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 26451103  49 EKWEEKITEAnshgKILVVNFKASWCLPSKTILPIYQELASTYTSMIFVTIDVEELAEFSHEWNVDATPTVVFLKDGRQM 128
Cdd:cd02947   1 EEFEELIKSA----KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEV 76

                        90
                ....*....|
gi 26451103 129 DKLVGGDAAE 138
Cdd:cd02947  77 DRVVGADPKE 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 26451103  49 EKWEEKITEAnshgKILVVNFKASWCLPSKTILPIYQELASTYTSMIFVTIDVEELAEFSHEWNVDATPTVVFLKDGRQM 128
Cdd:cd02947   1 EEFEELIKSA----KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEV 76

                        90
                ....*....|
gi 26451103 129 DKLVGGDAAE 138
Cdd:cd02947  77 DRVVGADPKE 86

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 26451103  48 MEKWEEKITEANshgKILVVNFKASWCLPSKTILPIYQELASTYT-SMIFVTIDVEELAEFSHEWNVDATPTVVFLKDGR 126
Cdd:COG3118   7 DENFEEEVLESD---KPVLVDFWAPWCGPCKMLAPVLEELAAEYGgKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQ 83

                ....*..
gi 26451103 127 QMDKLVG 133
Cdd:COG3118  84 PVDRFVG 90

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 26451103    49 EKWEEKIteANSHgKILVVNFKASWCLPSKTILPIYQELASTYTSMI-FVTIDVEELAEFSHEWNVDATPTVVFLKDGRQ 127
Cdd:pfam00085   8 ANFDEVV--QKSS-KPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVvFAKVDVDENPDLASKYGVRGYPTLIFFKNGQP 84

                          90
                  ....*....|....*....
gi 26451103   128 MDKLVGG-DAAELQKKTAA 145
Cdd:pfam00085  85 VDDYVGArPKDALAAFLKA 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 26451103  49 EKWEEKITEAnshgKILVVNFKASWCLPSKTILPIYQELASTYTSMIFVTIDVEELAEFSHEWNVDATPTVVFLKDGRQM 128
Cdd:cd02947   1 EEFEELIKSA----KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEV 76

                        90
                ....*....|
gi 26451103 129 DKLVGGDAAE 138
Cdd:cd02947  77 DRVVGADPKE 86

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26451103   42 VHPVSRMEKWEeKITEANShgkILVVNFKASWCLPSKTILPIYQELASTYTSMIFVTIDVEELAEFSHEWNVDATPTVVF 121
Cdd:PTZ00051   2 VHIVTSQAEFE-STLSQNE---LVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKV 77

                         90
                 ....*....|....*....
gi 26451103  122 LKDGRQMDKLVGGDAAELQ 140
Cdd:PTZ00051  78 FKNGSVVDTLLGANDEALK 96

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 26451103    49 EKWEEKITEANshgKILVVNFKASWCLPSKTILPIYQELASTYTSMI-FVTIDVEELAEFSHEWNVDATPTVVFLKDGRQ 127
Cdd:TIGR01068   4 ANFDETIASSD---KPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVkFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                  ....*.
gi 26451103   128 MDKLVG 133
Cdd:TIGR01068  81 VDRSVG 86

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 26451103    49 EKWEEKIteANSHgKILVVNFKASWCLPSKTILPIYQELASTYTSMI-FVTIDVEELAEFSHEWNVDATPTVVFLKDGRQ 127
Cdd:pfam00085   8 ANFDEVV--QKSS-KPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVvFAKVDVDENPDLASKYGVRGYPTLIFFKNGQP 84

                          90
                  ....*....|....*....
gi 26451103   128 MDKLVGG-DAAELQKKTAA 145
Cdd:pfam00085  85 VDDYVGArPKDALAAFLKA 103

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 26451103  65 LVVNFKASWCLPSKTILPIYQELASTY-TSMIFVTIDVEELAEFSHEWNVDATPTVVFLKDGRQMDKLVGG-DAAELQ 140
Cdd:cd02956  15 VVVDFWAPRSPPSKELLPLLERLAEEYqGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDGFQGAqPEEQLR 92

