml (200nm), |
| Clone Names | D1(A12) |
| Calculated MW | 93021 Da |
| Description | This cross-domain human antibody is a selective ADAM17 (TACE) antagonist and provides a unique alternative to small molecule metalloprotease inhibition. ADAM multidomain topology was exploited by first isolating an inhibitory human antibody (D1) that bound ADAM17-specific non-catalytic regions exclusively through its variable heavy (VH) domain. A D1-VH biased scFv phage-display library was then used to selectively isolate a new variable light (VL) chain that could simultaneously bind to the ADAM17 catalytic domain. |
| Gene ID | 6868 |
|---|---|
| Other Names | TNF-α-converting Enzyme; Disintegrin and Metalloproteinase Domain-containing Protein 17; CD156b |
| Target/Specificity | Recognizes the catalytic and non-catalytic domain of human ADAM17 (TACE) through its variable light (VL) domain and variable heavy (VH) domain, respectively. Does not bind recombinant mouse ADAM17 ectodomain. |
| Format | Liquid. In PBS. |
| Reconstitution & Storage | Stable for at least 1 year after receipt when stored at -20°C. |
| Precautions | Functional ADAM17 (human) Antibody, mAb (recombinant) (blocking) (preservative free) is for research use only and not for use in diagnostic or therapeutic procedures. |
| Name | ADAM17 (HGNC:195) |
|---|---|
| Synonyms | CSVP, TACE |
| Function | Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammation and immunity (PubMed:24226769, PubMed:24227843, PubMed:28060820, PubMed:28923481). Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:9034191, PubMed:36078095). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF- receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells. Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:28923481). |
| Cellular Location | Cell membrane; Single-pass type I membrane protein |
| Tissue Location | Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney. Expressed in natural killer cells (at protein level) (PubMed:24337742). |
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Background
ADAM17 (Disintegrin and metalloproteinase domain-containing protein 17), also called TACE (Tumor necrosis factor-α-converting enzyme) is the prototype of the ADAM family of ectodomain shedding proteases (sheddase). ADAM17 is understood to be involved in the processing of TNF-α at the surface of the cell and from within the intracellular membranes of the trans-Golgi network. This process involves the cleavage and release of a soluble ectodomain from membrane-bound pro-proteins (such as pro-TNF-α) and is of known physiological importance. ADAM17 is responsible for the processing of a diverse variety of membrane-anchored cytokines, cell adhesion molecules, receptors, ligands and enzymes, including cleaving epidermal growth factor receptor (EGFR) ligands and extracellular Notch1. The proteolytic cleavage is an indispensable activation event for many of these substrates, ADAM17 has emerged as an attractive therapeutic target for the treatment of inflammatory diseases (e.g. rheumatoid arthritis) or inflammation associated cancer.
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