Cloning and characterization of a fourth human lysyl oxidase isoenzyme

We report here the complete cDNA sequence and exon-intron organization of t he human lysyl oxidase-like (LOXL)3 gene, a new member of the lysyl oxidase (LO) gene family. The predicted polypeptide is 753 amino acids in length, including a signal peptide of 25 residues. The C-terminal region, residues 529-729, contains a LO domain similar to those in the LOX (the first charac terized LO isoenzyme), LOXL and LOXL2 polypeptides. It possesses the putati ve copper binding sequence. and the lysine and tyrosine residues that form the lysyltyrosyl quinone cofactor. The N-terminal region, which is similar to that in LOXL2 but not those in LOX and LOXL, contains four subregions si milar to scavenger receptor cysteine-rich domains and a putative nuclear lo calization signal. Recombinant LOXL3, expressed in HT-1080 cells, was secre ted into the culture medium but was not detected by immunofluorescence stai ning in nuclei. The LOXL3 mRNA is 3.1 kb in size and is expressed in many t issues, the highest levels among the tissues studied being seen in the plac enta, heart. ovary, testis, small intestine and spleen.