Fig. 6

Structural representation of five subfamilies of calcium-regulated transmembrane NOX proteins. Displaying A NOX5 in animals, B NOXC in amoeba and C red algae, D DspNOX in marine sponges A. queenslandica, X. bergquistia and T. wilhelma and E DspNOX in freshwater sponge E. muelleri. Located at the c-terminal are the cytoplasmic NADPH-(purple, PF08030) and FAD (brown; PF08022) binding domains, leading to the heme-containing ferric reductase transmembrane domain composed of 6 α-helices (dark pink; PF01794), on which four conserved histidine residues bind two heme molecules. Together, these three domains form the canonical structure shared by all NOX enzymes. The presence of one or more EF-hand binding domains (orange) makes these subfamilies sensitive to activation via calcium/calmodulin binding, except for C red algae NOXC and in E E. muelleri DspNOX. Red algae NOXC is hypothesised to be calcium activated via alternative mechanisms [31], whilst E. muelleri DspNOX encodes two cupredoxin-blue copper binding domains (green). Long intrinsically disordered protein (IDP) regions are present in NOXC B, C and DspNOX D and E. Additionally, D and E DspNOX sequences comprise a cytoplasmic PAS domain (black; PF00989) and five (three in E. muelleri) additional transmembrane components. Transmembrane components in D sponges A. queenslandica and X. bergquistia are composed of eukaryotic cytochrome B561 (dark blue; PF03188) domains, whilst in sponges T. wilhelma and E. muelleri a domain of unknown function (light blue; DUF247; PF10348)