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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  45 SLPDTQFVTLSGQTIPLLA-KDKPTLVYIFAPWCTICRISINNLDSLNSDKVNVVRIGVDY-QYIEELTHFVDEVGVKGE 122
Cdd:COG0526     7 PAPDFTLTDLDGKPLSLADlKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVdENPEAVKAFLKELGLPYP 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1945486558 123 ILLGNNQTI-RDFQVTAYPSIYILQPDGTVVGRSVGYTTSLGLK 165
Cdd:COG0526    87 VLLDPDGELaKAYGVRGIPTTVLIDKDGKIVARHVGPLSPEELE 130

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  45 SLPDTQFVTLSGQTIPLLA-KDKPTLVYIFAPWCTICRISINNLDSLNSDKVNVVRIGVDY-QYIEELTHFVDEVGVKGE 122
Cdd:COG0526     7 PAPDFTLTDLDGKPLSLADlKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVdENPEAVKAFLKELGLPYP 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1945486558 123 ILLGNNQTI-RDFQVTAYPSIYILQPDGTVVGRSVGYTTSLGLK 165
Cdd:COG0526    87 VLLDPDGELaKAYGVRGIPTTVLIDKDGKIVARHVGPLSPEELE 130

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  65 DKPTLVYIFAPWCTICRISINNLDSLNS-----DKVNVVRIGVDyQYIEELTHFVDEVGVKGEIL---LGNNQTI-RDFQ 135
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEklkkkKNVEIVFVSLD-RDLEEFKDYLKKMPKDWLSVpfdDDERNELkRKYG 79

                          90
                  ....*....|....*.
gi 1945486558 136 VTAYPSIYILQPDGTV 151
Cdd:pfam13905  80 VNAIPTLVLLDPNGEV 95

bifunctional peptide-methionine (S)-S-oxide reductase MsrA/peptide-methionine (R)-S-oxide reductase MsrB;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  35 RNMLPSDgSVSLPDT--QFVTLSGQT-IPLLAKDKPTLVYIFAPWCTICRISINNLDSL----NSDKVNVVRI------- 100
Cdd:PRK14018   24 PKILDAG-TATVPHTlsTLKTADNRPaSVYLKKDKPTLIKFWASWCPLCLSELGETEKWaqdaKFSSANLITVaspgflh 102

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1945486558 101 ------------GVDYQYIEELThfvDEVGvkgeillgnnQTIRDFQVTAYPSIYILQPDGTVVGRSVG 157
Cdd:PRK14018  103 ekkdgdfqkwyaGLDYPKLPVLT---DNGG----------TLAQSLNISVYPSWAIIGKDGDVQRIVKG 158

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  45 SLPDTQFVTLSGQTIPLLA-KDKPTLVYIFAPWCTICRISINNLDSLNSDKVNVVRIGVDY-QYIEELTHFVDEVGVKGE 122
Cdd:COG0526     7 PAPDFTLTDLDGKPLSLADlKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVdENPEAVKAFLKELGLPYP 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1945486558 123 ILLGNNQTI-RDFQVTAYPSIYILQPDGTVVGRSVGYTTSLGLK 165
Cdd:COG0526    87 VLLDPDGELaKAYGVRGIPTTVLIDKDGKIVARHVGPLSPEELE 130

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 1945486558  48 DTQFVTLSGQTIPLLA-KDKPTLVYIFAPWCTICRISINNLDSLN----SDKVNVVRIGVDYQYIEELTHFVDEVGVKGE 122
Cdd:cd02966     1 DFSLPDLDGKPVSLSDlKGKVVLVNFWASWCPPCRAEMPELEALAkeykDDGVEVVGVNVDDDDPAAVKAFLKKYGITFP 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1945486558 123 ILLGNNQTI-RDFQVTAYPSIYILQPDGTVVGRSVG 157
Cdd:cd02966    81 VLLDPDGELaKAYGVRGLPTTFLIDRDGRIRARHVG 116

