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 499520488  49 VTGTGPAVLHFSAEWCGPCAAVRRVVagvtADLAAEPHPPQDIEIDIDAEPALARELNVLSLPTTFVFDaAGRERFRISG 128
Cdd:cd02947    7 IKSAKPVVVDFWAPWCGPCKAIAPVL----EELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFK-NGKEVDRVVG 81

                         90
                 ....*....|..
gi 499520488 129 VPKAGDLRSALA 140
Cdd:cd02947   82 ADPKEELEEFLE 93

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 499520488  49 VTGTGPAVLHFSAEWCGPCAAVRRVVagvtADLAAEPHPPQDIEIDIDAEPALARELNVLSLPTTFVFDaAGRERFRISG 128
Cdd:cd02947    7 IKSAKPVVVDFWAPWCGPCKAIAPVL----EELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFK-NGKEVDRVVG 81

                         90
                 ....*....|..
gi 499520488 129 VPKAGDLRSALA 140
Cdd:cd02947   82 ADPKEELEEFLE 93

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 499520488   50 TGTGPAVLHFSAEWCGPCaavrRVVAGVTADLAAEPHPPQDI-EIDIDAEPALARELNVLSLPTTFVFDaAGRERFRISG 128
Cdd:TIGR01068  12 SSDKPVLVDFWAPWCGPC----KMIAPILEELAKEYEGKVKFvKLNVDENPDIAAKYGIRSIPTLLLFK-NGKEVDRSVG 86

                  ....*
gi 499520488  129 V-PKA 132
Cdd:TIGR01068  87 AlPKA 91

thioredoxin 2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 499520488  54 PAVLHFSAEWCGPCaavrRVVAGVTADLAAEPHPP-QDIEIDIDAEPALARELNVLSLPTTFVF 116
Cdd:PRK10996  54 PVVIDFWAPWCGPC----RNFAPIFEDVAAERSGKvRFVKVNTEAERELSARFRIRSIPTIMIF 113

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 499520488  49 VTGTGPAVLHFSAEWCGPCAAVRRVVagvtADLAAEPHPPQDIEIDIDAEPALARELNVLSLPTTFVFDaAGRERFRISG 128
Cdd:cd02947    7 IKSAKPVVVDFWAPWCGPCKAIAPVL----EELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFK-NGKEVDRVVG 81

                         90
                 ....*....|..
gi 499520488 129 VPKAGDLRSALA 140
Cdd:cd02947   82 ADPKEELEEFLE 93

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499520488  54 PAVLHFSAEWCGPCAAVRRVVAgvtaDLAAEPHPPQDIEIDIDAEPA----------------------LARELNVLSLP 111
Cdd:COG0526   30 PVLVNFWATWCPPCRAEMPVLK----ELAEEYGGVVFVGVDVDENPEavkaflkelglpypvlldpdgeLAKAYGVRGIP 105

                         90       100       110
                 ....*....|....*....|....*....|....
gi 499520488 112 TTFVFDAAGRERFRISGVPKAGDLRSALAPLTAA 145
Cdd:COG0526  106 TTVLIDKDGKIVARHVGPLSPEELEEALEKLLAK 139

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499520488  54 PAVLHFSAEWCGPCAAVRRVVagvtADLAAEPHPP-QDIEIDIDAEPALARELNVLSLPtTFVFDAAGRERFRISGVpKA 132
Cdd:cd02984   16 LLVLHFWAPWAEPCKQMNQVF----EELAKEAFPSvLFLSIEAEELPEISEKFEITAVP-TFVFFRNGTIVDRVSGA-DP 89

                 ....*...
gi 499520488 133 GDLRSALA 140
Cdd:cd02984   90 KELAKKVE 97

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 499520488  54 PAVLHFSAEWCGPCaavrRVVAGVTADLAAEpHPPQDIEI-----D---------------------IDAEPALARELNV 107
Cdd:cd02966   21 VVLVNFWASWCPPC----RAEMPELEALAKE-YKDDGVEVvgvnvDdddpaavkaflkkygitfpvlLDPDGELAKAYGV 95

                         90       100
                 ....*....|....*....|.
gi 499520488 108 LSLPTTFVFDAAGRERFRISG 128
Cdd:cd02966   96 RGLPTTFLIDRDGRIRARHVG 116

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499520488   53 GPAVLHFSAEWCGPCaavrRVVAGVTADLAAEphPPQDI---EIDIDAEPALARELNVLSLPtTFVFDAAGRERFRISGV 129
Cdd:pfam00085  19 KPVLVDFYAPWCGPC----KMLAPEYEELAQE--YKGNVvfaKVDVDENPDLASKYGVRGYP-TLIFFKNGQPVDDYVGA 91

