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Gene Review

MMP3  -  matrix metallopeptidase 3 (stromelysin 1,...

Homo sapiens

Synonyms: CHDS6, MMP-3, Matrix metalloproteinase-3, SL-1, STMY, ...
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Disease relevance of MMP3


Psychiatry related information on MMP3


High impact information on MMP3

  • Str1 also promotes spontaneous premalignant changes and malignant conversion in mammary glands of transgenic mice [10].
  • Transforming growth factor beta 1 (TGF-beta 1) inhibits the growth factor and oncogene induction of transin/stromelysin, a secreted matrix-degrading metalloprotease [11].
  • Here we report the crystal structure of an MMP-TIMP complex formed between the catalytic domain of human stromelysin-1 (MMP-3) and human TIMP-1 [12].
  • With its long edge, consisting of five different chain regions, it occupies the entire length of the active-site cleft of MMP-3 [12].
  • Cys 1 bidentally coordinates this zinc, and the Thr-2 side chain extends into the large specificity pocket of MMP-3 [12].

Chemical compound and disease context of MMP3


Biological context of MMP3

  • The frequencies of two of the three "risk-associated" genotypes were significantly higher in the AA population: GJA4 C1019T T/T: AA, 20%, EA, 7% (p = 0.053); MMP3 -1171delA A/A: AA, 78%, EA, 24% (p < 0.001); PAI-1 -668delG G/G: AA, 55%, EA, 16% (p < 0.001) [17].
  • Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex [18].
  • CONCLUSIONS: These data imply the involvement of MMP3 in chronic remodelling after conventional balloon angioplasty, and suggest that the 6A6A MMP3 genotype is a genetic susceptibility factor for restenosis after angioplasty without stenting [19].
  • A single adenine insertion/deletion polymorphism (6A/5A) in the MMP3 promoter region causes transcriptional elevation [4].
  • The results implicate MMP2, MMP3 and TIMP1 in the invasive phenotype of pancreatic and ampullary cancer [20].

Anatomical context of MMP3


Associations of MMP3 with chemical compounds

  • To determine whether variants within MMP3 are responsible for its altered expression, MMP3 was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses [1].
  • Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians [1].
  • Doxazosin had no effect on the modulators of matrix turnover matrix metalloproteinases MMP3, MMP9 and tissue inhibitor of matrix metalloproteinases (TIMP-1), although a significant reduction in tissue plasminogen activator (tPA); (36.5 +/- 2.6%, P < 0.001) was observed [24].
  • During the activation by MMP-3, proMMP-9 is converted to an active species of M(r) 64,000 that lacks both NH2- and COOH-terminal peptides [25].
  • Serum levels of hyaluronan, antigenic keratan sulfate, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 change predictably in rheumatoid arthritis patients who have begun activity after a night of bed rest [26].

Physical interactions of MMP3

  • In contrast to the cysteine proteinases, MMP-1 and MMP-3 as well as MT complex are elevated in RA [27].
  • These results suggest that neutrophil elastase may participate in the connective tissue destruction at the inflammatory sites not only by its direct action on matrix macromolecules but also by rendering pro-MMP-9 in the pro-MMP-9.TIMP-1 complex activable by MMP-3 as well as activating pro-MMP-3 [28].
  • Matrix metalloproteinase-3 (MMP-3 or stromelysin-1) specifically binds to tissue-type plasminogen activator (t-PA), without however, hydrolyzing the protein [29].
  • Essential structural features linked to affinity can be extracted using statistical analysis of (15)N and (1)H amide chemical shift differences in congeneric series relative to uncomplexed protein spectra, as demonstrated for 20 MMP-3 inhibitors in complex with human matrix metalloproteinase stromelysin (MMP-3) [30].

Enzymatic interactions of MMP3


Regulatory relationships of MMP3


Other interactions of MMP3

  • This unusual architecture of the interface between MMP-3 and TIMP-1 suggests new possibilities for designing TIMP variants and synthetic MMP inhibitors with potential therapeutic applications [12].
  • Immunohistochemical analysis of human coronary atheromata colocalized MMP-1 and MMP-3 with CD40-positive SMCs [38].
  • Our data indicate that the MMP-3 promoter constitutes a novel target of the defective mismatch repair machinery in sporadic colorectal tumors, resulting in a dramatic decrease in the levels of the active MMP-9 form, which may result in a lessened capacity for invasion [39].
  • The first of these substrates, NFF-1 (Mca-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Lys-(Dnp)-Gly, where Mca is (7-methoxycoumarin-4-yl)acetyl and Dnp is 2,4-dinitrophenyl), was hydrolyzed equally well by MMP-3 and MMP-2 (kcat/Km approximately 11,000 s-1 M-1) [40].
  • The increase in serum levels of MMP-3 and TIMP-1 appears to reflect systemic inflammation in RA [41].

