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 1330198087   4 IVNVNTQNFET-LLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:COG3118     2 VVELTDENFEEeVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                          90       100
                  ....*....|....*....|....
gi 1330198087  83 GAEAGRTVGAMPKPQLRAEIEKYL 106
Cdd:COG3118    82 GQPVDRFVGALPKEQLREFLDKVL 105

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 1330198087   4 IVNVNTQNFET-LLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:COG3118     2 VVELTDENFEEeVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                          90       100
                  ....*....|....*....|....
gi 1330198087  83 GAEAGRTVGAMPKPQLRAEIEKYL 106
Cdd:COG3118    82 GQPVDRFVGALPKEQLREFLDKVL 105

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 1330198087  10 QNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVElAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKNGAEAGRT 89
Cdd:cd02947     1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                          90
                  ....*....|....
gi 1330198087  90 VGAMPKPQLRAEIE 103
Cdd:cd02947    80 VGADPKEELEEFLE 93

thioredoxin 2; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087   3 EIVNVNTQNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:PRK10996   36 EVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKN 115

                          90
                  ....*....|....*
gi 1330198087  83 GAEAGRTVGAMPKPQ 97
Cdd:PRK10996  116 GQVVDMLNGAVPKAP 130

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 1330198087   4 IVNVNTQNFET-LLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:COG3118     2 VVELTDENFEEeVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                          90       100
                  ....*....|....*....|....
gi 1330198087  83 GAEAGRTVGAMPKPQLRAEIEKYL 106
Cdd:COG3118    82 GQPVDRFVGALPKEQLREFLDKVL 105

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 1330198087  10 QNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVElAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKNGAEAGRT 89
Cdd:cd02947     1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                          90
                  ....*....|....
gi 1330198087  90 VGAMPKPQLRAEIE 103
Cdd:cd02947    80 VGADPKEELEEFLE 93

thioredoxin 2; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087   3 EIVNVNTQNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:PRK10996   36 EVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKN 115

                          90
                  ....*....|....*
gi 1330198087  83 GAEAGRTVGAMPKPQ 97
Cdd:PRK10996  116 GQVVDMLNGAVPKAP 130

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 1330198087   5 VNVNTQNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELA--GRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:cd02961     1 VELTDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPN 80

                  ...
gi 1330198087  83 GAE 85
Cdd:cd02961    81 GSK 83

thioredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087   1 MSEIVNVNTQnFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVaKCNVDENQDIAMRYRVMSIPTLIVL 80
Cdd:PTZ00051    1 MVHIVTSQAE-FESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFV-KVDVDELSEVAEKENITSMPTFKVF 78

                          90
                  ....*....|..
gi 1330198087  81 KNGAEAGRTVGA 92
Cdd:PTZ00051   79 KNGSVVDTLLGA 90

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 1330198087  10 QNFETLLQSDL--PVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKNGAEAG 87
Cdd:cd02984     3 EEFEELLKSDAskLLVLHFWAPWAEPCKQMNQVFEELAKEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTIVD 82

                          90
                  ....*....|....*.
gi 1330198087  88 RTVGAMPkPQLRAEIE 103
Cdd:cd02984    83 RVSGADP-KELAKKVE 97

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 1330198087   3 EIVNVNTQNFETL-LQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLK 81
Cdd:cd03001     1 DVVELTDSNFDKKvLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                          90
                  ....*....|....*..
gi 1330198087  82 NGAEA------GRTVGA 92
Cdd:cd03001    81 AGKNSpqdyqgGRTAKA 97

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 1330198087   2 SEIVNVNTQNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVEL------AGRVLVAKCNVDENQDIAMRYRVMSIP 75
Cdd:cd02996     1 SEIVSLTSGNIDDILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIkeefpdAGKVVWGKVDCDKESDIADRYRINKYP 80

                  ....*...
gi 1330198087  76 TLIVLKNG 83
Cdd:cd02996    81 TLKLFRNG 88

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087   2 SEIVNVNTQNFETLLQSDL-----PVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPT 76
Cdd:PTZ00443   30 NALVLLNDKNFEKLTQASTgattgPWFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPT 109

                  ....*..
gi 1330198087  77 LIVLKNG 83
Cdd:PTZ00443  110 LLLFDKG 116

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 1330198087   3 EIVNVNTQNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVEL---AGRVLVA-KCNVDENQDIAMRYRVMSIPTLI 78
Cdd:cd02997     1 DVVHLTDEDFRKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELkedGKGVLAAvDCTKPEHDALKEEYNVKGFPTFK 80

