Family

Peptidase M12B, ADAM-TS5 (IPR013276)

Short name: Pept_M12B_ADAM-TS5

Family relationships

Description

This entry represents members of the ADAM-TS5 family of metallopeptidases that belong to MEROPS peptidase family M12, subfamily M12B: adamalysin (clan MA), M12.225.

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]. 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 [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]. ADAM-TS5, also termed aggrecanase 2, was identified through expressed sequence tag database searching, pursuing sequences similar to ADAM-TS1-4 [PMID: 10417273]. In vitro studies have shown that ADAM-TS5, like ADAM-TS4, is an aggrecanase able to cleave cartilage aggrecan [PMID: 12392761].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0008237 metallopeptidase activity
GO:0008270 zinc ion binding

Cellular Component

GO:0005578 proteinaceous extracellular matrix

Contributing signatures

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