ADAMTS5

ADAMTS5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RJQ, 3B8Z, 3HY7, 3HY9, 3HYG, 3LJT
Identifiers
Aliases	ADAMTS5 , ADAM-TS 11, ADAM-TS 5, ADAM-TS5, ADAMTS-11, ADAMTS-5, ADAMTS11, ADMP-2, ADAM metallopeptidase with thrombospondin type 1 motif 5
External IDs	OMIM: 605007; MGI: 1346321; HomoloGene: 5109; GeneCards: ADAMTS5; OMA:ADAMTS5 - orthologs
Gene location (Human) Chr. Chromosome 21 (human) [1] Band 21q21.3 Start 26,917,922 bp [1] End 26,967,088 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16 C3.3|16 48.34 cM Start 85,653,061 bp [2] End 85,698,716 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lactiferous duct synovial joint stromal cell of endometrium skin of hip decidua synovial membrane Epithelium of choroid plexus endothelial cell buccal mucosa cell gastric mucosa Top expressed in decidua gastrula stroma of bone marrow white adipose tissue aortic valve ascending aorta sciatic nerve iris efferent ductule trigeminal ganglion More reference expression data BioGPS n/a
Gene ontology Molecular function heparin binding zinc ion binding extracellular matrix binding metal ion binding integrin binding peptidase activity protein binding hydrolase activity metallopeptidase activity metalloendopeptidase activity Cellular component endoplasmic reticulum lumen extracellular region extracellular space extracellular matrix collagen-containing extracellular matrix Biological process extracellular matrix disassembly proteolysis defense response to bacterium tooth eruption negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 11096 23794 Ensembl ENSG00000154736 ENSMUSG00000022894 UniProt Q9UNA0 Q9R001 RefSeq (mRNA) NM_007038 NM_011782 RefSeq (protein) NP_008969 NP_035912 Location (UCSC) Chr 21: 26.92 – 26.97 Mb Chr 16: 85.65 – 85.7 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene. ^{[5] [6]}

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. ^[7] ADAMTS5 may also have a role in the pathogenesis of human osteoarthritis. ^[8]

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. ^[9] ADAMTS5 is the major aggrecanase in mouse cartilage in a mouse model of inflammatory arthritis. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000154736 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022894 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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 (Aug 1999). "Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family". The Journal of Biological Chemistry. 274 (33): 23443–50. doi: 10.1074/jbc.274.33.23443 . PMID   10438522.
6. Hurskainen TL, Hirohata S, Seldin MF, Apte SS (Sep 1999). "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. doi: 10.1074/jbc.274.36.25555 . PMID   10464288.
7. "Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif".
8. Verma P, Dalal K (Dec 2011). "ADAMTS-4 and ADAMTS-5: key enzymes in osteoarthritis". Journal of Cellular Biochemistry. 112 (12): 3507–14. doi:10.1002/jcb.23298. PMID   21815191. S2CID   30611107.
9. Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA (Mar 2005). "Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis". Nature. 434 (7033): 644–8. Bibcode:2005Natur.434..644G. doi:10.1038/nature03369. PMID   15800624. S2CID   4339874.
10. Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ (Mar 2005). "ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro". Nature. 434 (7033): 648–52. Bibcode:2005Natur.434..648S. doi:10.1038/nature03417. PMID   15800625. S2CID   4366441.

