NOX-2S is a new member of the NOX family of NADPH oxidases

A novel isoform of the NOX-2 subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has been identified using expressed sequence tag (EST) database mining. The novel isoform, NOX-2S, is a splice variant of NOX-2 and includes a previously unidentified exon, mapped 6.4 kb downstream of exon 111, and encodes an in-frame stop codon generating a predicted truncated protein of approximately 12.7 kDa, the smallest reported member of the NOX family. Thus, NOX-2S is predicted to have only two transmembrane domains, however, the new C-terminal sequence includes two new potential protein kinase C (PKC) phosphorylation sites. Expression of NOX-2S mRNA was detected in many mouse tissues, and several human cell lines including the myeloid cell line HL-60, and the B cell line Ramos, indicating that the splice variant is conserved in mouse and man. NOX-2S is found co-expressed together with NOX-2 in all of the tissues and cells under investigation, both nonphagocytic and phagocytic. Induction of the myeloid cell line HL-60 into the neutrophil phagocytic lineage by dimethyl sulphoxide (DMSO), led to a marked increase in NOX-2S and NOX-2 expression in the myelocyte rather than promyelocyte stages of differentiation. Furthermore, in the B-cell line Ramos, differentiated with the cytokine interferon-gamina (IFN-gamma), splicing was altered to increase NOX-2S mRNA generation over NOX-2. Here we have identified NOX-2S, the first reported normally occurring splice variant of NOX-2. The sequence identity between mouse and human NOX-2S strongly implies conservation in function and possibly a role for NOX-2S in the regulation of NADPH oxidase activity. (C) 2004 Elsevier B.V. All rights reserved.