The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

By R. Kelwick, Inès Desanlis, G. Wheeler, D. Edwards. 2015

595 citations recorded by the source corpus.

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future.

Subfields: Cancer Research, Immunology and Allergy, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. D. Edwards
2. Z. Kassiri

In Immunology and Allergy

1. S. Takeda

In Molecular Biology

1. S. Takeda
2. Carlos Fernandez-Patron
3. D. Edwards
4. Pu Zhang
5. Mengcheng Shen
6. Z. Kassiri

Citations in the corpus

• Role of Matrix Metalloproteinases in Angiogenesis and Cancer (2019, background): “Othermembers of the superfamily include A Disintegrin and metalloproteinases (ADAMs), and ADAMs with thrombospondinmotifs (ADAMTSs), which contain a conserved methionine (Met or M) residue adjacent to the active site (15, 16).”
• ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview (2016, background): “ADAMTS members contain a varying number of C-terminal thrombospondin type-1 motifs in place of the ADAM transmembrane and cytoplasmic domains and thus function as secreted proteinases [14,15].”
• Increased ADAMTS1 mediates SPARC-dependent collagen deposition in the aging myocardium. (2016, unknown): “ADAMTS1, a metalloprotease, regulates ECM turnover (26).”
• ADAMs family and relatives in cardiovascular physiology and pathology. (2016, background): “ADAM-TSs are numbered 1 to 20, with ADAM-TS11 and ADAMTS5 referring to the same gene [102].”
• ADAMTS9, a member of the ADAMTS family, in Xenopus development (2018, background): “In ADAMTS7 and 12, a mucin/proteoglycan domain is interposed between the 7 additional TSRs, precisely between TSR4 and TSR5 (figure 1) (Kelwick et al., 2015).”
• A Disintegrin and Metalloproteinase with Thrombospondin Motifs 18 Deficiency Leads to Visceral Adiposity and Associated Metabolic Syndrome in Mice. (2017, background): “…2, 3, and 14) 11 e 14 ; spermatogenesis (ADAMTS2) 15 ; follicular rupture and ovulation (ADAMTS1) 16 ; angiogenesis inhibition (ADAMTSs 1, 8, and 9) 17,18 ; degradation of cartilage oligomeric matrix protein (ADAMTSs 7 and 12) 19 ; cleavage of the matrix proteoglycan aggrecan, versican, and…”