A gene cluster encoding human epidermis-type lipoxygenases at chromosome 17p13.1: Cloning, physical mapping, and expression

Epidermis-type lipoxygenases, a distinct subclass within the multigene fami ly of mammalian lipoxygenases (LOX), comprise recently discovered novel iso enzymes isolated from human and mouse skin including human 15-LOX-2, human and mouse 12R-LOX, mouse 8S-LOX, and mouse e-LOX-3. We have isolated the hu man homologue of mouse e-LOX-3. The cDNA of 3362 bp encodes a 711-amino-aci d protein displaying 89% sequence identity with the mouse protein and exhib iting the same unusual structural feature, i.e., an extra segment of 41 ami no acids, which can be located beyond the N-terminal p-barrel domain at the surface of the C-terminal catalytic domain. The gene encoding e-LOX-3, ALO XE3 was found to be part of a gene cluster of approximately 100 kb on human chromosome 17p13.1 containing in addition the 12R-LOX gene, ALOX12B, the 1 5-LOX-21 gene, ALOX15B, and a novel 15-LOX pseudogene, ALOX15P. ALOXE3 and ALOX12B are arranged in a head-to-tail fashion separated by 8.5 kb. The gen es are split into 15 exons and 14 introns spanning 22 and 15 kb, respective ly. ALOX15P was found on the opposite DNA strand directly adjacent to the 3 '-untranslated region of ALOX12B. ALOX15B is located in the same orientatio n 25 kb downstream of ALOX12B, and is composed of 14 exons and 13 introns s panning a total of 9.7 kb of genomic sequence. RT-PCR analysis demonstrated a predominant expression of ALOXE3, ALOX12B, and ALOX15B in skin, (C) 2001 Academic Press.