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26451103  51 WEEKITEANSHGKILVVNFKASWC----------LPSKTILPIYQElastytSMIFVTIDVEEL-------------AEF 107
Cdd:COG2143  29 LEEDLALAKAEGKPILLFFESDWCpyckklhkevFSDPEVAAYLKE------NFVVVQLDAEGDkevtdfdgetlteKEL 102

                        90       100
                ....*....|....*....|....*..
gi 26451103 108 SHEWNVDATPTVVFL-KDGRQMDKLVG 133
Cdd:COG2143 103 ARKYGVRGTPTLVFFdAEGKEIARIPG 129

thioredoxin 2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 26451103   66 VVNFKASWCLPSKTILPIYQELASTYTSMI-FVTIDVEELAEFSHEWNVDATPTVVFLKDGRQMDKLVG 133
Cdd:PRK10996  56 VIDFWAPWCGPCRNFAPIFEDVAAERSGKVrFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNG 124

TlpA-like family, suppressor for copper sensitivity D protein (ScsD) and actinobacterial DsbE homolog subfamily; composed of ScsD, the DsbE homolog of Mycobacterium tuberculosis (MtbDsbE) and similar proteins, all containing a redox-active CXXC motif. The Salmonella typhimurium ScsD is a thioredoxin-like protein which confers copper tolerance to copper-sensitive mutants of E. coli. MtbDsbE has been characterized as an oxidase in vitro, catalyzing the disulfide bond formation of substrates like hirudin. The reduced form of MtbDsbE is more stable than its oxidized form, consistent with an oxidase function. This is in contrast to the function of DsbE from gram-negative bacteria which is a specific reductase of apocytochrome c.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26451103  56 TEANShGKILVVNFKASWCLPSKTILPIYQELASTYTsmiFVTI-----DVEELAEF------------------SHEWN 112
Cdd:cd03011  15 LESLS-GKPVLVYFWATWCPVCRFTSPTVNQLAADYP---VVSValrsgDDGAVARFmqkkgygfpvindpdgviSARWG 90

                        90
                ....*....|....
gi 26451103 113 VDATPTVVFLKDGR 126
Cdd:cd03011  91 VSVTPAIVIVDPGG 104

PDIa family, C-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 composed of the three TRX domains located at the C-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. Also included in the alignment is the single complete TRX domain of an uncharacterized protein from Tetraodon nigroviridis, which also contains a DnaJ domain at its N-terminus.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 26451103  55 ITEANSHGKIL------VVNFKASWCLPSKTILPIYQELASTYTSMI-FVTIDVEELAEFSHEWNVDATPTVVFLKDGR 126
Cdd:cd03004   6 LTPEDFPELVLnrkepwLVDFYAPWCGPCQALLPELRKAARALKGKVkVGSVDCQKYESLCQQANIRAYPTIRLYPGNA 84

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26451103    60 SHGKILVVNFKASWC----LPSKTILPiYQELASTYTS---MIFVTI-----------DVEELAEFSHEWNVDATPTVVF 121
Cdd:pfam13098   2 GNGKPVLVVFTDPDCpyckKLKKELLE-DPDVTVYLGPnfvFIAVNIwcakevakaftDILENKELGRKYGVRGTPTIVF 80

                          90       100
                  ....*....|....*....|...
gi 26451103   122 LkDGRQMDKLVGG--DAAELQKK 142
Cdd:pfam13098  81 F-DGKGELLRLPGyvPAEEFLAL 102

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 26451103  58 ANSHGKILVVNFKASWCLPSKTILPIYQELASTYT--SMIFVTIDVEELAEFSHEWNVDAT------PTVVFLKDGRQMD 129
Cdd:cd02962  43 ERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNnnNLKFGKIDIGRFPNVAEKFRVSTSplskqlPTIILFQGGKEVA 122

