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Gene Review

LOXL3  -  lysyl oxidase-like 3

Homo sapiens

Synonyms: LOXL, Lysyl oxidase homolog 3, Lysyl oxidase-like protein 3
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High impact information on LOXL3

  • Overexpression of LOXL2 or LOXL3 in epithelial cells induces an EMT process, supporting their implication in tumor progression [1].
  • Using BLASTN searches, we identified a LOXL3 variant LOXL3-sv1 that lacked the sequences corresponding to exons 1, 2, 3, and 5 of LOXL3 [2].
  • These findings strongly indicate that LOXL3 encodes two variants, LOXL3 and LOXL3-sv1, both of which function as amine oxidases with distinct tissue and substrate specificities from one another [2].
  • 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 [2].
  • A Tissue-specific Variant of the Human Lysyl Oxidase-like Protein 3 (LOXL3) Functions as an Amine Oxidase with Substrate Specificity [2].

Biological context of LOXL3

  • However, specific novel functions, such as a potential role in cell adhesion and cell growth control, will be determined by other, conserved domains such as the cytokine receptor-like domain that is shared by all LOXs and by multiple scavenger receptor cysteine-rich (SRCR) domains present in LOXL2 and LOXL3 [3].
  • A BLASTN search of the human EST database indicated the presence of ESTs, corresponding to alternative splice variants of LOXL3, that lacked exon 5 and exon 8 [4].
  • The gene encoding this new cDNA, which we have referred to as human lysyl oxidase-like 3 (humanLOXL3), has been mapped to chromosome 2p13.3, overlapping at its 3' end the HtrA2 serine protease gene [4].
  • Indeed, recent findings reveal that LOX and LOXL proteins markedly influence cell behavior including chemotactic responses, proliferation, and shifts between the normal and malignant phenotypes [5].
  • The predicted amino acid sequence of the hLOXL3 gene was highly homologous to mLOR2 [6].

Anatomical context of LOXL3

  • The LOXL3 mRNA is 3.1 kb in size and is expressed in many tissues, the highest levels among the tissues studied being seen in the placenta, heart, ovary, testis, small intestine and spleen [7].
  • This study deals with the expression of two isoforms, LOX and LOX-like (LOXL), in human foreskin and in a human skin-equivalent (SE) model that allows the formation of elastic fibers [8].
  • LOX and LOXL were detected by immunohistochemistry in the dermis and the epidermis of both normal skin and in a SE [8].
  • We screened a library of about 1000 active ingredients to find activators capable to stimulate specifically the LOXL gene expression in adult dermal fibroblasts [9].

Analytical, diagnostic and therapeutic context of LOXL3

  • In RT-PCR assays with various human tissues, LOXL3-sv1 and LOXL3 showed distinct expression patterns [2].
  • Recombinant LOXL3, expressed in HT-1080 cells, was secreted into the culture medium but was not detected by immunofluorescence staining in nuclei [7].
  • Using the PCR primers generated from human expressed sequence tag (EST), the cDNA of lysyl oxidase-like gene 3 (LOXL3), a new member of human lysyl oxidases gene family, was cloned from the human fetal brain mRNA [6].


  1. A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. Peinado, H., Del Carmen Iglesias-de la Cruz, M., Olmeda, D., Csiszar, K., Fong, K.S., Vega, S., Nieto, M.A., Cano, A., Portillo, F. EMBO J. (2005) [Pubmed]
  2. 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]
  3. Lysyl oxidases: a novel multifunctional amine oxidase family. Csiszar, K. Prog. Nucleic Acid Res. Mol. Biol. (2001) [Pubmed]
  4. 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]
  5. Lysyl oxidase: an oxidative enzyme and effector of cell function. Lucero, H.A., Kagan, H.M. Cell. Mol. Life Sci. (2006) [Pubmed]
  6. Cloning and characterization of a human lysyl oxidase-like 3 gene (hLOXL3). Huang, Y., Dai, J., Tang, R., Zhao, W., Zhou, Z., Wang, W., Ying, K., Xie, Y., Mao, Y. Matrix Biol. (2001) [Pubmed]
  7. Cloning and characterization of a fourth human lysyl oxidase isoenzyme. Mäki, J.M., Kivirikko, K.I. Biochem. J. (2001) [Pubmed]
  8. 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]
  9. 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]
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