TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  53 VAFSDANGKPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLATKFKADQFALLPISIDAGGKQQVQPFLTSLGmANFN 132
Cdd:cd02966    2 FSLPDLDGKPVSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKDDGVEVVGVNVDDDDPAAVKAFLKKYG-ITFP 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 739571822 133 SYYDPTQNLGQVFPLDTIPATFILDQNGQLIAFV 166
Cdd:cd02966   81 VLLDPDGELAKAYGVRGLPTTFLIDRDGRIRARH 114

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  53 VAFSDANGKPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLATKFKADQFALLPISIDAGGKQQVQPFLTSLGmANFN 132
Cdd:cd02966    2 FSLPDLDGKPVSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKDDGVEVVGVNVDDDDPAAVKAFLKKYG-ITFP 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 739571822 133 SYYDPTQNLGQVFPLDTIPATFILDQNGQLIAFV 166
Cdd:cd02966   81 VLLDPDGELAKAYGVRGLPTTFLIDRDGRIRARH 114

thiol-disulfide oxidoreductase ResA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  54 AFSDANGKPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLATKFKADQFALLPISIDaGGKQQVQPFLTSLGMaNFNS 133
Cdd:PRK03147  45 VLTDLEGKKIELKDLKGKGVFLNFWGTWCKPCEKEMPYMNELYPKYKEKGVEIIAVNVD-ETELAVKNFVNRYGL-TFPV 122

                         90       100       110
                 ....*....|....*....|....*....|
gi 739571822 134 YYDPTQNLGQVFPLDTIPATFILDQNGQLI 163
Cdd:PRK03147 123 AIDKGRQVIDAYGVGPLPTTFLIDKDGKVV 152

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822   69 KGKVVMVNMWATWCPPCVRELPAIERLATKFkadqfalLPI-SID-AGGKQQVQPFLTSLGMANFNSYYDPTQNLGQVFP 146
Cdd:TIGR00385  62 QGKPVLLNVWASWCPPCRAEHPYLNELAKQG-------LPIvGVDyKDDRQNAIKFLKELGNPYQLSLFDPDGMLGLDLG 134

                          90
                  ....*....|....
gi 739571822  147 LDTIPATFILDQNG 160
Cdd:TIGR00385 135 VYGAPETFLVDGNG 148

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  53 VAFSDANGKPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLATKFKADQFALLPISIDAGGKQQVQPFLTSLGmANFN 132
Cdd:cd02966    2 FSLPDLDGKPVSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKDDGVEVVGVNVDDDDPAAVKAFLKKYG-ITFP 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 739571822 133 SYYDPTQNLGQVFPLDTIPATFILDQNGQLIAFV 166
Cdd:cd02966   81 VLLDPDGELAKAYGVRGLPTTFLIDRDGRIRARH 114

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  57 DANGKPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLATKFKADQFALLPISIDagGKQQVQPFLTSLGMaNFNSYYD 136
Cdd:COG1225    8 DLDGKTVSLSDLRGKPVVLYFYATWCPGCTAELPELRDLYEEFKDKGVEVLGVSSD--SDEAHKKFAEKYGL-PFPLLSD 84

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 739571822 137 PTQNLGQVFPLDTIPATFILDQNGQLIAFVRSFVDWDD 174
Cdd:COG1225   85 PDGEVAKAYGVRGTPTTFLIDPDGKIRYVWVGPVDPRP 122

AhpC/TSA family; This family contains proteins related to alkyl hydroperoxide reductase (AhpC) and thiol specific antioxidant (TSA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822   57 DANGKPIDFSQYKGKVVMVNMWAT-WCPPCVRELPAIERLATKFKADQFALLPISIDagGKQQVQPFLTSLGMaNFNSYY 135
Cdd:pfam00578  12 DGDGGTVSLSDYRGKWVVLFFYPAdWTPVCTTELPALADLYEEFKKLGVEVLGVSVD--SPESHKAFAEKYGL-PFPLLS 88

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 739571822  136 DPTQNLGQVF------PLDTIPATFILDQNGQLIA 164
Cdd:pfam00578  89 DPDGEVARAYgvlneeEGGALRATFVIDPDGKVRY 123

