thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   1 MNTVCTHCQAINRIPDDRLQDAAKCGRCGHELFDGEVINATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE 80
Cdd:PRK10996   1 MNTVCTSCQAINRLPDERIEDAAKCGRCGHDLFDGEVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 447021478  81 RSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQVVDMLNGAVPKAPFDNWLNEAL 139
Cdd:PRK10996  81 RSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   1 MNTVCTHCQAINRIPDDRLQDAAKCGRCGHELFDGEVINATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE 80
Cdd:PRK10996   1 MNTVCTSCQAINRLPDERIEDAAKCGRCGHDLFDGEVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 447021478  81 RSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQVVDMLNGAVPKAPFDNWLNEAL 139
Cdd:PRK10996  81 RSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

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 447021478   40 ATSETLDKLLKD-DLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQV 118
Cdd:TIGR01068   1 LTDANFDETIASsDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 447021478  119 VDMLNGAVPKAPFDNWLNEAL 139
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 101

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   36 EVINATSETLDK-LLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFK 114
Cdd:pfam00085   1 VVVVLTDANFDEvVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFK 80

                          90       100
                  ....*....|....*....|...
gi 447021478  115 HGQVVDMLNGAVPKAPFDNWLNE 137
Cdd:pfam00085  81 NGQPVDDYVGARPKDALAAFLKA 103

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   1 MNTVCTHCQAINRIPDDRLQDAAKCGRCGHELFDGEVINATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE 80
Cdd:PRK10996   1 MNTVCTSCQAINRLPDERIEDAAKCGRCGHDLFDGEVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 447021478  81 RSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQVVDMLNGAVPKAPFDNWLNEAL 139
Cdd:PRK10996  81 RSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

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 447021478   40 ATSETLDKLLKD-DLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQV 118
Cdd:TIGR01068   1 LTDANFDETIASsDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 447021478  119 VDMLNGAVPKAPFDNWLNEAL 139
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 101

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   36 EVINATSETLDK-LLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFK 114
Cdd:pfam00085   1 VVVVLTDANFDEvVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFK 80

                          90       100
                  ....*....|....*....|...
gi 447021478  115 HGQVVDMLNGAVPKAPFDNWLNE 137
Cdd:pfam00085  81 NGQPVDDYVGARPKDALAAFLKA 103

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 447021478  41 TSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE--RSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHG 116
Cdd:cd02961    4 TDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKElkGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  36 EVINATSETLDK-LLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFK 114
Cdd:PRK09381   4 KIIHLTDDSFDTdVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83

                         90       100
                 ....*....|....*....|....*
gi 447021478 115 HGQVVDMLNGAVPKAPFDNWLNEAL 139
Cdd:PRK09381  84 NGEVAATKVGALSKGQLKEFLDANL 108

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 447021478  36 EVINATSETLDKL-LKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFK 114
Cdd:cd03001    1 DVVELTDSNFDKKvLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                 ..
gi 447021478 115 HG 116
Cdd:cd03001   81 AG 82

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  31 ELFDGEVINATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAE---ERSGKVRFVKVDTEAERELSARFGIRSI 107
Cdd:PTZ00102  28 HFISEHVTVLTDSTFDKFITENEIVLVKFYAPWCGHCKRLAPEYKKAAKmlkEKKSEIVLASVDATEEMELAQEFGVRGY 107

                         90       100       110
                 ....*....|....*....|....*....|
gi 447021478 108 PTIMIFKHGQVVDmLNGAVPKAPFDNWLNE 137
Cdd:PTZ00102 108 PTIKFFNKGNPVN-YSGGRTADGIVSWIKK 136

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 447021478  36 EVINATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE--RSGKVRFVKVD-TEAERE-LSARFGIRSIPTIM 111
Cdd:cd02997    1 DVVHLTDEDFRKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATElkEDGKGVLAAVDcTKPEHDaLKEEYNVKGFPTFK 80

                         90       100
                 ....*....|....*....|....
gi 447021478 112 IFKHGQVVDMLNGAVPKAPFDNWL 135
Cdd:cd02997   81 YFENGKFVEKYEGERTAEDIIEFM 104

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 447021478  37 VINATSETLDKLLKDD-LPVVIDFWAPWCGPCRNFAPIFKDVAE--ERSGKVRFVKVD-TEAERELSARFGIRSIPTIMI 112
Cdd:cd02998    2 VVELTDSNFDKVVGDDkKDVLVEFYAPWCGHCKNLAPEYEKLAAvfANEDDVVIAKVDaDEANKDLAKKYGVSGFPTLKF 81

                 .
gi 447021478 113 F 113
Cdd:cd02998   82 F 82

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 447021478  52 DLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQVVDMLNGAVPKAPF 131
Cdd:cd02949   13 DRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKSEY 92

