This entry represents the ADAM-TS1 family of metallopeptidases that belong to MEROPS peptidase family M12, subfamily M12B: adamalysin (clan MA).
\r\n\r\nProteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions [[cite:PUB00017286]]. The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) [[cite:PUB00017286]]. Recently, a new MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with thrombospondin type I modules) has been identified. The family consists of at least 20 members that share a high degree of sequence similarity and conserved domain organisation [[cite:PUB00017264], [cite:PUB00017277]]. The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain [[cite:PUB00017277]]. Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. Members of the ADAM-TS family have been implicated in a range of diseases. ADAM-TS1, for example, is reported to be involved in inflammation and cancer cachexia [[cite:PUB00017264]], whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility [[cite:PUB00017294]]. ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage [[cite:PUB00017271]]. ADAM-TS1 was originally cloned in mice [[cite:PUB00017264]]. Human and rat orthologues have also been identified. Expression of ADAMTS-1 is closely associated with acute inflammation [[cite:PUB00017264]].
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