The gp91^phox/p22^phox NADPH oxidase-associated, cytochrome b₅₅₈, Nox2. TMS2 is important for stability and electron transfer (Picciocchi et al., 2011). The integral membrane flavocytochrome of Nox 2 transfers an electron from intracellular NADPH to extracellular O₂, generating superoxide anion, O₂^- (Fisher 2009).

Animals 

gp91^phox (β-chain) of Homo sapiens (Nox2) (P04839)
p22^phox (α-chain) of Homo sapiens (P13498)

Two component NADPH oxidase, one designated the heavy chain subunit, CCA70369, of 564 aas and 6 N-terminal TMSs plus 1 or 2 TMSs in the C-terminal domain, and the other designated the cytosolic protein p67^phox, CCA67529, of 254 aas and either 0 or 4-5 TMSs (based on 4-5 moderate peaks of hydrophobicity) (Shikata et al. 2019). This latter protein shows limited sequence similarity with the P07213 protein (TC# 3.A.8.1.1) and the corresponding reagion of the homologous Q9MUK5 protein (TC# 3.A.9.1.1).

NADPH oxidase of Serendipita indica

NADPH oxidase of 775 aas and 10 - 12 TMSs in a 5-6 TMS plus another 5-6 TMS segment, separated by a hydrophilic domain. Algal NADPH oxidases, which produces superoxide near the cell membrane, can be of two types: one with 5-6 TMSs and another with 10 - 12 TMSs (Shikata et al. 2019).

NADPH oxidase of Galdieria sulphuraria (Red alga)

Superoxide-generating NADPH oxidase with three subunits: B of 698 aas and 6 TMSs, Q86GL4; C of 1142 aas and 6 TMSs, Q54F44; and light chain of 118 aas and 3 TMSs, Q867X6 (Peracino et al. 2022). It may function as a ferric iron or ferric chelate reductase (Peracino et al. 2022).

3 subunit NADPH oxidase of Dictyostelium discoideum

Nucleus/kidney/muscle/endothelial cell superoxide-generating NADPH oxidase (Nox4) (may regulate gene expression) (Cheng et al., 2001; Kuroda et al., 2005). Integrated analyses of heterodimerization, trafficking and catalytic activity have identified determinants for the NOX4-p22phox interaction such as heme incorporation into NOX4 and hot spot residues in TMSs 1 and 4 in p22phox; their effects on NOX4 maturation and ROS generation have been analyzed (O'Neill et al. 2018). The topology has been determined using a novel method that shows 6 TMSs with N- and C-termini facing the cytosol (Rousset et al. 2019).

Animals and slime molds

Kidney superoxide-generating NADPH oxidase of Homo sapiens

Multiple tissue mitogenic oxidase, subunit 65 (Mox1 or Nox1) (alternative splicing yields a 191 aa protein with H⁺ channel activity) (Bánfi et al., 2000; Suh et al., 1999). Structural information elucidate the role of NOX1 in the epithelial generation of ROS (Liu et al. 2023).

Animals and slime molds

Mitogenic oxidase (Nox1) of Homo sapiens

NADPH oxidase 5 (Nox5) of 765 aas and 6 TMSs (Cheng et al., 2001).  It is found in the ER and peri-nuclear regions, but upon activation, migrates to the plasma membrane.  It's properties and involvment in human pathophysiology have been reviewed (Touyz et al. 2019).

Animals

Nox5 of Homo sapiens (Q96PH1)

Thyroid NADPH oxidase/peroxidase 1 (Dual oxidase 1; Duox1) with two EF band domains, responsive to Ca²⁺ regulation (De Deken et al., 2000; Edens et al., 2001).  Duox enzyme activities in epithelia are inhibited by compounds that block Hv1, but inhibition occurs through Hv1-independent mechanisms, supporting the idea that Hv1 is not required for Duox activity (Gattas et al. 2019).

Animals

Duox1 of Homo sapiens (Q9NRD9)

Thyroid NADPH oxidase/peroxidase 2 (Dual oxidase 2; Duox2) with two EF band domains, responsive to Ca²⁺ regulation (De Deken et al., 2000; Edens et al., 2001).  Duox enzyme activities in epithelia are inhibited by compounds that block Hv1, but inhibition occurs through Hv1-independent mechanisms, supporting the idea that Hv1 is not required for Duox activity (Gattas et al. 2019).

Animals

Duox2 of Homo sapiens (Q9NRD8)

Respiratory burst oxidase homologue F, RBOHF, of 944 aas and 6 TMSs.  Calcium-dependent NADPH oxidase that generates superoxide. Generates reactive oxygen species (ROS) during incompatible interactions with pathogens and is important in the regulation of the hypersensitive response (HR). Involved in abscisic acid-induced stomatal closing and in UV-B and abscisic acid ROS-dependent signaling (Song et al. 2006; Desikan et al. 2006; Kwak et al. 2003).

RBOHF of Arabidopsis thaliana (Mouse-ear cress)

NADPH oxido-reductase of 450 aas and 7 TMSs.  These proteins have been characterized in prokaryotes as well as eukaryotes (Hajjar et al. 2017).