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 447021478  50 KDDLPVViDFWAPWCGPCRNFAPIFKDVAEE--RSGK-VRFVKVDTEAERELSARFGIRSIPTIMIFKHGQVVD 120
Cdd:cd03000   14 KEDIWLV-DFYAPWCGHCKKLEPVWNEVGAElkSSGSpVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAYN 86

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 447021478  37 VINATSETLDKLLKDDLP-VVIDFWAPWCGPCRNFAPIFKDVAEERSG--KVRFVKVDTEAErELSARFGIRSIPTIMIF 113
Cdd:cd02995    2 VKVVVGKNFDEVVLDSDKdVLVEFYAPWCGHCKALAPIYEELAEKLKGddNVVIAKMDATAN-DVPSEFVVDGFPTILFF 80

                 ...
gi 447021478 114 KHG 116
Cdd:cd02995   81 PAG 83

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 447021478  43 ETLDKLLKDDLPVVIDFWAPWCGPCR-NFAPIFKD--VAEERSGKVRFVKVD----TEAERELSARFGIRSIPTIMIFKH 115
Cdd:cd02953    2 AALAQALAQGKPVFVDFTADWCVTCKvNEKVVFSDpeVQAALKKDVVLLRADwtknDPEITALLKRFGVFGPPTYLFYGP 81

                 ..
gi 447021478 116 GQ 117
Cdd:cd02953   82 GG 83

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 447021478  43 ETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE--------RSGKV----RFVK-------VDTEAERELSARFG 103
Cdd:cd03011   11 EQFDLESLSGKPVLVYFWATWCPVCRFTSPTVNQLAADypvvsvalRSGDDgavaRFMQkkgygfpVINDPDGVISARWG 90

                         90       100
                 ....*....|....*....|.
gi 447021478 104 IRSIPTIMIFKHGQVVDMLNG 124
Cdd:cd03011   91 VSVTPAIVIVDPGGIVFVTTG 111

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 447021478  35 GEVINATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE------RSGKVRFVKVDTEAERELSARFGIRSIP 108
Cdd:cd02996    1 SEIVSLTSGNIDDILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKikeefpDAGKVVWGKVDCDKESDIADRYRINKYP 80

                         90
                 ....*....|.
gi 447021478 109 TIMIFKHGQVV 119
Cdd:cd02996   81 TLKLFRNGMMM 91

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  34 DGEVINATSETLDKL-LKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEE--RSGKVRFVKVDTEAERELSARFGIRSIPTI 110
Cdd:PTZ00102 356 DGPVKVVVGNTFEEIvFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKykDNDSIIVAKMNGTANETPLEEFSWSAFPTI 435

                         90
                 ....*....|.
gi 447021478 111 MIFKHGQVVDM 121
Cdd:PTZ00102 436 LFVKAGERTPI 446

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 447021478  56 VIDFWAPWCGPCRNFAPIFKDVAEERSGkVRFVKVDT---EAERELSARFGIRSIPTIMIFKHGQVVDM 121
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKG-VKFEAVDVdedPALEKELKRYGVGGVPTLVVFGPGIGVKY 68

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   54 PVVIDFWAPWCGPCR------------------NFAPIFKDVAEERSGKVRFVKVDTEaeRELSARFGIRSIPTIMIFKH 115
Cdd:pfam13098   6 PVLVVFTDPDCPYCKklkkelledpdvtvylgpNFVFIAVNIWCAKEVAKAFTDILEN--KELGRKYGVRGTPTIVFFDG 83

                          90       100
                  ....*....|....*....|
gi 447021478  116 GQVVDMLNGAVPKAPFDNWL 135
Cdd:pfam13098  84 KGELLRLPGYVPAEEFLALL 103

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 447021478  56 VIDFWAPWCGPCRNFAPIFKDVAE---ERSGKVRFVKVDTEAE--RELSARFGIRSIPTIMIFK 114
Cdd:cd02992   23 LVEFYASWCGHCRAFAPTWKKLARdlrKWRPVVRVAAVDCADEenVALCRDFGVTGYPTLRYFP 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 447021478  54 PVVIDFWAPWCGPCRNFAPIFKDVAEERSG-KVRFVKVDTEAERELSARFGIRSIPTIMIFKHGQVVDMLNGAVPK 128
Cdd:cd02963   26 PYLIKITSDWCFSCIHIEPVWKEVIQELEPlGVGIATVNAGHERRLARKLGAHSVPAIVGIINGQVTFYHDSSFTK 101