                .
gi 26451103 130 K 130
Cdd:cd02962 123 R 123

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26451103  62 GKILVVNFKASWCLPSKTILPIYQELASTYTSMIFVTI-----DVEELAEFSHE------------------WNVDATPT 118
Cdd:COG1225  21 GKPVVLYFYATWCPGCTAELPELRDLYEEFKDKGVEVLgvssdSDEAHKKFAEKyglpfpllsdpdgevakaYGVRGTPT 100

                ....*....
gi 26451103 119 VVFL-KDGR 126
Cdd:COG1225 101 TFLIdPDGK 109

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 26451103  53 EKITEANSHG-KILVVNFKASWC----------LPSKTILPIYQE-----LASTYTSMIFVTIDVEEL--AEFSHEWNVD 114
Cdd:cd02951   4 EDLAEAAADGkKPLLLLFSQPGCpycdklkrdyLNDPAVQAYIRAhfvvvYINIDGDKEVTDFDGEALseKELARKYRVR 83

                        90       100
                ....*....|....*....|.
gi 26451103 115 ATPTVVFL--KDGRQMDKLVG 133
Cdd:cd02951  84 FTPTVIFLdpEGGKEIARLPG 104

Tryparedoxin (TryX)-like family; composed of TryX and related proteins including nucleoredoxin (NRX), rod-derived cone viability factor (RdCVF) and the nematode homolog described as a 16-kD class of TRX. Most members of this family, except RdCVF, are protein disulfide oxidoreductases containing an active site CXXC motif, similar to TRX.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26451103  52 EEKITEANSHGKILVVNFKASWCLPSKTILPI----YQELASTYTSM--IFVTID--VEELAEFSHE---W--------- 111
Cdd:cd02964   7 EGVVPVSALEGKTVGLYFSASWCPPCRAFTPKlvefYEKLKEEGKNFeiVFVSRDrsEESFNEYFSEmppWlavpfedee 86

                        90       100       110
                ....*....|....*....|....*....|....
gi 26451103 112 ---------NVDATPTVVFLK--------DGRQM 128
Cdd:cd02964  87 lrellekqfKVEGIPTLVVLKpdgdvvttNARDE 120

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 26451103  40 GKVHPVSrMEKWEEKITEAnSHGKILVVNFKASWCLPSKTILPIYQELASTYTSMIFVTIDVEElAEFSHEWNVDATPTV 119
Cdd:cd02957   4 GEVREIS-SKEFLEEVTKA-SKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEK-AFLVNYLDIKVLPTL 80

                        90
                ....*....|....
gi 26451103 120 VFLKDGRQMDKLVG 133
Cdd:cd02957  81 LVYKNGELIDNIVG 94

Tryparedoxin (TryX)-like family, TryX and nucleoredoxin (NRX) subfamily; TryX and NRX are thioredoxin (TRX)-like protein disulfide oxidoreductases that alter the redox state of target proteins via the reversible oxidation of an active center CXXC motif. TryX is involved in the regulation of oxidative stress in parasitic trypanosomatids by reducing TryX peroxidase, which in turn catalyzes the reduction of hydrogen peroxide and organic hydroperoxides. TryX derives reducing equivalents from reduced trypanothione, a polyamine peptide conjugate unique to trypanosomatids, which is regenerated by the NADPH-dependent flavoprotein trypanothione reductase. Vertebrate NRX is a 400-amino acid nuclear protein with one redox active TRX domain containing a CPPC active site motif followed by one redox inactive TRX-like domain. Mouse NRX transcripts are expressed in all adult tissues but is restricted to the nervous system and limb buds in embryos. Plant NRX, longer than the vertebrate NRX by about 100-200 amino acids, is a nuclear protein containing a redox inactive TRX-like domain between two redox active TRX domains. Both vertebrate and plant NRXs show thiol oxidoreductase activity in vitro. Their localization in the nucleus suggests a role in the redox regulation of nuclear proteins such as transcription factors.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 26451103  61 HGKILVVNFKASWCLPSKTILP----IYQELASTYTSM--IFVTIDVEE 103
Cdd:cd03009  17 EGKTVGLYFSASWCPPCRAFTPklveFYEKLKESGKNFeiVFISWDRDE 65