Analytical, diagnostic and therapeutic context of MMP3


  1. Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians. Traurig, M.T., Permana, P.A., Nair, S., Kobes, S., Bogardus, C., Baier, L.J. Diabetes (2006) [Pubmed]
  2. The 5A/6A polymorphism of the matrix metalloproteinase 3 gene promoter and breast cancer. Krippl, P., Langsenlehner, U., Renner, W., Yazdani-Biuki, B., Köppel, H., Leithner, A., Wascher, T.C., Paulweber, B., Samonigg, H. Clin. Cancer Res. (2004) [Pubmed]
  3. Matrix metalloproteinase 3 polymorphism: a predictive factor of response to neoadjuvant chemotherapy in head and neck squamous cell carcinoma. Blons, H., Gad, S., Zinzindohoué, F., Manière, I., Beauregard, J., Tregouet, D., Brasnu, D., Beaune, P., Laccourreye, O., Laurent-Puig, P. Clin. Cancer Res. (2004) [Pubmed]
  4. The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma. Zhang, J., Jin, X., Fang, S., Li, Y., Wang, R., Guo, W., Wang, N., Wang, Y., Wen, D., Wei, L., Kuang, G., Dong, Z. Carcinogenesis (2004) [Pubmed]
  5. Influence of matrix metalloproteinase genotype on cardiovascular disease susceptibility and outcome. Ye, S. Cardiovasc. Res. (2006) [Pubmed]
  6. Matrix metalloproteinase3 and 9 gene promoter polymorphisms: joint action of two loci as a risk factor for coronary artery complicated plaques. Pöllänen, P.J., Lehtimäki, T., Mikkelsson, J., Ilveskoski, E., Kunnas, T., Perola, M., Penttilä, A., Mattila, K.M., Nikkari, S.T., Syrjäkoski, K., Karhunen, P.J. Atherosclerosis (2005) [Pubmed]
  7. Interaction between matrix metalloproteinase 3 and the epsilon4 allele of apolipoprotein E increases the risk of Alzheimer's disease in Finns. Saarela, M.S., Lehtimäki, T., Rinne, J.O., Hervonen, A., Jylhä, M., Röyttä, M., Ahonen, J.P., Mattila, K.M. Neurosci. Lett. (2004) [Pubmed]
  8. Redox regulation of matrix metalloproteinase gene family in small cell lung cancer cells. Savaraj, N., Wei, Y., Unate, H., Liu, P.M., Wu, C.J., Wangpaichitr, M., Xia, D., Xu, H.J., Hu, S.X., Tien Kuo, M. Free Radic. Res. (2005) [Pubmed]
  9. A potential role for free radical-mediated skeletal muscle soreness in the pathophysiology of acute mountain sickness. Bailey, D.M., Davies, B., Young, I.S., Hullin, D.A., Seddon, P.S. Aviation, space, and environmental medicine. (2001) [Pubmed]
  10. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Sternlicht, M.D., Lochter, A., Sympson, C.J., Huey, B., Rougier, J.P., Gray, J.W., Pinkel, D., Bissell, M.J., Werb, Z. Cell (1999) [Pubmed]
  11. TGF-beta 1 inhibition of transin/stromelysin gene expression is mediated through a Fos binding sequence. Kerr, L.D., Miller, D.B., Matrisian, L.M. Cell (1990) [Pubmed]
  12. Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Gomis-Rüth, F.X., Maskos, K., Betz, M., Bergner, A., Huber, R., Suzuki, K., Yoshida, N., Nagase, H., Brew, K., Bourenkov, G.P., Bartunik, H., Bode, W. Nature (1997) [Pubmed]
  13. Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis. Hahm, E.R., Gho, Y.S., Park, S., Park, C., Kim, K.W., Yang, C.H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  14. Histamine stimulates matrix metalloproteinase-3 and -13 production by human articular chondrocytes in vitro. Tetlow, L.C., Woolley, D.E. Ann. Rheum. Dis. (2002) [Pubmed]
  15. Polymorphisms in the MMP1 and MMP3 promoter and non-small cell lung carcinoma in North China. Fang, S., Jin, X., Wang, R., Li, Y., Guo, W., Wang, N., Wang, Y., Wen, D., Wei, L., Zhang, J. Carcinogenesis (2005) [Pubmed]
