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 2230564619   5 VDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSG 84
Cdd:COG3118     3 VELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDG 82

                          90       100
                  ....*....|....*....|..
gi 2230564619  85 AKVASLVGAQSKSQLTQFIDQN 106
Cdd:COG3118    83 QPVDRFVGALPKEQLREFLDKV 104

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 2230564619   5 VDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSG 84
Cdd:COG3118     3 VELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDG 82

                          90       100
                  ....*....|....*....|..
gi 2230564619  85 AKVASLVGAQSKSQLTQFIDQN 106
Cdd:COG3118    83 QPVDRFVGALPKEQLREFLDKV 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 2230564619  10 ANFEQEVLNAEtPVLLKFWAPWCGPCKVMAPVVDEVAEErEGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSGAKVAS 89
Cdd:cd02947     1 EEFEELIKSAK-PVVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                          90
                  ....*....|....*
gi 2230564619  90 LVGAQSKSQLTQFID 104
Cdd:cd02947    79 VVGADPKEELEEFLE 93

thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSG 84
Cdd:PRK09381    6 IHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNG 85

                          90       100
                  ....*....|....*....|..
gi 2230564619  85 AKVASLVGAQSKSQLTQFIDQN 106
Cdd:PRK09381   86 EVAATKVGALSKGQLKEFLDAN 107

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 2230564619   5 VDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSG 84
Cdd:COG3118     3 VELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDG 82

                          90       100
                  ....*....|....*....|..
gi 2230564619  85 AKVASLVGAQSKSQLTQFIDQN 106
Cdd:COG3118    83 QPVDRFVGALPKEQLREFLDKV 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 2230564619  10 ANFEQEVLNAEtPVLLKFWAPWCGPCKVMAPVVDEVAEErEGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSGAKVAS 89
Cdd:cd02947     1 EEFEELIKSAK-PVVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                          90
                  ....*....|....*
gi 2230564619  90 LVGAQSKSQLTQFID 104
Cdd:cd02947    79 VVGADPKEELEEFLE 93

thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSG 84
Cdd:PRK09381    6 IHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNG 85

                          90       100
                  ....*....|....*....|..
gi 2230564619  85 AKVASLVGAQSKSQLTQFIDQN 106
Cdd:PRK09381   86 EVAATKVGALSKGQLKEFLDAN 107

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQEVLNaETPVLLKFWAPWCGPCKVMAPVVDEVAEE--REGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFK 82
Cdd:cd02961     1 VELTDDNFDELVKD-SKDVLVEFYAPWCGHCKALAPEYEKLAKElkGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                          90       100
                  ....*....|....*....|..
gi 2230564619  83 SGAK-VASLVGAQSKSQLTQFI 103
Cdd:cd02961    80 NGSKePVKYEGPRTLESLVEFI 101

Thiol-disulfide isomerase or thioredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  22 PVLLKFWAPWCGPCKVMAPVVDEVAEEREGsLKIVSINVDDAPE----------------------IAAEQGVRGVPTVM 79
Cdd:COG0526    30 PVLVNFWATWCPPCRAEMPVLKELAEEYGG-VVFVGVDVDENPEavkaflkelglpypvlldpdgeLAKAYGVRGIPTTV 108

                          90       100
                  ....*....|....*....|....*..
gi 2230564619  80 LF-KSGAKVASLVGAQSKSQLTQFIDQ 105
Cdd:COG0526   109 LIdKDGKIVARHVGPLSPEELEEALEK 135

TRX domain, novel NADPH thioredoxin reductase (NTR) family; composed of fusion proteins found only in oxygenic photosynthetic organisms containing both TRX and NTR domains. The TRX domain functions as a protein disulfide reductase via the reversible oxidation of an active center dithiol present in a CXXC motif, while the NTR domain functions as a reductant to oxidized TRX. The fusion protein is bifunctional, showing both TRX and NTR activities, but it is not an independent NTR/TRX system. In plants, the protein is found exclusively in shoots and mature leaves and is localized in the chloroplast. It is involved in plant protection against oxidative stress.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  22 PVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSGAKVASLVGAQSKSQLTQ 101
Cdd:cd02949    15 LILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKSEYRE 94

