MMP8

Protein-coding gene in the species Homo sapiens
MMP8
Available structures
PDBOrtholog 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
AliasesMMP8, CLG1, HNC, MMP-8, PMNL-CL, matrix metallopeptidase 8
External IDsOMIM: 120355; MGI: 1202395; HomoloGene: 22482; GeneCards: MMP8; OMA:MMP8 - orthologs
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for MMP8
Genomic location for MMP8
Band11q22.2Start102,711,796 bp[1]
End102,727,050 bp[1]
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)[2]
Chromosome 9 (mouse)
Genomic location for MMP8
Genomic location for MMP8
Band9|9 A1Start7,558,457 bp[2]
End7,568,486 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
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
BioGPS
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
SpeciesHumanMouse
Entrez

4317

17394

Ensembl

ENSG00000118113

ENSMUSG00000005800

UniProt

P22894

O70138

RefSeq (mRNA)

NM_001304441
NM_001304442
NM_002424

NM_008611

RefSeq (protein)

NP_001291370
NP_001291371
NP_002415

NP_032637

Location (UCSC)Chr 11: 102.71 – 102.73 MbChr 9: 7.56 – 7.57 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000118113 – Ensembl, May 2017
  2. ^ a b c 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.
  5. ^ a b "Entrez Gene: MMP8 matrix metallopeptidase 8 (neutrophil collagenase)".
  6. ^ Hasty KA, Pourmotabbed TF, Goldberg GI, Thompson JP, Spinella DG, Stevens RM, Mainardi CL (July 1990). "Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases". J. Biol. Chem. 265 (20): 11421–4. doi:10.1016/S0021-9258(19)38413-3. PMID 2164002.
  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): 2731–8. doi:10.1182/blood.V77.12.2731.2731. PMID 1646048.
  8. ^ Decock, Julie; Hendrickx, Wouter; Thirkettle, Sally; Gutiérrez-Fernández, Ana; Robinson, Stephen D; Edwards, Dylan R (2015). "Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice". Breast Cancer Res. 17 (1): 38. doi:10.1186/s13058-015-0545-8. PMC 4380014. PMID 25848906.
  9. ^ Thirkettle, Sally; Decock, Julie; Arnold, Hugh; Pennington, Caroline J; Jaworski, Diane M; Edwards, Dylan R (2013). "Matrix metalloproteinase 8 (collagenase 2) induces the expression of interleukins 6 and 8 in breast cancer cells". J Biol Chem. 288 (23): 16282–16294. doi:10.1074/jbc.M113.464230. PMC 3675567. PMID 23632023.