TlpA-like family, DsbE (also known as CcmG and CycY) subfamily; DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  57 DANGKPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLAtkfKADQFALLPISI-DAggKQQVQPFLTSLGmanfNSY- 134
Cdd:cd03010   12 PGPDKTLTSADLKGKPYLLNVWASWCAPCREEHPVLMALA---RQGRVPIYGINYkDN--PENALAWLARHG----NPYa 82

                         90       100
                 ....*....|....*....|....*....
gi 739571822 135 ---YDPTQNLGQVFPLDTIPATFILDQNG 160
Cdd:cd03010   83 avgFDPDGRVGIDLGVYGVPETFLIDGDG 111

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822   69 KGKVVMVNMWATWCPPCVRELPAIERLATKFkadqfalLPI-SID-AGGKQQVQPFLTSLGMANFNSYYDPTQNLGQVFP 146
Cdd:TIGR00385  62 QGKPVLLNVWASWCPPCRAEHPYLNELAKQG-------LPIvGVDyKDDRQNAIKFLKELGNPYQLSLFDPDGMLGLDLG 134

                          90
                  ....*....|....
gi 739571822  147 LDTIPATFILDQNG 160
Cdd:TIGR00385 135 VYGAPETFLVDGNG 148

Cytochrome oxidase Cu insertion factor, SCO1/SenC/PrrC family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  54 AFSDANGKPIDFSQYKGKVVMVNMWATWCP-PCVRELPAIERLATKFKA---DQFALLPISID----------------- 112
Cdd:COG1999    4 TLTDQDGKPVTLADLRGKPVLVFFGYTSCPdVCPTTLANLAQVQEALGEdggDDVQVLFISVDperdtpevlkayaeafg 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 739571822 113 -------AGGKQQVQPFLTSLGManfnsYYDPTQNLGQVFplDTIPATFILDQNGQLIAFVRSFVDWDDAKA 177
Cdd:COG1999   84 aprwiglTGDPEEIAALAKAFGV-----YYEKVPDGDYTF--DHSAAVYLVDPDGRLRGYYPAGEDPEELAA 148

thiol:disulfide interchange protein DsbE; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  69 KGKVVMVNMWATWCPPCVRELPAIERLATK--------FKADqfallpisidaggKQQVQPFLTSLGMANFNSYYDPTQN 140
Cdd:PRK15412  67 QGKPVLLNVWATWCPTCRAEHQYLNQLSAQgirvvgmnYKDD-------------RQKAISWLKELGNPYALSLFDGDGM 133

                         90       100
                 ....*....|....*....|
gi 739571822 141 LGQVFPLDTIPATFILDQNG 160
Cdd:PRK15412 134 LGLDLGVYGAPETFLIDGNG 153

SCO (an acronym for Synthesis of Cytochrome c Oxidase) family; composed of proteins similar to Sco1, a membrane-anchored protein possessing a soluble domain with a TRX fold. Members of this family are required for the proper assembly of cytochrome c oxidase (COX). They contain a metal binding motif, typically CXXXC, which is located in a flexible loop. COX, the terminal enzyme in the respiratory chain, is imbedded in the inner mitochondrial membrane of all eukaryotes and in the plasma membrane of some prokaryotes. It is composed of two subunits, COX I and COX II. It has been proposed that Sco1 specifically delivers copper to the CuA site, a dinuclear copper center, of the COX II subunit. Mutations in human Sco1 and Sco2 cause fatal infantile hepatoencephalomyopathy and cardioencephalomyopathy, respectively. Both disorders are associated with severe COX deficiency in affected tissues. More recently, it has been argued that the redox sensitivity of the copper binding properties of Sco1 implies that it participates in signaling events rather than functioning as a chaperone that transfers copper to COX II.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  53 VAFSDANGKPIDFSQYKGKVVMVNMWATWCP-PCVRELPAIERLATKFKAD---QFALLPISID---------------- 112
Cdd:cd02968    5 FTLTDQDGRPVTLSDLKGKPVLVYFGYTHCPdVCPTTLANLAQALKQLGADggdDVQVVFISVDperdtpevlkayakaf 84

