TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
5.B.1.1.1









The gp91phox/p22phox 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).

Eukaryota
Metazoa, Chordata
gp91phox (β-chain) of Homo sapiens (Nox2) (P04839)
p22phox (α-chain) of Homo sapiens (P13498)
5.B.1.1.2









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).

Eukaryota
Metazoa, Chordata
Kidney superoxide-generating NADPH oxidase of Homo sapiens
5.B.1.1.3









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).

Eukaryota
Metazoa, Chordata
Mitogenic oxidase (Nox1) of Homo sapiens
5.B.1.1.4









Mitogenic NADPH oxidase 3, Nox3 (Cheng et al., 2001). Critical for formation of otoconia, mineral crystals in the inner ear; mutants are defective for motion and gravity sensing (Paffenholz et al., 2004).
Eukaryota
Metazoa, Chordata
Nox3 of Homo sapiens (Q9HBY0)
5.B.1.1.5









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).

Eukaryota
Metazoa, Chordata
Nox5 of Homo sapiens (Q96PH1)
5.B.1.1.6









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).

Eukaryota
Metazoa, Chordata
Duox1 of Homo sapiens (Q9NRD9)
5.B.1.1.7









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).

Eukaryota
Metazoa, Chordata
Duox2 of Homo sapiens (Q9NRD8)
5.B.1.1.8









Respiratory burst oxidase proteins A-F
Eukaryota
Viridiplantae, Streptophyta
Respiratory burst oxidase A of Arabidopsis thaliana
5.B.1.1.9









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).

Eukaryota
Viridiplantae, Streptophyta
RBOHF of Arabidopsis thaliana (Mouse-ear cress)
5.B.1.1.10









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 p67phox, 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).

Eukaryota
Fungi, Basidiomycota
NADPH oxidase of Serendipita indica
5.B.1.1.11









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).

Eukaryota
Rhodophyta
NADPH oxidase of Galdieria sulphuraria (Red alga)
5.B.1.1.12









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).

Eukaryota
Evosea
3 subunit NADPH oxidase of Dictyostelium discoideum
5.B.1.2.1









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
Pseudomonadota
Putative oxido-reductase of Vibrio cholerae
5.B.1.2.2









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

Bacteria
Actinomycetota
Putative oxidoreductase of Streptomyces sp.
5.B.1.2.3









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

Bacteria
Bacteroidota
Ferric reductase of Thermophagus xiamenensis
5.B.1.2.4









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

Bacteria
Planctomycetota
UP of Planctomycetes bacterium
5.B.1.2.5









Uncharacterized protein of 215 aas and 6 TMSs.

Bacteria
Candidatus Curtissbacteria
UP of Candidatus Curtissbacteria bacterium
5.B.1.2.6









Uncharacterized protein of 205 aas and 6 TMSs.

Bacteria
Candidatus Saccharibacteria
UP of Candidatus Saccharibacteria bacterium
5.B.1.2.7









Uncharacterized protein of 210 aas and 6 TMSs.

Bacteria
Candidatus Nomurabacteria
UP of Candidatus Nomurabacteria bacterium
5.B.1.2.8









Uncharacterized protein of 222 aas and 6 TMSs.

Bacteria
Bacillota
UP of Alicyclobacillus sendaiensis
5.B.1.2.9









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

Bacteria
Candidatus Moranbacteria
UP of Candidatus Moranbacteria bacterium
5.B.1.2.11









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.

Eukaryota
Metazoa, Chordata
Cyb5r3 of Homo sapiens
5.B.1.3.1









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

Bacteria
Pseudomonadota
CDP-6-deoxy-delta-3,4-glucoseen reductase of Yersinia pseudotuberculosis
5.B.1.3.2









Phenol hydroxylase (Yu et al. 2011).

Bacteria
Pseudomonadota
Phenol hydroxylase of Acinetobacter calcoaceticus
5.B.1.3.3









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

Bacteria
UP of Parcubacteria group bacterium GW2011_GWA2_38_13b (groundwater metagenome)
5.B.1.4.1









Ferric reductase/oxidase, FRO1
Eukaryota
Viridiplantae, Streptophyta
FRO1 of Arabidopsis thaliana
5.B.1.4.2









Iron chelate reductase, Fox1 (La Fontaine et al., 2002)
Eukaryota
Viridiplantae, Chlorophyta
Fox1 of Chlamydomonas reinhardtii (ABM66085)
5.B.1.4.3









Fro1, ferric chelate reductase (Enomoto et al., 2007).
Eukaryota
Viridiplantae, Streptophyta
Fro1 of Lycopersicon esculentum (Q6EMC0)
5.B.1.4.4









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).

Eukaryota
Viridiplantae, Streptophyta
Fro2 of Arabidopsis thaliana (Mouse-ear cress)
5.B.1.5.1









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).

Eukaryota
Fungi, Ascomycota
Fre1 of Saccharomyces cerevisiae
(P32791)
5.B.1.5.2









Vacuolar Fe3+ and Cu2+ reductase, Fre6 (transfers electrons from NADPH in the cytoplasm to Cu2+ in the vacuole) (Rees and Thiele, 2007).
Eukaryota
Fungi, Ascomycota
Fre6 of Saccharomyces cerevisiae
(Q12473)
5.B.1.5.3









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).

Eukaryota
Fungi, Ascomycota
Fre2 of Saccharomyces cerevisiae
5.B.1.5.4









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

Eukaryota
Fungi, Ascomycota
FreB of Verticillium dahliae (Verticillium wilt)
5.B.1.5.5









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).

Eukaryota
Fungi, Ascomycota
Frp1 of Schizosaccharomyces pombe (Fission yeast)
5.B.1.5.6









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).

Eukaryota
Fungi, Ascomycota
Frp2 of Schizosaccharomyces pombe (Fission yeast)