Biology:MMP8

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

Generic protein structure example

Neutrophil collagenase, also known as matrix metalloproteinase-8 (MMP-8) or PMNL collagenase (MNL-CL), is a collagen cleaving enzyme which is present in the connective tissue of most mammals. In humans, the MMP-8 protein is encoded by the MMP8 gene. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is stored in secondary granules within neutrophils and is activated by autolytic cleavage.

Function

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The primary function of MMP-8 is the degradation of type I, II and III collagens. In cancer, loss of MMP-8 in the murine MMTV-PyMT breast cancer model has been associated with increased tumor growth and metastatic burden, as well as enhanced tumor vascularity and altered immune cell infiltration. Furthermore, analysis of MMP-8 in breast cancer cell lines revealed a causal connection between MMP-8 activity and IL6 and IL8 production, suggesting a role for MMP-8 in the regulation of the innate immune system.

Further reading

• "Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview.". J. Neuroimmunol. 72 (2): 155–61. 1997. doi:10.1016/S0165-5728(96)00179-8. PMID 9042108. 
• "Matrix metalloproteinases: structures, evolution, and diversification.". FASEB J. 12 (25n26): 1075–95. 1998. doi:10.1142/S0217984998001256. PMID 9737711. 
• "Matrix metalloproteinases.". J. Biol. Chem. 274 (31): 21491–4. 1999. doi:10.1074/jbc.274.31.21491. PMID 10419448. 
• "Formation of a covalent Hg-Cys-bond during mercurial activation of PMNL procollagenase gives evidence of a cysteine-switch mechanism.". FEBS Lett. 313 (1): 59–61. 1992. doi:10.1016/0014-5793(92)81184-N. PMID 1330697. 
• "Structure and expression of the cDNA encoding human neutrophil collagenase.". Blood 77 (12): 2731–8. 1991. doi:10.1182/blood.V77.12.2731.2731. PMID 1646048. 
• "Mercurial activation of human polymorphonuclear leucocyte procollagenase.". Eur. J. Biochem. 202 (3): 1223–30. 1992. doi:10.1111/j.1432-1033.1991.tb16494.x. PMID 1662606. 
• "Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms.". Eur. J. Biochem. 189 (2): 295–300. 1990. doi:10.1111/j.1432-1033.1990.tb15489.x. PMID 2159879. 
• "Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases.". J. Biol. Chem. 265 (20): 11421–4. 1990. doi:10.1016/S0021-9258(19)38413-3. PMID 2164002. 
• "Partial amino acid sequence of human PMN leukocyte procollagenase.". Biol. Chem. Hoppe-Seyler 371 Suppl: 295–304. 1990. PMID 2169256. 
• "Partial amino-acid sequence of human PMN leukocyte procollagenase.". Biol. Chem. Hoppe-Seyler 371 (8): 733–734. 1990. doi:10.1515/bchm3.1990.371.2.733. PMID 2169766. 
• "Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase.". Biochemistry 29 (47): 10628–34. 1991. doi:10.1021/bi00499a008. PMID 2176876. 
• "Structure of human neutrophil collagenase reveals large S1' specificity pocket.". Nat. Struct. Biol. 1 (2): 119–23. 1995. doi:10.1038/nsb0294-119. PMID 7656015. 
• "Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan.". Biochem. J. 304 (2): 347–51. 1995. doi:10.1042/bj3040347. PMID 7998967. 
• "The X-ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity.". EMBO J. 13 (6): 1263–9. 1994. doi:10.1002/j.1460-2075.1994.tb06378.x. PMID 8137810. 
• "Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain.". Biochem. J. 295 (1): 273–6. 1993. doi:10.1042/bj2950273. PMID 8216228. 
• "Structural implications for the role of the N terminus in the 'superactivation' of collagenases. A crystallographic study.". FEBS Lett. 338 (2): 227–33. 1994. doi:10.1016/0014-5793(94)80370-6. PMID 8307185. 
• "Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils.". Kidney Int. 44 (2): 423–9. 1993. doi:10.1038/ki.1993.260. PMID 8397318. 
• "Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase.". J. Biol. Chem. 271 (18): 11023–6. 1996. doi:10.1074/jbc.271.18.11023. PMID 8631924. 
• "Amino acid sequence and carbohydrate structure of a recombinant human tissue factor pathway inhibitor expressed in Chinese hamster ovary cells: one N-and two O-linked carbohydrate chains are located between Kunitz domains 2 and 3 and one N-linked carbohydrate chain is in Kunitz domain 2.". Biochemistry 35 (20): 6450–9. 1996. doi:10.1021/bi9524880. PMID 8639592. 
• "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3.". Genomics 37 (2): 266–8. 1997. doi:10.1006/geno.1996.0557. PMID 8921407. 

External links

• The MEROPS online database for peptidases and their inhibitors: M10.002