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Gene Review

LOX  -  lysyl oxidase

Homo sapiens

Synonyms: Lysyl oxidase, Protein-lysine 6-oxidase
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Disease relevance of LOX


Psychiatry related information on LOX


High impact information on LOX

  • Silenced LOX mRNA in rabbit reticulocytes specifically coimmunoprecipitated with hnRNP K [7].
  • We have purified two proteins from rabbit reticulocytes that specifically mediate LOX silencing and identified them as hnRNPs K and E1 [7].
  • Although LOX mRNA accumulates early during differentiation, a differentiation control element in its 3' untranslated region confers translational silencing until late stage erythropoiesis [7].
  • The amounts of lysyl-derived aldehydes (the product formed in collagen and elastin by lysyl oxidase) and of cross-links formed from these products were decreased in dermal fibroblasts in culture [8].
  • X-linked cutis laxa: defective cross-link formation in collagen due to decreased lysyl oxidase activity [8].

Chemical compound and disease context of LOX


Biological context of LOX


Anatomical context of LOX

  • In addition, endogenous LOX mRNA expression was induced when MCF-7 cells were cultured in the presence of fibroblast conditioned medium or conditioned matrix, suggesting a role for stromal fibroblasts in LOX regulation in breast cancer cells [1].
  • Full-length LOX/LOXL and constructs containing just the pro-regions of each enzyme localized to elastic fibers when expressed in cultured cells [17].
  • LOX and LOXL were detected by immunohistochemistry in the dermis and the epidermis of both normal skin and in a SE [15].
  • The expression pattern of this new member of the LOX gene family appears to be different from that of the LOX and LOX-like genes, as the central nervous system, neurons, and also leukocytes expressed humanLOXL3 [18].
  • Thus by term, LOX was expressed predominantly in the amniotic epithelium, with little expression in the placenta, while LOXL showed highest gene expression in the placenta and lowest expression in the amnion [19].

Associations of LOX with chemical compounds

  • LOX has been traditionally known for one function, the extracellular catalysis of lysine-derived cross-links in fibrillar collagens and elastin [20].
  • Lysyl oxidase (LOX), a copper-containing amine oxidase, belongs to a heterogeneous family of enzymes that oxidize primary amine substrates to reactive aldehydes [20].
  • In addition, treatment of MDA-MB-231 and Hs578T cells with beta-aminopropionitrile (an irreversible inhibitor of LOX enzymatic activity) decreased invasive activity [1].
  • The LOXL3 protein contains four scavenger receptor cysteine-rich domains in the N terminus in addition to the C-terminal characteristic domains of the LOX family, such as a copper binding domain, a cytokine receptor-like domain and residues for the lysyl-tyrosyl quinone cofactor [21].
  • Lysyl oxidase was partially purified from serum by a diethylaminoethyl batch procedure in the presence of 6 mol/L urea and dialyzed against 3 mol/L KSCN [22].

Enzymatic interactions of LOX

  • Tropoelastin is encoded by a single human gene that spans 36 exons and is oxidized in vivo by mammalian lysyl oxidase at the epsilon amino group of available lysines to give the adipic semialdehyde, which then facilitates covalent cross-link formation in an enzyme-free process involving tropoelastin association [23].
  • Lysyl oxidase from P. pastoris has a similar substrate specificity to the mammalian enzyme (both have been shown to oxidize peptidyl lysine residues) and is 30% identical to the human kidney diamine oxidase (the highest of any non-mammalian source) [24].

Co-localisations of LOX

  • Furthermore, LO was found to co-localize in the areas stained strongly for collagen and elastin by histochemical stains [25].