                  ...
gi 2230564619 102 FID 104
Cdd:cd02949    95 FIE 97

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are 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. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   7 VTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVD-DAPEIAAEQGVRGVPTVMLFKSGA 85
Cdd:cd02995     5 VVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDaTANDVPSEFVVDGFPTILFFPAGD 84

                  .
gi 2230564619  86 K 86
Cdd:cd02995    85 K 85

TRX domain, PICOT (for PKC-interacting cousin of TRX) subfamily; PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT contains an N-terminal TRX-like domain, which does not contain the catalytic CXXC motif, followed by one to three glutaredoxin domains. The TRX-like domain is required for interaction with PKC theta. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2230564619  18 NAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSGAKVASLVGA 93
Cdd:cd02984    12 DASKLLVLHFWAPWAEPCKQMNQVFEELAKEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTIVDRVSGA 87

PDI family, MPD1-like subfamily; composed of eukaryotic proteins similar to Saccharomyces cerevisiae MPD1 protein, which contains a single redox active TRX domain located at the N-terminus, and an ER retention signal at the C-terminus indicative of an ER-resident protein. MPD1 has been shown to suppress the maturation defect of carboxypeptidase Y caused by deletion of the yeast PDI1 gene. Other characterized members of this subfamily include the Aspergillus niger prpA protein and Giardia PDI-1. PrpA is non-essential to strain viability, however, its transcript level is induced by heterologous protein expression suggesting a possible role in oxidative protein folding during high protein production. Giardia PDI-1 has the ability to refold scrambled RNase and exhibits transglutaminase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   3 NNVDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAP--EIAAEQGVRGVPTVML 80
Cdd:cd03002     1 PVYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKnkPLCGKYGVQGFPTLKV 80

                  ....*....
gi 2230564619  81 FKSGAKVAS 89
Cdd:cd03002    81 FRPPKKASK 89

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQEVLNAETpVLLKFWAPWCGPCKVMAPVVDEVAEE--REGS-LKIVSINVDDAPEIAAEQGVRGVPTVMLF 81
Cdd:PTZ00102   35 TVLTDSTFDKFITENEI-VLVKFYAPWCGHCKRLAPEYKKAAKMlkEKKSeIVLASVDATEEMELAQEFGVRGYPTIKFF 113

                          90       100
                  ....*....|....*....|....
gi 2230564619  82 KSGAKVaSLVGAQSKSQLTQFIDQ 105
Cdd:PTZ00102  114 NKGNPV-NYSGGRTADGIVSWIKK 136

PDIa family, PDIR subfamily; composed of proteins similar to human PDIR (for Protein Disulfide Isomerase Related). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress. Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQeVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEE----REGSLKIVSINVDDAPEIAAEQGVRGVPTVML 80
Cdd:cd02997     3 VHLTDEDFRK-FLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATElkedGKGVLAAVDCTKPEHDALKEEYNVKGFPTFKY 81

                          90       100
                  ....*....|....*....|...
gi 2230564619  81 FKSGAKVASLVGAQSKSQLTQFI 103
Cdd:cd02997    82 FENGKFVEKYEGERTAEDIIEFM 104

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   7 VTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEE--REGSLKIVSINvDDAPEIAAEQ-GVRGVPTVMLFKS 83
Cdd:PTZ00102  362 VVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKykDNDSIIVAKMN-GTANETPLEEfSWSAFPTILFVKA 440

                          90       100
                  ....*....|....*....|....*
gi 2230564619  84 GAKVA-SLVGAQSKSQLTQFIDQNA 107
Cdd:PTZ00102  441 GERTPiPYEGERTVEGFKEFVNKHA 465

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 2230564619  22 PVLLKFWAPWCGPCKVMAPVVDEVAEE-REGSLKIVSINVDDAPEIAAEQ-----------------------GVRGVPT 77
Cdd:cd02966    21 VVLVNFWASWCPPCRAEMPELEALAKEyKDDGVEVVGVNVDDDDPAAVKAflkkygitfpvlldpdgelakayGVRGLPT 100

