ADAMTS3

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene is the major procollagen II N-propeptidase.

Because of the high similarity to ADAMTS2, the major substrate of ADAMTS3 had been erroneously assumed to be procollagen II.{{cite journal | vauthors = Fernandes RJ, Hirohata S, Engle JM, Colige A, Cohn DH, Eyre DR, Apte SS | title = Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 34 | pages = 31502–9 | date = August 2001 | pmid = 11408482 | doi = 10.1074/jbc.M103466200 | doi-access = free }} However, ADAMTS3 appears largely irrelevant for collagen maturation but instead is required for the activation of the lymphangiogenic growth factor VEGF-C.{{cite journal | vauthors = Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K | title = CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation | journal = Circulation | volume = 129 | issue = 19 | pages = 1962–71 | date = May 2014 | pmid = 24552833 | doi = 10.1161/CIRCULATIONAHA.113.002779 | doi-access = free }} Hence, ADAMTS3 is essential for the development and growth of lymphatic vessels. The proteolytic processing of VEGF-C by ADAMTS3 is regulated by the CCBE1 protein.

ADAMTS3 has been shown to cleave reelin, a protein that regulates the proper lamination of the brain cortex and whose signal activity is found to be disrupted in a number of neuropsychiatric conditions.{{cite journal | vauthors = Hattori M, Kohno T | title = Regulation of Reelin functions by specific proteolytic processing in the brain | journal = Journal of Biochemistry | volume = 169| issue = 5| pages = 511–516| date = February 2021 | pmid = 33566063 | doi = 10.1093/jb/mvab015 | url = | doi-access = free }}

A deficiency of this protein may be responsible for dermatosparaxis, a genetic defect of connective tissues.

Some hereditary forms of lymphedema are caused by mutations in ADAMTS3.{{cite journal | vauthors = Jha SK, Rauniyar K, Karpanen T, Leppänen VM, Brouillard P, Vikkula M, Alitalo K, Jeltsch M | title = Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1 | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 4916 | date = July 2017 | pmid = 28687807 | pmc = 5501841 | doi = 10.1038/s41598-017-04982-1 | bibcode = 2017NatSR...7.4916J }}{{cite journal | vauthors = Brouillard P, Dupont L, Helaers R, Coulie R, Tiller GE, Peeden J, Colige A, Vikkula M | title = Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3 | journal = Human Molecular Genetics | volume = 26 | issue = 21 | pages = 4095–4104 | date = November 2017 | pmid = 28985353 | doi = 10.1093/hmg/ddx297 | doi-access = free }}

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• {{cite journal | vauthors = Tang BL | title = ADAMTS: a novel family of extracellular matrix proteases | journal = The International Journal of Biochemistry & Cell Biology | volume = 33 | issue = 1 | pages = 33–44 | date = January 2001 | pmid = 11167130 | doi = 10.1016/S1357-2725(00)00061-3 }}
• {{cite journal | vauthors = Martel-Pelletier J, Welsch DJ, Pelletier JP | title = Metalloproteases and inhibitors in arthritic diseases | journal = Best Practice & Research. Clinical Rheumatology | volume = 15 | issue = 5 | pages = 805–29 | date = December 2001 | pmid = 11812023 | doi = 10.1053/berh.2001.0195 }}
• {{cite journal | vauthors = Hirohata S | title = [ADAMTS family--new extracellular matrix degrading enzyme] | journal = Seikagaku. The Journal of Japanese Biochemical Society | volume = 73 | issue = 11 | pages = 1333–7 | date = November 2001 | pmid = 11831030 }}
• {{cite journal | vauthors = Hurskainen TL, Hirohata S, Seldin MF, Apte SS | title = 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 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 36 | pages = 25555–63 | date = September 1999 | pmid = 10464288 | doi = 10.1074/jbc.274.36.25555 | doi-access = free }}
• {{cite journal | vauthors = Colige A, Vandenberghe I, Thiry M, Lambert CA, Van Beeumen J, Li SW, Prockop DJ, Lapiere CM, Nusgens BV | title = Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 8 | pages = 5756–66 | date = February 2002 | pmid = 11741898 | doi = 10.1074/jbc.M105601200 | doi-access =free }}

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• The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M12.220 M12.220]
• {{UCSC gene info|ADAMTS3}}

{{Metalloproteinases}}

Category:ADAMTS

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