Sheddase
Encyclopedia
Sheddases are membrane-bound enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s that cleave extracellular portions of transmembrane protein
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...

s, releasing the soluble ectodomain
Ectodomain
An ectodomain is the domain of a membrane protein that extends into the extracellular space . Ectodomains are usually the part of a protein that initiate contact with surface which leads to signal transduction. In SARS-CoV the ectodomain of the spike protein is responsible for attachment to and...

s from the cell surface. Many sheddases are members of the ADAM
ADAM Protein
ADAM is a family of peptidase proteins. It is also known as the adamalysin family or MDC family. ADAMs are classified as sheddases because they cut off or shed extracellular portions of transmembrane proteins. For example, ADAM10 can cut off part of the HER2 receptor, activating it...

 or aspartic protease (BACE
Bace
Bace is a village in the municipality of Prokuplje, Serbia. According to the 2002 census, the village has a population of 284 people.-References:...

) protein families.

They can activate a transmembrane protein if it is a receptor (e.g., HER2), or cut off the part of the transmembrane protein which has already bound an agonist (e.g., in the case of EGFR
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...

), allowing this agonist to go and stimulate a receptor on another cell. Hence sheddases demultiply the yield of agonists. Sheddase inhibitors active on ADAM10
ADAM10
Disintegrin and metalloproteinase domain-containing protein 10, also known as ADAM10 or CDw156 or CD156c is a protein that in humans is encoded by the ADAM10 gene.- Function :...

 and ADAM17
ADAM17
ADAM metallopeptidase domain 17 , also called TACE , is a 70-kDa enzyme that belongs to the ADAM protein family of disintegrins and metalloproteases.- Chemical characteristics :...

can potentiate anti-cancer therapy.
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