thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950    1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PRK09381   1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80

                         90       100
                 ....*....|....*....|....*....
gi 67005950   81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109
Cdd:PRK09381  81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950    1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PRK09381   1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80

                         90       100
                 ....*....|....*....|....*....
gi 67005950   81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109
Cdd:PRK09381  81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109

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 67005950     8 LTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEV 87
Cdd:TIGR01068   1 LTDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 67005950    88 AATKVGALSKGQLKEFLDANL 108
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 101

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 67005950  11 DSFDtDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYqGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAAT 90
Cdd:cd02947   1 EEFE-ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                        90
                ....*....|....*
gi 67005950  91 KVGALSKGQLKEFLD 105
Cdd:cd02947  79 VVGADPKEELEEFLE 93

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950    1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PRK09381   1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80

                         90       100
                 ....*....|....*....|....*....
gi 67005950   81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109
Cdd:PRK09381  81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109

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 67005950     8 LTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEV 87
Cdd:TIGR01068   1 LTDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 67005950    88 AATKVGALSKGQLKEFLDANL 108
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 101

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 67005950  11 DSFDtDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYqGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAAT 90
Cdd:cd02947   1 EEFE-ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                        90
                ....*....|....*
gi 67005950  91 KVGALSKGQLKEFLD 105
Cdd:cd02947  79 VVGADPKEELEEFLE 93

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 67005950   6 IHLTDDSFDtDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQ--GKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83
Cdd:cd02961   1 VELTDDNFD-ELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                        90       100
                ....*....|....*....|..
gi 67005950  84 NGEVAATK-VGALSKGQLKEFL 104
Cdd:cd02961  80 NGSKEPVKyEGPRTLESLVEFI 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  24 ILVDFWAEWCGPCKMIAPILDEIADEYQGkLTVAKLNIDQNPGTAPK----------------------YGIRGIPTLLL 81
Cdd:COG0526  31 VLVNFWATWCPPCRAEMPVLKELAEEYGG-VVFVGVDVDENPEAVKAflkelglpypvlldpdgelakaYGVRGIPTTVL 109

                        90       100
                ....*....|....*....|....*....
gi 67005950  82 F-KNGEVAATKVGALSKGQLKEFLDANLA 109
Cdd:COG0526 110 IdKDGKIVARHVGPLSPEELEEALEKLLA 138

PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the endoplasmic reticulum (ER) and displays both isomerase and chaperone activities, which are independent of each other. Compared to PDI, the isomerase and chaperone activities of P5 are lower. The first cysteine in the CXXC motif of both redox active domains in P5 is necessary for isomerase activity. The P5 gene was first isolated as an amplified gene from a hydroxyurea-resistant hamster cell line. The zebrafish P5 homolog has been implicated to play a critical role in establishing left/right asymmetries in the embryonic midline. Some members of this subfamily are P5-like proteins containing only one redox active TRX domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950   5 IIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKN 84
Cdd:cd03001   2 VVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGA 81

                ....*.
gi 67005950  85 GEVAAT 90
Cdd:cd03001  82 GKNSPQ 87

PDIa family, endoplasmic reticulum protein 38 (ERp38) subfamily; composed of proteins similar to the P5-like protein first isolated from alfalfa, which contains two redox active TRX (a) domains at the N-terminus, like human P5, and a C-terminal domain with homology to the C-terminal domain of ERp29, unlike human P5. The cDNA clone of this protein (named G1) was isolated from an alfalfa cDNA library by screening with human protein disulfide isomerase (PDI) cDNA. The G1 protein is constitutively expressed in all major organs of the plant and its expression is induced by treatment with tunicamycin, indicating that it may be a glucose-regulated protein. The G1 homolog in the eukaryotic social amoeba Dictyostelium discoideum is also described as a P5-like protein, which is located in the endoplasmic reticulum (ER) despite the absence of an ER-retrieval signal. G1 homologs from Aspergillus niger and Neurospora crassa have also been characterized, and are named TIGA and ERp38, respectively. Also included in the alignment is an atypical PDI from Leishmania donovani containing a single a domain, and the C-terminal a domain of a P5-like protein from Entamoeba histolytica.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950   5 IIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQG--KLTVAKLNIDQ-NPGTAPKYGIRGIPTLLL 81
Cdd:cd02998   2 VVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANedDVVIAKVDADEaNKDLAKKYGVSGFPTLKF 81