                          90
                  ....*....|.
gi 499520488  130 PKAGDLRSALA 140
Cdd:pfam00085  92 RPKDALAAFLK 102

thioredoxin 2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 499520488  54 PAVLHFSAEWCGPCaavrRVVAGVTADLAAEPHPP-QDIEIDIDAEPALARELNVLSLPTTFVF 116
Cdd:PRK10996  54 PVVIDFWAPWCGPC----RNFAPIFEDVAAERSGKvRFVKVNTEAERELSARFRIRSIPTIMIF 113

ybbN protein family; ybbN is a hypothetical protein containing a redox-inactive TRX-like domain. Its gene has been sequenced from several gammaproteobacteria and actinobacteria.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 499520488  54 PAVLHFSAEWCGPCAAVRRVVAGVTA------DLAAephppqdieIDIDAEPALARELNVLSLPTTFVFDAA 119
Cdd:cd02956   14 PVVVDFWAPRSPPSKELLPLLERLAEeyqgqfVLAK---------VNCDAQPQIAQQFGVQALPTVYLFAAG 76

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 499520488  53 GPAVLHFSAEWCGPCA---------AVRRVV-----------AGVTADLAAEPHPPQDIEIDIDAEpaLARELNVLSLPT 112
Cdd:cd03010   26 KPYLLNVWASWCAPCReehpvlmalARQGRVpiyginykdnpENALAWLARHGNPYAAVGFDPDGR--VGIDLGVYGVPE 103

                         90
                 ....*....|....*.
gi 499520488 113 TFVFDAAGRERFRISG 128
Cdd:cd03010  104 TFLIDGDGIIRYKHVG 119

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 499520488   26 GRARPAAPASTNPERAGLLAAAGVTGTGPAVLHFSAEWCGPCAAVRRVVAGVTAD-------------------LAAEPH 86
Cdd:TIGR00385  37 GKPVPAFRLASLDEPGQFYTADVLTQGKPVLLNVWASWCPPCRAEHPYLNELAKQglpivgvdykddrqnaikfLKELGN 116

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 499520488   87 PPQDIEIDIDAEPALarELNVLSLPTTFVFDAAGRERFRISGVPKAGDLRSALAPL 142
Cdd:TIGR00385 117 PYQLSLFDPDGMLGL--DLGVYGAPETFLVDGNGVIRYRHAGPLNPEVWTEEFLPL 170

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 499520488  59 FSAEWCGPCAAVRRVV--AGVTADlaaephppqdiEIDIDAEPALAREL----NVLSLPTTFV 115
Cdd:COG0695    5 YTTPGCPYCARAKRLLdeKGIPYE-----------EIDVDEDPEAREELrersGRRTVPVIFI 56

SoxW family; SoxW is a bacterial periplasmic TRX, containing a redox active CXXC motif, encoded by a genetic locus (sox operon) involved in thiosulfate oxidation. Sulfur bacteria oxidize sulfur compounds to provide reducing equivalents for carbon dioxide fixation during autotrophic growth and the respiratory electron transport chain. It is unclear what the role of SoxW is, since it has been found to be dispensable in the oxidation of thiosulfate to sulfate. SoxW is specifically kept in the reduced state by SoxV, which is essential in thiosulfate oxidation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499520488  44 LAAAGVTGTGPAVLHFSAEWCGPCAAVRRVV---AGVTADLAAEPHPPQdieIDIDA-------------EPALARELNV 107
Cdd:cd02951    6 LAEAAADGKKPLLLLFSQPGCPYCDKLKRDYlndPAVQAYIRAHFVVVY---INIDGdkevtdfdgealsEKELARKYRV 82

                         90       100       110
                 ....*....|....*....|....*....|...
gi 499520488 108 LSLPTTFVFDA-AGRERFRISGVPKAGDLRSAL 139
Cdd:cd02951   83 RFTPTVIFLDPeGGKEIARLPGYLPPDEFLAYL 115

thiol:disulfide interchange protein precursor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 499520488  44 LAAAGVTGTgPAVLHFSAEWCGPC----------AAVRRVVAGVT---ADLAAepHPPQDIEididaepaLARELNVLSL 110
Cdd:PRK00293 467 LAEAKGKGK-PVMLDLYADWCVACkefekytfsdPQVQQALADTVllqADVTA--NNAEDVA--------LLKHYNVLGL 535

                         90       100
                 ....*....|....*....|....*.
gi 499520488 111 PTTFVFDAAGRER--FRISGVPKAGD 134
Cdd:PRK00293 536 PTILFFDAQGQEIpdARVTGFMDAAA 561

PDIa family, TMX3 subfamily; composed of eukaryotic proteins similar to human TMX3, a TRX related transmembrane protein containing one redox active TRX domain at the N-terminus and a classical ER retrieval sequence for type I transmembrane proteins at the C-terminus. The TMX3 transcript is found in a variety of tissues with the highest levels detected in skeletal muscle and the heart. In vitro, TMX3 showed oxidase activity albeit slightly lower than that of protein disulfide isomerase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 499520488  59 FSAEWCGPCAAVRRVVAGVTADLAAEPHPPQDIEIDIDAEPALARELNVLSLPTTFVF 116
Cdd:cd03000   22 FYAPWCGHCKKLEPVWNEVGAELKSSGSPVRVGKLDATAYSSIASEFGVRGYPTIKLL 79