TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*3.D.4.1.1









Quinol oxidase, SoxABC (Lubben et al., 1992)
Archaea
Crenarchaeota
SoxABC of Sulfolobus acidocaldarius
SoxA (168 aas; P39479)
SoxB (517 aas; P98004)
SoxC (563 aas; P39480)
*3.D.4.1.2









The cytochrome ba complex consisting of the Sox/CbsA/cytb protein of 553 aas and 12 TMSs, and the CbsB or cytochrome b573 protein of 311 aas and 9 TMSs (Bandeiras et al. 2009).  May function with SoxL (Q3LCJ1; 329 aas and 2 TMSs) and CbsB (Q3LCJ3; 311 aas and 2 TMSs).

Archaea
Crenarchaeota
Cytba of Acidianus ambivalens (Desulfurolobus ambivalens)
*3.D.4.2.1









Cytochrome ba3 oxidase, CbaABC. The 3-d structure is known (PDB# 1EHK) (Lee et al., 2012). Proton transfer has been reviewed (von Ballmoos et al., 2012). A mutation in subunit A, D372I, a probable pump H+ binding site, uncouples H+ transport from electron flow (von Ballmoos et al. 2015). In this cytochrome ba3, O2 molecules that arrive at the reduction site diffuse through the X-ray-observed tunnel, supporting its role as the main O2 delivery pathway in cytochrome this ba3 as well as the cytokchrome aa3 of Rhodobacter spheroides (Mahinthichaichan et al. 2018).

Bacteria
Deinococcus-Thermus
CbaABC of Thermus thermophilus
CbaA (Q56408)
CbaB (P98052)
CbaC (P82543) 
*3.D.4.3.1









Cytochrome oxidase
Archaea
Euryarchaeota
Coxl,2 of Halobacterium halobium
Cox1 (P33518)
Cox2 (AAC82824)
*3.D.4.3.2









Cytochrome bd quinol oxidoreductase, CydA/CydB. Borisov et al. (2011) have presented evidence concerning a proton channel connecting the site of oxygen reduction to the bacteria cytoplasm and the molecular mechanism by which a membrane potential is generated. The CydX protein of 37 aas and 1 TMS, is encoded in the cydAB operon and functions as a subunit of the Cytochrome bd oxidase complex, activating its activity (VanOrsdel et al. 2013). The AppX protein of 30 aas and 1 TMS, is a paralogue of CydX and can substitute for it in activating the Cytochrome bd oxidase complex (VanOrsdel et al. 2013). The AppX protein of 30 aas and 1 TMS, is a paralogue of CydX and can substitute for it in activating the Cytochrome bd oxidase complex (VanOrsdel et al. 2013).

Bacteria
Proteobacteria
CydA/CydB/CydX/AppX of E. coli
CydA (P0ABJ9) 
CydB (P0ABK2)
CydX (P56100)
AppX (P24244)

*3.D.4.3.3









Cbb3 cytochrome c oxidase (COX; Cbb3; CcoNOP).  The 3-d structure is known to 3.2 Å resolution (PDB# 3MK7; 5DJQ) (Buschmann et al. 2010Lee et al., 2012).  The structure explains a proton-pumping mechanism and the high activity of family-C heme-copper oxidases compared to that of families A and B (Buschmann et al., 2010Lee et al., 2012). A small subunit of 36 aas and 1 TMS, CcoM, was identified in the structure and plays a role in assembly and stability (Kohlstaedt et al. 2016; Carvalheda and Pisliakov 2017). CcoQ, another small protein of 62 aas (acc # F8H837) is an assembly factor for Cbb3-1 and Cbb3-2 (Kohlstaedt et al. 2017). The A-, B- and C-type oxygen reductases each have an active-site tyrosine that forms a unique cross-linked histidine-tyrosine cofactor. In the C-type oxygen reductases (also called cbb3 oxidases), this post-translationally generated co-factor occurs in a different TMS than for the A- and B-type reductases (Hemp et al. 2006).

Bacteria
Proteobacteria
CcoNOP of Pseudomonas stutzeri
CcoN (Chain A) (H7F0T0)
CcoO (Chain B) (F8H841)
CcoP (Chain C) (D9IA45)
CcoM (Chain D) (H7ESS5)
CcoQ (assembly factor) (Q8KS20)
*3.D.4.3.4









Cytochrome oxidase subunit I (CydA) of 481 aas and 9 or 10 TMSs, and subunit II (CydB) of 337 aas and 9 TMSs (Soo et al. 2017).

Bacteria
Cyanobacteria
CydAB of Thermosynechococcus elongatus
*3.D.4.4.1









Cytochrome oxidase

Bacteria
Firmicutes
CtaACDEF of Bacillus subtilis
*3.D.4.4.2









Cytochrome c oxidase (Cytaa3, subunits 1-4) (Niebisch and Bott, 2003)
Bacteria
Actinobacteria
Cytaa3 of Corynebacterium glutamicum
subunit I (584 aas) (Q79VD7)
subunit II (359 aas) (Q8NNK2)
subunit III (205 aas) (Q9AEL8)
subunit IV (143 aas) (Q8NNK3)
*3.D.4.4.3









The proton pumping Caa3-type cytochrome oxidase chains A-F. The crystal structure (PDB: 2YEV) is known (2.36Å resolution; Lyons et al., 2012). It has a covalently teathered cytochrome c domain. In the cytochrome aa3, O2 molecules that arrive at the reduction site diffuse through the X-ray-observed tunnel, supporting its role as the main O2 delivery pathway in this cytochrome ba3 as well as the cytochrome aa3 of Rhodobacter spheroides (Mahinthichaichan et al. 2018).