Regulatory relationships of LOX


Other interactions of LOX


Analytical, diagnostic and therapeutic context of LOX


  1. A molecular role for lysyl oxidase in breast cancer invasion. Kirschmann, D.A., Seftor, E.A., Fong, S.F., Nieva, D.R., Sullivan, C.M., Edwards, E.M., Sommer, P., Csiszar, K., Hendrix, M.J. Cancer Res. (2002) [Pubmed]
  2. The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model. Bouez, C., Reynaud, C., Noblesse, E., Thépot, A., Gleyzal, C., Kanitakis, J., Perrier, E., Damour, O., Sommer, P. Clin. Cancer Res. (2006) [Pubmed]
  3. Association of positional and functional candidate genes FGF1, FBN2, and LOX on 5q31 with intracranial aneurysm. Yoneyama, T., Kasuya, H., Onda, H., Akagawa, H., Jinnai, N., Nakajima, T., Hori, T., Inoue, I. J. Hum. Genet. (2003) [Pubmed]
  4. Lysyl oxidase mediates hypoxic control of metastasis. Erler, J.T., Giaccia, A.J. Cancer Res. (2006) [Pubmed]
  5. The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells. Zhao, Y., Min, C., Vora, S.R., Trackman, P.C., Sonenshein, G.E., Kirsch, K.H. J. Biol. Chem. (2009) [Pubmed]
  6. Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer's disease brain. Gilad, G.M., Kagan, H.M., Gilad, V.H. Neurosci. Lett. (2005) [Pubmed]
  7. mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3' end. Ostareck, D.H., Ostareck-Lederer, A., Wilm, M., Thiele, B.J., Mann, M., Hentze, M.W. Cell (1997) [Pubmed]
  8. X-linked cutis laxa: defective cross-link formation in collagen due to decreased lysyl oxidase activity. Byers, P.H., Siegel, R.C., Holbrook, K.A., Narayanan, A.S., Bornstein, P., Hall, J.G. N. Engl. J. Med. (1980) [Pubmed]
  9. Lysyl oxidase regulates breast cancer cell migration and adhesion through a hydrogen peroxide-mediated mechanism. Payne, S.L., Fogelgren, B., Hess, A.R., Seftor, E.A., Wiley, E.L., Fong, S.F., Csiszar, K., Hendrix, M.J., Kirschmann, D.A. Cancer Res. (2005) [Pubmed]
  10. Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus. Buckingham, B., Reiser, K.M. J. Clin. Invest. (1990) [Pubmed]
  11. Site-dependent differences in sensitivity of LOX human melanoma tumors in nude rats to dacarbazine and mitozolomide, but not to doxorubicin and cisplatin. Kjønniksen, I., Breistøl, K., Fodstad, O. Cancer Res. (1992) [Pubmed]
  12. Studies on the mechanism of action of abrin-9.2.27 immunotoxin in human melanoma cell lines. Godal, A., Fodstad, O., Pihl, A. Cancer Res. (1987) [Pubmed]
  13. The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues. Jourdan-Le Saux, C., Tronecker, H., Bogic, L., Bryant-Greenwood, G.D., Boyd, C.D., Csiszar, K. J. Biol. Chem. (1999) [Pubmed]
  14. Cellular fibronectin binds to lysyl oxidase with high affinity and is critical for its proteolytic activation. Fogelgren, B., Polgár, N., Szauter, K.M., Ujfaludi, Z., Laczkó, R., Fong, K.S., Csiszar, K. J. Biol. Chem. (2005) [Pubmed]
  15. Lysyl oxidase-like and lysyl oxidase are present in the dermis and epidermis of a skin equivalent and in human skin and are associated to elastic fibers. Noblesse, E., Cenizo, V., Bouez, C., Borel, A., Gleyzal, C., Peyrol, S., Jacob, M.P., Sommer, P., Damour, O. J. Invest. Dermatol. (2004) [Pubmed]
  16. Whole-body gene expression by data mining. Pires Martins, R., Leach, R.E., Krawetz, S.A. Genomics (2001) [Pubmed]
  17. The Pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. Thomassin, L., Werneck, C.C., Broekelmann, T.J., Gleyzal, C., Hornstra, I.K., Mecham, R.P., Sommer, P. J. Biol. Chem. (2005) [Pubmed]
  18. Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein. Jourdan-Le Saux, C., Tomsche, A., Ujfalusi, A., Jia, L., Csiszar, K. Genomics (2001) [Pubmed]
