Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 May 30;16(1):113.
doi: 10.1186/s13059-015-0676-3.

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

Richard Kelwick  1 , Ines Desanlis  2 , Grant N Wheeler  3 , Dylan R Edwards  4
Affiliations
Review

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

Richard Kelwick et al. Genome Biol. .

Abstract

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
The ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family. The basic domain organization of the 19 ADAMTS family members and their major functional groups. Structurally the ADAMTS members are broadly organized into a proteinase domain and an ancillary domain. The proteinase domain comprises the signal, pro, metalloproteinase and disintegrin-like domains. The greatest variability between ADAMTS members is found in the ancillary domain, which is composed of one or more thrombospondin type 1 sequence repeats (TSRs), a cysteine-rich domain and a spacer domain. Some family members also have one or more specialist domains as part of their ancillary domain, as listed in the key on the right. The diagram is drawn to scale
Fig. 2
Fig. 2
Evolution of the ADAMTS family. a A schematic representation of the relationships of the eight vertebrate ADAMTS clades and the probable events (gene duplications and a retrotransposition) that have contributed to the expansion of the family. The figure is not to scale in terms of evolutionary distance. COMP, cartilage oligomeric protein; vWFCP, von-Willebrand-factor-cleaving protease. b Phylogenetic tree of the ADAMTS genes inferred by the maximum likelihood method based on the JTT matrix-based model [144]. The bootstrap consensus tree inferred from 1,000 replicates was taken to represent the evolutionary history of the taxa analyzed [145]. Branches corresponding to partitions reproduced in less than 50 % bootstrap replicates were collapsed. Initial tree(s) for the heuristic search were obtained by applying the neighbor-joining method to a matrix of pairwise distances estimated using a JTT model. The analysis involved 70 amino acid sequences. All positions containing gaps and missing data were eliminated. Evolutionary analyses were conducted in MEGA6 [146]. The vertebrate ADAMTS genes are indicated by a number followed by a single letter code indicating the species: for example, 1 t represents 1_t ADAMTS1 from Xenopus tropicalis; 15 h is 15_h ADAMTS15 from Homo sapiens; 8 m is ADAMTS8 from Mus musculus. For Drosophila melanogaster (dro), Caenorhabditis elegans (cel) and Ciona intestinalis (cio), the annotation is species followed by the gene number; for example, cio 6 is cio_6 ADAMTS6 from Ciona
See this image and copyright information in PMC

References

    1. Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS metalloproteinases. Biochem J. 2005;386:15–27. - PMC - PubMed
    1. Apte SS. A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem. 2009;284:31493–7. - PMC - PubMed
    1. Gomis-Ruth FX. Catalytic domain architecture of metzincin metalloproteases. J Biol Chem. 2009;284:15353–7. - PMC - PubMed
    1. Dubail J, Apte SS. Insights on ADAMTS proteases and ADAMTS-like proteins from mammalian genetics. Matrix Biol. 2015. doi: 10.1016/j.matbio.2015.03.001. - PubMed
    1. Stanton H, Melrose J, Little CB, Fosang AJ. Proteoglycan degradation by the ADAMTS family of proteinases. Biochim Biophys Acta. 1812;2011:1616–29. - PubMed

Publication types

MeSH terms