ADAMTS5 explained

A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.^{[1] [2]}

Function

ADAMTS5 is 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 enzyme encoded by this gene contains two C-terminal TS motifs and functions as aggrecanase to cleave aggrecan, a major proteoglycan of cartilage.^[3] ADAMTS5 may also have a role in the pathogenesis of human osteoarthritis.^[4]

Animal studies

Genetically modified mice in which the catalytic domain of ADAMTS5 was deleted are resistant to cartilage destruction in an experimental model of osteoarthritis.^[5] ADAMTS5 is the major aggrecanase in mouse cartilage in a mouse model of inflammatory arthritis.^[6]

Further reading

• Mosyak L, Georgiadis K, Shane T, Svenson K, Hebert T, McDonagh T, Mackie S, Olland S, Lin L, Zhong X, Kriz R, Reifenberg EL, Collins-Racie LA, Corcoran C, Freeman B, Zollner R, Marvell T, Vera M, Sum PE, Lavallie ER, Stahl M, Somers W . Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5 . Protein Science . 17 . 1 . 16–21 . Jan 2008 . 18042673 . 2144589 . 10.1110/ps.073287008 .
• Malfait AM, Arner EC, Song RH, Alston JT, Markosyan S, Staten N, Yang Z, Griggs DW, Tortorella MD . Proprotein convertase activation of aggrecanases in cartilage in situ . Archives of Biochemistry and Biophysics . 478 . 1 . 43–51 . Oct 2008 . 18671934 . 10.1016/j.abb.2008.07.012 .
• Matsumoto T, Tojyo I, Kiga N, Hiraishi Y, Fujita S . Expression of ADAMTS-5 in deformed human temporomandibular joint discs . Histology and Histopathology . 23 . 12 . 1485–93 . Dec 2008 . 18830934 .
• Thirunavukkarasu K, Pei Y, Wei T . Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter . Molecular Biology Reports . 34 . 4 . 225–31 . Dec 2007 . 17211519 . 10.1007/s11033-006-9037-3 . 20729185 .
• Patel KP, Sandy JD, Akeda K, Miyamoto K, Chujo T, An HS, Masuda K . Aggrecanases and aggrecanase-generated fragments in the human intervertebral disc at early and advanced stages of disc degeneration . Spine . 32 . 23 . 2596–603 . Nov 2007 . 17978660 . 10.1097/BRS.0b013e318158cb85 . 6965994 .
• Wheeler HE, Metter EJ, Tanaka T, Absher D, Higgins J, Zahn JM, Wilhelmy J, Davis RW, Singleton A, Myers RM, Ferrucci L, Kim SK . Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging . PLOS Genetics . 5 . 10 . e1000685 . Oct 2009 . 19834535 . 2752811 . 10.1371/journal.pgen.1000685 . Gibson . Greg . free .
• Shieh HS, Mathis KJ, Williams JM, Hills RL, Wiese JF, Benson TE, Kiefer JR, Marino MH, Carroll JN, Leone JW, Malfait AM, Arner EC, Tortorella MD, Tomasselli A . High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2) . The Journal of Biological Chemistry . 283 . 3 . 1501–7 . Jan 2008 . 17991750 . 10.1074/jbc.M705879200 . free.
• Grogan SP, Barbero A, Diaz-Romero J, Cleton-Jansen AM, Soeder S, Whiteside R, Hogendoorn PC, Farhadi J, Aigner T, Martin I, Mainil-Varlet P . Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity . Arthritis and Rheumatism . 56 . 2 . 586–95 . Feb 2007 . 17265493 . 10.1002/art.22408 . free .
• Nakada M, Miyamori H, Kita D, Takahashi T, Yamashita J, Sato H, Miura R, Yamaguchi Y, Okada Y . Human glioblastomas overexpress ADAMTS-5 that degrades brevican . Acta Neuropathologica . 110 . 3 . 239–46 . Sep 2005 . 16133547 . 10.1007/s00401-005-1032-6 . 25744956 .
• Gendron C, Kashiwagi M, Lim NH, Enghild JJ, Thøgersen IB, Hughes C, Caterson B, Nagase H . Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4 . The Journal of Biological Chemistry . 282 . 25 . 18294–306 . Jun 2007 . 17430884 . 10.1074/jbc.M701523200 . free .
• Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H . Toward a confocal subcellular atlas of the human proteome . Molecular & Cellular Proteomics . 7 . 3 . 499–508 . Mar 2008 . 18029348 . 10.1074/mcp.M700325-MCP200 . free .
• Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M, Malizos KN, Rego I, Blanco FJ, Tsezou A, Loughlin J, Gomez-Reino JJ, Gonzalez A . Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis . Arthritis and Rheumatism . 58 . 2 . 435–41 . Feb 2008 . 18240210 . 10.1002/art.23201 .
• Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA, Flannery CR . Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18 . Biochimica et Biophysica Acta (BBA) - General Subjects . 1760 . 3 . 517–24 . Mar 2006 . 16507336 . 10.1016/j.bbagen.2006.01.013 .
• Zhu H, Leung PC, MacCalman CD . Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines . Human Reproduction . 22 . 1 . 63–74 . Jan 2007 . 17067994 . 10.1093/humrep/del356 . free .
• Hirohata S . [ADAMTS family--new extracellular matrix degrading enzyme] . Seikagaku. The Journal of Japanese Biochemical Society . 73 . 11 . 1333–7 . Nov 2001 . 11831030 .
• Fushimi K, Troeberg L, Nakamura H, Lim NH, Nagase H . Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity . The Journal of Biological Chemistry . 283 . 11 . 6706–16 . Mar 2008 . 18156631 . 10.1074/jbc.M708647200 . free .
• Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T . Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis . Nature Medicine . 15 . 9 . 1072–6 . Sep 2009 . 19684582 . 10.1038/nm.1998 . 10914435 .
• Tang BL . ADAMTS: a novel family of extracellular matrix proteases . The International Journal of Biochemistry & Cell Biology . 33 . 1 . 33–44 . Jan 2001 . 11167130 . 10.1016/S1357-2725(00)00061-3 .
• Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW . Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5 . Arthritis and Rheumatism . 56 . 2 . 575–85 . Feb 2007 . 17265492 . 10.1002/art.22334 .
• Barthel KK, Liu X . A transcriptional enhancer from the coding region of ADAMTS5 . PLOS ONE . 3 . 5 . e2184 . 2008 . 18478108 . 2364661 . 10.1371/journal.pone.0002184 . Abraham . Edathara . 2008PLoSO...3.2184B . free .