Further reading

  • Chandler S, Miller KM, Clements JM, et al. (1997). "Matrix metalloproteinases, tumor necrosis factor and multiple sclerosis: an overview". J. Neuroimmunol. 72 (2): 155–61. doi:10.1016/S0165-5728(96)00179-8. PMID 9042108. S2CID 26495949.
  • Massova I, Kotra LP, Fridman R, Mobashery S (1998). "Matrix metalloproteinases: structures, evolution, and diversification". FASEB J. 12 (25n26): 1075–95. CiteSeerX 10.1.1.31.3959. doi:10.1142/S0217984998001256. PMID 9737711.
  • Nagase H, Woessner JF (1999). "Matrix metalloproteinases". J. Biol. Chem. 274 (31): 21491–4. doi:10.1074/jbc.274.31.21491. PMID 10419448.
  • Bläser J, Triebel S, Reinke H, Tschesche H (1992). "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. doi:10.1016/0014-5793(92)81184-N. PMID 1330697. S2CID 36829374.
  • Devarajan P, Mookhtiar K, Van Wart H, Berliner N (1991). "Structure and expression of the cDNA encoding human neutrophil collagenase". Blood. 77 (12): 2731–8. doi:10.1182/blood.V77.12.2731.2731. PMID 1646048.
  • Bläser J, Knäuper V, Osthues A, et al. (1992). "Mercurial activation of human polymorphonuclear leucocyte procollagenase". Eur. J. Biochem. 202 (3): 1223–30. doi:10.1111/j.1432-1033.1991.tb16494.x. PMID 1662606.
  • Knäuper V, Krämer S, Reinke H, Tschesche H (1990). "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. doi:10.1111/j.1432-1033.1990.tb15489.x. PMID 2159879.
  • Hasty KA, Pourmotabbed TF, Goldberg GI, et al. (1990). "Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases". J. Biol. Chem. 265 (20): 11421–4. doi:10.1016/S0021-9258(19)38413-3. PMID 2164002.
  • Knäuper V, Krämer S, Reinke H, Tschesche H (1990). "Partial amino acid sequence of human PMN leukocyte procollagenase". Biol. Chem. Hoppe-Seyler. 371 Suppl: 295–304. PMID 2169256.
  • Knäuper V, Krämer S, Reinke H, Tschesche H (1990). "Partial amino-acid sequence of human PMN leukocyte procollagenase". Biol. Chem. Hoppe-Seyler. 371 (8): 733–734. doi:10.1515/bchm3.1990.371.2.733. PMID 2169766.
  • Mallya SK, Mookhtiar KA, Gao Y, et al. (1991). "Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase". Biochemistry. 29 (47): 10628–34. doi:10.1021/bi00499a008. PMID 2176876.
  • Stams T, Spurlino JC, Smith DL, et al. (1995). "Structure of human neutrophil collagenase reveals large S1' specificity pocket". Nat. Struct. Biol. 1 (2): 119–23. doi:10.1038/nsb0294-119. PMID 7656015. S2CID 35458800.
  • Fosang AJ, Last K, Neame PJ, et al. (1995). "Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A374 in the interglobular domain of cartilage aggrecan". Biochem. J. 304 (2): 347–51. doi:10.1042/bj3040347. PMC 1137499. PMID 7998967.
  • Bode W, Reinemer P, Huber R, et al. (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". EMBO J. 13 (6): 1263–9. doi:10.1002/j.1460-2075.1994.tb06378.x. PMC 394940. PMID 8137810.
  • Fosang AJ, Last K, Knäuper V, et al. (1993). "Fibroblast and neutrophil collagenases cleave at two sites in the cartilage aggrecan interglobular domain". Biochem. J. 295 (1): 273–6. doi:10.1042/bj2950273. PMC 1134849. PMID 8216228.
  • Reinemer P, Grams F, Huber R, et al. (1994). "Structural implications for the role of the N terminus in the 'superactivation' of collagenases. A crystallographic study". FEBS Lett. 338 (2): 227–33. doi:10.1016/0014-5793(94)80370-6. PMID 8307185. S2CID 2454182.
  • Thomas DB, Davies M, Peters JR, Williams JD (1993). "Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils". Kidney Int. 44 (2): 423–9. doi:10.1038/ki.1993.260. PMID 8397318.
  • Cole AA, Chubinskaya S, Schumacher B, et al. (1996). "Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase". J. Biol. Chem. 271 (18): 11023–6. doi:10.1074/jbc.271.18.11023. PMID 8631924.
  • Nakahara Y, Miyata T, Hamuro T, et al. (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): 6450–9. doi:10.1021/bi9524880. PMID 8639592.
  • Pendás AM, Santamaría I, Alvarez MV, et al. (1997). "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3". Genomics. 37 (2): 266–8. doi:10.1006/geno.1996.0557. PMID 8921407.

