thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   1 MSDKIIHLTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PRK09381    1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80

                          90       100
                  ....*....|....*....|....*....
gi 1036260248  81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109
Cdd:PRK09381   81 LFKNGEVAATKVGALSKGQLKEFLDANLA 109

thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   1 MSDKIIHLTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PRK09381    1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80

                          90       100
                  ....*....|....*....|....*....
gi 1036260248  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 1036260248   8 LTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEV 87
Cdd:TIGR01068   1 LTDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 1036260248  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 1036260248  11 DSFDtDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYqGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAAT 90
Cdd:cd02947     1 EEFE-ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                          90
                  ....*....|....*
gi 1036260248  91 KVGALSKGQLKEFLD 105
Cdd:cd02947    79 VVGADPKEELEEFLE 93

thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   1 MSDKIIHLTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PRK09381    1 MSDKIIHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80

                          90       100
                  ....*....|....*....|....*....
gi 1036260248  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 1036260248   8 LTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEV 87
Cdd:TIGR01068   1 LTDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 1036260248  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 1036260248  11 DSFDtDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYqGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAAT 90
Cdd:cd02947     1 EEFE-ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                          90
                  ....*....|....*
gi 1036260248  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 1036260248   6 IHLTDDSFDtDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQ--GKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83
Cdd:cd02961     1 VELTDDNFD-ELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                          90       100
                  ....*....|....*....|..
gi 1036260248  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 1036260248  24 TLVDFWAEWCGPCKMIAPILDEIAEEYQGkLTVAKLNIDQNPGTAPK----------------------YGIRGIPTLLL 81
Cdd:COG0526    31 VLVNFWATWCPPCRAEMPVLKELAEEYGG-VVFVGVDVDENPEAVKAflkelglpypvlldpdgelakaYGVRGIPTTVL 109

                          90       100
                  ....*....|....*....|....*....
gi 1036260248  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 1036260248   5 IIHLTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKN 84
Cdd:cd03001     2 VVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGA 81

                  ....*.
gi 1036260248  85 GEVAAT 90
Cdd:cd03001    82 GKNSPQ 87

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 1036260248   4 KIIHLTDDSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83
Cdd:cd03004     2 SVITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYP 81

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   5 IIHLTDDSFDTDVLKADGLT----LVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:PTZ00443   32 LVLLNDKNFEKLTQASTGATtgpwFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPTLL 111

                          90       100
                  ....*....|....*....|...
gi 1036260248  81 LFKNGEVAATKVGALSKGQLKEF 103
Cdd:PTZ00443  112 LFDKGKMYQYEGGDRSTEKLAAF 134

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 1036260248  10 DDSFdTDVlKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQG---KLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKnGE 86
Cdd:cd03000     6 DDSF-KDV-RKEDIWLVDFYAPWCGHCKKLEPVWNEVGAELKSsgsPVRVGKLDATAYSSIASEFGVRGYPTIKLLK-GD 82

                          90
                  ....*....|....*..
gi 1036260248  87 VAATKVGALSKGQLKEF 103
Cdd:cd03000    83 LAYNYRGPRTKDDIVEF 99

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 1036260248  19 KADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGALSKG 98
Cdd:cd02949    11 ESDRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKS 90

                  ....*..
gi 1036260248  99 QLKEFLD 105
Cdd:cd02949    91 EYREFIE 97

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   2 SDKIIHLTDDSFDtDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAE---EYQGKLTVAKLNIDQNPGTAPKYGIRGIPT 78
Cdd:PTZ00102   31 SEHVTVLTDSTFD-KFITENEIVLVKFYAPWCGHCKRLAPEYKKAAKmlkEKKSEIVLASVDATEEMELAQEFGVRGYPT 109

