ADAMTS/ADAMTS-like (IPR013273)

Short name: ADAMTS/ADAMTS-like

Overlapping homologous superfamilies

Family relationships


ADAMTS proteins are a superfamily of 26 secreted molecules comprising two related, but distinct families. ADAMTS proteases are zinc metalloendopeptidases, most of whose substrates are extracellular matrix (ECM) components, whereas ADAMTS-like proteins lack a metalloprotease domain, reside in the ECM and have regulatory roles [PMID: 29885460]. Examples of ADAMTS-like proteins are papilin [PMID: 11076767] and punctin [PMID: 11805097].

Proteolysis 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 [PMID: 9390552]. The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) [PMID: 9390552]. The MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with thrombospondin type I modules), consists of at least 20 members that share a high degree of sequence similarity and conserved domain organisation [PMID: 8995297, PMID: 10464288]. 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 [PMID: 10464288]. 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 [PMID: 8995297], whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility [PMID: 10417273]. ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage [PMID: 10356395].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.