                ....
gi 67005950  82 FKNG 85
Cdd:cd02998  82 FPKG 85

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950   4 KIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83
Cdd:cd03004   2 SVITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYP 81

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  19 KADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGALSKG 98
Cdd:cd02949  11 ESDRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKS 90

                ....*..
gi 67005950  99 QLKEFLD 105
Cdd:cd02949  91 EYREFIE 97

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950    2 SDKIIHLTDDSFDtDVLKADGAILVDFWAEWCGPCKMIAPILDEIAD---EYQGKLTVAKLNIDQNPGTAPKYGIRGIPT 78
Cdd:PTZ00102  31 SEHVTVLTDSTFD-KFITENEIVLVKFYAPWCGHCKRLAPEYKKAAKmlkEKKSEIVLASVDATEEMELAQEFGVRGYPT 109

                 ....*...
gi 67005950   79 LLLFKNGE 86
Cdd:PTZ00102 110 IKFFNKGN 117

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  10 DDSFdTDVlKADGAILVDFWAEWCGPCKMIAPILDEIADEYQG---KLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKnGE 86
Cdd:cd03000   6 DDSF-KDV-RKEDIWLVDFYAPWCGHCKKLEPVWNEVGAELKSsgsPVRVGKLDATAYSSIASEFGVRGYPTIKLLK-GD 82

                        90
                ....*....|....*..
gi 67005950  87 VAATKVGALSKGQLKEF 103
Cdd:cd03000  83 LAYNYRGPRTKDDIVEF 99

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 67005950    11 DSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQG---KLTVAKLNIDQNpgTAPKYGIRGIPTLLLFKNGE 86
Cdd:TIGR01130 354 KNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDaesDVVIAKMDATAN--DVPPFEVEGFPTIKFVPAGK 430

PDIa family, endoplasmic reticulum protein 44 (ERp44) subfamily; ERp44 is an ER-resident protein, induced during stress, involved in thiol-mediated ER retention. It contains an N-terminal TRX domain, similar to that of PDIa, with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. The CXFS motif in the N-terminal domain allows ERp44 to form stable reversible mixed disulfides with its substrates. Through this activity, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. It also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950   5 IIHLTDDSFDtDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQ------GKLTVAKLNIDQNPGTAPKYGIRGIPT 78
Cdd:cd02996   3 IVSLTSGNID-DILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKeefpdaGKVVWGKVDCDKESDIADRYRINKYPT 81

                        90
                ....*....|
gi 67005950  79 LLLFKNGEVA 88
Cdd:cd02996  82 LKLFRNGMMM 91

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  25 LVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDqNPGTAP---KYGIRGIPTLLLFKN-GEVAATKVGALSKGQL 100
Cdd:cd02950  24 LVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVD-NPKWLPeidRYRVDGIPHFVFLDReGNEEGQSIGLQPKQVL 102

                ....*.
gi 67005950 101 KEFLDA 106
Cdd:cd02950 103 AQNLDA 108

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950   12 SFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQ--GKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAA 89
Cdd:PTZ00102 366 TFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKdnDSIIVAKMNGTANETPLEEFSWSAFPTILFVKAGERTP 445

                         90
                 ....*....|....*....
gi 67005950   90 TKV-GALSKGQLKEFLDAN 107
Cdd:PTZ00102 446 IPYeGERTVEGFKEFVNKH 464

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 67005950   5 IIHLTDDSFDtDVLKADGAI--LVDFWAEWCGPCKMIAPILDEIADEYQGK-LTVAKLNIDQNPGTAPKYGI------RG 75
Cdd:cd02962  30 IKYFTPKTLE-EELERDKRVtwLVEFFTTWSPECVNFAPVFAELSLKYNNNnLKFGKIDIGRFPNVAEKFRVstsplsKQ 108

                        90
                ....*....|....
gi 67005950  76 IPTLLLFKNG-EVA 88
Cdd:cd02962 109 LPTIILFQGGkEVA 122

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  24 ILVDFWAEWCGPC-KMIAPIL--DEIADEYQGKLTVAKLNIDQN------PGT-------APKYGIRGIPTLLLF-KNGE 86
Cdd:COG2143  43 ILLFFESDWCPYCkKLHKEVFsdPEVAAYLKENFVVVQLDAEGDkevtdfDGEtltekelARKYGVRGTPTLVFFdAEGK 122