                  ....*...
gi 1036260248  79 LLLFKNGE 86
Cdd:PTZ00102  110 IKFFNKGN 117

PDIa family, PDIR subfamily; composed of proteins similar to human PDIR (for Protein Disulfide Isomerase Related). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress. Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   5 IIHLTDDSFDtDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQ--GKLTVAKLNI--DQNPGTAPKYGIRGIPTLL 80
Cdd:cd02997     2 VVHLTDEDFR-KFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKedGKGVLAAVDCtkPEHDALKEEYNVKGFPTFK 80

                  ....*.
gi 1036260248  81 LFKNGE 86
Cdd:cd02997    81 YFENGK 86

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 1036260248   5 IIHLTDDSFDtDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQ------GKLTVAKLNIDQNPGTAPKYGIRGIPT 78
Cdd:cd02996     3 IVSLTSGNID-DILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKeefpdaGKVVWGKVDCDKESDIADRYRINKYPT 81

                          90
                  ....*....|
gi 1036260248  79 LLLFKNGEVA 88
Cdd:cd02996    82 LKLFRNGMMM 91

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 1036260248  11 DSFDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEEYQG---KLTVAKLNIDQNpgTAPKYGIRGIPTLLLFKNGE 86
Cdd:TIGR01130 354 KNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDaesDVVIAKMDATAN--DVPPFEVEGFPTIKFVPAGK 430

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 1036260248  25 LVDFWAEWCGPCKMIAPILDEIAEEYQGkLTVAKLNIDQNPGTAP---KYGIRGIPTLLLFKNGEV 87
Cdd:cd01659     1 LVLFYAPWCPFCQALRPVLAELALLNKG-VKFEAVDVDEDPALEKelkRYGVGGVPTLVVFGPGIG 65

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 1036260248   5 IIHLTDDSFDtDVLKADGLT--LVDFWAEWCGPCKMIAPILDEIAEEYQGK-LTVAKLNIDQNPGTAPKYGI------RG 75
Cdd:cd02962    30 IKYFTPKTLE-EELERDKRVtwLVEFFTTWSPECVNFAPVFAELSLKYNNNnLKFGKIDIGRFPNVAEKFRVstsplsKQ 108

                          90
                  ....*....|....
gi 1036260248  76 IPTLLLFKNG-EVA 88
Cdd:cd02962   109 LPTIILFQGGkEVA 122

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 1036260248  24 TLVDFWAEWCGPCKMIAPILDEIAEEYQgKLTVAKL-------------------NIDQNPGT-APKYGIRGIPTLLLFK 83
Cdd:cd03011    23 VLVYFWATWCPVCRFTSPTVNQLAADYP-VVSVALRsgddgavarfmqkkgygfpVINDPDGViSARWGVSVTPAIVIVD 101

                          90
                  ....*....|...
gi 1036260248  84 NGEVAATKVGALS 96
Cdd:cd03011   102 PGGIVFVTTGVTS 114

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 1036260248   4 KIIHLTDDSFdTDVLKadGLTLVDFWAEWCGPCKMIAPILDEIAEeyQGK---LTVAKLNIDQNPGTAPKYGIRGIPTLL 80
Cdd:cd02994     2 NVVELTDSNW-TLVLE--GEWMIEFYAPWCPACQQLQPEWEEFAD--WSDdlgINVAKVDVTQEPGLSGRFFVTALPTIY 76

                  ....*.
gi 1036260248  81 LFKNGE 86
Cdd:cd02994    77 HAKDGV 82

TlpA-like family, DsbE (also known as CcmG and CycY) subfamily; DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   9 TDDSFDTDVLKaDGLTLVDFWAEWCGPCKMIAPILDEIAEeyQGKLTVAKLNI-DQ------------NPG--------- 66
Cdd:cd03010    14 PDKTLTSADLK-GKPYLLNVWASWCAPCREEHPVLMALAR--QGRVPIYGINYkDNpenalawlarhgNPYaavgfdpdg 90

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1036260248  67 -TAPKYGIRGIP-TLLLFKNGEVAATKVGAL 95
Cdd:cd03010    91 rVGIDLGVYGVPeTFLIDGDGIIRYKHVGPL 121

