title: NOX-2S is a new member of the NOX family of NADPH oxidases.
abstract: 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 III, 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-gamma (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.
authors.affiliation: Department of Cardiology, GKT School of Medicine, King's College London, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Heidari
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
authors.forename: Chris
authors.initials: C
authors.lastname: Gove
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D020224:Expressed Sequence Tags; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
chemical_list: D007527:Isoenzymes; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D007371:Interferon-gamma; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases