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 488221424   8 EELAGYVETGKSVF-FFTAGWCGDCRFIKPQMPEIENDFSDWQFIEVDRDKYIDVAAEWNIFGIPSFVVIQDGKELGRLV 86
Cdd:cd02947    1 EEFEELIKSAKPVVvDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 488221424  87 NKDrkTKQEIESFLE 101
Cdd:cd02947   81 GAD--PKEELEEFLE 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 488221424   8 EELAGYVETGKSVF-FFTAGWCGDCRFIKPQMPEIENDFSDWQFIEVDRDKYIDVAAEWNIFGIPSFVVIQDGKELGRLV 86
Cdd:cd02947    1 EEFEELIKSAKPVVvDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 488221424  87 NKDrkTKQEIESFLE 101
Cdd:cd02947   81 GAD--PKEELEEFLE 93

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 488221424   20 VFFFTAGWCGDCRFIKPQMPEIENDFS-DWQFIEVDRDKYIDVAAEWNIFGIPSFVVIQDGKELGRLVNkdRKTKQEIES 98
Cdd:pfam00085  22 LVDFYAPWCGPCKMLAPEYEELAQEYKgNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVG--ARPKDALAA 99

                  ....
gi 488221424   99 FLES 102
Cdd:pfam00085 100 FLKA 103

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 488221424   8 EELAGYVETGKSVF-FFTAGWCGDCRFIKPQMPEIENDFSDWQFIEVDRDKYIDVAAEWNIFGIPSFVVIQDGKELGRLV 86
Cdd:cd02947    1 EEFEELIKSAKPVVvDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 488221424  87 NKDrkTKQEIESFLE 101
Cdd:cd02947   81 GAD--PKEELEEFLE 93

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488221424   4 PNSLEELAGYVetgkSVFFFTAGWCGDCRFIKPQMPEIENDFSDWQFIEVDRDK------------------YID----V 61
Cdd:COG0526   20 PLSLADLKGKP----VLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDEnpeavkaflkelglpypvLLDpdgeL 95

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 488221424  62 AAEWNIFGIPSFVVI-QDGKELGRLVNkdRKTKQEIESFLESVIKG 106
Cdd:COG0526   96 AKAYGVRGIPTTVLIdKDGKIVARHVG--PLSPEELEEALEKLLAK 139

thioredoxin; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488221424  23 FTAGWCGDCRFIKPQMPEIENDFSDWQFIEVDRDKYIDVAAEWNIFGIPSFVVIQDGKELGRLV--NKDR 90
Cdd:PTZ00051  25 FYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVVDTLLgaNDEA 94

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 488221424  20 VFFFTAGWCGDCRFIKPQMPEIendfsDWQFIEVDRDKYIDVAAEWNIFGIPSFV 74
Cdd:PHA02125   2 IYLFGAEWCANCKMVKPMLANV-----EYTYVDVDTDEGVELTAKHHIRSLPTLV 51

Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488221424   4 PNSLEELAGYVETGKSVFF-FTAGWCGDCRFIKPQM---PEIENDFS-DWQFIEVD---RDKYI-DVAAEWNIFGIPSFV 74
Cdd:COG4232  307 ADLEAALAEARAEGKPVFVdFTADWCVTCKENERTVfsdPEVQAALAdDVVLLKADvtdNDPEItALLKRFGRFGVPTYV 386

                         90       100       110
                 ....*....|....*....|....*....|
gi 488221424  75 VI-QDGKELGRLVNKdrKTKQEIESFLESV 103
Cdd:COG4232  387 FYdPDGEELPRLGFM--LTADEFLAALEKA 414

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488221424   4 PNSLEELagyVETGKSVFF---FTAGWCGDCRFIKPQMPEIENDFS--DWQFIEVDRDKYIDVAAEWNIFG------IPS 72
Cdd:cd02962   35 PKTLEEE---LERDKRVTWlveFFTTWSPECVNFAPVFAELSLKYNnnNLKFGKIDIGRFPNVAEKFRVSTsplskqLPT 111

                         90       100
                 ....*....|....*....|
gi 488221424  73 FVVIQDGKELGRLVNKDRKT 92
Cdd:cd02962  112 IILFQGGKEVARRPYYNDSK 131

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 488221424  20 VFFFTAGWCGDCRFIKPQMPEIENDFSDWQFIEVDRDKYIDVAAEW---NIFGIPSFVVIQDG 79
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDPALEKELkryGVGGVPTLVVFGPG 63

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 488221424   8 EELAGYVETGKSVF-FFTAGWCGDC----RFIKPQmPEIENDFSD-WQFIEVDRDKYIDV-------------AAEWNIF 68
Cdd:COG2143   31 EDLALAKAEGKPILlFFESDWCPYCkklhKEVFSD-PEVAAYLKEnFVVVQLDAEGDKEVtdfdgetltekelARKYGVR 109

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 488221424  69 GIPSFVVI-QDGKELGRLVNKdrKTKQEIESFLESVIKG 106
Cdd:COG2143  110 GTPTLVFFdAEGKEIARIPGY--LKPETFLALLKYVAEG 146

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 488221424  23 FTAGWCGDCRFIKPQMPEIENDFSD-WQFIEVDRDKYI--DVAAEWNIFGIPSFVVIQDGKELGRLVNKDRKTKQEIESF 99
Cdd:cd03002   25 FYAPWCGHCKNLKPEYAKAAKELDGlVQVAAVDCDEDKnkPLCGKYGVQGFPTLKVFRPPKKASKHAVEDYNGERSAKAI 104

                 ....
gi 488221424 100 LESV 103
Cdd:cd03002  105 VDFV 108