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MMP8

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

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.{{cite web | title = Entrez Gene: MMP8 matrix metallopeptidase 8 (neutrophil collagenase)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4317}} In humans, the MMP-8 protein is encoded by the MMP8 gene.{{cite journal | vauthors = Hasty KA, Pourmotabbed TF, Goldberg GI, Thompson JP, Spinella DG, Stevens RM, Mainardi CL | title = Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases | journal = J. Biol. Chem. | volume = 265 | issue = 20 | pages = 11421–4 | date = July 1990 | doi = 10.1016/S0021-9258(19)38413-3 | pmid = 2164002 | doi-access = free }}{{cite journal | vauthors = Devarajan P, Mookhtiar K, Van Wart H, Berliner N | title = Structure and expression of the cDNA encoding human neutrophil collagenase | journal = Blood | volume = 77 | issue = 12 | pages = 2731–8 | date = June 1991 | pmid = 1646048 | doi = 10.1182/blood.V77.12.2731.2731| doi-access = free }}

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.{{cite journal |last1=Decock |first1=Julie |last2=Hendrickx |first2=Wouter |last3=Thirkettle |first3=Sally |last4=Gutiérrez-Fernández |first4=Ana |last5=Robinson |first5=Stephen D |last6=Edwards |first6=Dylan R |title=Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice. |journal=Breast Cancer Res |date=2015 |volume=17 |issue=1 |page=38 |doi=10.1186/s13058-015-0545-8 |pmid=25848906|pmc=4380014 |doi-access=free }} 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.{{cite journal |last1=Thirkettle |first1=Sally |last2=Decock |first2=Julie |last3=Arnold |first3=Hugh |last4=Pennington |first4=Caroline J |last5=Jaworski |first5=Diane M |last6=Edwards |first6=Dylan R |title=Matrix metalloproteinase 8 (collagenase 2) induces the expression of interleukins 6 and 8 in breast cancer cells. |journal=J Biol Chem |date=2013 |volume=288 |issue=23 |pages=16282–16294 |doi=10.1074/jbc.M113.464230 |pmid=23632023|pmc=3675567 |doi-access=free }}

