Biology:ADAMTS5

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

A disintegrin and metalloproteinase with thrombospondin motifs 5 also known as ADAMTS5 is an enzyme that in humans is encoded by the ADAMTS5 gene.

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. ADAMTS5 may also have a role in the pathogenesis of human osteoarthritis.

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. ADAMTS5 is the major aggrecanase in mouse cartilage in a mouse model of inflammatory arthritis.

Further reading

• "Crystal structures of the two major aggrecan degrading enzymes, ADAMTS4 and ADAMTS5". Protein Science 17 (1): 16–21. Jan 2008. doi:10.1110/ps.073287008. PMID 18042673. 
• "Proprotein convertase activation of aggrecanases in cartilage in situ". Archives of Biochemistry and Biophysics 478 (1): 43–51. Oct 2008. doi:10.1016/j.abb.2008.07.012. PMID 18671934. 
• "Expression of ADAMTS-5 in deformed human temporomandibular joint discs". Histology and Histopathology 23 (12): 1485–93. Dec 2008. PMID 18830934. 
• "Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter". Molecular Biology Reports 34 (4): 225–31. Dec 2007. doi:10.1007/s11033-006-9037-3. PMID 17211519. 
• "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. doi:10.1097/BRS.0b013e318158cb85. PMID 17978660. 
• Gibson, Greg, ed (Oct 2009). "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. PMID 19834535. 
• "High resolution crystal structure of the catalytic domain of ADAMTS-5 (aggrecanase-2)". The Journal of Biological Chemistry 283 (3): 1501–7. Jan 2008. doi:10.1074/jbc.M705879200. PMID 17991750. 
• "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. doi:10.1002/art.22408. PMID 17265493. http://edoc.unibas.ch/6811/1/Grogan%20et%20al.%202007.pdf. 
• "Human glioblastomas overexpress ADAMTS-5 that degrades brevican". Acta Neuropathologica 110 (3): 239–46. Sep 2005. doi:10.1007/s00401-005-1032-6. PMID 16133547. 
• "Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4". The Journal of Biological Chemistry 282 (25): 18294–306. Jun 2007. doi:10.1074/jbc.M701523200. PMID 17430884. 
• "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics 7 (3): 499–508. Mar 2008. doi:10.1074/mcp.M700325-MCP200. PMID 18029348. 
• "Genetic variation including nonsynonymous polymorphisms of a major aggrecanase, ADAMTS-5, in susceptibility to osteoarthritis". Arthritis and Rheumatism 58 (2): 435–41. Feb 2008. doi:10.1002/art.23201. PMID 18240210. 
• "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. doi:10.1016/j.bbagen.2006.01.013. PMID 16507336. 
• "Expression of ADAMTS-5/implantin in human decidual stromal cells: regulatory effects of cytokines". Human Reproduction 22 (1): 63–74. Jan 2007. doi:10.1093/humrep/del356. PMID 17067994. 
• "[ADAMTS family--new extracellular matrix degrading enzyme]". Seikagaku. The Journal of Japanese Biochemical Society 73 (11): 1333–7. Nov 2001. PMID 11831030. 
• "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. doi:10.1074/jbc.M708647200. PMID 18156631. 
• "Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis". Nature Medicine 15 (9): 1072–6. Sep 2009. doi:10.1038/nm.1998. PMID 19684582. 
• "ADAMTS: a novel family of extracellular matrix proteases". The International Journal of Biochemistry & Cell Biology 33 (1): 33–44. Jan 2001. doi:10.1016/S1357-2725(00)00061-3. PMID 11167130. 
• "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. doi:10.1002/art.22334. PMID 17265492. 
• Abraham, Edathara, ed (2008). "A transcriptional enhancer from the coding region of ADAMTS5". PLOS ONE 3 (5): e2184. doi:10.1371/journal.pone.0002184. PMID 18478108. Bibcode: 2008PLoSO...3.2184B. 

External links

• The MEROPS online database for peptidases and their inhibitors: M12.225
• Rat Genome Database
• Human ADAMTS5 genome location and ADAMTS5 gene details page in the UCSC Genome Browser.