  19. Lysyl oxidases: expression in the fetal membranes and placenta. Hein, S., Yamamoto, S.Y., Okazaki, K., Jourdan-LeSaux, C., Csiszar, K., Bryant-Greenwood, G.D. Placenta (2001) [Pubmed]
  20. Lysyl oxidases: a novel multifunctional amine oxidase family. Csiszar, K. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  21. A Tissue-specific Variant of the Human Lysyl Oxidase-like Protein 3 (LOXL3) Functions as an Amine Oxidase with Substrate Specificity. Lee, J.E., Kim, Y. J. Biol. Chem. (2006) [Pubmed]
  22. Serum lysyl oxidase activity in chronic liver disease in comparison with serum levels of prolyl hydroxylase and laminin. Murawaki, Y., Kusakabe, Y., Hirayama, C. Hepatology (1991) [Pubmed]
  23. A model two-component system for studying the architecture of elastin assembly in vitro. Mithieux, S.M., Wise, S.G., Raftery, M.J., Starcher, B., Weiss, A.S. J. Struct. Biol. (2005) [Pubmed]
  24. Cloning, sequence analysis, and characterization of the 'lysyl oxidase' from Pichia pastoris. Kucha, J.A., Dooley, D.M. J. Inorg. Biochem. (2001) [Pubmed]
  25. The upregulation of lysyl oxidase in oral submucous fibrosis and squamous cell carcinoma. Trivedy, C., Warnakulasuriya, K.A., Hazarey, V.K., Tavassoli, M., Sommer, P., Johnson, N.W. J. Oral Pathol. Med. (1999) [Pubmed]
  26. Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2. Vadasz, Z., Kessler, O., Akiri, G., Gengrinovitch, S., Kagan, H.M., Baruch, Y., Izhak, O.B., Neufeld, G. J. Hepatol. (2005) [Pubmed]
  27. Regulation of lysyl oxidase, collagen, and connective tissue growth factor by TGF-beta1 and detection in human gingiva. Hong, H.H., Uzel, M.I., Duan, C., Sheff, M.C., Trackman, P.C. Lab. Invest. (1999) [Pubmed]
  28. Lysyl oxidase activates the transcription activity of human collagene III promoter. Possible involvement of Ku antigen. Giampuzzi, M., Botti, G., Di Duca, M., Arata, L., Ghiggeri, G., Gusmano, R., Ravazzolo, R., Di Donato, A. J. Biol. Chem. (2000) [Pubmed]
  29. Cytokine regulation of gingival fibroblast lysyl oxidase, collagen, and elastin. Hong, H.H., Trackman, P.C. J. Periodontol. (2002) [Pubmed]
  30. Regulation of lysyl oxidase by interferon-gamma in rat aortic smooth muscle cells. Song, Y.L., Ford, J.W., Gordon, D., Shanley, C.J. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  31. A new gene with sequence and structural similarity to the gene encoding human lysyl oxidase. Kim, Y., Boyd, C.D., Csiszar, K. J. Biol. Chem. (1995) [Pubmed]
  32. Reactivity of human leukocyte elastase and porcine pancreatic elastase toward peptide 4-nitroanilides containing model desmosine residues. Evidence that human leukocyte elastase is selective for cross-linked regions of elastin. Yasutake, A., Powers, J.C. Biochemistry (1981) [Pubmed]
  33. Mutations in the lysyl oxidase gene are not associated with amyotrophic lateral sclerosis. Chioza, B.A., Ujfalusy, A., Csiszar, K., Leigh, P.N., Powell, J.F., Radunović, A. Amyotroph. Lateral Scler. Other Motor Neuron Disord. (2001) [Pubmed]
  34. LOXL as a target to increase the elastin content in adult skin: a dill extract induces the LOXL gene expression. Cenizo, V., André, V., Reymermier, C., Sommer, P., Damour, O., Perrier, E. Exp. Dermatol. (2006) [Pubmed]
  35. Somatic mutations of the lysyl oxidase gene on chromosome 5q23.1 in colorectal tumors. Csiszar, K., Fong, S.F., Ujfalusi, A., Krawetz, S.A., Salvati, E.P., Mackenzie, J.W., Boyd, C.D. Int. J. Cancer (2002) [Pubmed]
  36. Transforming growth factor-beta1 mediated up-regulation of lysyl oxidase in the kidneys of hereditary nephrotic mouse with chronic renal fibrosis. Goto, Y., Uchio-Yamada, K., Anan, S., Yamamoto, Y., Ogura, A., Manabe, N. Virchows Arch. (2005) [Pubmed]
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