Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5

gp91phox is the catalytic subunit of the respiratory burst oxidase, an NADP H-dependent, superoxide generating enzyme present in phagocytes. In pha,ooc ytes, the enzyme functions in host defense, but reactive oxygen generation has also been described in a variety of non-phagocytic cells, including can cer cells. We previously reported the cloning of Nox1 (NADPH oxidase1), a h omolog of gp91phox, its expression in colon and vascular smooth muscle, and its oncogenic properties when overexpressed [Suh et al. (1999). Nature 401 , 79-82]. Herein, we report the cloning and tissue expression of three addi tional homologs of gp91phox, termed Nox3. Nox4 and Nox5, members of a growi ng family of gp91phos homologs. All are predicted to encode proteins of aro und 65 kDa, and like gp9lphox, all show 5-6 conserved predicted transmembra ne cr-helices containing putative heme binding regions as well as a flavopr otein homology domain containing predicted binding sites for both FAD and N ADPH. Nox3 is expressed primarily in fetal tissues, and Nox4 is expressed i n not only fetal tissues, but also kidney, placenta and glioblastoma cells. Nox5 is expressed in a variety of fetal tissues as well as in adult spleen and uterus. Nor isoforms are aberrantly expressed in several cells derived from human cancers, with Nox4 being the isoform most frequently expressed in the tumor cells investigated. Thus, expression of Nor family members is likely to account for some of the reactive oxygen generation seen in non-ph agocytic cells. (C) 2001 Elsevier Science B.V. All rights reserved.