  16. Ciprofloxacin enhances the stimulation of matrix metalloproteinase 3 expression by interleukin-1beta in human tendon-derived cells. A potential mechanism of fluoroquinolone-induced tendinopathy. Corps, A.N., Harrall, R.L., Curry, V.A., Fenwick, S.A., Hazleman, B.L., Riley, G.P. Arthritis Rheum. (2002) [Pubmed]
  17. Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans. Lanfear, D.E., Marsh, S., Cresci, S., Shannon, W.D., Spertus, J.A., McLeod, H.L. J. Am. Coll. Cardiol. (2004) [Pubmed]
  18. Erg, an Ets-family member, differentially regulates human collagenase1 (MMP1) and stromelysin1 (MMP3) gene expression by physically interacting with the Fos/Jun complex. Butticè, G., Duterque-Coquillaud, M., Basuyaux, J.P., Carrère, S., Kurkinen, M., Stéhelin, D. Oncogene (1996) [Pubmed]
  19. The 5A6A polymorphism in the promoter of the stromelysin-1 (MMP3) gene as a risk factor for restenosis. Humphries, S., Bauters, C., Meirhaeghe, A., Luong, L., Bertrand, M., Amouyel, P. Eur. Heart J. (2002) [Pubmed]
  20. Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease. Bramhall, S.R., Stamp, G.W., Dunn, J., Lemoine, N.R., Neoptolemos, J.P. Br. J. Cancer (1996) [Pubmed]
  21. Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint. Kubota, E., Imamura, H., Kubota, T., Shibata, T., Murakami, K. J. Oral Maxillofac. Surg. (1997) [Pubmed]
  22. Immunohistochemical expression of matrix metalloproteinases in bile duct cancer tissue. Sakai, T. The Kurume medical journal. (2004) [Pubmed]
  23. Interleukin-6 involvement in brain arteriovenous malformations. Chen, Y., Pawlikowska, L., Yao, J.S., Shen, F., Zhai, W., Achrol, A.S., Lawton, M.T., Kwok, P.Y., Yang, G.Y., Young, W.L. Ann. Neurol. (2006) [Pubmed]
  24. The role of the {alpha}-1 adrenoceptor in modulating human mesangial cell matrix production. Pawluczyk, I.Z., Patel, S.R., Harris, K.P. Nephrol. Dial. Transplant. (2006) [Pubmed]
  25. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. Okada, Y., Gonoji, Y., Naka, K., Tomita, K., Nakanishi, I., Iwata, K., Yamashita, K., Hayakawa, T. J. Biol. Chem. (1992) [Pubmed]
  26. Serum levels of hyaluronan, antigenic keratan sulfate, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 change predictably in rheumatoid arthritis patients who have begun activity after a night of bed rest. Manicourt, D.H., Poilvache, P., Nzeusseu, A., van Egeren, A., Devogelaer, J.P., Lenz, M.E., Thonar, E.J. Arthritis Rheum. (1999) [Pubmed]
  27. Matrix metalloproteinases, but not cathepsins B, H, and L or their inhibitors in peripheral blood of patients with rheumatoid arthritis are potentially useful markers of disease activity. Keyszer, G., Lambiri, I., Keysser, M., Keysser, C., Nagel, R., Burmester, G.R., Jung, K. Zeitschrift für Rheumatologie. (1998) [Pubmed]
  28. Preferential inactivation of tissue inhibitor of metalloproteinases-1 that is bound to the precursor of matrix metalloproteinase 9 (progelatinase B) by human neutrophil elastase. Itoh, Y., Nagase, H. J. Biol. Chem. (1995) [Pubmed]
  29. Prostromelysin-1 (proMMP-3) stimulates plasminogen activation by tissue-type plasminogen activator. Arza, B., Hoylaerts, M.F., Félez, J., Collen, D., Lijnen, H.R. Eur. J. Biochem. (2000) [Pubmed]
  30. QSAR-by-NMR: quantitative insights into structural determinants for binding affinity by analysis of 1H/15N chemical shift differences in MMP-3 ligands. Matter, H., Schudok, M., Elshorst, B., Jacobs, D.M., Saxena, K., Kogler, H. Bioorg. Med. Chem. Lett. (2005) [Pubmed]
  31. Inactivation of plasminogen activator inhibitor-1 by specific proteolysis with stromelysin-1 (MMP-3). Lijnen, H.R., Arza, B., Van Hoef, B., Collen, D., Declerck, P.J. J. Biol. Chem. (2000) [Pubmed]
  32. Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand. Matsuno, H., Yudoh, K., Watanabe, Y., Nakazawa, F., Aono, H., Kimura, T. J. Rheumatol. (2001) [Pubmed]
  33. Characterization of glycosaminoglycan-binding domains present in insulin-like growth factor-binding protein-3. Fowlkes, J.L., Serra, D.M. J. Biol. Chem. (1996) [Pubmed]
  34. Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. Ogata, Y., Enghild, J.J., Nagase, H. J. Biol. Chem. (1992) [Pubmed]
  35. Pro-MMP-9 is a specific macrophage product and is activated by osteoarthritic chondrocytes via MMP-3 or a MT1-MMP/MMP-13 cascade. Dreier, R., Grässel, S., Fuchs, S., Schaumburger, J., Bruckner, P. Exp. Cell Res. (2004) [Pubmed]
  36. Increased matrix metalloproteinases as possible cause of osseoarticular tissue destruction in long-term haemodialysis and beta 2-microglobulin amyloidosis. Ohashi, K., Kawai, R., Hara, M., Okada, Y., Tachibana, S., Ogura, Y. Virchows Arch. (1996) [Pubmed]
  37. Lectin-like oxidized low-density lipoprotein receptor 1 mediates matrix metalloproteinase 3 synthesis enhanced by oxidized low-density lipoprotein in rheumatoid arthritis cartilage. Kakinuma, T., Yasuda, T., Nakagawa, T., Hiramitsu, T., Akiyoshi, M., Akagi, M., Sawamura, T., Nakamura, T. Arthritis Rheum. (2004) [Pubmed]
  38. Regulation of matrix metalloproteinase expression in human vascular smooth muscle cells by T lymphocytes: a role for CD40 signaling in plaque rupture? Schönbeck, U., Mach, F., Sukhova, G.K., Murphy, C., Bonnefoy, J.Y., Fabunmi, R.P., Libby, P. Circ. Res. (1997) [Pubmed]
  39. Stromelysin-1 promoter mutations impair gelatinase B activation in high microsatellite instability sporadic colorectal tumors. Morán, A., Iniesta, P., de Juan, C., González-Quevedo, R., Sánchez-Pernaute, A., Díaz-Rubio, E., Ramón y Cajal, S., Torres, A., Balibrea, J.L., Benito, M. Cancer Res. (2002) [Pubmed]
  40. Design and characterization of a fluorogenic substrate selectively hydrolyzed by stromelysin 1 (matrix metalloproteinase-3). Nagase, H., Fields, C.G., Fields, G.B. J. Biol. Chem. (1994) [Pubmed]
  41. Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation. Manicourt, D.H., Fujimoto, N., Obata, K., Thonar, E.J. Arthritis Rheum. (1995) [Pubmed]
  42. Genetic analysis of MMP3, MMP9, and PAI-1 in Finnish patients with abdominal aortic or intracranial aneurysms. Yoon, S., Tromp, G., Vongpunsawad, S., Ronkainen, A., Juvonen, T., Kuivaniemi, H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  43. Single nucleotide polymorphisms in MMP1 and MMP3 gene promoters as risk factor in head and neck squamous cell carcinoma. Zinzindohoué, F., Blons, H., Hans, S., Loriot, M.A., Houllier, A.M., Brasnu, D., Laccourreye, O., Tregouet, D.A., Stucker, I., Laurent-Puig, P. Anticancer Res. (2004) [Pubmed]
  44. Reduction of synovial sublining layer inflammation and proinflammatory cytokine expression in psoriatic arthritis treated with methotrexate. Kane, D., Gogarty, M., O'leary, J., Silva, I., Bermingham, N., Bresnihan, B., Fitzgerald, O. Arthritis Rheum. (2004) [Pubmed]
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