Fig. 1
A Schematic representing enzymatic processes of H2O2 generation in animals. Incomplete reductive processes within the mitochondrial electron transport chain (ETC) generate a basal level of ROS, in accordance with the rate of metabolic activity which mitochondrial SOD2 converts into H2O2. Specialised transmembrane NOX enzymes produce relatively small and precise spatiotemporal fluctuations of ROS across membranes, either intra- or extracellularly. NOXs may either generate H2O2 directly or O2•− that is subsequently converted into H2O2 either spontaneously or via activity of SODs localised within proximity, e.g. extracellular SOD3 or cytoplasmic SOD1. B Generalised domain structure for SOD enzyme families used in the identification of protein sequences. CuZnSOD enzymes comprise a copper/zinc binding domain (Sod_Cu; F00080; IPR001424), whilst MnSOD comprise a C-terminal Mn/Fe SOD domain (Sod_Fe_C; PF02777; IPR019832) and an N-terminal Mn/Fe SOD domain (Sod_Fe_N; PF00081; IPR019831). Green rectangles indicate signal peptides and grey rectangles indicate transmembrane regions. Domain structure for Rsod and SOD2X is variable from that depicted; the observed number of Cu_SOD domains within Rsod varied from 2 to 6, but in total, we found 43 sequences comprise at least three domains. Additionally, signal peptides observed on 35 Rsod sequences and transmembrane regions are found only in membrane-bound Rsods. Signal peptides are not present on all SOD2X sequences. C Generalised domain structure for NOX enzyme families used in the identification of protein sequences. All NOX enzymes comprise a Ferric reductase NAD binding_6 domain (purple; PF08030; IPR013121), FAD-binding_8 domain (brown; PF08022; IPR013112) and heme-containing ferric reductase transmembrane domain composed of 6 α-helices (Ferric_reduct; PF01794; IPR013121). The ferric reductase transmembrane domain, responsible for the electron transfer that generates O2•−, is distributed in a superfamily spanning both prokaryotic and eukaryotic lineages [17]. NOX5 and Duox additionally comprise calcium-sensitive EF-hand binding domains (orange), and Duox comprises animal haem peroxidase (green; PF03098; IPR019791)