View source for ADAMTS5

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''A disintegrin and metalloproteinase with thrombospondin motifs 5''' also known as '''ADAMTS5''' is an [[enzyme]] that in humans is encoded by the ''ADAMTS5'' [[gene]].<ref name="pmid10438522">{{cite journal | vauthors = 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 | title = Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family | journal = The Journal of Biological Chemistry | volume = 274 | issue = 33 | pages = 23443–50 | date = Aug 1999 | pmid = 10438522 | doi = 10.1074/jbc.274.33.23443 | doi-access = free }}</ref><ref name="pmid10464288">{{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 = Sep 1999 | pmid = 10464288 | doi = 10.1074/jbc.274.36.25555 | doi-access = free }}</ref>

== 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]].<ref name="entrez">{{cite web | title = Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11096}}</ref> ADAMTS5 may also have a role in the [[pathogenesis]] of human [[osteoarthritis]].<ref>{{cite journal | vauthors = Verma P, Dalal K | title = ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis | journal = Journal of Cellular Biochemistry | volume = 112 | issue = 12 | pages = 3507–14 | date = Dec 2011 | pmid = 21815191 | doi = 10.1002/jcb.23298 | s2cid = 30611107 }}</ref>

== 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]].<ref name="pmid15800624">{{cite journal | vauthors = Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA | title = Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis | journal = Nature | volume = 434 | issue = 7033 | pages = 644–8 | date = Mar 2005 | pmid = 15800624 | doi = 10.1038/nature03369 | bibcode = 2005Natur.434..644G | s2cid = 4339874 }}</ref> ADAMTS5 is the major aggrecanase in mouse cartilage in a [[mouse model]] of [[inflammatory arthritis]].<ref name="pmid15800625">{{cite journal | vauthors = Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ | title = ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro | journal = Nature | volume = 434 | issue = 7033 | pages = 648–52 | date = Mar 2005 | pmid = 15800625 | doi = 10.1038/nature03417 | bibcode = 2005Natur.434..648S | s2cid = 4366441 }}</ref>