References

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Further reading

{{refbegin | 2}}

  • {{cite journal |vauthors=Chandler S, Miller KM, Clements JM, etal |title=Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview. |journal=J. Neuroimmunol. |volume=72 |issue= 2 |pages= 155–61 |year= 1997 |pmid= 9042108 |doi=10.1016/S0165-5728(96)00179-8 |s2cid=26495949 }}
  • {{cite journal |vauthors=Massova I, Kotra LP, Fridman R, Mobashery S |title=Matrix metalloproteinases: structures, evolution, and diversification. |journal=FASEB J. |volume=12 |issue= 25n26 |pages= 1075–95 |year= 1998 |pmid= 9737711 |doi= 10.1142/S0217984998001256|citeseerx=10.1.1.31.3959 }}
  • {{cite journal |vauthors=Nagase H, Woessner JF |title=Matrix metalloproteinases. |journal=J. Biol. Chem. |volume=274 |issue= 31 |pages= 21491–4 |year= 1999 |pmid= 10419448 |doi=10.1074/jbc.274.31.21491 |doi-access=free }}
  • {{cite journal |vauthors=Bläser J, Triebel S, Reinke H, Tschesche H |title=Formation of a covalent Hg-Cys-bond during mercurial activation of PMNL procollagenase gives evidence of a cysteine-switch mechanism. |journal=FEBS Lett. |volume=313 |issue= 1 |pages= 59–61 |year= 1992 |pmid= 1330697 |doi=10.1016/0014-5793(92)81184-N |s2cid=36829374 |doi-access=free |bibcode=1992FEBSL.313...59B }}
  • {{cite journal |vauthors=Devarajan P, Mookhtiar K, Van Wart H, Berliner N |title=Structure and expression of the cDNA encoding human neutrophil collagenase. |journal=Blood |volume=77 |issue= 12 |pages= 2731–8 |year= 1991 |pmid= 1646048 |doi= 10.1182/blood.V77.12.2731.2731|doi-access=free }}
  • {{cite journal |vauthors=Bläser J, Knäuper V, Osthues A, etal |title=Mercurial activation of human polymorphonuclear leucocyte procollagenase. |journal=Eur. J. Biochem. |volume=202 |issue= 3 |pages= 1223–30 |year= 1992 |pmid= 1662606 |doi=10.1111/j.1432-1033.1991.tb16494.x |doi-access=free }}
  • {{cite journal |vauthors=Knäuper V, Krämer S, Reinke H, Tschesche H |title=Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms. |journal=Eur. J. Biochem. |volume=189 |issue= 2 |pages= 295–300 |year= 1990 |pmid= 2159879 |doi=10.1111/j.1432-1033.1990.tb15489.x |doi-access=free }}
  • {{cite journal |vauthors=Hasty KA, Pourmotabbed TF, Goldberg GI, etal |title=Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases. |journal=J. Biol. Chem. |volume=265 |issue= 20 |pages= 11421–4 |year= 1990 |doi=10.1016/S0021-9258(19)38413-3 |pmid= 2164002 |doi-access=free }}
  • {{cite journal |vauthors=Knäuper V, Krämer S, Reinke H, Tschesche H |title=Partial amino acid sequence of human PMN leukocyte procollagenase. |journal=Biol. Chem. Hoppe-Seyler |volume=371 Suppl |pages= 295–304 |year= 1990 |pmid= 2169256 }}
  • {{cite journal |vauthors=Knäuper V, Krämer S, Reinke H, Tschesche H |title=Partial amino-acid sequence of human PMN leukocyte procollagenase. |journal=Biol. Chem. Hoppe-Seyler |volume=371 |issue= 8 |pages= 733–734 |year= 1990 |pmid= 2169766 |doi= 10.1515/bchm3.1990.371.2.733}}
  • {{cite journal |vauthors=Mallya SK, Mookhtiar KA, Gao Y, etal |title=Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase. |journal=Biochemistry |volume=29 |issue= 47 |pages= 10628–34 |year= 1991 |pmid= 2176876 |doi=10.1021/bi00499a008 }}
  • {{cite journal |vauthors=Stams T, Spurlino JC, Smith DL, etal |title=Structure of human neutrophil collagenase reveals large S1' specificity pocket. |journal=Nat. Struct. Biol. |volume=1 |issue= 2 |pages= 119–23 |year= 1995 |pmid= 7656015 |doi=10.1038/nsb0294-119 |s2cid=35458800 }}
  • {{cite journal |vauthors=Fosang AJ, Last K, Neame PJ, etal |title=Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan. |journal=Biochem. J. |volume=304 |issue= 2|pages= 347–51 |year= 1995 |pmid= 7998967 |doi= 10.1042/bj3040347| pmc=1137499 }}
  • {{cite journal |vauthors=Bode W, Reinemer P, Huber R, etal |title=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. |journal=EMBO J. |volume=13 |issue= 6 |pages= 1263–9 |year= 1994 |pmid= 8137810 |doi= 10.1002/j.1460-2075.1994.tb06378.x| pmc=394940 }}
  • {{cite journal |vauthors=Fosang AJ, Last K, Knäuper V, etal |title=Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain. |journal=Biochem. J. |volume=295 |issue= 1|pages= 273–6 |year= 1993 |pmid= 8216228 |doi= 10.1042/bj2950273| pmc=1134849 }}
  • {{cite journal |vauthors=Reinemer P, Grams F, Huber R, etal |title=Structural implications for the role of the N terminus in the 'superactivation' of collagenases. A crystallographic study. |journal=FEBS Lett. |volume=338 |issue= 2 |pages= 227–33 |year= 1994 |pmid= 8307185 |doi=10.1016/0014-5793(94)80370-6 |s2cid=2454182 |doi-access=free |bibcode=1994FEBSL.338..227R }}
  • {{cite journal |vauthors=Thomas DB, Davies M, Peters JR, Williams JD |title=Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils. |journal=Kidney Int. |volume=44 |issue= 2 |pages= 423–9 |year= 1993 |pmid= 8397318 |doi=10.1038/ki.1993.260 |doi-access=free }}
  • {{cite journal |vauthors=Cole AA, Chubinskaya S, Schumacher B, etal |title=Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase. |journal=J. Biol. Chem. |volume=271 |issue= 18 |pages= 11023–6 |year= 1996 |pmid= 8631924 |doi= 10.1074/jbc.271.18.11023|doi-access=free }}
  • {{cite journal |vauthors=Nakahara Y, Miyata T, Hamuro T, etal |title=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. |journal=Biochemistry |volume=35 |issue= 20 |pages= 6450–9 |year= 1996 |pmid= 8639592 |doi= 10.1021/bi9524880 }}
  • {{cite journal |vauthors=Pendás AM, Santamaría I, Alvarez MV, etal |title=Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3. |journal=Genomics |volume=37 |issue= 2 |pages= 266–8 |year= 1997 |pmid= 8921407 |doi=10.1006/geno.1996.0557 }}

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External links

  • The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=M10.002 M10.002]

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Category:Matrix metalloproteinases

Category:EC 3.4.24

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