Biology:MMP28

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

Generic protein structure example

Matrix metalloproteinase 28 also known as epilysin is an enzyme that in humans is encoded by the MMP28 gene.

Function

Matrix metalloproteinase 28, also known as epilysin, belongs to a family of proteins known as matrix metalloproteinases which are common to tissue regulation. Matrix metalloproteinases are commonly known to degrade the extracellular matrix, alongside regulating cell surface receptors MMP-28 releases growth factors and adhesion molecules to modulate inflammation. MMP-28 is unique in that it can be found in many regular tissues, denoting a potential role in maintaining the healthy structure and function of most tissue. MMPs commonly modulate their expression via negative and positive feedback loops as a result of releasing and responding to growth hormones.

MMP-28 is less frequently found in tissues such as the brain, colon, heart, and lungs. However, MMP-28 is expressed heavily in organs such as the testes. Epilysin is also found in high concentration in basal keratinocytes in injured skin, even at some distance away from the wound, showing a role in repairing damaged tissue. MMP-28 also can alter the cell membrane to become more adhesive, and not allowing the cell to migrate.

Structure

MMP-28 is a 520 amino acid long protein. The estimated signal peptide sequence appears as a long tail of random coil coming off of the protein that helps to guide the protein to excretion with the sequence PRCGVTD. The zinc binding catalytic site is tucked within an alpha helix within the center of the protein with a HEIGHTLGLTH sequence at positions 240–250 with a hemopexin-like domain. Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.

Epilysin contains 8 exons, 5 of which are splice sites unique to MMP-28 and not used by any other metalloproteinase in the MMP family.

The full amino acid sequence is listed on uniprot.

Clinical implications

The overexpression of MMP-28 is linked to the metastasis of tumors in cancer. Expression of MMP-28 can be linked to tumor diameter, depth of invasion, and stage of metastasis. In patients with positive overexpression of MMP-28, survival may be significantly less likely compared to negative expression of this protein, making it a potentially important marker for proactive prognosis of some forms of cancer.

MMP-28 may also play an important role in the breakdown of myelin, an important component of nervous system functionality. Demyelination may interrupt nerve signaling or even halt it completely, which can create severe neurological effects such as multiple sclerosis transverse myelitis and neuromyelitis optica.

Further reading

• "Promoter characterization of the human and mouse epilysin (MMP-28) genes". Gene 275 (1): 185–194. September 2001. doi:10.1016/S0378-1119(01)00664-3. PMID 11574168. 
• "Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair". The Journal of Investigative Dermatology 119 (1): 14–21. July 2002. doi:10.1046/j.1523-1747.2002.01790.x. PMID 12164918. 
• "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America 99 (26): 16899–16903. December 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research 13 (10): 2265–2270. October 2003. doi:10.1101/gr.1293003. PMID 12975309. 
• "Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis". Brain 126 (Pt 12): 2738–2749. December 2003. doi:10.1093/brain/awg285. PMID 14506071. 
• "Expression profiling of metalloproteinases and their inhibitors in cartilage". Arthritis and Rheumatism 50 (1): 131–141. January 2004. doi:10.1002/art.11433. PMID 14730609. 
• "Differential expression of three matrix metalloproteinases, MMP-19, MMP-26, and MMP-28, in normal and inflamed intestine and colon cancer". Digestive Diseases and Sciences 49 (4): 653–661. April 2004. doi:10.1023/B:DDAS.0000026314.12474.17. PMID 15185874. 
• "Matrix metalloproteinase 28/epilysin expression in cartilage from patients with rheumatoid arthritis and osteoarthritis: comment on the article by Kevorkian et al". Arthritis and Rheumatism 50 (12): 4074–5; author reply 4075. December 2004. doi:10.1002/art.20799. PMID 15593191. 
• "Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars". Wound Repair and Regeneration 13 (3): 255–261. 2005. doi:10.1111/j.1067-1927.2005.130307.x. PMID 15953044. 

External links

• The MEROPS online database for peptidases and their inhibitors: M10.030