PR01861

ADAM-TS8

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameADAMTS8

Description

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 []. The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) []. 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 [,]. 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 []. 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 [], whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility []. ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage []. ADAM-TS8, also termed METH2, was identified by searching expressed sequence tag databases for sequences that contained TS modules []. In vitro studies have shown recombinant ADAM-TS8 to be effective in blocking angiogenesis, and to inhibit endothelial cell growth [].

References

1. ECM and cell surface proteolysis: regulating cellular ecology. Werb Z. Cell 91, 439-42, (1997). View articlePMID: 9390552

2. Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. Kuno K, Kanada N, Nakashima E, Fujiki F, Ichimura F, Matsushima K. J. Biol. Chem. 272, 556-62, (1997). View articlePMID: 8995297

3. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. Colige A, Sieron AL, Li SW, Schwarze U, Petty E, Wertelecki W, Wilcox W, Krakow D, Cohn DH, Reardon W, Byers PH, Lapiere CM, Prockop DJ, Nusgens BV. Am. J. Hum. Genet. 65, 308-17, (1999). View articlePMID: 10417273

4. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. Tortorella MD, Burn TC, Pratta MA, Abbaszade I, Hollis JM, Liu R, Rosenfeld SA, Copeland RA, Decicco CP, Wynn R, Rockwell A, Yang F, Duke JL, Solomon K, George H, Bruckner R, Nagase H, Itoh Y, Ellis DM, Ross H, Wiswall BH, Murphy K, Hillman MC Jr, Hollis GF, Newton RC, Magolda RL, Trzaskos JM, Arner EC. Science 284, 1664-6, (1999). View articlePMID: 10356395

5. New leads to cancer, arthritis therapies. Hagmann M. Science 284, 1600-1, (1999). View articlePMID: 10383332

6. ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family. Hurskainen TL, Hirohata S, Seldin MF, Apte SS. J. Biol. Chem. 274, 25555-63, (1999). View articlePMID: 10464288

7. Expert testimony. Project offers judges neutral science advice. Kaiser J. Science 284, 1600, (1999). View articlePMID: 10383331

8. Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K. Science 284, 1667-70, (1999). View articlePMID: 10356396

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