Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein

A BLASTN search using the mouse lor-2 cDNA identified three overlapping EST s (AI752772, AA852888, and R557o6) in the GenBank database. These expressed sequence tags were assembled into a contig of 3121 nucleotides with an ope n reading frame of 2262 bp. The encoded putative polypeptide of 754 amino a cids presented all structural characteristics of the lysyl oxidase (LOX) en zyme family, a copper-binding site with four histidyl residues, the lysyl a nd tyrosyl residues known to be involved in LOX enzyme in the formation of the quinone cofactor and surrounding sequences, and the cytokine receptor-l ike domain. In addition, four scavenger receptor cysteine-rich (SRCR) domai ns were found in the N-terminal region of the protein. The gene encoding th is new cDNA, which we have referred to as human lysyl oxidase-like 3 (human LOXL3), has been mapped to chromosome 2p13.3, overlapping at its 3 ' end th e HtrA2 serine protease gene. The structure of the humanLOXL3 gene was dedu ced from the BAC clone bac91a19 sequence and contained 14 exons. The expres sion pattern of this new member of the LOX gene family appears to be differ ent from that of the LOX and LOX-like genes, as the central nervous system, neurons, and also leukocytes expressed humanLOXL3. A BLASTN search of the human EST database indicated the presence of ESTs, corresponding to alterna tive splice variants of LOXL3, that lacked exon 5 and exon 8. The putative resulting protein retained the region encoding the structural and functiona l elements of the amine oxidase but the second and fourth SRCR domains were truncated and the potential BMP-1 cleavage site was not present. The prese nce of domains unrelated to the traditional amine oxidase activity is a str ong indication that humanLOXL3 might fulfill other functions in addition to intrinsic enzyme activity. (C) 2001 Academic Press.