ADAMTS5
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]
Clinical significance
Genetically modified mice in which the catalytic domain of ADAMTS5 was deleted are resistant to cartilage destruction in an experimental model of osteoarthritis.[4] ADAMTS5 is the major aggrecanase in mouse cartilage in a mouse model of inflammatory arthritis.[5]
References
- ↑ 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 (August 1999). "Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family". J. Biol. Chem. 274 (33): 23443–50. doi:10.1074/jbc.274.33.23443. PMID 10438522.
- ↑ Hurskainen TL, Hirohata S, Seldin MF, Apte SS (September 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". J. Biol. Chem. 274 (36): 25555–63. doi:10.1074/jbc.274.36.25555. PMID 10464288.
- ↑ "Entrez Gene: ADAM metallopeptidase with thrombospondin type 1 motif".
- ↑ Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, Morris EA (March 2005). "Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis". Nature 434 (7033): 644–8. doi:10.1038/nature03369. PMID 15800624.
- ↑ Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, Fosang AJ (March 2005). "ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro". Nature 434 (7033): 648–52. doi:10.1038/nature03417. PMID 15800625.
Further reading
- Mosyak L, Georgiadis K, Shane T et al. (2008). "Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5.". Protein Sci. 17 (1): 16–21. doi:10.1110/ps.073287008. PMC 2144589. PMID 18042673.
- Malfait AM, Arner EC, Song RH et al. (2008). "Proprotein convertase activation of aggrecanases in cartilage in situ.". Arch. Biochem. Biophys. 478 (1): 43–51. doi:10.1016/j.abb.2008.07.012. PMID 18671934.
- Matsumoto T, Tojyo I, Kiga N et al. (2008). "Expression of ADAMTS-5 in deformed human temporomandibular joint discs.". Histol. Histopathol. 23 (12): 1485–93. PMID 18830934.
- Thirunavukkarasu K, Pei Y, Wei T (2007). "Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter.". Mol. Biol. Rep. 34 (4): 225–31. doi:10.1007/s11033-006-9037-3. PMID 17211519.
- Patel KP, Sandy JD, Akeda K et al. (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.
- Wheeler HE, Metter EJ, Tanaka T et al. (2009). Gibson, Greg, ed. "Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.". PLoS Genet. 5 (10): e1000685. doi:10.1371/journal.pgen.1000685. PMC 2752811. PMID 19834535.
- Shieh HS, Mathis KJ, Williams JM et al. (2008). "High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2).". J. Biol. Chem. 283 (3): 1501–7. doi:10.1074/jbc.M705879200. PMID 17991750.
- Grogan SP, Barbero A, Diaz-Romero J et al. (2007). "Identification of markers to characterize and sort human articular chondrocytes with enhanced in vitro chondrogenic capacity.". Arthritis Rheum. 56 (2): 586–95. doi:10.1002/art.22408. PMID 17265493.
- Nakada M, Miyamori H, Kita D et al. (2005). "Human glioblastomas overexpress ADAMTS-5 that degrades brevican.". Acta Neuropathol. 110 (3): 239–46. doi:10.1007/s00401-005-1032-6. PMID 16133547.
- Gendron C, Kashiwagi M, Lim NH et al. (2007). "Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4.". J. Biol. Chem. 282 (25): 18294–306. doi:10.1074/jbc.M701523200. PMID 17430884.
- Barbe L, Lundberg E, Oksvold P et al. (2008). "Toward a confocal subcellular atlas of the human proteome.". Mol. Cell Proteomics 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- Rodriguez-Lopez J, Mustafa Z, Pombo-Suarez M et al. (2008). "Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis.". Arthritis Rheum. 58 (2): 435–41. doi:10.1002/art.23201. PMID 18240210.
- Zeng W, Corcoran C, Collins-Racie LA et al. (2006). "Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18.". Biochim. Biophys. Acta 1760 (3): 517–24. doi:10.1016/j.bbagen.2006.01.013. PMID 16507336.
- Zhu H, Leung PC, MacCalman CD (2007). "Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines.". Hum. Reprod. 22 (1): 63–74. doi:10.1093/humrep/del356. PMID 17067994.
- Hirohata S (2001). "[ADAMTS family--new extracellular matrix degrading enzyme]". Seikagaku 73 (11): 1333–7. PMID 11831030.
- Fushimi K, Troeberg L, Nakamura H et al. (2008). "Functional differences of the catalytic and non-catalytic domains in human ADAMTS-4 and ADAMTS-5 in aggrecanolytic activity.". J. Biol. Chem. 283 (11): 6706–16. doi:10.1074/jbc.M708647200. PMID 18156631.
- Echtermeyer F, Bertrand J, Dreier R et al. (2009). "Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis.". Nat. Med. 15 (9): 1072–6. doi:10.1038/nm.1998. PMID 19684582.
- Tang BL (2001). "ADAMTS: a novel family of extracellular matrix proteases.". Int. J. Biochem. Cell Biol. 33 (1): 33–44. doi:10.1016/S1357-2725(00)00061-3. PMID 11167130.
- Song RH, Tortorella MD, Malfait AM et al. (2007). "Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5.". Arthritis Rheum. 56 (2): 575–85. doi:10.1002/art.22334. PMID 17265492.
- Barthel KK, Liu X (2008). Abraham, Edathara, ed. "A transcriptional enhancer from the coding region of ADAMTS5.". PLoS ONE 3 (5): e2184. doi:10.1371/journal.pone.0002184. PMC 2364661. PMID 18478108.
External links
PDB gallery |
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| | 2rjq: Crystal structure of ADAMTS5 with inhibitor bound |
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