Identification and Characterization of ADAMTS-20 Defines a Novel Subfamily of Metalloproteinases-Disintegrins with Multiple Thrombospondin-1 Repeats and a Unique GON Domain*

By M. Llamazares, S. Cal, V. Quesada, C. López‐Otín. 2003

70 citations recorded by the source corpus.

We have cloned a mouse brain cDNA encoding a new protein of the ADAMTS family (a disintegrinand metalloproteinase domain, withthrombospondin type-1 repeats), which has been called ADAMTS-20. This protein shows a domain organization similar to that described for other ADAMTSs including signal sequence, propeptide, metalloproteinase domain, disintegrin domain, central TS-1 motif, cysteine-rich region, and C-terminal TS module. However, this last module is more complex than that of other ADAMTSs, being composed of a total of 14 repeats. The structural complexity of ADAMTS-20 is further increased by the presence of an additional domain 200 residues long and located immediately adjacent to the TS module. This domain has been tentatively called GON domain and can also be recognized in some ADAMTSs such as gon-1 from Caenorhabditis elegans and human and mouse ADAMTS-9. The presence of this domain is a hallmark of a novel subfamily of structurally and evolutionarily related ADAMTSs, called GON-ADAMTSs. Expression analysis demonstrated thatADAMTS-20 transcripts can be detected at low levels in several human and mouse tissues, especially in testis. This gene is also overexpressed in some human malignant tumors, including brain, colon, and breast carcinomas. Western blot analysis using polyclonal antibodies raised against recombinant ADAMTS-20 produced inEscherichia coli showed the presence of a 70-kDa band in mouse brain and testis extracts. This recombinant ADAMTS-20 hydrolyzed a synthetic peptide used for assaying matrix metalloproteinases. These data suggest that this novel enzyme may play a role in the tissue remodeling process occurring in both normal and pathological conditions.

Subfields: Cancer Research, Molecular Biology, Oncology

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In Cancer Research

1. C. López‐Otín
2. Christopher M. Overall
3. Luis M. Sánchez
4. B. Turk

In Molecular Biology

1. C. López‐Otín
2. Christopher M. Overall
3. Luis M. Sánchez
4. Xose S. Puente
5. Eleanor Feingold
6. B. Turk

In Oncology

1. C. López‐Otín
2. Christopher M. Overall
3. Luis M. Sánchez
4. B. Turk

Citations in the corpus

• Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate (2015, background): “ADAMTS20 cleaves the ECM proteoglycan, versican[26,31], and is involved in a variety of biological processes including promotion of melanoblast survival, palatogenesis, and interdigital web regression[31–33].”
• Human and mouse proteases: a comparative genomic approach (2003, methodology): “This is the case with ADAMTSs, which contain as many as 15 thrombospondin (TS) repeats in their structur”