External links

  • The MEROPS online database for peptidases and their inhibitors: M10.002
  • v
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  • 1a85: MMP8 WITH MALONIC AND ASPARAGINE BASED INHIBITOR
    1a85: MMP8 WITH MALONIC AND ASPARAGINE BASED INHIBITOR
  • 1a86: MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR
    1a86: MMP8 WITH MALONIC AND ASPARTIC ACID BASED INHIBITOR
  • 1bzs: CRYSTAL STRUCTURE OF MMP8 COMPLEXED WITH HMR2909
    1bzs: CRYSTAL STRUCTURE OF MMP8 COMPLEXED WITH HMR2909
  • 1i73: COMPLEX OF PRO-LEU-L-TRP PHOSPHONATE WITH THE CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
    1i73: COMPLEX OF PRO-LEU-L-TRP PHOSPHONATE WITH THE CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
  • 1i76: COMPLEX OF 2-(BIPHENYL-4-SULFONYL)-1,2,3,4-TETRAHYDRO-ISOQUINOLINE-3-CARBOXYLIC ACID (D-TIC DERIVATIVE) WITH T CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
    1i76: COMPLEX OF 2-(BIPHENYL-4-SULFONYL)-1,2,3,4-TETRAHYDRO-ISOQUINOLINE-3-CARBOXYLIC ACID (D-TIC DERIVATIVE) WITH T CATALITIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
  • 1jan: COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (PHE79 FORM)
    1jan: COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (PHE79 FORM)
  • 1jao: COMPLEX OF 3-MERCAPTO-2-BENZYLPROPANOYL-ALA-GLY-NH2 WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
    1jao: COMPLEX OF 3-MERCAPTO-2-BENZYLPROPANOYL-ALA-GLY-NH2 WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
  • 1jap: COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
    1jap: COMPLEX OF PRO-LEU-GLY-HYDROXYLAMINE WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
  • 1jaq: COMPLEX OF 1-HYDROXYLAMINE-2-ISOBUTYLMALONYL-ALA-GLY-NH2 WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
    1jaq: COMPLEX OF 1-HYDROXYLAMINE-2-ISOBUTYLMALONYL-ALA-GLY-NH2 WITH THE CATALYTIC DOMAIN OF MATRIX METALLO PROTEINASE-8 (MET80 FORM)
  • 1jh1: Crystal Structure of MMP-8 complexed with a 6H-1,3,4-thiadiazine derived inhibitor
    1jh1: Crystal Structure of MMP-8 complexed with a 6H-1,3,4-thiadiazine derived inhibitor
  • 1jj9: Crystal Structure of MMP8-Barbiturate Complex Reveals Mechanism for Collagen Substrate Recognition
    1jj9: Crystal Structure of MMP8-Barbiturate Complex Reveals Mechanism for Collagen Substrate Recognition
  • 1kbc: PROCARBOXYPEPTIDASE TERNARY COMPLEX
    1kbc: PROCARBOXYPEPTIDASE TERNARY COMPLEX
  • 1mmb: COMPLEX OF BB94 WITH THE CATALYTIC DOMAIN OF MATRIX METALLOPROTEINASE-8
    1mmb: COMPLEX OF BB94 WITH THE CATALYTIC DOMAIN OF MATRIX METALLOPROTEINASE-8
  • 1mnc: STRUCTURE OF HUMAN NEUTROPHIL COLLAGENASE REVEALS LARGE S1' SPECIFICITY POCKET
    1mnc: STRUCTURE OF HUMAN NEUTROPHIL COLLAGENASE REVEALS LARGE S1' SPECIFICITY POCKET
  • 1zp5: Crystal structure of the complex between MMP-8 and a N-hydroxyurea inhibitor
    1zp5: Crystal structure of the complex between MMP-8 and a N-hydroxyurea inhibitor
  • 1zs0: Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)
    1zs0: Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)
  • 1zvx: Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (R-enantiomer)
    1zvx: Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (R-enantiomer)
  • 2oy2: Human MMP-8 in complex with peptide IAG
    2oy2: Human MMP-8 in complex with peptide IAG
  • 2oy4: Uninhibited human MMP-8
    2oy4: Uninhibited human MMP-8
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