MMP8

MMP8
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1A86, 1JAP, 1I76, 1ZVX, 3TT4, 2OY2, 1ZS0, 1JAN, 1MMB, 1I73, 1A85, 1KBC, 1ZP5, 1JH1, 3DPF, 1JAQ, 3DPE, 1BZS, 4QKZ, 1JAO, 3DNG, 2OY4, 1MNC
Identifiers
Aliases	MMP8, CLG1, HNC, MMP-8, PMNL-CL, matrix metallopeptidase 8
External IDs	OMIM: 120355; MGI: 1202395; HomoloGene: 22482; GeneCards: MMP8; OMA:MMP8 - orthologs
Gene location (Human)
Chr.	Chromosome 11 (human)
End	102,727,050 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	7,568,486 bp
RNA expression pattern
	Top expressed in
	trabecular bone; ; bone marrow; ; bone marrow cells; ; testicle; ; monocyte; ; blood; ; amniotic fluid; ; spleen; ; granulocyte; ; upper lobe of left lung;
	Top expressed in
	granulocyte; ; tibiofemoral joint; ; muscle of thorax; ; third toe; ; bone marrow; ; blood; ; second toe; ; cartilage tissue; ; hallux; ; bones of free part of lower limb;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	zinc ion binding; peptidase activity; hydrolase activity; metallopeptidase activity; metal ion binding; serine-type endopeptidase activity; metalloendopeptidase activity; endopeptidase activity;
Cellular component	extracellular matrix; extracellular region; specific granule lumen; tertiary granule lumen; extracellular space; collagen-containing extracellular matrix;
Biological process	collagen catabolic process; extracellular matrix disassembly; endodermal cell differentiation; proteolysis; neutrophil degranulation; positive regulation of gene expression; negative regulation of gene expression; negative regulation of interleukin-10 production; positive regulation of interleukin-6 production; positive regulation of DNA binding; positive regulation of MAPK cascade; positive regulation of nitric oxide biosynthetic process; positive regulation of JNK cascade; regulation of neuroinflammatory response; positive regulation of neuroinflammatory response; positive regulation of NIK/NF-kappaB signaling; positive regulation of reactive oxygen species biosynthetic process; regulation of microglial cell activation; positive regulation of microglial cell activation; extracellular matrix organization;
	Sources:Amigo / QuickGO
Orthologs
	4317
	17394
	ENSG00000118113
	ENSMUSG00000005800
	P22894
	O70138
	NM_001304441; NM_001304442; NM_002424
	NM_008611
	NP_001291370; NP_001291371; NP_002415
	NP_032637
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5] In humans, the MMP-8 protein is encoded by the MMP8 gene.^[6]^[7] The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.^[5] 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.^[8] 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.^[9]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000118113 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000005800 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: MMP8 matrix metallopeptidase 8 (neutrophil collagenase)".
^ Hasty KA, Pourmotabbed TF, Goldberg GI, Thompson JP, Spinella DG, Stevens RM, et al. (July 1990). "Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases". Journal of Biological Chemistry. 265 (20): 11421–11424. doi:10.1016/S0021-9258(19)38413-3. PMID 2164002.
^ Devarajan P, Mookhtiar K, Van Wart H, Berliner N (June 1991). "Structure and expression of the cDNA encoding human neutrophil collagenase". Blood. 77 (12): 2731–2738. doi:10.1182/blood.V77.12.2731.2731. PMID 1646048.
^ Decock J, Hendrickx W, Thirkettle S, Gutiérrez-Fernández A, Robinson SD, Edwards DR (2015). "Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice". Breast Cancer Research : BCR. 17 (1): 38. doi:10.1186/s13058-015-0545-8. PMC 4380014. PMID 25848906.
^ Thirkettle S, Decock J, Arnold H, Pennington CJ, Jaworski DM, Edwards DR (2013). "Matrix metalloproteinase 8 (collagenase 2) induces the expression of interleukins 6 and 8 in breast cancer cells". Journal of Biological Chemistry. 288 (23): 16282–16294. doi:10.1074/jbc.M113.464230. PMC 3675567. PMID 23632023.