                          90
                  ....*....|....*.
gi 2230564619  78 VMLF-KSGAKVASLVG 92
Cdd:cd02966   101 TFLIdRDGRIRARHVG 116

PDIa family, N-terminal ERdj5 subfamily; ERdj5, also known as JPDI and macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox active TRX domains. This subfamily is comprised of the first TRX domain of ERdj5 located after the DnaJ domain at the N-terminal half of the protein. ERdj5 is a ubiquitous protein localized in the endoplasmic reticulum (ER) and is abundant in secretory cells. It's transcription is induced during ER stress. It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQEVlNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSG 84
Cdd:cd03003     4 VTLDRGDFDAAV-NSGEIWFVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSG 82

                          90
                  ....*....|....*...
gi 2230564619  85 AKVASLVGAQSKSQLTQF 102
Cdd:cd03003    83 MNPEKYYGDRSKESLVKF 100

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  22 PVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDA---PEIaAEQGVRGVPTVMLF-KSGAKVASLVGAQSKS 97
Cdd:cd02950    22 PTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPkwlPEI-DRYRVDGIPHFVFLdREGNEEGQSIGLQPKQ 100

                  ....*..
gi 2230564619  98 QLTQFID 104
Cdd:cd02950   101 VLAQNLD 107

DsbD gamma family; DsbD gamma is the C-terminal periplasmic domain of the bacterial protein DsbD. It contains a CXXC motif in a TRX fold and shuttles the reducing potential from the membrane domain (DsbD beta) to the N-terminal periplasmic domain (DsbD alpha). DsbD beta, a transmembrane domain comprising of eight helices, acquires its reducing potential from the cytoplasmic thioredoxin. DsbD alpha transfers the acquired reducing potential from DsbD gamma to target proteins such as the periplasmic protein disulphide isomerases, DsbC and DsbG. This flow of reducing potential from the cytoplasm through DsbD allows DsbC and DsbG to act as isomerases in the oxidizing environment of the bacterial periplasm. DsbD also transfers reducing potential from the cytoplasm to specific reductases in the periplasm which are involved in the maturation of cytochromes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  22 PVLLKFWAPWCGPCKVMAPVV---DEVAEEREGSLKIVSINV-DDAPEIAA---EQGVRGVPTVMLFKSGakvaslvGAQ 94
Cdd:cd02953    13 PVFVDFTADWCVTCKVNEKVVfsdPEVQAALKKDVVLLRADWtKNDPEITAllkRFGVFGPPTYLFYGPG-------GEP 85

                          90
                  ....*....|...
gi 2230564619  95 SKSQLTQFIDQNA 107
Cdd:cd02953    86 EPLRLPGFLTADE 98

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
                  ....*....|....*....|....*....|....*....|....*...
gi 2230564619  22 PVLLKFWAPWCGPCKVMAPVVDEVAeeREGSLKIVSINVDDAPEIAAE 69
Cdd:cd03010    27 PYLLNVWASWCAPCREEHPVLMALA--RQGRVPIYGINYKDNPENALA 72

Thioredoxin-related protein SoxW [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  11 NFEQEVLNAET---PVLLKFWAPWCGPCKVM------APVVDEVAEERegsLKIVSINVDDAPEI-------------AA 68
Cdd:COG2143    28 DLEEDLALAKAegkPILLFFESDWCPYCKKLhkevfsDPEVAAYLKEN---FVVVQLDAEGDKEVtdfdgetltekelAR 104

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2230564619  69 EQGVRGVPTVMLF-KSGAKVASLVGAQSKSQLTQFID 104
Cdd:COG2143   105 KYGVRGTPTLVFFdAEGKEIARIPGYLKPETFLALLK 141

thiol-disulfide oxidoreductase ResA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  23 VLLKFWAPWCGPCKVMAPVVDEVAEE-REGSLKIVSINVDDaPEIAAEQ-----------------------GVRGVPTV 78
Cdd:PRK03147   64 VFLNFWGTWCKPCEKEMPYMNELYPKyKEKGVEIIAVNVDE-TELAVKNfvnrygltfpvaidkgrqvidayGVGPLPTT 142

                          90       100
                  ....*....|....*....|....*.
gi 2230564619  79 MLFKSGAKVASLV-GAQSKSQLTQFI 103
Cdd:PRK03147  143 FLIDKDGKVVKVItGEMTEEQLEEYL 168