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  55 VVIDFWAPWCGPCRNFAPIFKDVAEE--RSGK---VRFVKVDTEAE-----------------------RELSARFGIRS 106
Cdd:cd02964   20 VGLYFSASWCPPCRAFTPKLVEFYEKlkEEGKnfeIVFVSRDRSEEsfneyfsemppwlavpfedeelrELLEKQFKVEG 99

                         90
                 ....*....|....
gi 447021478 107 IPTIMIFK-HGQVV 119
Cdd:cd02964  100 IPTLVVLKpDGDVV 113

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 447021478  40 ATSETLDKLLKDDLPVVIDFWAPWCGPCRNFAPIFKDVAEERSGK-VRFVKVdtEAERELSA-RFGIRSIPTIMIFKHGQ 117
Cdd:cd02948    5 NNQEEWEELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDDlLHFATA--EADTIDTLkRYRGKCEPTFLFYKNGE 82

                         90
                 ....*....|...
gi 447021478 118 VVDMLNGAvpKAP 130
Cdd:cd02948   83 LVAVIRGA--NAP 93

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  57 IDFWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVDTEAERELSARFGIRSIPTIMIFKHG 116
Cdd:cd03003   23 VNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSG 82

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 447021478   37 VINATSETLDKLLKDDLP--VVIDFWAPW----CGPCRNFAPIFKDVA-------EERSGKVRFVKVDTEAERELSARFG 103
Cdd:pfam04756  13 VIKLNDSNYKRLLSGPRDysVVVLLTALDprfgCQLCREFQPEFELVAkswfkdhKAGSSKLFFATLDFDDGKDVFQSLG 92

                          90
                  ....*....|
gi 447021478  104 IRSIPTIMIF 113
Cdd:pfam04756  93 LQTAPHLLLF 102

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  59 FWAPWCGPCRNFAPIFKDVAEE--RSGK---VRFVKVDTEAE----------------------RELSARFGIRSIPT-I 110
Cdd:cd03009   25 FSASWCPPCRAFTPKLVEFYEKlkESGKnfeIVFISWDRDEEsfndyfskmpwlavpfsdrerrSRLNRTFKIEGIPTlI 104

                 ....*....
gi 447021478 111 MIFKHGQVV 119
Cdd:cd03009  105 ILDADGEVV 113

thioredoxin-like protein

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  59 FWAPWCGPCRNFAPIFKDVaeersgKVRFVKVDTEAERELSARFGIRSIPTIMifkHGQVVDMLNGaVPK 128
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANV------EYTYVDVDTDEGVELTAKHHIRSLPTLV---NTSTLDRFTG-VPR 64

Thioredoxin;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478   38 INATSETLDKLLKDDLPV-VIDFWAPWCGPCRNFAPIFKDVAEERSG-KVRFvkVDTEAERELSARF---GIRSIPTIMI 112
Cdd:pfam14595  26 FELSEELIEKIKSIEKPLrILVITEDWCGDAAQNVPVLAKIAELNPNiELRI--LLRDENLELMDQYltgGGRAIPTFIF 103

                  .
gi 447021478  113 F 113
Cdd:pfam14595 104 L 104

Intermembrane transporter PqiABC subunit PqiA [Cell wall/membrane/envelope biogenesis];

                         10        20        30
                 ....*....|....*....|....*....|.
gi 447021478   3 TVCTHCQAINRIPDDRLQDAAKCGRCGHELF 33
Cdd:COG2995   14 IACPHCDLLLRRPPLPPGERARCPRCGAVLH 44

thiol:disulfide interchange protein precursor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 447021478  54 PVVIDFWAPWCGPCRNFAPI-FKDVA-EERSGKVRFVKVD----TEAERELSARFGIRSIPTIMIF-KHGQVVDML--NG 124
Cdd:PRK00293 476 PVMLDLYADWCVACKEFEKYtFSDPQvQQALADTVLLQADvtanNAEDVALLKHYNVLGLPTILFFdAQGQEIPDArvTG 555

                         90
                 ....*....|....*
gi 447021478 125 AVPKAPFDNWLNEAL 139
Cdd:PRK00293 556 FMDAAAFAAHLRQLQ 570

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 447021478  33 FDGEVINATSETLD-KLLKDDlPVVIDFWAPWCGPCRNFAPIFKDVAEErsGKVRFVKVDTEAERELSARF 102
Cdd:cd03010    6 FSLPALPGPDKTLTsADLKGK-PYLLNVWASWCAPCREEHPVLMALARQ--GRVPIYGINYKDNPENALAW 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 447021478   59 FWAPWCGPCRNFAPIFKDVAEERSGKVRFVKVD---------TEAERELSARFGIRSIPTIMIF 113
Cdd:pfam13728 136 FYRGDCPYCEAQAPILQAFADKYGWTVRPVSVDgrplpgfpnYRVDNGQAARLGVKRTPALFLV 199