A disintegrin and metalloproteinase with thrombospondin motifs 4
A disintegrin like and metalloprotease (reprolysin type) with thrombospondin type 1 motif 4
A disintegrin like and metalloprotease with thrombospondin type 1 motif 4
ADAM metallopeptidase with thrombospondin type 1 motif 4
ADAM TS 4
FunctionCleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in Alzheimer disease. Cleaves aggrecan at the '392-Glu- -Ala-393' site.
Tissue specificityExpressed in brain, lung and heart. Expressed at very low level in placenta and skeletal muscles.
DomainThe spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Post-translational modificationsThe precursor is cleaved by a furin endopeptidase.
Cellular localizationSecreted > extracellular space > extracellular matrix.