PDIa family, N-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 comprised of the first TRX domain of ERdj5 located after the DnaJ domain at the N-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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248   4 KIIHLTDDSFDTDVLKADgLTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83
Cdd:cd03003     2 EIVTLDRGDFDAAVNSGE-IWFVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFP 80

                          90       100
                  ....*....|....*....|
gi 1036260248  84 NGEVAATKVGALSKGQLKEF 103
Cdd:cd03003    81 SGMNPEKYYGDRSKESLVKF 100

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248  23 LTLVDFWAEWCGPCKMIAPILDEIAEEYQGKLTVA-------------KLNIDQNPGTAP--------------KYGIRG 75
Cdd:pfam13905   3 VVLLYFGASWCKPCRRFTPLLKELYEKLKKKKNVEivfvsldrdleefKDYLKKMPKDWLsvpfdddernelkrKYGVNA 82

                          90
                  ....*....|...
gi 1036260248  76 IPTLLLF-KNGEV 87
Cdd:pfam13905  83 IPTLVLLdPNGEV 95

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 1036260248  24 TLVDFWAEWCGPCKMIAPILDEIAEEYQgklTVAKLNID---QNPGTAPKYGIRGIPTLLLF 82
Cdd:cd02999    21 TAVLFYASWCPFSASFRPHFNALSSMFP---QIRHLAIEessIKPSLLSRYGVVGFPTILLF 79

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1036260248  13 FDTDVLKADGLTLVDFWAEWCGPCKMIAPILDEIAEE 49
Cdd:TIGR00385  55 YTADVLTQGKPVLLNVWASWCPPCRAEHPYLNELAKQ 91

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248  28 FWAEWCGPCKMIAPILDEIAEEYQgkltvaKLNIDQNPGTAP----KYGIRGIPTllLFKNGEVaatkVGALSKGQLKEF 103
Cdd:COG0695     5 YTTPGCPYCARAKRLLDEKGIPYE------EIDVDEDPEAREelreRSGRRTVPV--IFIGGEH----LGGFDEGELDAL 72

                  ..
gi 1036260248 104 LD 105
Cdd:COG0695    73 LA 74

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1036260248  25 LVDFWAEWCGPCK-MIAPIL--DEIAEEYQGKLTVAKLNI-DQNPGTAP---KYGIRGIPTLLLF-KNGEVAATKVGALS 96
Cdd:COG4232   324 FVDFTADWCVTCKeNERTVFsdPEVQAALADDVVLLKADVtDNDPEITAllkRFGRFGVPTYVFYdPDGEELPRLGFMLT 403

                          90
                  ....*....|
gi 1036260248  97 KGQLKEFLDA 106
Cdd:COG4232   404 ADEFLAALEK 413

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 1036260248   2 SDKIIHLTDDSFDtDVLKA--DGLTLVDFWAEW----CGPCKMIAPILDEIA-------EEYQGKLTVAKLNIDQNPGTA 68
Cdd:pfam04756  10 SNGVIKLNDSNYK-RLLSGprDYSVVVLLTALDprfgCQLCREFQPEFELVAkswfkdhKAGSSKLFFATLDFDDGKDVF 88

                          90
                  ....*....|....
gi 1036260248  69 PKYGIRGIPTLLLF 82
Cdd:pfam04756  89 QSLGLQTAPHLLLF 102

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 1036260248  11 DSFDTDVLKADG-LTLVDFWAEWCGPCKMIAPILDEIAEEyQGKLTVAKLNIDQNPGTAP---KYGIRGIPTLLLFKNGE 86
Cdd:cd02985     4 EELDEALKKAKGrLVVLEFALKHSGPSVKIYPTMVKLSRT-CNDVVFLLVNGDENDSTMElcrREKIIEVPHFLFYKDGE 82

                          90
                  ....*....|....
gi 1036260248  87 VAATKVGaLSKGQL 100
Cdd:cd02985    83 KIHEEEG-IGPDEL 95