                        90
                ....*....|....*....
gi 67005950  87 VAATKVGALSKGQLKEFLD 105
Cdd:COG2143 123 EIARIPGYLKPETFLALLK 141

PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950   4 KIIHLTDDSFdTDVLKadGAILVDFWAEWCGPCKMIAPILDEIADeyQGK---LTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:cd02994   2 NVVELTDSNW-TLVLE--GEWMIEFYAPWCPACQQLQPEWEEFAD--WSDdlgINVAKVDVTQEPGLSGRFFVTALPTIY 76

                ....*.
gi 67005950  81 LFKNGE 86
Cdd:cd02994  77 HAKDGV 82

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950    24 ILVDFWAEWCGPCKMIAPIL---DEIADEYQGKLTVAKLNIDQNPGT-------------APKYGIRGIPTLLLFKNGEV 87
Cdd:pfam13098   7 VLVVFTDPDCPYCKKLKKELledPDVTVYLGPNFVFIAVNIWCAKEVakaftdilenkelGRKYGVRGTPTIVFFDGKGE 86

                          90
                  ....*....|....*..
gi 67005950    88 AATKVGALSKGQLKEFL 104
Cdd:pfam13098  87 LLRLPGYVPAEEFLALL 103

DsbD gamma family; DsbD gamma is the C-terminal periplasmic domain of the bacterial protein DsbD. It contains a CXXC motif in a TRX fold and shuttles the reducing potential from the membrane domain (DsbD beta) to the N-terminal periplasmic domain (DsbD alpha). DsbD beta, a transmembrane domain comprising of eight helices, acquires its reducing potential from the cytoplasmic thioredoxin. DsbD alpha transfers the acquired reducing potential from DsbD gamma to target proteins such as the periplasmic protein disulphide isomerases, DsbC and DsbG. This flow of reducing potential from the cytoplasm through DsbD allows DsbC and DsbG to act as isomerases in the oxidizing environment of the bacterial periplasm. DsbD also transfers reducing potential from the cytoplasm to specific reductases in the periplasm which are involved in the maturation of cytochromes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  18 LKADG-AILVDFWAEWCGPCKMIAPIL---DEIADEYQGKLTVAKLNI-DQNPGTAP---KYGIRGIPTLLLF--KNGEV 87
Cdd:cd02953   7 ALAQGkPVFVDFTADWCVTCKVNEKVVfsdPEVQAALKKDVVLLRADWtKNDPEITAllkRFGVFGPPTYLFYgpGGEPE 86

                        90
                ....*....|....*...
gi 67005950  88 AATKVGALSKGQLKEFLD 105
Cdd:cd02953  87 PLRLPGFLTADEFLEALE 104

PDIa family, endoplasmic reticulum protein 44 (ERp44)-like subfamily; composed of uncharacterized PDI-like eukaryotic proteins containing only one redox active TRX (a) domain with a CXXS motif, similar to ERp44. CXXS is still a redox active motif; however, the mixed disulfide formed with the substrate is more stable than those formed by CXXC motif proteins. PDI-related proteins are usually involved in the oxidative protein folding in the ER by acting as catalysts and folding assistants. ERp44 is involved in thiol-mediated retention in the ER.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 67005950  23 AILVDFWAEWCGPCKMIAPILDEIADEYQgklTVAKLNID---QNPGTAPKYGIRGIPTLLLF 82
Cdd:cd02999  20 YTAVLFYASWCPFSASFRPHFNALSSMFP---QIRHLAIEessIKPSLLSRYGVVGFPTILLF 79

TRX domain, DnaJ domain containing protein family; composed of uncharacterized proteins of about 500-800 amino acids, containing an N-terminal DnaJ domain followed by one redox active TRX domain. DnaJ is a member of the 40 kDa heat-shock protein (Hsp40) family of molecular chaperones, which regulate the activity of Hsp70s. TRX is involved in the redox regulation of many protein substrates through the reduction of disulfide bonds. TRX has been implicated to catalyse the reduction of Hsp33, a chaperone holdase that binds to unfolded protein intermediates. The presence of DnaJ and TRX domains in members of this family suggests that they could be involved in a redox-regulated chaperone network.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  25 LVDFWAEWCGPCKMIAPILDEIADEYQG-KLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGALSKGQLKEF 103
Cdd:cd02963  28 LIKITSDWCFSCIHIEPVWKEVIQELEPlGVGIATVNAGHERRLARKLGAHSVPAIVGIINGQVTFYHDSSFTKQHVVDF 107