Bacteria

Putative oxido-reductase of Vibrio cholerae

NADH-cytochrome b5 reductase 3, Cyb5r3, of 301 aas and 1 or 2 TMSs, N-terminal and possibly near the C-terminus of the protein. It catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor. Multidimensional plasticity contributes to rapid acclimation to environmental challenges during biological invasions (Huang et al. 2023), and thus, complex plastic mechanisms allow adaptation to environmental changes.

Cyb5r3 of Homo sapiens

Uncharacterized oxidoreductase of 445 aas and 6 N-terminal TMSs.

Putative oxidoreductase of Streptomyces sp.

Ferric reductase like transmembrane component of 220 aas and 6 TMSs.

Ferric reductase of Thermophagus xiamenensis

Uncharacterized protein of 441 aas and 6 N-terminal TMSs.

UP of Planctomycetes bacterium

Uncharacterized protein of 215 aas and 6 TMSs.

UP of Candidatus Curtissbacteria bacterium

Uncharacterized protein of 205 aas and 6 TMSs.

UP of Candidatus Saccharibacteria bacterium

Uncharacterized protein of 210 aas and 6 TMSs.

UP of Candidatus Nomurabacteria bacterium

Uncharacterized protein of 222 aas and 6 TMSs.

UP of Alicyclobacillus sendaiensis

Uncharacterized ferric reductase domain protein transmembrane component of 287 aas and 6 TMSs.

UP of Candidatus Moranbacteria bacterium

CDP-6-deoxy-delta-3,4-glucoseen reductase (Han et al. 1990).

Proteobacteria

CDP-6-deoxy-delta-3,4-glucoseen reductase of Yersinia pseudotuberculosis

Phenol hydroxylase (Yu et al. 2011).

Proteobacteria

Phenol hydroxylase of Acinetobacter calcoaceticus

Uncharacterized protein of 249 aas and possibly 4 TMSs in a 1 + 2 + 1 TMS arrangement.

UP of Parcubacteria group bacterium GW2011_GWA2_38_13b (groundwater metagenome)

Ferric reduction oxidase 2, Fro2 or Frd1, of 725 aas. Flavocytochrome that transfers electrons across the plasma membrane to reduce ferric iron chelates and form soluble ferrous iron in the rhizosphere. May be involved in the delivery of iron to developing pollen grains. Acts also as a copper-chelate reductase. Involved in glycine betaine-mediated chilling tolerance and reactive oxygen species accumulation (Robinson et al. 1999; Wu et al. 2005; Connolly et al. 2003; Einset et al. 2008).

Fro2 of Arabidopsis thaliana (Mouse-ear cress)

Plasma membrane Fe³⁺ and Cu²⁺ reductase, Fre1 (transfers electrons from NADPH in the cytoplasm to Fe³⁺ and Cu²⁺ in the extracellular millieu) (Rees and Thiele, 2007).  Thus, it, as well as Fre2 (TC# 5.B.1.7.2), mediate the reductive uptake of Fe³⁺-salts and Fe³⁺ bound to catecholate or hydroxamate siderophores. Fe³⁺ is reduced to Fe²⁺, which then dissociates from the siderophore and can be imported by the high-affinity Fe²⁺ transport complex in the plasma membrane. Also participates in Cu²⁺ reduction and Cu⁺ uptake (Dancis et al. 1992; Hassett and Kosman 1995; Lesuisse et al. 1996; Georgatsou et al. 1997; Shi et al. 2003).

Yeast

Fre1 of Saccharomyces cerevisiae
(P32791)

Fre2 Fe³⁺/Cu²⁺ oxidoreductase of 711 aas; similar in catalytic function to Fre1 (TC# 5.B.1.5.1), but induced only by Fe³⁺, not Cu²⁺ (Georgatsou et al. 1997; Yun et al. 2001).

Fre2 of Saccharomyces cerevisiae

Ferric reductase, FreB of 582 aas and 7 TMSs (Rehman et al. 2017).

FreB of Verticillium dahliae (Verticillium wilt)

Frp1 of 564 aas and 10 TMSs.

Metalloreductase responsible for reducing extracellular iron and copper prior to import (By similarity).

Catalyzes the reductive uptake of Fe³⁺-salts and Fe³⁺ bound to catecholate or hydroxamate siderophores. Fe³⁺ is reduced to Fe²⁺, which then dissociates from the siderophore and can be imported by the high-affinity Fe²⁺ transport complex in the plasma membrane. It may also participate in Cu²⁺ reduction and Cu⁺ uptake. Frp1 harbors a ferric reductase domain with three-candidate heme-binding ligands (Ahmad et al. 2022).

Frp1 of Schizosaccharomyces pombe (Fission yeast)

Frp2 of 564 aas and up to 11 TMSs, ferric/cupric reductase transmembrane component 2. It probably functions as does Frp1 (TC# 5.B.1.5.5) (Ahmad et al. 2022).

Frp2 of Schizosaccharomyces pombe (Fission yeast)