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 518777032  23 SLTLADGRQQTLNDFKGNWLVVNYFAEWCQPCLRELPLLNELNDR---QGPKVLAVSFDALAPEALQALGERHQMTMPVA 99
Cdd:cd02966    3 SLPDLDGKPVSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEykdDGVEVVGVNVDDDDPAAVKAFLKKYGITFPVL 82

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 518777032 100 ----ASLSGPWPfesPRVLPTTFVIDPDGQLAERHQG 132
Cdd:cd02966   83 ldpdGELAKAYG---VRGLPTTFLIDRDGRIRARHVG 116

thiol-disulfide oxidoreductase ResA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  19 GEPA---SLTLADGRQQTLNDFKGNWLVVNYFAEWCQPCLRELPLLNELND---RQGPKVLAVSFDAlAPEALQALGERH 92
Cdd:PRK03147  38 GKEApnfVLTDLEGKKIELKDLKGKGVFLNFWGTWCKPCEKEMPYMNELYPkykEKGVEIIAVNVDE-TELAVKNFVNRY 116

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 518777032  93 QMTMPVA---------ASLSGPwpfesprvLPTTFVIDPDGQLAERHQGELKAEDIVRWREK 145
Cdd:PRK03147 117 GLTFPVAidkgrqvidAYGVGP--------LPTTFLIDKDGKVVKVITGEMTEEQLEEYLEK 170

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 518777032  23 SLTLADGRQQTLNDFKGNWLVVNYFAEWCQPCLRELPLLNELNDR---QGPKVLAVSFDALAPEALQALGERHQMTMPVA 99
Cdd:cd02966    3 SLPDLDGKPVSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEykdDGVEVVGVNVDDDDPAAVKAFLKKYGITFPVL 82

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 518777032 100 ----ASLSGPWPfesPRVLPTTFVIDPDGQLAERHQG 132
Cdd:cd02966   83 ldpdGELAKAYG---VRGLPTTFLIDRDGRIRARHVG 116

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 518777032   19 GEPA---SLTLADGRQQTLNDFKGNWLVVNYFAE-WCQPCLRELPLLNELNDR---QGPKVLAVSFDalAPEALQALGER 91
Cdd:pfam00578   2 GDKApdfELPDGDGGTVSLSDYRGKWVVLFFYPAdWTPVCTTELPALADLYEEfkkLGVEVLGVSVD--SPESHKAFAEK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 518777032   92 HQMTMPVAASLSGP-------WPFESPRVLPTTFVIDPDGQLAER 129
Cdd:pfam00578  80 YGLPFPLLSDPDGEvaraygvLNEEEGGALRATFVIDPDGKVRYI 124

Redoxin; This family of redoxins includes peroxiredoxin, thioredoxin and glutaredoxin proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032   23 SLTLADGRQQTLNDFKGNWLVVNYFA-EWCQPCLRELPLLNELNDRQGPK---VLAVSFDALAPEALQALGERHqMTMPV 98
Cdd:pfam08534  12 PDAATDGNTVSLSDFKGKKVVLNFWPgAFCPTCSAEHPYLEKLNELYKEKgvdVVAVNSDNDAFFVKRFWGKEG-LPFPF 90

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 518777032   99 AASLSG----------PWPFESPRVLPTTFVIDPDGQLAERHQGELKAEDI 139
Cdd:pfam08534  91 LSDGNAaftkalglpiEEDASAGLRSPRYAVIDEDGKVVYLFVGPEPGVDV 141

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  43 VVNYFAEWCQPCLRELPLLNELNDRQGPKVLAVSFDAlapEALQALGERHQMtmpvaaslsgpwpfespRVLPTTFVIDp 122
Cdd:COG3118   22 LVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDV---DENPELAAQFGV-----------------RSIPTLLLFK- 80

                         90       100
                 ....*....|....*....|....
gi 518777032 123 DGQLAERHQGELKAEDIVRWREKY 146
Cdd:COG3118   81 DGQPVDRFVGALPKEQLREFLDKV 104

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  38 KGNWLVVNYFAEWCQPCLRELPLLNELNDrQGPKVLAVSFDAlapEALQALGERHQMtmpvaaslsgpwpfespRVLPTT 117
Cdd:cd02947    9 SAKPVVVDFWAPWCGPCKAIAPVLEELAE-EYPKVKFVKVDV---DENPELAEEYGV-----------------RSIPTF 67

                         90       100
                 ....*....|....*....|....*
gi 518777032 118 FVIDpDGQLAERHQGELKAEDIVRW 142
Cdd:cd02947   68 LFFK-NGKEVDRVVGADPKEELEEF 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  23 SLTLADGRQQTLNDFKGNWLVVNYFAEWCQ-PCLRELPLLNELNDRQGPK------VLAVSFDALA--PEALQALGERH- 92
Cdd:COG1999    4 TLTDQDGKPVTLADLRGKPVLVFFGYTSCPdVCPTTLANLAQVQEALGEDggddvqVLFISVDPERdtPEVLKAYAEAFg 83

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 518777032  93 -----------QMTMPVAASL--------SGPWPFE-SPRVlpttFVIDPDGQLAERHQGELKAEDIVR 141
Cdd:COG1999   84 aprwigltgdpEEIAALAKAFgvyyekvpDGDYTFDhSAAV----YLVDPDGRLRGYYPAGEDPEELAA 148