                ..
gi 67005950 104 LD 105
Cdd:cd02963 108 VR 109

F plasmid transfer operon protein; TraF protein undergoes proteolytic processing associated with export. The 19 amino acids at the amino terminus of the polypeptides appear to constitute a typical membrane leader peptide - not included in this family, while the remainder of the molecule is predicted to be primarily hydrophilic in character. F plasmid TraF and TraH are required for F pilus assembly and F plasmid transfer, and they are both localized to the outer membrane in the presence of the complete F transfer region, especially TraV, the putative anchor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950    18 LKADGAILVdFWAEWCGPCKMIAPILDEIADEYqgKLTVAKLNIDQNP-----------GTAPKYGIRGIPTLLLF--KN 84
Cdd:pfam13728 127 LAEEFGLIF-FYRGDCPYCEAQAPILQAFADKY--GWTVRPVSVDGRPlpgfpnyrvdnGQAARLGVKRTPALFLVnpPS 203

                          90
                  ....*....|....*...
gi 67005950    85 GEVAATKVGALSKGQLKE 102
Cdd:pfam13728 204 GDVVPVAAGVLSLDELEE 221

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  18 LKADGAILVDFWAEWCGPCKMIAPILDEIADEYQG---KLTVAKL-NIDqnpgTAPKYGIRGIPTLLLFKNGEVAATKVG 93
Cdd:cd02948  14 LSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDdllHFATAEAdTID----TLKRYRGKCEPTFLFYKNGELVAVIRG 89

                .
gi 67005950  94 A 94
Cdd:cd02948  90 A 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  18 LKADG-AILVDFWAEWCGPCK-MIAPIL--DEIADEYQGKLTVAKLNI-DQNPGTAP---KYGIRGIPTLLLF-KNGEVA 88
Cdd:COG4232 316 ARAEGkPVFVDFTADWCVTCKeNERTVFsdPEVQAALADDVVLLKADVtDNDPEITAllkRFGRFGVPTYVFYdPDGEEL 395

                        90
                ....*....|....*...
gi 67005950  89 ATKVGALSKGQLKEFLDA 106
Cdd:COG4232 396 PRLGFMLTADEFLAALEK 413

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 67005950   5 IIHLTDDSFDTdvlkadgailvdfwaewcgpCKMIAPILDEIADEYQG----KLTVAKLNIDQNPGtapkygIRGIPTLL 80
Cdd:cd02957  28 VVHFYEPGFPR--------------------CKILDSHLEELAAKYPEtkfvKINAEKAFLVNYLD------IKVLPTLL 81

                        90
                ....*....|...
gi 67005950  81 LFKNGEVAATKVG 93
Cdd:cd02957  82 VYKNGELIDNIVG 94

TRX family, chloroplastic drought-induced stress protein of 32 kD (CDSP32); CDSP32 is composed of two TRX domains, a C-terminal TRX domain which contains a redox active CXXC motif and an N-terminal TRX-like domain which contains an SXXS sequence instead of the redox active motif. CDSP32 is a stress-inducible TRX, i.e., it acts as a TRX by reducing protein disulfides and is induced by environmental and oxidative stress conditions. It plays a critical role in plastid defense against oxidative damage, a role related to its function as a physiological electron donor to BAS1, a plastidic 2-cys peroxiredoxin. Plants lacking CDSP32 exhibit decreased photosystem II photochemical efficiencies and chlorophyll retention compared to WT controls, as well as an increased proportion of BAS1 in its overoxidized monomeric form.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67005950  11 DSFDTDVLKADGA-ILVDFWAEWCGPCKMIAPILDEIAdEYQGKLTVAKLNIDQNPGTAP---KYGIRGIPTLLLFKNGE 86
Cdd:cd02985   4 EELDEALKKAKGRlVVLEFALKHSGPSVKIYPTMVKLS-RTCNDVVFLLVNGDENDSTMElcrREKIIEVPHFLFYKDGE 82

                        90
                ....*....|....
gi 67005950  87 VAATKVGaLSKGQL 100
Cdd:cd02985  83 KIHEEEG-IGPDEL 95