Bacteria
Deinococcus-Thermus
Caa(3)-type cytochrome oxidase of Thermus thermophilus 
Subunit I + III, Chain A 791aas; 19 TMSs. (P98005)
Subunit II; Chain B 337aas; 2 TMSs. (Q5SLI2)
Subunit IV; Chain C 66aas; 2 TMSs. (Q5SH67) 
*3.D.4.4.4









Cytochrome c oxidase, subunits CtaC (337 aas) CtaD (552 aas) and CtaE (201 aas) (also called CoxABC; Soo et al. 2017).

Bacteria
Cyanobacteria
CtaCDE of Thermosynechococcus elongatus
*3.D.4.5.1









Quinol oxidase (CyoABCD)

Bacteria
Proteobacteria
CyoABCD of E. coli
*3.D.4.6.1









Cytochrome oxidase (CtaBD/CycA)
Bacteria
Proteobacteria
CtaBD/CycA of Paracoccus denitrificans
CtaB (subunit 2) (P08306)
CtaD (subunit 1) (P98002)
CycA (P00096)
*3.D.4.6.2









Cytochrome c aa3 oxidase (COX). The 3-d structure is known (PDB# 1M56) (Lee et al., 2012).  There are three hydrophobic channels connecting the hydrophobic membrane through the protein to the heme A3/CuB binuclear center (BNC), two of which are probably preferred for O2 diffusion (Oliveira et al. 2014). The D channel is the proton transporting channel, and mutations in residues along this channel, especially N139 in subunit 1, uncouple H+ transport from electron flow (Han et al. 2005). Liang et al. 2017 provided insight into the decoupling mechanisms of CcO mutants, and explained how kinetic gating in the D-channel is imperative to achieving high proton-pumping efficiency in the WT CcO. The O2 molecules that arrived in the reduction site diffuse through the X-ray-observed tunnel, despite its apparent constriction, supporting its role as the main O2 delivery pathway in cytochrome aa3 (Mahinthichaichan et al. 2018).

Bacteria
Proteobacteria
COX chains A-D of Rhodobacter spheroides 
Chain A (P33517)
Chain B (Q03736)
Chain C (Q3J5F6)
Chain D (Q3IZW6) 
*3.D.4.7.1









Cytochrome oxidase (Cox1-3)
Eukaryota
Metazoa
Coxl-3 of Bos taurus
*3.D.4.8.1









Cytochrome oxidase (Cox)

Eukaryota
Fungi
Cytochrome oxidase (Cox) of Saccharomyces cerevisiae
Cox1p; Cox subunit I [Q0045] (NP_009305)
Cox2p; Cox subunit II [Q0250] (NP_009326)
Cox3p; Cox subunit III [Q0275] (NP_009328)
Cox4p; Cox subunit IV [YGL187c] (NP_011328)
Cox5Ap; Cox subunit Va [YNL052w] (aerobically induced) (NP_014346)
Cox5Bp; Cox subunit Vb [YIL111w] (anaerobically induced) (NP_012155)
Cox6p; Cox subunit VI [YHR051w] (NP_011918)
Cox7p; Cox subunit VII [YMR256c] (NP_013983)
Cox8p; Cox subunit VIII [YLR395c] (NP_013499)
Cox9p; Cox subunit VIIa [YDL067c] (NP_010216)
Cox11p; Cox assembly protein [YPL132w] (NP_015193)
Cox12p; Cox subunit VIb [YLR038c] (NP_013139)
Cox13p; Cox subunit VIa [YGL191w] (NP_011324)
Shylp; Cox chaperone [YGR112w] (NP_011627)
*3.D.4.9.1









Quinol oxidase (proton gradient generated only by chemical charge separation) (Purschke et al., 1997) [DoxA + DoxD comprise a novel membrane-bound thiosulfate: quinone oxidoreductase, Dox (Müller et al., 2004)]

Archaea
Crenarchaeota
DoxABCDEF of Acidianus ambivalens
DoxA (173 aas) (CAA69987)
DoxB (587 aas) (CAA69980)
DoxC (344 aas) (CAA69981)
DoxD (174 aas) (CAA69986)
DoxE (64 aas) (CAA69982)
DoxF (67 aas) (CAA69983)
*3.D.4.10.1