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 739571822 113 -------AGGKQQVQPFLTSLGManfnsYYDPTQNLGQVFPLDTIPATFILDQNGQLIAFVR 167
Cdd:cd02968   85 gpgwiglTGTPEEIEALAKAFGV-----YYEKVPEDDGDYLVDHSAAIYLVDPDGKLVRYYG 141

TlpA-like family, DipZ-like subfamily; composed uncharacterized proteins containing a TlpA-like TRX domain. Some members show domain architectures similar to that of E. coli DipZ protein (also known as DsbD). The only eukaryotic members of the TlpA family belong to this subfamily. TlpA is a disulfide reductase known to have a crucial role in the biogenesis of cytochrome aa3.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 739571822  61 KPIDFSQYKGKVVMVNMWATWCPPCVRELPAIERLATKFKAD 102
Cdd:cd03012   14 KPLSLAQLRGKVVLLDFWTYCCINCLHTLPYLTDLEQKYKDD 55

Peroxiredoxin (PRX)-like 2 family; hypothetical proteins that show sequence similarity to PRXs. Members of this group contain a CXXC motif, similar to TRX. The second cysteine in the motif corresponds to the peroxidatic cysteine of PRX, however, these proteins do not contain the other two residues of the catalytic triad of PRX. PRXs confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF. TRXs alter the redox state of target proteins by catalyzing the reduction of their disulfide bonds via the CXXC motif using reducing equivalents derived from either NADPH or ferredoxins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 739571822  57 DANGKPIDFSQYKGKVVMVNMWAT--WCPPCVRELPAIERLATKFKADQFALLPISIDAGGKQQVQPFLTSLgmaNFNSY 134
Cdd:cd02970    9 DAGGETVTLSALLGEGPVVVVFYRgfGCPFCREYLRALSKLLPELDALGVELVAVGPESPEKLEAFDKGKFL---PFPVY 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 739571822 135 YDPT----QNLGQVFPLDT-------------------------IPATFILDQNGQLiafVRSFVDW 172
Cdd:cd02970   86 ADPDrklyRALGLVRSLPWsntpralwknaaigfrgndegdglqLPGVFVIGPDGTI---LFAHVDR 149

Protein Disulfide Isomerase (PDIa) family, redox active TRX domains; composed of eukaryotic proteins involved in oxidative protein folding in the endoplasmic reticulum (ER) by acting as catalysts and folding assistants. Members of this family include PDI and PDI-related proteins like ERp72, ERp57 (or ERp60), ERp44, P5, PDIR, ERp46 and the transmembrane PDIs. PDI, ERp57, ERp72, P5, PDIR and ERp46 are all oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. These proteins usually contain multiple copies of a redox active TRX (a) domain containing a CXXC motif, and may also contain one or more redox inactive TRX-like (b) domains. Only one a domain is required for the oxidase function but multiple copies are necessary for the isomerase function. The different types of PDIs may show different substrate specificities and tissue-specific expression, or may be induced by stress. PDIs are in their reduced form at steady state and are oxidized to the active form by Ero1, which is localized in the ER through ERp44. Some members of this family also contain a DnaJ domain in addition to the redox active a domains; examples are ERdj5 and Pfj2. Also included in the family is the redox inactive N-terminal TRX-like domain of ERp29.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 739571822  69 KGKVVMVNMWATWCPPCVRELPAIERLATKFKAD 102
Cdd:cd02961   14 DSKDVLVEFYAPWCGHCKALAPEYEKLAKELKGD 47

Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per subunit, which is involved in catalysis. Different isoenzymes are known in mammals,which are involved in protection against reactive oxygen species, redox regulation of many metabolic processes, peroxinitrite scavenging, and modulation of inflammatory processes.

                         10
                 ....*....|....*....
gi 739571822  57 DANGKPIDFSQYKGKVVMV 75
Cdd:cd00340    9 DIDGEPVSLSKYKGKVLLI 27

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 739571822   71 KVVMVNMWATWCPPCVRELPAIERLATKFKAD 102
Cdd:pfam00085  19 KPVLVDFYAPWCGPCKMLAPEYEELAQEYKGN 50