Aggrecanase
Encyclopedia
Aggrecanases are proteolytic 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 are members of the ADAM protein
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...

 (A Disintegrin
Disintegrin
Disintegrins are a family of small proteins from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion....

 And Metalloprotease) family. Aggrecanases act on large proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...

s known as aggrecan
Aggrecan
Aggrecan also known as cartilage-specific proteoglycan core protein or chondroitin sulfate proteoglycan 1 is a protein that in humans is encoded by the ACAN gene. This gene is a member of the aggrecan/versican proteoglycan family...

s, which are components of connective tissues such as cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...

. The inappropriate activity of aggrecanase is a mechanism by which cartilage degradation occurs in diseases such as arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

. At least two forms of aggrecanase exist in humans: ADAMTS4
ADAMTS4
A disintegrin and metalloproteinase with thrombospondin motifs 4 is an enzyme that in humans is encoded by the ADAMTS4 gene.-External links:* The MEROPS online database for peptidases and their inhibitors:...

 or aggrecanase-1 and ADAMTS5
ADAMTS5
A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.- Function :...

 or aggrecanase-2. Both proteins contain thrombospondin
Thrombospondin
Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.-Types:The thrombospondins are a family of multifunctional proteins...

 (TS) motifs
Structural motif
In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a supersecondary structure, which appears also in a variety of other molecules...

required for proper recognition of substrates. Although both proteins can cleave the substrate aggrecan at the same position, they differ in kinetics and in secondary cleavage sites.
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