External links

• The MEROPS online database for peptidases and their inhibitors: M12.225
• Rat Genome Database

Notes and References

1. Abbaszade I, Liu RQ, Yang F, Rosenfeld SA, Ross OH, Link JR, Ellis DM, Tortorella MD, Pratta MA, Hollis JM, Wynn R, Duke JL, George HJ, Hillman MC, Murphy K, Wiswall BH, Copeland RA, Decicco CP, Bruckner R, Nagase H, Itoh Y, Newton RC, Magolda RL, Trzaskos JM, Burn TC . Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family . The Journal of Biological Chemistry . 274 . 33 . 23443–50 . Aug 1999 . 10438522 . 10.1074/jbc.274.33.23443 . free .
2. Hurskainen TL, Hirohata S, Seldin MF, Apte SS . 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 . The Journal of Biological Chemistry . 274 . 36 . 25555–63 . Sep 1999 . 10464288 . 10.1074/jbc.274.36.25555 . free .
3. Web site: Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif.
4. Verma P, Dalal K . ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis . Journal of Cellular Biochemistry . 112 . 12 . 3507–14 . Dec 2011 . 21815191 . 10.1002/jcb.23298 . 30611107 .
5. Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA . Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis . Nature . 434 . 7033 . 644–8 . Mar 2005 . 15800624 . 10.1038/nature03369 . 2005Natur.434..644G . 4339874 .
6. Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ . ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro . Nature . 434 . 7033 . 648–52 . Mar 2005 . 15800625 . 10.1038/nature03417 . 2005Natur.434..648S . 4366441 .