title: Origin and evolution of lysyl oxidases.
abstract: Lysyl oxidases (LOX) are copper-dependent enzymes that oxidize primary amine substrates to reactive aldehydes. The best-studied role of LOX enzymes is the remodeling of the extracellular matrix (ECM) in animals by cross-linking collagens and elastin, although intracellular functions have been reported as well. Five different LOX enzymes have been identified in mammals, LOX and LOX-like (LOXL) 1 to 4, showing a highly conserved catalytic carboxy terminal domain and more divergence in the rest of the sequence. Here we have surveyed a wide selection of genomes in order to infer the evolutionary history of LOX. We identified LOX proteins not only in animals, but also in many other eukaryotes, as well as in bacteria and archaea - which reveals a pre-metazoan origin for this gene family. LOX genes expanded during metazoan evolution resulting in two superfamilies, LOXL2/L3/L4 and LOX/L1/L5. Considering the current knowledge on the function of mammalian LOX isoforms in ECM remodeling, we propose that LOXL2/L3/L4 members might have preferentially been involved in making cross-linked collagen IV-based basement membrane, whereas the diversification of LOX/L1/L5 forms contributed to chordate/vertebrate-specific ECM innovations, such as elastin and fibronectin. Our work provides a novel view on the evolution of this family of enzymes.
authors.affiliation: Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Grau-Bové
authors.affiliation: 1] Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona, Spain [2] Departament de Genètica, Universitat de Barcelona, Barcelona, Spain [3] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Ruiz-Trillo
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" Consejo Superior de Investigaciones Científicas (C.S.I.C.) / Universidad Autónoma de Madrid (Madrid), Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez-Pascual
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002384:Catalysis; D005057:Eukaryotic Cells / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes; D008969:Molecular Sequence Data; D010802:Phylogeny; D011387:Prokaryotic Cells / Q000201:enzymology; D008249:Protein-Lysine 6-Oxidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D007527:Isoenzymes; D008249:Protein-Lysine 6-Oxidase