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 (Jan 2008). "Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5". Protein Science. 17 (1): 16–21. doi:10.1110/ps.073287008. PMC   2144589 . PMID   18042673.
• Malfait AM, Arner EC, Song RH, Alston JT, Markosyan S, Staten N, Yang Z, Griggs DW, Tortorella MD (Oct 2008). "Proprotein convertase activation of aggrecanases in cartilage in situ". Archives of Biochemistry and Biophysics. 478 (1): 43–51. doi:10.1016/j.abb.2008.07.012. PMID   18671934.
• Matsumoto T, Tojyo I, Kiga N, Hiraishi Y, Fujita S (Dec 2008). "Expression of ADAMTS-5 in deformed human temporomandibular joint discs". Histology and Histopathology. 23 (12): 1485–93. PMID   18830934.
• Thirunavukkarasu K, Pei Y, Wei T (Dec 2007). "Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter". Molecular Biology Reports. 34 (4): 225–31. doi:10.1007/s11033-006-9037-3. PMID   17211519. S2CID   20729185.
• Patel KP, Sandy JD, Akeda K, Miyamoto K, Chujo T, An HS, Masuda K (Nov 2007). "Aggrecanases and aggrecanase-generated fragments in the human intervertebral disc at early and advanced stages of disc degeneration". Spine. 32 (23): 2596–603. doi:10.1097/BRS.0b013e318158cb85. PMID   17978660. S2CID   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 (Oct 2009). Gibson G (ed.). "Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging". PLOS Genetics. 5 (10) e1000685. doi: 10.1371/journal.pgen.1000685 . PMC   2752811 . PMID   19834535.
• 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 (Jan 2008). "High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2)". The Journal of Biological Chemistry. 283 (3): 1501–7. doi: 10.1074/jbc.M705879200 . PMID   17991750.
• 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 (Feb 2007). "Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity" (PDF). Arthritis and Rheumatism. 56 (2): 586–95. doi: 10.1002/art.22408 . PMID   17265493.
• Nakada M, Miyamori H, Kita D, Takahashi T, Yamashita J, Sato H, Miura R, Yamaguchi Y, Okada Y (Sep 2005). "Human glioblastomas overexpress ADAMTS-5 that degrades brevican". Acta Neuropathologica. 110 (3): 239–46. doi:10.1007/s00401-005-1032-6. PMID   16133547. S2CID   25744956.
• Gendron C, Kashiwagi M, Lim NH, Enghild JJ, Thøgersen IB, Hughes C, Caterson B, Nagase H (Jun 2007). "Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4". The Journal of Biological Chemistry. 282 (25): 18294–306. doi: 10.1074/jbc.M701523200 . PMID   17430884.
• Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (Mar 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi: 10.1074/mcp.M700325-MCP200 . PMID   18029348.
• Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M, Malizos KN, Rego I, Blanco FJ, Tsezou A, Loughlin J, Gomez-Reino JJ, Gonzalez A (Feb 2008). "Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis". Arthritis and Rheumatism. 58 (2): 435–41. doi:10.1002/art.23201. PMID   18240210.
• Zeng W, Corcoran C, Collins-Racie LA, Lavallie ER, Morris EA, Flannery CR (Mar 2006). "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. doi:10.1016/j.bbagen.2006.01.013. PMID   16507336.
• Zhu H, Leung PC, MacCalman CD (Jan 2007). "Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines". Human Reproduction. 22 (1): 63–74. doi: 10.1093/humrep/del356 . PMID   17067994.
• Hirohata S (Nov 2001). "[ADAMTS family--new extracellular matrix degrading enzyme]". Seikagaku. The Journal of Japanese Biochemical Society. 73 (11): 1333–7. PMID   11831030.
• Fushimi K, Troeberg L, Nakamura H, Lim NH, Nagase H (Mar 2008). "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. doi: 10.1074/jbc.M708647200 . PMID   18156631.
• Echtermeyer F, Bertrand J, Dreier R, Meinecke I, Neugebauer K, Fuerst M, Lee YJ, Song YW, Herzog C, Theilmeier G, Pap T (Sep 2009). "Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis". Nature Medicine. 15 (9): 1072–6. doi:10.1038/nm.1998. PMID   19684582. S2CID   10914435.
• Tang BL (Jan 2001). "ADAMTS: a novel family of extracellular matrix proteases". The International Journal of Biochemistry & Cell Biology. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID   11167130.
• Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, Arner EC, Griggs DW (Feb 2007). "Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5". Arthritis and Rheumatism. 56 (2): 575–85. doi:10.1002/art.22334. PMID   17265492.
• Barthel KK, Liu X (2008). Abraham E (ed.). "A transcriptional enhancer from the coding region of ADAMTS5". PLOS ONE. 3 (5) e2184. Bibcode:2008PLoSO...3.2184B. doi: 10.1371/journal.pone.0002184 . PMC   2364661 . PMID   18478108.

External links

• The MEROPS online database for peptidases and their inhibitors: M12.225 ^{[ permanent dead link ]}
• Rat Genome Database
• Human ADAMTS5 genome location and ADAMTS5 gene details page in the UCSC Genome Browser .