Chandler S, Miller KM, Clements JM, Lury J, Corkill D, Anthony DC, et al. (Feb 1997). "Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview". Journal of Neuroimmunology. 72 (2): 155–161. doi:10.1016/S0165-5728(96)00179-8. PMID 9042108. S2CID 26495949.
Massova I, Kotra LP, Fridman R, Mobashery S (Sep 1998). "Matrix metalloproteinases: structures, evolution, and diversification". FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. 12 (12): 1075–1095. CiteSeerX 10.1.1.31.3959. doi:10.1142/S0217984998001256. PMID 9737711.
Nagase H, Woessner JF (Jul 1999). "Matrix metalloproteinases". Journal of Biological Chemistry. 274 (31): 21491–21494. doi:10.1074/jbc.274.31.21491. PMID 10419448.
Bläser J, Triebel S, Reinke H, Tschesche H (Nov 1992). "Formation of a covalent Hg-Cys-bond during mercurial activation of PMNL procollagenase gives evidence of a cysteine-switch mechanism". FEBS Letters. 313 (1): 59–61. Bibcode:1992FEBSL.313...59B. doi:10.1016/0014-5793(92)81184-N. PMID 1330697. S2CID 36829374.
Devarajan P, Mookhtiar K, Van Wart H, Berliner N (Jun 1991). "Structure and expression of the cDNA encoding human neutrophil collagenase". Blood. 77 (12): 2731–2738. doi:10.1182/blood.V77.12.2731.2731. PMID 1646048.
Blaser J, Knauper V, Osthues A, Reinke H, Tschesche H (Dec 1991). "Mercurial activation of human polymorphonuclear leucocyte procollagenase". European Journal of Biochemistry. 202 (3): 1223–1230. doi:10.1111/j.1432-1033.1991.tb16494.x. PMID 1662606.
Knäuper V, Krämer S, Reinke H, Tschesche H (Apr 1990). "Characterization and activation of procollagenase from human polymorphonuclear leucocytes. N-terminal sequence determination of the proenzyme and various proteolytically activated forms". European Journal of Biochemistry. 189 (2): 295–300. doi:10.1111/j.1432-1033.1990.tb15489.x. PMID 2159879.
Hasty KA, Pourmotabbed TF, Goldberg GI, et al. (Jul 1990). "Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases". Journal of Biological Chemistry. 265 (20): 11421–11424. doi:10.1016/S0021-9258(19)38413-3. PMID 2164002.
Knäuper V, Krämer S, Reinke H, Tschesche H (May 1990). "Partial amino acid sequence of human PMN leukocyte procollagenase". Biological Chemistry Hoppe-seyler. 371 (Suppl): 295–304. PMID 2169256.
Knäuper V, Krämer S, Reinke H, Tschesche H (Aug 1990). "Partial amino-acid sequence of human PMN leukocyte procollagenase". Biological Chemistry Hoppe-seyler. 371 (8): 733. doi:10.1515/bchm3.1990.371.2.733. PMID 2169766.
Mallya SK, Mookhtiar KA, Gao Y, Brew K, Dioszegi M, Birkedal-Hansen H, et al. (Nov 1990). "Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase". Biochemistry. 29 (47): 10628–10634. doi:10.1021/bi00499a008. PMID 2176876.
Stams T, Spurlino JC, Smith DL, Wahl RC, Ho TF, Qoronfleh MW, et al. (Feb 1994). "Structure of human neutrophil collagenase reveals large S1' specificity pocket". Nature Structural Biology. 1 (2): 119–123. doi:10.1038/nsb0294-119. PMID 7656015. S2CID 35458800.
Fosang AJ, Last K, Neame PJ, Murphy G, Knauper V, Tschesche H, et al. (Dec 1994). "Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan". The Biochemical Journal. 304 ( Pt 2) (Pt 2): 347–351. doi:10.1042/bj3040347. PMC 1137499. PMID 7998967.
Bode W, Reinemer P, Huber R, Kleine T, Schnierer S, Tschesche H (Mar 1994). "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". The EMBO Journal. 13 (6): 1263–1269. doi:10.1002/j.1460-2075.1994.tb06378.x. PMC 394940. PMID 8137810.
Fosang AJ, Last K, Knauper V, Neame PJ, Murphy G, Hardingham TE, et al. (Oct 1993). "Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain". The Biochemical Journal. 295 ( Pt 1) (Pt 1): 273–276. doi:10.1042/bj2950273. PMC 1134849. PMID 8216228.
Reinemer P, Grams F, Huber R, Kleine T, Schnierer S, Piper M, et al. (Jan 1994). "Structural implications for the role of the N terminus in the 'superactivation' of collagenases. A crystallographic study". FEBS Letters. 338 (2): 227–233. Bibcode:1994FEBSL.338..227R. doi:10.1016/0014-5793(94)80370-6. PMID 8307185. S2CID 2454182.
Thomas DB, Davies M, Peters JR, Williams JD (Aug 1993). "Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils". Kidney International. 44 (2): 423–429. doi:10.1038/ki.1993.260. PMID 8397318.
Cole AA, Chubinskaya S, Schumacher B, Huch K, Szabo G, Yao J, et al. (May 1996). "Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase". Journal of Biological Chemistry. 271 (18): 11023–11026. doi:10.1074/jbc.271.18.11023. PMID 8631924.
Nakahara Y, Miyata T, Hamuro T, Funatsu A, Miyagi M, Tsunasawa S, et al. (May 1996). "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): 6450–6459. doi:10.1021/bi9524880. PMID 8639592.
Pendas AM, Santamaria I, Alvarez MV, Pritchard M, Lopez-Otin C (Oct 1996). "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3". Genomics. 37 (2): 266–268. doi:10.1006/geno.1996.0557. PMID 8921407.

