ADAMTS3

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Domain organization of the ADAMTS3 protease

A Disintegrin and Metalloprotease With Thrombospondin Motifs-3 (ADAMTS3) is a protein-splitting enzyme ( proteinase ). ADAMTS3 belongs to the group of metalloproteinases , more specifically to the ADAMTS family, which comprises 19 members in humans.

Functions

Although ADAMTS3 belongs to the ADAMTS subgroup of procollagenases and proteolytically cuts procollagen in vitro, its main substrate is the growth factor VEGF-C . VEGF-C is activated by ADAMTS3 proteolytically cleaving an N-terminal propeptide . Accordingly, the main function of ADAMTS3 is to regulate the growth of lymph vessels ( lymphangiogenesis ). During embryonic development , ADAMTS3 is essential for the development of the lymphatic system . Whether ADAMTS3 is also necessary in the adult organism for the maintenance and regeneration of lymph vessels (e.g. for wound healing) is e.g. Currently unclear, as other enzymes (e.g. plasmin ) can activate VEGF-C at least in vitro.

Disease relevance

Mutations in the ADAMTS3 gene are responsible for the hereditary disease Hennekam syndrome type III.

Individual evidence

  1. ↑ Chad N. Brocker, Vasilis Vasiliou, Daniel W. Nebert: Evolutionary divergence and functions of the ADAM and ADAMTS gene families . In: Human Genomics . 4, No. 1, October 1, 2009, ISSN  1479-7364 , p. 43. doi : 10.1186 / 1479-7364-4-1-43 . Retrieved April 25, 2014.
  2. ↑ KE Dombrowski, DJ Prockop: Cleavage of type I and type II procollagens by type I / II procollagen N-proteinase. Correlation of kinetic constants with the predicted conformations of procollagen substrates. . In: Journal of Biological Chemistry . 263, No. 32, November 15, 1988, ISSN  0021-9258 , pp. 16545-16552. PMID 3053692 . Retrieved April 10, 2019.
  3. ↑ Michael Jeltsch, Sawan Kumar Jha, Denis Tvorogov, Andrey Anisimov, Veli-Matti Leppänen, Tanja Holopainen, Riikka Kivelä, Sagrario Ortega, Terhi Kärpanen, Kari Alitalo: CCBE1 Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease Vascular-3-Mediated Motifs Endothelial Growth Factor-C Activation . In: Circulation . 129, No. 19, May 13, 2014, ISSN  0009-7322 , pp. 1962–1971. doi : 10.1161 / CIRCULATIONAHA.113.002779 . PMID 24552833 .
  4. ↑ Lauriane Janssen, Laura Dupont, Mourad Bekhouche, Agnès Noel, Cédric Leduc, Marianne Voz, Bernard Peers, Didier Cataldo, Suneel S. Apte, Johanne Dubail, Alain Colige: ADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis . In: Angiogenesis . October 7, 2015, ISSN  0969-6970 , pp. 1-13. doi : 10.1007 / s10456-015-9488-z .
  5. ↑ Bradley K. McColl, Megan E. Baldwin, Sally Roufail, Craig Freeman, Robert L. Moritz, Richard J. Simpson, Kari Alitalo, Steven A. Stacker, Marc G. Achen: Plasmin Activates the Lymphangiogenic Growth Factors VEGF-C and VEGF-D . In: The Journal of Experimental Medicine . 198, No. 6, September 15, 2003, ISSN  0022-1007 , pp. 863-868. doi : 10.1084 / jem.20030361 . PMID 12963694 . PMC 2194198 (free full text).
  6. ↑ Sawan Kumar Jha, Khushbu Rauniyar, Terhi Karpanen, Veli-Matti Leppänen, Pascal Brouillard, Miikka Vikkula, Kari Alitalo, Michael Jeltsch: Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1 . In: Scientific Reports . 7, No. 1, July 7, 2017, ISSN  2045-2322 , p. 4916. doi : 10.1038 / s41598-017-04982-1 . Retrieved July 7, 2017.
  7. ↑ Pascal Brouillard, Laura Dupont, Raphael Helaers, Richard Coulie, George E. Tiller, Joseph Peeden, Alain Colige, Miikka Vikkula: Loss of ADAMTS3 activity causes Hennekam lymphangiectasia – lymphedema syndrome 3 . In: Human Molecular Genetics . 26, No. 21, November 1, 2017, ISSN  0964-6906 , pp. 4095-4104. doi : 10.1093 / hmg / ddx297 . Retrieved May 22, 2018.