Nitric oxide reductase (EC #1.7.99.7) (NorBC) (component of the anerobic, respiratory chain that converts NO3- to N2; denitrification) [reaction catalyzed by Nor: 2 nitric oxide (NO) + 2e- + 2H+ → nitrous oxide (N20) + H2O].  This enzyme does not pump protons across the bacterial membrane (Reimann et al. 2007), but the protons needed for the reaction are taken from the periplasmic side of the membrane (from which side the electrons are donated). P. denitrificans NOR uses a single defined proton pathway with residues Glu-58 and Lys-54 from the NorC subunit at the entrance (ter Beek et al. 2016).  norC and norB encode the cytochrome-c-containing subunit II and cytochrome b-containing subunit I of nitric-oxide reductase (NO reductase), respectively. norQ encodes a protein with an ATP-binding motif and is similar to NirQ from Pseudomonas stutzeri and Pseudomonas aeruginosa and CbbQ from Pseudomonas hydrogenothermophila. norE encodes a protein with five putative transmembrane alpha-helices and has similarity to CoxIII, the third subunit of the aa3-type cytochrome-c oxidases. norF encodes a small protein with two putative transmembrane alpha-helices. Mutagenesis of norC, norB, norQ or norD resulted in cells unable to grow anaerobically. Nitrite reductase and NO reductase (with succinate or ascorbate as substrates) and nitrous oxide reductase (with succinate as substrate) activities were not detected in these mutant strains. Nitrite extrusion was detected in the medium, indicating that nitrate reductase was active. The norQ and norD mutant strains retained about 16% and 23% of the wild-type level of NorC, respectively. The norE and norF mutant strains had specific growth rates and NorC contents similar to those of the wild-type strain, but had reduced NOR and NIR activities, indicating that their gene products are involved in regulation of enzyme activity (de Boer et al. 1996).

Bacteria
Proteobacteria
NorBC of Paracoccus denitrificans
NorB (Q51603; 462 aas; 12 TMSs)
NorC (Q51662; 150 aas; 1 N-terminal TMS)
NorD (Q51665;638 aas; 0 TMSs)
NorE (Q51666; 167 aas; 5 TMSs)
NorF (Q51667; 77 aas and 2 TMSs)
*3.D.4.10.2









Bacterial respiratory, anaerobic, nitric oxide reductase (NorBC) (not a proton pump; Flock et al., 2008 )

Bacteria
Proteobacteria
NorBC of Pseudomonas stutzeri
NorB (cytochrome b subunit; 474 aas) (P98008)
NorC (cytochrom c subunit, 146 aas) (Q52527)
*3.D.4.10.3









Nitric oxide reductase, NorBC. 3-d structure known (PDB# 3o0R) (Lee et al., 2012)

Bacteria
Proteobacteria
NorBC of Pseudomonas aeruginosa 
NorB (Chain B) (Q59647)
NorC (Chain C) (Q59646) 
*3.D.4.10.4









Nitric oxide reductase of 787 aas and 14 TMSs, NorZ.  This copper-A-dependent NOR uses cytochrome c₅₅₁ as electron donor but lacks menaquinol activity (Al-Attar and de Vries 2015).  Employing reduced phenazine ethosulfate (PESH) as electron donor, the main NO reduction pathway catalyzed by Cu(A)Nor reconstituted in liposomes involves transmembrane cycling of the PES radical. Cu(A)Nor reconstituted in liposomes generates a proton electrochemical gradient across the membrane similar in magnitude to cytochrome aa₃, suggesting that bacilli using Cu(A)Nor to exploit NO reduction to increase cellular ATP production (Al-Attar and de Vries 2015).

NOR of Bacillus azotoformans
*3.D.4.10.5









Nitric oxide reductase large subunit, NorB, of 753 aas and 14 TMSs (Al-Attar and de Vries 2015). 

NorB of Bacillus azotoformans
*3.D.4.11.1









Cytochrome oxidase (Cox or CcO).  Reversible hydration-level changes of the cavity can be a key factor that regulates the branching of proton transfer events and therefore contributes to the vectorial efficiency of proton transport (Son et al. 2017). Cox16 is required for the assembly of the mitochondrial cytochrome c oxidase (respiratory chain complex IV (CIV)), possibly by promoting the insertion of copper into the active site of cytochrome c oxidase subunit II (MT-CO2/COX2) (Cerqua et al. 2018; Aich et al. 2018).

Eukaryota
Metazoa
Cox of Homo sapiens (CoxI-VIII3)
CoxI (Cox1) (P00395)
CoxII (Cox2) (P00403)
CoxIII (Cox3) (P00414)
CoxIV-1 (isoform 1) (Cox41) (P13073)
CoxIV-2 (isoform 2) (Cox42) (Q96KJ9)
CoxVa (Cox5a) (P20674)
CoxVb (Cox5b) (P10601)
CoxVIa (Cox6A2) (Q02221)
CoxVIb (Cox6B2) (Q6YFQ2)
CoxVIIa-H (Cox7A1) (P24310)
CoxVIIa-L (Cox7A2) (P14406)
CoxVIIb2 (Cox7B2) (Q8TF08)
CoxVIIc (Cox7c) (P15954)
CoxVIII-1 (Cox 81) (P48772) (Mouse; human not available)
CoxVIII-2 (Cox82) (P10176)
CoxVIII-3 (Cox83) (Q7Z4L0)
Cox 16, auxillary subunit (Q9P0S2)