                  ....*
gi 1330198087  79 VLKNG 83
Cdd:cd02997    81 YFENG 85

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are 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. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087   4 IVNVNTQNF-ETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGR--VLVAKCNVDENqDIAMRYRVMSIPTLIVL 80
Cdd:cd02995     2 VKVVVGKNFdEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDdnVVIAKMDATAN-DVPSEFVVDGFPTILFF 80

                  ...
gi 1330198087  81 KNG 83
Cdd:cd02995    81 PAG 83

PDI family, MPD1-like subfamily; composed of eukaryotic proteins similar to Saccharomyces cerevisiae MPD1 protein, which contains a single redox active TRX domain located at the N-terminus, and an ER retention signal at the C-terminus indicative of an ER-resident protein. MPD1 has been shown to suppress the maturation defect of carboxypeptidase Y caused by deletion of the yeast PDI1 gene. Other characterized members of this subfamily include the Aspergillus niger prpA protein and Giardia PDI-1. PrpA is non-essential to strain viability, however, its transcript level is induced by heterologous protein expression suggesting a possible role in oxidative protein folding during high protein production. Giardia PDI-1 has the ability to refold scrambled RNase and exhibits transglutaminase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087   4 IVNVNTQNFETLLQ-SDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVA--KCNVDENQDIAMRYRVMSIPTLIVL 80
Cdd:cd03002     2 VYELTPKNFDKVVHnTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAavDCDEDKNKPLCGKYGVQGFPTLKVF 81

                  ....*...
gi 1330198087  81 KNGAEAGR 88
Cdd:cd03002    82 RPPKKASK 89

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087  18 SDL---PVLVDFWAPWCGPCRTVSPIVDELAVELAGR---VL-------------VAKCNV------DENQDIAMRYRVM 72
Cdd:COG1225    17 SDLrgkPVVLYFYATWCPGCTAELPELRDLYEEFKDKgveVLgvssdsdeahkkfAEKYGLpfpllsDPDGEVAKAYGVR 96

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1330198087  73 SIPTLIVL-KNGAEAGRTVGAM-PKPQLRAEIEKYL 106
Cdd:COG1225    97 GTPTTFLIdPDGKIRYVWVGPVdPRPHLEEVLEALL 132

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 1330198087  13 ETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDEN--QDIAMRYRVMSIPTLIVLKN-GAEAGRT 89
Cdd:cd02950    14 EVALSNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPkwLPEIDRYRVDGIPHFVFLDReGNEEGQS 93

                          90
                  ....*....|....
gi 1330198087  90 VGAMPKPQLRAEIE 103
Cdd:cd02950    94 IGLQPKQVLAQNLD 107

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1330198087  23 LVDFWAPWCGPCRTVSPIVDELAVEL---AGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKNG 83
Cdd:cd03000    19 LVDFYAPWCGHCKKLEPVWNEVGAELkssGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGD 82

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087  11 NFETL-LQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELA--GRVLVAKCNVDENqDIAMR-YRVMSIPTLIVLKNGA-- 84
Cdd:PTZ00102  366 TFEEIvFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKdnDSIIVAKMNGTAN-ETPLEeFSWSAFPTILFVKAGErt 444

                          90
                  ....*....|
gi 1330198087  85 ----EAGRTV 90
Cdd:PTZ00102  445 pipyEGERTV 454

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 1330198087  21 PVLVDFWAPWCGPCRTVSPIVDELAVELAGR---VLVA--------------------KCNV----DENQDIAMRYRVMS 73
Cdd:pfam13905   3 VVLLYFGASWCKPCRRFTPLLKELYEKLKKKknvEIVFvsldrdleefkdylkkmpkdWLSVpfddDERNELKRKYGVNA 82

                          90
                  ....*....|.
gi 1330198087  74 IPTLIVL-KNG 83
Cdd:pfam13905  83 IPTLVLLdPNG 93

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 1330198087   4 IVNVNTQN-FETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVL---VAKCnvdENQDIAMRYRVMSIPTLIV 79
Cdd:cd02948     1 QVEINNQEeWEELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDDLLhfaTAEA---DTIDTLKRYRGKCEPTFLF 77

                          90
                  ....*....|...
gi 1330198087  80 LKNGAEAGRTVGA 92
Cdd:cd02948    78 YKNGELVAVIRGA 90

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087  21 PVLVDFWAPWCGPCR--------------TVSPIVDELAVEL--AGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKNGA 84
Cdd:pfam13098   6 PVLVVFTDPDCPYCKklkkelledpdvtvYLGPNFVFIAVNIwcAKEVAKAFTDILENKELGRKYGVRGTPTIVFFDGKG 85

                          90
                  ....*....|....*...
gi 1330198087  85 EAGRTVGAMPKPQLRAEI 102
Cdd:pfam13098  86 ELLRLPGYVPAEEFLALL 103

