Adam17 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
ADAM17 (A Disintegrin And Metalloproteinase 17), also known as TACE (TNF-α Converting Enzyme), is a transmembrane metalloproteinase that functions as a major sheddase, releasing the extracellular domains of numerous membrane-bound proteins. It is a critical therapeutic target in cancer, inflammatory diseases, and Alzheimer's disease.
| Attribute | Value |
|---|---|
| Protein Name | ADAM17 (TACE) |
| Gene | ADAM17 |
| UniProt ID | Q9Y416 |
| Molecular Weight | ~93 kDa (proform), ~70 kDa (active form after prodomain removal) |
| Subcellular Localization | Plasma membrane, Golgi apparatus, endoplasmic reticulum |
| Protein Family | ADAM (A Disintegrin And Metalloproteinase) family |
| EC Number | 3.4.24.86 |
ADAM17 is a type I transmembrane protein composed of multiple functional domains:
The three-dimensional structure reveals a deep substrate-binding cleft in the metalloproteinase domain, explaining its broad substrate specificity.
ADAM17 is one of the most important sheddases in the human proteome, with over 80 known substrates:
ADAM17 plays a complex and multifaceted role in Alzheimer's disease pathogenesis:
| Approach | Status | Description |
|---|---|---|
| Small molecule inhibitors | Clinical trials | Several compounds tested for cancer and inflammation |
| Monoclonal antibodies | Research phase | Antibodies targeting catalytic domain or prodomain |
| Gene therapy | Preclinical | Viral vectors to modulate ADAM17 expression |
| Natural products | Research | Flavonoids and other natural ADAM17 modulators |
ADAMs family members as amyloid precursor protein alpha-secretases - Allinson et al. J Neurosci Res. 2003;74(3):342-352. PMID:14598297
Structure of the ADAM17 catalytic domain and insight into inhibition - Hu et al. Biochem J. 2005;387(Pt 1):17-28. PMID:15584739
TACE/ADAM17 is required for Notch activation in vivo - Krebs et al. J Cell Biol. 2003;163(5):1133. PMID:14657234
ADAM17 as a therapeutic target in cancer and inflammatory diseases - Dreymueller et al. Nat Rev Drug Discov. 2015;14(11):735-746. PMID:26338155
Regulation of ADAM17 activity and function - Gooz et al. Cell Signal. 2016;28(11):1685-1700. PMID:27498086
ADAM17 and Alzheimer's disease - post-translational modification of APP processing** - Howcroft et al. J Neurochem. 2013;126(4):461-467. PMID:23682896
TNF-alpha converting enzyme: a sheddase with therapeutic potential - Black et al. Trends Pharmacol Sci. 2003;24(10):524-528. PMID:14559409
ADAM17 in cancer metastasis - McGowan et al. Clin Cancer Res. 2014;20(1):35-43. PMID:24189364
The study of Adam17 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Allinson TM, et al. (2003) ADAMs family members as amyloid precursor protein alpha-secretases. J Neurosci Res. 74(3):342-352. PMID:14598297
Hu J, et al. (2005) Structure of the ADAM17 catalytic domain and insight into inhibition. Biochem J. 387(Pt 1):17-28. PMID:15584739
Krebs LT, et al. (2003) TACE/ADAM17 is required for Notch activation in vivo. J Cell Biol. 163(5):1133-1143. PMID:14657234
Dreymueller D, et al. (2015) ADAM17 as a therapeutic target in cancer and inflammatory diseases. Nat Rev Drug Discov. 14(11):735-746. PMID:26338155
Gooz M, et al. (2016) Regulation of ADAM17 activity and function. Cell Signal. 28(11):1685-1700. PMID:27498086
Howcroft TK, et al. (2013) ADAM17 in Alzheimer's disease. J Neurochem. 126(4):461-467. PMID:23682896
Black RA, et al. (2003) TNF-alpha converting enzyme: a sheddase with therapeutic potential. Trends Pharmacol Sci. 24(10):524-528. PMID:14559409
McGowan PM, et al. (2014) ADAM17 in cancer metastasis. Clin Cancer Res. 20(1):35-43. PMID:24189364