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 1945486558  61 LLAKDKPTLVYIFAPWCTICRISINNLDSL---NSDKVNVVRigVDyqyieelthfVDEvgvkgeillgNNQTIRDFQVT 137
Cdd:COG3118    14 VLESDKPVLVDFWAPWCGPCKMLAPVLEELaaeYGGKVKFVK--VD----------VDE----------NPELAAQFGVR 71

                          90       100
                  ....*....|....*....|...
gi 1945486558 138 AYPSIYILQpDGTVVGRSVGYTT 160
Cdd:COG3118    72 SIPTLLLFK-DGQPVDRFVGALP 93

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  65 DKPTLVYIFAPWCTICRISINNLDSLNS-----DKVNVVRIGVDyQYIEELTHFVDEVGVKGEIL---LGNNQTI-RDFQ 135
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEklkkkKNVEIVFVSLD-RDLEEFKDYLKKMPKDWLSVpfdDDERNELkRKYG 79

                          90
                  ....*....|....*.
gi 1945486558 136 VTAYPSIYILQPDGTV 151
Cdd:pfam13905  80 VNAIPTLVLLDPNGEV 95

thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  61 LLAKDKPTLVYIFAPWCTICRISINNLDSLNSDKVNVVRIG-VDyqyieelthfVDEvgvkgeillgNNQTIRDFQVTAY 139
Cdd:TIGR01068  10 IASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVkLN----------VDE----------NPDIAAKYGIRSI 69

                          90
                  ....*....|....*...
gi 1945486558 140 PSIyILQPDGTVVGRSVG 157
Cdd:TIGR01068  70 PTL-LLFKNGKEVDRSVG 86

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 1945486558  61 LLAKDKPTLVYIFAPWCTICRISINNLDSLNSDKVNVVRIGVDyqyieelthfVDEvgvkgeillgNNQTIRDFQVTAYP 140
Cdd:cd02947     6 LIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVD----------VDE----------NPELAEEYGVRSIP 65

                          90
                  ....*....|....*...
gi 1945486558 141 SIYILQpDGTVVGRSVGY 158
Cdd:cd02947    66 TFLFFK-NGKEVDRVVGA 82

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 1945486558  52 VTLSGQTI-PLLAKDKPTLVYIFAPWCTICRISINNLDSL-----NSDKVNVVRIGVDYqyieelthfvdevgvkgeill 125
Cdd:cd02961     1 VELTDDNFdELVKDSKDVLVEFYAPWCGHCKALAPEYEKLakelkGDGKVVVAKVDCTA--------------------- 59

                          90       100
                  ....*....|....*....|..
gi 1945486558 126 gNNQTIRDFQVTAYPSIYILQP 147
Cdd:cd02961    60 -NNDLCSEYGVRGYPTIKLFPN 80

thiol:disulfide interchange protein DsbE; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1945486558  61 LLAKDKPTLVYIFAPWCTICRISINNLDSLNSDKVNVVriGVDYQ--------YIEELTHFVDEVGVKGEILLGnnqtiR 132
Cdd:PRK15412   64 VLTQGKPVLLNVWATWCPTCRAEHQYLNQLSAQGIRVV--GMNYKddrqkaisWLKELGNPYALSLFDGDGMLG-----L 136

                          90       100
                  ....*....|....*....|....*
gi 1945486558 133 DFQVTAYPSIYILQPDGTVVGRSVG 157
Cdd:PRK15412  137 DLGVYGAPETFLIDGNGIIRYRHAG 161

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
                  ....*....|....*....|....*....|....
gi 1945486558  52 VTLSGQTIPLLAK----DKPTLVYIFAPWCTICR 81
Cdd:cd02993     4 VTLSRAEIEALAKgerrNQSTLVVLYAPWCPFCQ 37

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
                  ....*....|....*....|..
gi 1945486558  60 PLLAKDKPTLVYIFAPWCTICR 81
Cdd:cd02997    12 KFLKKEKHVLVMFYAPWCGHCK 33