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ADAMTS3
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<h2 id="structure">Structure</h2> <p>This gene encodes a member of the <a href="/facts/ADAMTS/oPxHwcRB">ADAMTS</a> (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family share several distinct protein modules, including a propeptide region, a <a href="/facts/Metalloproteinase/ShDT6dbf">metalloproteinase</a> domain, a <a href="/facts/Disintegrin/8bEkxtMe">disintegrin</a>-like domain, and a <a href="/facts/Thrombospondin/IFrmnAwX">thrombospondin</a> 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.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="function">Function</h2> <p>Because of the high similarity to <a href="/facts/ADAMTS2/QmQceWwa">ADAMTS2</a>, the major substrate of ADAMTS3 had been erroneously assumed to be procollagen II.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> However, ADAMTS3 appears largely irrelevant for collagen maturation but instead is required for the activation of the lymphangiogenic growth factor <a href="/facts/VEGF-C/QxpzHS3e">VEGF-C</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> Hence, ADAMTS3 is essential for the development and growth of <a href="/facts/Lymphatic_vessel/jND0hlDu">lymphatic vessels</a>. The proteolytic processing of VEGF-C by ADAMTS3 is regulated by the <a href="/facts/CCBE1/KIWz6LDX">CCBE1</a> protein. </p><p>ADAMTS3 has been shown to cleave <a href="/facts/Reelin/PzkFDjn2">reelin</a>, 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.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p>A deficiency of this protein may be responsible for <a href="/facts/Dermatosparaxis/yubUWs0x">dermatosparaxis</a>, a genetic defect of connective tissues.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>Some hereditary forms of <a href="/facts/Lymphedema/BLCUBCvY">lymphedema</a> are caused by mutations in ADAMTS3.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Tang BL (January 2001). "ADAMTS: a novel family of extracellular matrix proteases". <i>The International Journal of Biochemistry & Cell Biology</i>. 33 (1): 33–44. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS1357-2725%2800%2900061-3">10.1016/S1357-2725(00)00061-3</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11167130">11167130</a>.</li> <li>Martel-Pelletier J, Welsch DJ, Pelletier JP (December 2001). "Metalloproteases and inhibitors in arthritic diseases". <i>Best Practice & Research. Clinical Rheumatology</i>. 15 (5): 805–29. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1053%2Fberh.2001.0195">10.1053/berh.2001.0195</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11812023">11812023</a>.</li> <li>Hirohata S (November 2001). "[ADAMTS family--new extracellular matrix degrading enzyme]". <i>Seikagaku. The Journal of Japanese Biochemical Society</i>. 73 (11): 1333–7. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11831030">11831030</a>.</li> <li>Hurskainen TL, Hirohata S, Seldin MF, Apte SS (September 1999). <a href="https://doi.org/10.1074%2Fjbc.274.36.25555">"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"</a>. <i>The Journal of Biological Chemistry</i>. 274 (36): 25555–63. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.274.36.25555">10.1074/jbc.274.36.25555</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10464288">10464288</a>.</li> <li>Colige A, Vandenberghe I, Thiry M, Lambert CA, Van Beeumen J, Li SW, Prockop DJ, Lapiere CM, Nusgens BV (February 2002). <a href="https://doi.org/10.1074%2Fjbc.M105601200">"Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3"</a>. <i>The Journal of Biological Chemistry</i>. 277 (8): 5756–66. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M105601200">10.1074/jbc.M105601200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11741898">11741898</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li>The <a href="/facts/MEROPS/kgboIz3H">MEROPS</a> online database for peptidases and their inhibitors: <a href="http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M12.220">M12.220</a></li> <li>Human <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=ADAMTS3"><i>ADAMTS3</i></a> genome location and <a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=ADAMTS3"><i>ADAMTS3</i></a> gene details page in the <a href="/facts/UCSC_Genome_Browser/kwumPyLb">UCSC Genome Browser</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Tang BL, Hong W (February 1999). "ADAMTS: a novel family of proteases with an ADAM protease domain and thrombospondin 1 repeats". FEBS Letters. 445 (2–3): 223–5. doi:10.1016/S0014-5793(99)00119-2. PMID 10094461. S2CID 37955930. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Fernandes RJ, Hirohata S, Engle JM, Colige A, Cohn DH, Eyre DR, Apte SS (August 2001). "Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis". The Journal of Biological Chemistry. 276 (34): 31502–9. doi:10.1074/jbc.M103466200. PMID 11408482. <a href="https://doi.org/10.1074%2Fjbc.M103466200" target="_blank">https://doi.org/10.1074%2Fjbc.M103466200</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K (May 2014). "CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation". Circulation. 129 (19): 1962–71. doi:10.1161/CIRCULATIONAHA.113.002779. PMID 24552833. <a href="https://doi.org/10.1161%2FCIRCULATIONAHA.113.002779" target="_blank">https://doi.org/10.1161%2FCIRCULATIONAHA.113.002779</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Hattori M, Kohno T (February 2021). "Regulation of Reelin functions by specific proteolytic processing in the brain". Journal of Biochemistry. 169 (5): 511–516. doi:10.1093/jb/mvab015. PMID 33566063. <a href="https://doi.org/10.1093%2Fjb%2Fmvab015" target="_blank">https://doi.org/10.1093%2Fjb%2Fmvab015</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>"Entrez Gene: ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif, 3". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9508</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Jha SK, Rauniyar K, Karpanen T, Leppänen VM, Brouillard P, Vikkula M, Alitalo K, Jeltsch M (July 2017). "Efficient activation of the lymphangiogenic growth factor VEGF-C requires the C-terminal domain of VEGF-C and the N-terminal domain of CCBE1". Scientific Reports. 7 (1): 4916. Bibcode:2017NatSR...7.4916J. doi:10.1038/s41598-017-04982-1. PMC 5501841. PMID 28687807. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501841" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501841</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Brouillard P, Dupont L, Helaers R, Coulie R, Tiller GE, Peeden J, Colige A, Vikkula M (November 2017). "Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3". Human Molecular Genetics. 26 (21): 4095–4104. doi:10.1093/hmg/ddx297. PMID 28985353. <a href="https://doi.org/10.1093%2Fhmg%2Fddx297" target="_blank">https://doi.org/10.1093%2Fhmg%2Fddx297</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> </ol>