PDIa family, 5'-Adenylylsulfate (APS) reductase subfamily; composed of plant-type APS reductases containing a C-terminal redox active TRX domain and an N-terminal reductase domain which is part of a superfamily that includes N type ATP PPases. APS reductase catalyzes the reduction of activated sulfate to sulfite, a key step in the biosynthesis of sulfur-containing metabolites. Sulfate is first activated by ATP sulfurylase, forming APS, which can be phosphorylated to 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Depending on the organism, either APS or PAPS can be used for sulfate reduction. Prokaryotes and fungi use PAPS, whereas plants use both APS and PAPS. Since plant-type APS reductase uses glutathione (GSH) as its electron donor, the C-terminal domain may function like glutaredoxin, a GSH-dependent member of the TRX superfamily. The flow of reducing equivalents goes from GSH -> C-terminal TRX domain -> N-terminal reductase domain -> APS. Plant-type APS reductase shows no homology to that of dissimilatory sulfate-reducing bacteria, which is an iron-sulfur flavoenzyme. Also included in the alignment is EYE2 from Chlamydomonas reinhardtii, a protein required for eyespot assembly.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2230564619  18 NAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGS-LKIVSINVDDAPEIAAEQ--GVRGVPTVMLFKSGAK 86
Cdd:cd02993    19 RRNQSTLVVLYAPWCPFCQAMEASYEELAEKLAGSnVKVAKFNADGEQREFAKEelQLKSFPTILFFPKNSR 90

TRX domain, DnaJ domain containing protein family; composed of uncharacterized proteins of about 500-800 amino acids, containing an N-terminal DnaJ domain followed by one redox active TRX domain. DnaJ is a member of the 40 kDa heat-shock protein (Hsp40) family of molecular chaperones, which regulate the activity of Hsp70s. TRX is involved in the redox regulation of many protein substrates through the reduction of disulfide bonds. TRX has been implicated to catalyse the reduction of Hsp33, a chaperone holdase that binds to unfolded protein intermediates. The presence of DnaJ and TRX domains in members of this family suggests that they could be involved in a redox-regulated chaperone network.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   7 VTNANFEQEVL--NAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREG-SLKIVSINVDDAPEIAAEQGVRGVPTVMLFKS 83
Cdd:cd02963     9 LTFSQYENEIVpkSFKKPYLIKITSDWCFSCIHIEPVWKEVIQELEPlGVGIATVNAGHERRLARKLGAHSVPAIVGIIN 88

                          90       100
                  ....*....|....*....|..
gi 2230564619  84 GAKVASLVGAQSKSQLTQFIDQ 105
Cdd:cd02963    89 GQVTFYHDSSFTKQHVVDFVRK 110

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   5 VDVTNANFEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGSLKIVSINVDDAPE-----IAAEQGVRGVPTVM 79
Cdd:cd02992     4 IVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADeenvaLCRDFGVTGYPTLR 83

                          90
                  ....*....|
gi 2230564619  80 LFKSGAKVAS 89
Cdd:cd02992    84 YFPPFSKEAT 93

Phosducin (Phd)-like family; composed of Phd and Phd-like proteins (PhLP), characterized as cytosolic regulators of G protein functions. Phd and PhLPs specifically bind G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane and impeding G protein-mediated signal transduction by inhibiting the formation of a functional G protein trimer (G protein alphabetagamma). Phd also inhibits the GTPase activity of G protein alpha. Phd can be phosphorylated by protein kinase A and G protein-coupled receptor kinase 2, leading to its inactivation. Phd was originally isolated from the retina, where it is highly expressed and has been implicated to play an important role in light adaptation. It is also found in the pineal gland, liver, spleen, striated muscle and the brain. The C-terminal domain of Phd adopts a thioredoxin fold, but it does not contain a CXXC motif. Phd interacts with G protein beta mostly through the N-terminal helical domain. Also included in this family is a PhLP characterized as a viral inhibitor of apoptosis (IAP)-associated factor, named VIAF, that functions in caspase activation during apoptosis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619   6 DVTNANFEQEVLNA--ETPVLLKFWAPWCGPCKVMAPVVDEVAEeREGSLKIVSINVDDApEIAAEQGVRGVPTVMLFKS 83
Cdd:cd02957     8 EISSKEFLEEVTKAskGTRVVVHFYEPGFPRCKILDSHLEELAA-KYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYKN 85

