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ADAMs (a disintegrin and metalloproteases) are a family of transmembrane metalloproteinases that function as proteases and/or adhesion molecules. They are members of the M12B adamalysin protease subfamily, which also includes reprolysins and ADAMTs.
|Cat No||Product Name / Activity|
|Selective ADAM10 metalloprotease inhibitor|
|Adam 17 (TACE) and MMP inhibitor; orally bioavailable|
ADAMs (a disintegrin and metalloproteases) are a family of transmembrane metalloproteinases that function as proteases and/or adhesion molecules. They are members of the M12B adamalysin protease subfamily, which also includes reprolysins and ADAMTs. There have been 25 human ADAM genes identified to date, 21 of them are functional, and 13 have proteolytic activity. The ADAMs with proteolytic activity are ADAMDEC-1, ADAM-8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30 and 33, while ADAM-2, 7, 11, 18, 22, 23, 29 and 32 are catalytically inactive, and have roles in protein folding and protein-protein interaction.
The ADAM family has a varied tissue distribution profile. ADAM-2, 18, 20, 21, 29 and 30 are primarily expressed in the testes and have been associated with fertility, consistent with their role in spermatogenesis and sperm-egg interaction. The other ADAMs are expressed in a variety of tissues and have been associated with biological processes such as cell fate determination in the nervous system, axon guidance, cell migration, muscle development, immunity and wound healing.
Proteolytic ADAMs function by cleaving transmembrane proteins, such as cytokines, chemokines and growth factors, to modulate their activity. Cleavage of the protein's ectodomain, a process termed 'shedding', results in the transmembrane and cytoplasmic domains being released into the cytoplasm. This mechanism regulates substrate activity by either resulting in a non-functional cell surface molecule, or inducing signal transduction through the release of intracellular or extracellular components. Non-proteolytic ADAMs interact with integrins to either positively or negatively regulate cell-cell adhesion. ADAM activity is regulated endogenously by TIMPs (tissue inhibitors of metalloproteinases), although ADAM-8, 9 and 19 are insensitive to TIMP inhibition.
ADAM substrates include EGF, TNF-α, Notch and amyloid precursor protein (APP). EGF and TNF-α require cleavage by ADAM-17 before being released from the cell membrane and binding to their receptors to initiate signaling. Following ligand binding Notch is cleaved by ADAM-10 and then γ-secretase, releasing the intracellular component of Notch, and initiating Notch signaling. ADAM-10 and 17 have been shown to act as α-secretases, and are therefore able to cleave APP to form soluble APPsα. Overexpression of ADAM-10 has been shown to reduce amyloid plaque formation and improve cognitive deficits in a mouse model of Alzheimer's disease (AD).
ADAMs have been implicated in cancer, being involved in the promotion of tumor invasion and metastasis, as well as having a role in breast cancer through the initiation of EGF receptor signaling. ADAMs may also be important in the pathology of neurological and cardiovascular diseases, including AD and atherosclerosis, as well as in asthma, inflammation, rheumatoid arthritis and diabetes.
External sources of pharmacological information for ADAMs :
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.
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