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 490732257   4 VILFTQETCGACATQREKNEGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIGIVDRDELEAAIE 83
Cdd:cd02947   14 VVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGADPKEELEEFLE 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 490732257   4 VILFTQETCGACATQREKNEGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIGIVDRDELEAAIE 83
Cdd:cd02947   14 VVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGADPKEELEEFLE 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 490732257    4 VILFTQETCGACatqreKN-----EGIEDAYP-DVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIGIVDRDE 77
Cdd:TIGR01068  18 LVDFWAPWCGPC-----KMiapilEELAKEYEgKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRSVGALPKAA 92

                  ....*..
gi 490732257   78 LEAAIES 84
Cdd:TIGR01068  93 LKQLINK 99

thioredoxin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 490732257   4 VILFTQETCGACATQREKNEGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIG 71
Cdd:PTZ00051  22 IVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVVDTLLG 89

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 490732257   4 VILFTQETCGACATQREKNEGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIGIVDRDELEAAIE 83
Cdd:cd02947   14 VVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGADPKEELEEFLE 93

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490732257   4 VILFTQETCGACATQREKNEGIEDAYPDVEFREVDIQTDLE----------------------TAEEYGVRKTPTTLVY- 60
Cdd:COG0526   32 LVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDENPEavkaflkelglpypvlldpdgeLAKAYGVRGIPTTVLId 111

                         90       100
                 ....*....|....*....|....*
gi 490732257  61 ANGEQTAEFIGIVDRDELEAAIESA 85
Cdd:COG0526  112 KDGKIVARHVGPLSPEELEEALEKL 136

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490732257   3 EVILFTQETCGACATQRE--KNEGIEdaypdveFREVDIQTDLETAEE----YGVRKTPTTLVyaNGeqtaEFIGIVDRD 76
Cdd:COG0695    1 KVTLYTTPGCPYCARAKRllDEKGIP-------YEEIDVDEDPEAREElrerSGRRTVPVIFI--GG----EHLGGFDEG 67

                 ....*..
gi 490732257  77 ELEAAIE 83
Cdd:COG0695   68 ELDALLA 74

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 490732257    4 VILFTQETCGAC-ATQREKNEGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIGIVDRDELEAAI 82
Cdd:pfam00085  22 LVDFYAPWCGPCkMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVGARPKDALAAFL 101

                  ..
gi 490732257   83 ES 84
Cdd:pfam00085 102 KA 103

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490732257   4 VILFTQETCGACA-TQRE--KNEGIEDAY-PDVEFREVDI-----QTDL--------ETAEEYGVRKTPTTLVY-ANGEQ 65
Cdd:COG2143   44 LLFFESDWCPYCKkLHKEvfSDPEVAAYLkENFVVVQLDAegdkeVTDFdgetltekELARKYGVRGTPTLVFFdAEGKE 123

                         90
                 ....*....|....*...
gi 490732257  66 TAEFIGIVDRDELEAAIE 83
Cdd:COG2143  124 IARIPGYLKPETFLALLK 141

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 490732257   4 VILFTQETCGACATQREKNEGIEDAYPDVEFREVDIQTD---LETAEEYGVRKTPTTLVYANGEQT 66
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDpalEKELKRYGVGGVPTLVVFGPGIGV 66

thioredoxin TrxA;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 490732257   7 FTQETCGACATQREKNEGIEDAYP-DVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAEFIGIVDRDELEAAIES 84
Cdd:PRK09381  28 FWAEWCGPCKMIAPILDEIADEYQgKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGALSKGQLKEFLDA 106

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490732257   3 EVILFTQETCGACATQRE--KNEGIEdaypdveFREVDIQTDLETAEE----YGVRKTPTTLVyaNGEQTAEFigivDRD 76
Cdd:cd02976    1 EVTVYTKPDCPYCKATKRflDERGIP-------FEEVDVDEDPEALEElkklNGYRSVPVVVI--GDEHLSGF----RPD 67

                 ....*.
gi 490732257  77 ELEAAI 82
Cdd:cd02976   68 KLRALL 73

Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO)-like family, N-terminal TRX-fold subdomain; composed of proteins with similarity to PfPDO, a redox active thermostable protein believed to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI), which are both involved in oxidative protein folding. PfPDO contains two redox active CXXC motifs in two contiguous TRX-fold subdomains. The active site in the N-terminal TRX-fold subdomain is required for isomerase but not for reductase activity of PfPDO. The exclusive presence of PfPDO-like proteins in extremophiles may suggest that they have a special role in adaptation to extreme conditions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 490732257   3 EVILFTQET-CGACATQREKNEGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAE--FIGIVDRDELE 79
Cdd:cd02975   24 DLVVFSSKEgCQYCEVTKQLLEELSELSDKLKLEIYDFDEDKEKAEKYGVERVPTTIFLQDGGKDGGirYYGLPAGYEFA 103

                 ....
gi 490732257  80 AAIE 83
Cdd:cd02975  104 SLIE 107

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 490732257    4 VILFTQETCGACATQRE--KNEGiedaypdVEFREVDIQTDLETAEE----YGVRKTPTtlVYANGE 64
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRllKSLG-------VDFEEIDVDEDPEIREElkelSGWPTVPQ--VFIDGE 58

protein disulfide isomerase, eukaryotic; This model represents eukaryotic protein disulfide isomerases retained in the endoplasmic reticulum (ER) and closely related forms. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase and dolichyl-diphosphooligosaccharide-protein glycotransferase. Members of this family have at least two protein-disulfide domains, each similar to thioredoxin but with the redox-active disulfide in the motif PWCGHCK, and an ER retention signal at the extreme C-terminus (KDEL, HDEL, and similar motifs).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 490732257   12 CGAC---ATQREKN-EGIEDAYPDVEFREVDIQTDLETAEEYGVRKTPTTLVYANGEQTAE 68
Cdd:TIGR01130  30 CGHCkslAPEYEKAaDELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRNGEDSVS 90