                  ....*....
gi 2230564619  84 GAKVASLVG 92
Cdd:cd02957    86 GELIDNIVG 94

5'-adenylylsulfate reductase, thioredoxin-independent; This enzyme, involved in the assimilation of inorganic sulfate, is closely related to the thioredoxin-dependent PAPS reductase of Bacteria (CysH) and Saccharomyces cerevisiae. However, it has its own C-terminal thioredoxin-like domain and is not thioredoxin-dependent. Also, it has a substrate preference for 5'-adenylylsulfate (APS) over 3'-phosphoadenylylsulfate (PAPS) so the pathway does not require an APS kinase (CysC) to convert APS to PAPS. Arabidopsis thaliana appears to have three isozymes, all able to complement E. coli CysH mutants (even in backgrounds lacking thioredoxin or APS kinase) but likely localized to different compartments in Arabidopsis. [Central intermediary metabolism, Sulfur metabolism]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2230564619  18 NAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREGS-LKIVSINVDDAPEIAAEQGVR--GVPTVMLF 81
Cdd:TIGR00424 369 ERKEAWLVVLYAPWCPFCQAMEASYLELAEKLAGSgVKVAKFRADGDQKEFAKQELQlgSFPTILFF 435

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2230564619  22 PVLLKFWA-PWCGPCKVMAPVVDEVAEE-REGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSGAKVASLVGA 93
Cdd:pfam00578  27 WVVLFFYPaDWTPVCTTELPALADLYEEfKKLGVEVLGVSVDSPESHKAFAEKYGLPFPLLSDPDGEVARAYGV 100

thiol:disulfide interchange protein DsbE; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2230564619  12 FEQEVLNAETPVLLKFWAPWCGPCKVMAPVVDEVAEEregSLKIVSINVDD 62
Cdd:PRK15412   60 YQADVLTQGKPVLLNVWATWCPTCRAEHQYLNQLSAQ---GIRVVGMNYKD 107

PDIa family, endoplasmic reticulum protein 44 (ERp44)-like subfamily; composed of uncharacterized PDI-like eukaryotic proteins containing only one redox active TRX (a) domain with a CXXS motif, similar to ERp44. CXXS is still a redox active motif; however, the mixed disulfide formed with the substrate is more stable than those formed by CXXC motif proteins. PDI-related proteins are usually involved in the oxidative protein folding in the ER by acting as catalysts and folding assistants. ERp44 is involved in thiol-mediated retention in the ER.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2230564619  18 NAETPVLLKFWAPWCGPCKVMAPVVDEVAEEREgSLKIVSINVDDA-PEIAAEQGVRGVPTVMLFKSGAKV 87
Cdd:cd02999    16 NREDYTAVLFYASWCPFSASFRPHFNALSSMFP-QIRHLAIEESSIkPSLLSRYGVVGFPTILLFNSTPRV 85

Phosducin (Phd)-like family, Thioredoxin (TRX) domain containing protein 9 (TxnDC9) subfamily; composed of predominantly uncharacterized eukaryotic proteins, containing a TRX-like domain without the redox active CXXC motif. The gene name for the human protein is TxnDC9. The two characterized members are described as Phd-like proteins, PLP1 of Saccharomyces cerevisiae and PhLP3 of Dictyostelium discoideum. Gene disruption experiments show that both PLP1 and PhLP3 are non-essential proteins. Unlike Phd and most Phd-like proteins, members of this group do not contain the Phd N-terminal helical domain which is implicated in binding to the G protein betagamma subunit.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  12 FEQEVLNAETpVLLKFWAPWCGPCKVMAPVVDEVAEeREGSLKIVSINVDDAPEIAAEQGVRGVPTVMLFKSGAKVASLV 91
Cdd:cd02989    15 FFEIVKSSER-VVCHFYHPEFFRCKIMDKHLEILAK-KHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTVDRIV 92

                  .
gi 2230564619  92 G 92
Cdd:cd02989    93 G 93

Thioredoxin;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2230564619  12 FEQEVLNAETPV-LLKFWAPWCGPCKVMAPVVDEVAEEREG-SLKIVSinVDDAPEIAAEQ---GVRGVPTVMLFKSGAK 86
Cdd:pfam14595  32 LIEKIKSIEKPLrILVITEDWCGDAAQNVPVLAKIAELNPNiELRILL--RDENLELMDQYltgGGRAIPTFIFLDEDGE 109