Peroxiredoxin (PRX) family, Bacterioferritin comigratory protein (BCP) subfamily; composed of thioredoxin-dependent thiol peroxidases, widely expressed in pathogenic bacteria, that protect cells against toxicity from reactive oxygen species by reducing and detoxifying hydroperoxides. The protein was named BCP based on its electrophoretic mobility before its function was known. BCP shows substrate selectivity toward fatty acid hydroperoxides rather than hydrogen peroxide or alkyl hydroperoxides. BCP contains the peroxidatic cysteine but appears not to possess a resolving cysteine (some sequences, not all, contain a second cysteine but its role is still unknown). Unlike other PRXs, BCP exists as a monomer. The plant homolog of BCP is PRX Q, which is expressed only in leaves and is cellularly localized in the chloroplasts and the guard cells of stomata. Also included in this subfamily is the fungal nuclear protein, Dot5p (for disrupter of telomere silencing protein 5), which functions as an alkyl-hydroperoxide reductase during post-diauxic growth.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  23 SLTLADGRQQTLNDFKGNWLVVnYF----------AEWCQpcLRELplLNELNDRqGPKVLAVSFDAlaPEALQALGERH 92
Cdd:cd03017    7 TLPDQDGETVSLSDLRGKPVVL-YFypkddtpgctKEACD--FRDL--YEEFKAL-GAVVIGVSPDS--VESHAKFAEKY 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 518777032  93 QMTMPVAA----------SLSGPWPFESPRVLPTTFVIDPDGQLAERH 130
Cdd:cd03017   79 GLPFPLLSdpdgklakayGVWGEKKKKYMGIERSTFLIDPDGKIVKVW 126

Peroxiredoxin (PRX)-like 1 family; hypothetical proteins that show sequence similarity to PRXs. Members of this group contain a conserved cysteine that aligns to the first cysteine in the CXXC motif of TRX. This does not correspond to the peroxidatic cysteine found in PRXs, which aligns to the second cysteine in the CXXC motif of TRX. In addition, these proteins do not contain the other two conserved 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  19 GEPA---SLTLADGRQQTLNDFKGN-WLVVNYFAEWCqPCLRE-LPLLNELNDRQGPK---VLAVS------FDALAPEA 84
Cdd:cd02969    1 GSPApdfSLPDTDGKTYSLADFADGkALVVMFICNHC-PYVKAiEDRLNRLAKEYGAKgvaVVAINsndieaYPEDSPEN 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 518777032  85 LQALGERHQMTMP--------VAASLsgpwpfeSPRVLPTTFVIDPDGQLAER 129
Cdd:cd02969   80 MKAKAKEHGYPFPylldetqeVAKAY-------GAACTPDFFLFDPDGKLVYR 125

Peroxiredoxin (PRX) family, AhpE-like subfamily; composed of proteins similar to Mycobacterium tuberculosis AhpE. AhpE is described as a 1-cys PRX because of the absence of a resolving cysteine. The structure and sequence of AhpE, however, show greater similarity to 2-cys PRXs than 1-cys PRXs. PRXs are thiol-specific antioxidant (TSA) proteins that confer a protective 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. The first step of catalysis is the nucleophilic attack by the peroxidatic cysteine on the peroxide leading to the formation of a cysteine sulfenic acid intermediate. The absence of a resolving cysteine suggests that functional AhpE is regenerated by an external reductant. The solution behavior and crystal structure of AhpE show that it forms dimers and octamers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  19 GEPA-SLTLADGRQQT--LNDFKGNWLVVNYF--AEWCQPCLRELPLLNELNDRQ---GPKVLAVSFDAlaPEALQALGE 90
Cdd:cd03018    4 GDKApDFELPDQNGQEvrLSEFRGRKPVVLVFfpLAFTPVCTKELCALRDSLELFeaaGAEVLGISVDS--PFSLRAWAE 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 518777032  91 RHQMTMPVaasLSGPWPF-----------ESPRV-LPTTFVIDPDGqlaerhqgelkaedIVRWRE 144
Cdd:cd03018   82 ENGLTFPL---LSDFWPHgevakaygvfdEDLGVaERAVFVIDRDG--------------IIRYAW 130

Peroxiredoxin (PRX) family; composed of the different classes of PRXs including many proteins originally known as bacterioferritin comigratory proteins (BCP), based on their electrophoretic mobility before their function was identified. PRXs are thiol-specific antioxidant (TSA) proteins also known as TRX peroxidases and alkyl hydroperoxide reductase C22 (AhpC) proteins. They 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 TRX, glutathione, trypanothione and AhpF. They are distinct from other peroxidases in that they have no cofactors such as metals or prosthetic groups. The first step of catalysis, common to all PRXs, is the nucleophilic attack by the catalytic cysteine (also known as the peroxidatic cysteine) on the peroxide leading to cleavage of the oxygen-oxygen bond and the formation of a cysteine sulfenic acid intermediate. The second step of the reaction, the resolution of the intermediate, distinguishes the different types of PRXs. The presence or absence of a second cysteine (the resolving cysteine) classifies PRXs as either belonging to the 2-cys or 1-cys type. The resolving cysteine of 2-cys PRXs is either on the same chain (atypical) or on the second chain (typical) of a functional homodimer. Structural and motif analysis of this growing family supports the need for a new classification system. The peroxidase activity of PRXs is regulated in vivo by irreversible cysteine over-oxidation into a sulfinic acid, phosphorylation and limited proteolysis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 518777032  23 SLTLADGRQQTLNDFKGNWLVVnYFAewcqP------CLRELPLLNELND---RQGPKVLAVSFDalAPEALQALGERH- 92
Cdd:cd02971    6 TLPATDGGEVSLSDFKGKWVVL-FFY----PkdftpvCTTELCAFRDLAEefaKGGAEVLGVSVD--SPFSHKAWAEKEg 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 518777032  93 QMTMPVAA----SLS---GPWPFESP---RVLPTTFVIDPDG 124
Cdd:cd02971   79 GLNFPLLSdpdgEFAkayGVLIEKSAgggLAARATFIIDPDG 120