External links

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

This article on a gene on human chromosome 11 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000118113 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000005800 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: MMP8 matrix metallopeptidase 8 (neutrophil collagenase)".

[Hasty_1990-6] Hasty KA, Pourmotabbed TF, Goldberg GI, Thompson JP, Spinella DG, Stevens RM, et al. (July 1990). "Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases". Journal of Biological Chemistry. 265 (20): 11421–11424. doi:10.1016/S0021-9258(19)38413-3. PMID 2164002.

[Devarajan_1991-7] Devarajan P, Mookhtiar K, Van Wart H, Berliner N (June 1991). "Structure and expression of the cDNA encoding human neutrophil collagenase". Blood. 77 (12): 2731–2738. doi:10.1182/blood.V77.12.2731.2731. PMID 1646048.

[8] Decock J, Hendrickx W, Thirkettle S, Gutiérrez-Fernández A, Robinson SD, Edwards DR (2015). "Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice". Breast Cancer Research : BCR. 17 (1): 38. doi:10.1186/s13058-015-0545-8. PMC 4380014. PMID 25848906.

[9] Thirkettle S, Decock J, Arnold H, Pennington CJ, Jaworski DM, Edwards DR (2013). "Matrix metalloproteinase 8 (collagenase 2) induces the expression of interleukins 6 and 8 in breast cancer cells". Journal of Biological Chemistry. 288 (23): 16282–16294. doi:10.1074/jbc.M113.464230. PMC 3675567. PMID 23632023.

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v t e Proteases: metalloendopeptidases (EC 3.4.24)
ADAM proteins	Alpha secretases ADAM9 ADAM10 ADAM17 ADAM19 ADAM2 ADAM7 ADAM8 ADAM11 ADAM12 ADAM15 ADAM18 ADAM22 ADAM23 ADAM28 ADAM33 ADAMTS1 ADAMTS2 ADAMTS3 ADAMTS4 ADAMTS5 ADAMTS8 ADAMTS9 ADAMTS10 ADAMTS12 ADAMTS13
Matrix metalloproteinases	Collagenases MMP1 MMP8 Gelatinases MMP2 MMP9 MMP3 MMP7 MMP10 MMP11 MMP12 MMP13 MMP14 MMP15 MMP16 MMP17 MMP19 MMP20 MMP21 MMP23A MMP23B MMP24 MMP25 MMP26 MMP27 MMP28
Other	Neprilysin Procollagen peptidase Thermolysin Pregnancy-associated plasma protein A Bone morphogenetic protein 1 Lysostaphin Insulin-degrading enzyme ZMPSTE24

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Function

References

Further reading

External links