motifs/domains
| a signal sequence |
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a propeptide domain |
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a reprolysin-type catalytic domain |
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a zinc catalytic domain |
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non-catalytic ancillary domains |
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a disintegrin domain (Dis) |
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a thrombospondin domain |
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a cysteine-rich domain (Cysr) |
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a spacer domain (Sp) |
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a second thrombospondin domain follows the spacer domain |
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one C terminal TSP-like module, that govern the specificity of the enzymes by modulating substrate binding |
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CysR and Sp domains greatly increased its aggrecanolytic activity |
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C-terminal domains affect the structure around the active site, favouring interaction with TIMP3 |
basic FUNCTION
| cell surface adhesion protein cleaving the cartilage proteoglycan aggrecan, involved in the destruction of aggrecan in arthritic disease |
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may play a role in glioma cell invasion through the cleavage of brevican |
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major aggrecanase in cartilage metabolism and pathology |
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(aggrecanolytic activity of ADAMTS5 was much greater than ADAMTS4) |
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ADAMTS4 and ADAMTS5 not only play roles in the breakdown of cartilage extracellular matrix in osteoarthritis, but also mediate processing of matrilins in the secretory pathway |
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in the growth plate ADAMTS5, and not ADAMTS4, has a physiological function in the intracellular processing of matrilins and potentially of other extracellular matrix proteins |
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role of ADAMTS5 in tendon is to remove pericellular and interfibrillar aggrecan to maintain the molecular architecture responsible for normal tissue function |
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a function of ADAMTS5 in dermal fibroblasts is potentially to maintain optimal versican content and pericellular matrix volume by continually trimming versican in hyaluronan-versican aggregates |