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 1330198087   3 EIVNVNTQNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGRVLVAKCNVDENQDIAMRYRVMSIPTLIVLKN 82
Cdd:cd03003     2 EIVTLDRGDFDAAVNSGEIWFVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPS 81

                  .
gi 1330198087  83 G 83
Cdd:cd03003    82 G 82

PDIa family, 5'-Adenylylsulfate (APS) reductase subfamily; composed of plant-type APS reductases containing a C-terminal redox active TRX domain and an N-terminal reductase domain which is part of a superfamily that includes N type ATP PPases. APS reductase catalyzes the reduction of activated sulfate to sulfite, a key step in the biosynthesis of sulfur-containing metabolites. Sulfate is first activated by ATP sulfurylase, forming APS, which can be phosphorylated to 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Depending on the organism, either APS or PAPS can be used for sulfate reduction. Prokaryotes and fungi use PAPS, whereas plants use both APS and PAPS. Since plant-type APS reductase uses glutathione (GSH) as its electron donor, the C-terminal domain may function like glutaredoxin, a GSH-dependent member of the TRX superfamily. The flow of reducing equivalents goes from GSH -> C-terminal TRX domain -> N-terminal reductase domain -> APS. Plant-type APS reductase shows no homology to that of dissimilatory sulfate-reducing bacteria, which is an iron-sulfur flavoenzyme. Also included in the alignment is EYE2 from Chlamydomonas reinhardtii, a protein required for eyespot assembly.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1330198087  10 QNFETLLQSDLPVLVDFWAPWCGPCRTVSPIVDELAVELAGR-VLVAKCNVDENQDIAMR--YRVMSIPTLIVL 80
Cdd:cd02993    12 EALAKGERRNQSTLVVLYAPWCPFCQAMEASYEELAEKLAGSnVKVAKFNADGEQREFAKeeLQLKSFPTILFF 85

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
                  ....*....|....*....|....*....|..
gi 1330198087  21 PVLVDFWAPWCGPCRTVSPIVDELAVELAGRV 52
Cdd:cd03010    27 PYLLNVWASWCAPCREEHPVLMALARQGRVPI 58

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087  13 ETLLQSDLPVLVDFWAPWCGPCRTVSPIV---DELAVELAGRVLVAKCNVDEN--QDIAM--RYRVMSIPTLIVLKNGAE 85
Cdd:COG4232   314 AEARAEGKPVFVDFTADWCVTCKENERTVfsdPEVQAALADDVVLLKADVTDNdpEITALlkRFGRFGVPTYVFYDPDGE 393

                          90
                  ....*....|..
gi 1330198087  86 AGRTVGAMPKPQ 97
Cdd:COG4232   394 ELPRLGFMLTAD 405

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 1330198087  22 VLVDFWAPWCGPCRTVSPIVDELAVELaGRVLVAKCNVDEN---QDIAMRYRVMSIPTLIVLKNGAEAGRTVGAMPKpQL 98
Cdd:cd02985    18 VVLEFALKHSGPSVKIYPTMVKLSRTC-NDVVFLLVNGDENdstMELCRREKIIEVPHFLFYKDGEKIHEEEGIGPD-EL 95

                  ....*..
gi 1330198087  99 RAEIEKY 105
Cdd:cd02985    96 IGDVLYY 102

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
                  ....*....|....*....|....*....|....*....|...
gi 1330198087  63 QDIAMRYRVMSIPTLIVL--KNGAEAGRTVGAMPKPQLRAEIE 103
Cdd:cd02951    74 KELARKYRVRFTPTVIFLdpEGGKEIARLPGYLPPDEFLAYLE 116

thiol:disulfide interchange protein precursor; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1330198087  21 PVLVDFWAPWCGPCRTVSPIV--DELAVELAGRVLVAKCNVDEN--QDIAM--RYRVMSIPTLIVL-KNGAE--AGRTVG 91
Cdd:PRK00293  476 PVMLDLYADWCVACKEFEKYTfsDPQVQQALADTVLLQADVTANnaEDVALlkHYNVLGLPTILFFdAQGQEipDARVTG 555

                          90
                  ....*....|...
gi 1330198087  92 AMPKPQLRAEIEK 104
Cdd:PRK00293  556 FMDAAAFAAHLRQ 568

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 1330198087   4 IVNVNTQNFETLLQSDLP--VLVDFWAPW----CGPCRTVSPIVDELA-------VELAGRVLVAKCNVDENQDIAMRYR 70
Cdd:pfam04756  13 VIKLNDSNYKRLLSGPRDysVVVLLTALDprfgCQLCREFQPEFELVAkswfkdhKAGSSKLFFATLDFDDGKDVFQSLG 92

                  ....*....
gi 1330198087  71 VMSIPTLIV 79
Cdd:pfam04756  93 LQTAPHLLL 101