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 1430540346  10 EFKTFLTAAghKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQNVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFEF 89
Cdd:cd02947     2 EFEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                          90
                  ....*....|..
gi 1430540346  90 CGADAK-KLEAK 100
Cdd:cd02947    80 VGADPKeELEEF 91

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 1430540346  10 EFKTFLTAAghKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQNVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFEF 89
Cdd:cd02947     2 EFEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                          90
                  ....*....|..
gi 1430540346  90 CGADAK-KLEAK 100
Cdd:cd02947    80 VGADPKeELEEF 91

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 1430540346   7 DTNEFKTFLTAAgHKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQN-VFFANVDVNNSPELAETCHIKTIPTFQMFKKSQK 85
Cdd:COG3118     6 TDENFEEEVLES-DKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQP 84

                          90       100
                  ....*....|....*....|.
gi 1430540346  86 IFEFCGA-DAKKLEAKTQELM 105
Cdd:COG3118    85 VDRFVGAlPKEQLREFLDKVL 105

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 1430540346  10 EFKTFLtAAGHKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQN-VFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFE 88
Cdd:TIGR01068   5 NFDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDR 83

                  ....
gi 1430540346  89 FCGA 92
Cdd:TIGR01068  84 SVGA 87

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 1430540346  10 EFKTFLTAAghKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQNVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFEF 89
Cdd:cd02947     2 EFEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                          90
                  ....*....|..
gi 1430540346  90 CGADAK-KLEAK 100
Cdd:cd02947    80 VGADPKeELEEF 91

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 1430540346   7 DTNEFKTFLTAAgHKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQN-VFFANVDVNNSPELAETCHIKTIPTFQMFKKSQK 85
Cdd:COG3118     6 TDENFEEEVLES-DKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQP 84

                          90       100
                  ....*....|....*....|.
gi 1430540346  86 IFEFCGA-DAKKLEAKTQELM 105
Cdd:COG3118    85 VDRFVGAlPKEQLREFLDKVL 105

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 1430540346  10 EFKTFLTAAGHKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQ-NVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFE 88
Cdd:cd02984     4 EFEELLKSDASKLLVLHFWAPWAEPCKQMNQVFEELAKEAFpSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTIVDR 83

                          90
                  ....*....|....
gi 1430540346  89 FCGADAKKLEAKTQ 102
Cdd:cd02984    84 VSGADPKELAKKVE 97

TRX domain, novel NADPH thioredoxin reductase (NTR) family; composed of fusion proteins found only in oxygenic photosynthetic organisms containing both TRX and NTR domains. The TRX domain functions as a protein disulfide reductase via the reversible oxidation of an active center dithiol present in a CXXC motif, while the NTR domain functions as a reductant to oxidized TRX. The fusion protein is bifunctional, showing both TRX and NTR activities, but it is not an independent NTR/TRX system. In plants, the protein is found exclusively in shoots and mature leaves and is localized in the chloroplast. It is involved in plant protection against oxidative stress.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1430540346  21 KLAVVQFSSKRCGPCKRMFPVFHAMSVKYQN-VFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFEFCGADAKK 96
Cdd:cd02949    14 RLILVLYTSPTCGPCRTLKPILNKVIDEFDGaVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKS 90

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 1430540346   7 DTNEFKTFLtaAGHKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQ---NVFFANVDVNNSPELAETCHIKTIPTFQMFKKS 83
Cdd:cd02961     4 TDDNFDELV--KDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdgKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

                  ....*
gi 1430540346  84 QKIFE 88
Cdd:cd02961    82 SKEPV 86

thioredoxin 2; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430540346  24 VVQFSSKRCGPCKRMFPVFHAMSVKYQ-NVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQKIFEFCGA 92
Cdd:PRK10996   56 VIDFWAPWCGPCRNFAPIFEDVAAERSgKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGA 125

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430540346  10 EFKTFLTAagHKLAVVQFSSKRCGPCKRMFPVFHA----MSVKYQNVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQK 85
Cdd:PTZ00102   41 TFDKFITE--NEIVLVKFYAPWCGHCKRLAPEYKKaakmLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNP 118

                  ....*..
gi 1430540346  86 IfEFCGA 92
Cdd:PTZ00102  119 V-NYSGG 124

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 1430540346   8 TNEFKTFLTAAGHKLAVVQFSSKRCGPCKRMFPVFHAMSVKYQ--NVFFANVDVNNSPELAETCHI------KTIPTFQM 79
Cdd:cd02962    35 PKTLEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNnnNLKFGKIDIGRFPNVAEKFRVstsplsKQLPTIIL 114

                          90
                  ....*....|....*..
gi 1430540346  80 FKKSQKIFEFCGADAKK 96
Cdd:cd02962   115 FQGGKEVARRPYYNDSK 131

OST3 / OST6 family, transporter family; The proteins in this family are part of a complex of eight ER proteins that transfers core oligosaccharide from dolichol carrier to Asn-X-Ser/Thr motifs. This family includes both OST3 and OST6, each of which contains four predicted transmembrane helices. Disruption of OST3 and OST6 leads to a defect in the assembly of the complex. Hence, the function of these genes seems to be essential for recruiting a fully active complex necessary for efficient N-glycosylation. These proteins are also thought to be novel Mg2+ transporters.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1430540346   4 IIK-DTNEFKTFLTAAGHKLAVVQFSS----KRCGPCKRMFPVFHAMSVKYQ--------NVFFANVDVNNSPELAETCH 70
Cdd:pfam04756  13 VIKlNDSNYKRLLSGPRDYSVVVLLTAldprFGCQLCREFQPEFELVAKSWFkdhkagssKLFFATLDFDDGKDVFQSLG 92

                          90
                  ....*....|
gi 1430540346  71 IKTIPTFQMF 80
Cdd:pfam04756  93 LQTAPHLLLF 102

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 1430540346  27 FSSKRCGPCKRMFPVFHAMSVKYQNVFFANVDVNNSPELAET---CHIKTIPTFQMFKKSQKI 86
Cdd:cd01659     4 FYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDPALEKElkrYGVGGVPTLVVFGPGIGV 66

Phosducin (Phd)-like family, Thioredoxin (TRX) domain containing protein 9 (TxnDC9) subfamily; composed of predominantly uncharacterized eukaryotic proteins, containing a TRX-like domain without the redox active CXXC motif. The gene name for the human protein is TxnDC9. The two characterized members are described as Phd-like proteins, PLP1 of Saccharomyces cerevisiae and PhLP3 of Dictyostelium discoideum. Gene disruption experiments show that both PLP1 and PhLP3 are non-essential proteins. Unlike Phd and most Phd-like proteins, members of this group do not contain the Phd N-terminal helical domain which is implicated in binding to the G protein betagamma subunit.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1430540346  24 VVQFSSKRCGPCKRMFPVFHAMSVKYQNVFFANVDVNNSPELAETCHIKTIPTFQMFKKSQ 84
Cdd:cd02989    26 VCHFYHPEFFRCKIMDKHLEILAKKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGK 86