== References ==
{{Reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = 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 | title = Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5 | journal = Protein Science | volume = 17 | issue = 1 | pages = 16–21 | date = Jan 2008 | pmid = 18042673 | pmc = 2144589 | doi = 10.1110/ps.073287008 }}
* {{cite journal | vauthors = Malfait AM, Arner EC, Song RH, Alston JT, Markosyan S, Staten N, Yang Z, Griggs DW, Tortorella MD | title = Proprotein convertase activation of aggrecanases in cartilage in situ | journal = Archives of Biochemistry and Biophysics | volume = 478 | issue = 1 | pages = 43–51 | date = Oct 2008 | pmid = 18671934 | doi = 10.1016/j.abb.2008.07.012 }}
* {{cite journal | vauthors = Matsumoto T, Tojyo I, Kiga N, Hiraishi Y, Fujita S | title = Expression of ADAMTS-5 in deformed human temporomandibular joint discs | journal = Histology and Histopathology | volume = 23 | issue = 12 | pages = 1485–93 | date = Dec 2008 | pmid = 18830934 }}
* {{cite journal | vauthors = Thirunavukkarasu K, Pei Y, Wei T | title = Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter | journal = Molecular Biology Reports | volume = 34 | issue = 4 | pages = 225–31 | date = Dec 2007 | pmid = 17211519 | doi = 10.1007/s11033-006-9037-3 | s2cid = 20729185 }}
* {{cite journal | vauthors = Patel KP, Sandy JD, Akeda K, Miyamoto K, Chujo T, An HS, Masuda K | title = Aggrecanases and aggrecanase-generated fragments in the human intervertebral disc at early and advanced stages of disc degeneration | journal = Spine | volume = 32 | issue = 23 | pages = 2596–603 | date = Nov 2007 | pmid = 17978660 | doi = 10.1097/BRS.0b013e318158cb85 | s2cid = 6965994 }}
* {{cite journal | vauthors = Wheeler HE, Metter EJ, Tanaka T, Absher D, Higgins J, Zahn JM, Wilhelmy J, Davis RW, Singleton A, Myers RM, Ferrucci L, Kim SK | title = Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging | journal = PLOS Genetics | volume = 5 | issue = 10 | pages = e1000685 | date = Oct 2009 | pmid = 19834535 | pmc = 2752811 | doi = 10.1371/journal.pgen.1000685 | editor1-last = Gibson | editor1-first = Greg | doi-access = free }} {{open access}}
* {{cite journal | vauthors = 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 | title = High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2) | journal = The Journal of Biological Chemistry | volume = 283 | issue = 3 | pages = 1501–7 | date = Jan 2008 | pmid = 17991750 | doi = 10.1074/jbc.M705879200 | doi-access =  free}}
* {{cite journal | vauthors = 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 | title = Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity | journal = Arthritis and Rheumatism | volume = 56 | issue = 2 | pages = 586–95 | date = Feb 2007 | pmid = 17265493 | doi = 10.1002/art.22408 | url = http://edoc.unibas.ch/6811/1/Grogan%20et%20al.%202007.pdf | doi-access = free }}
* {{cite journal | vauthors = Nakada M, Miyamori H, Kita D, Takahashi T, Yamashita J, Sato H, Miura R, Yamaguchi Y, Okada Y | title = Human glioblastomas overexpress ADAMTS-5 that degrades brevican | journal = Acta Neuropathologica | volume = 110 | issue = 3 | pages = 239–46 | date = Sep 2005 | pmid = 16133547 | doi = 10.1007/s00401-005-1032-6 | s2cid = 25744956 }}
* {{cite journal | vauthors = Gendron C, Kashiwagi M, Lim NH, Enghild JJ, Thøgersen IB, Hughes C, Caterson B, Nagase H | title = Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4 | journal = The Journal of Biological Chemistry | volume = 282 | issue = 25 | pages = 18294–306 | date = Jun 2007 | pmid = 17430884 | doi = 10.1074/jbc.M701523200 | doi-access = free }}
* {{cite journal | vauthors = Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H | title = Toward a confocal subcellular atlas of the human proteome | journal = Molecular & Cellular Proteomics | volume = 7 | issue = 3 | pages = 499–508 | date = Mar 2008 | pmid = 18029348 | doi = 10.1074/mcp.M700325-MCP200 | doi-access = free }}
* {{cite journal | vauthors = Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M, Malizos KN, Rego I, Blanco FJ, Tsezou A, Loughlin J, Gomez-Reino JJ, Gonzalez A | title = Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis | journal = Arthritis and Rheumatism | volume = 58 | issue = 2 | pages = 435–41 | date = Feb 2008 | pmid = 18240210 | doi = 10.1002/art.23201 | doi-access =  }}
* {{cite journal | vauthors = Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA, Flannery CR | title = Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18 | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1760 | issue = 3 | pages = 517–24 | date = Mar 2006 | pmid = 16507336 | doi = 10.1016/j.bbagen.2006.01.013 }}
* {{cite journal | vauthors = Zhu H, Leung PC, MacCalman CD | title = Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines | journal = Human Reproduction | volume = 22 | issue = 1 | pages = 63–74 | date = Jan 2007 | pmid = 17067994 | doi = 10.1093/humrep/del356 | doi-access = free }}
* {{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 = Nov 2001 | pmid = 11831030 }}
* {{cite journal | vauthors = Fushimi K, Troeberg L, Nakamura H, Lim NH, Nagase H | title = Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity | journal = The Journal of Biological Chemistry | volume = 283 | issue = 11 | pages = 6706–16 | date = Mar 2008 | pmid = 18156631 | doi = 10.1074/jbc.M708647200 | doi-access = free }}
* {{cite journal | vauthors = Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T | title = Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis | journal = Nature Medicine | volume = 15 | issue = 9 | pages = 1072–6 | date = Sep 2009 | pmid = 19684582 | doi = 10.1038/nm.1998 | s2cid = 10914435 }}
* {{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 = Jan 2001 | pmid = 11167130 | doi = 10.1016/S1357-2725(00)00061-3 }}
* {{cite journal | vauthors = Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW | title = Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5 | journal = Arthritis and Rheumatism | volume = 56 | issue = 2 | pages = 575–85 | date = Feb 2007 | pmid = 17265492 | doi = 10.1002/art.22334 | doi-access =  }}
* {{cite journal | vauthors = Barthel KK, Liu X | title = A transcriptional enhancer from the coding region of ADAMTS5 | journal = PLOS ONE | volume = 3 | issue = 5 | pages = e2184 | year = 2008 | pmid = 18478108 | pmc = 2364661 | doi = 10.1371/journal.pone.0002184 | editor1-last = Abraham | editor1-first = Edathara | bibcode = 2008PLoSO...3.2184B | doi-access = free }} {{open access}}
{{refend}}

== External links ==
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M12.225 M12.225]
*[https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=304135 Rat Genome Database]
* {{UCSC gene info|ADAMTS5}}

{{PDB Gallery|geneid=11096}}
{{Metalloendopeptidases}}
{{Enzymes}}
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[[Category:EC 3.4.24]]
[[Category:ADAMTS]]