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 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:COG3118    3 VELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDG 82

                         90       100
                 ....*....|....*....|...
gi 319406426  84 KVSSNKVGATSKGHLVEWIKNSL 106
Cdd:COG3118   83 QPVDRFVGALPKEQLREFLDKVL 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 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:COG3118    3 VELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDG 82

                         90       100
                 ....*....|....*....|...
gi 319406426  84 KVSSNKVGATSKGHLVEWIKNSL 106
Cdd:COG3118   83 QPVDRFVGALPKEQLREFLDKVL 105

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 319406426    4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:pfam00085   3 VVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                          90       100
                  ....*....|....*....|
gi 319406426   84 KVSSNKVGATSKGHLVEWIK 103
Cdd:pfam00085  83 QPVDDYVGARPKDALAAFLK 102

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:PRK09381   6 IHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNG 85

                         90       100
                 ....*....|....*....|....
gi 319406426  84 KVSSNKVGATSKGHLVEWIKNSLG 107
Cdd:PRK09381  86 EVAATKVGALSKGQLKEFLDANLA 109

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 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:COG3118    3 VELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDG 82

                         90       100
                 ....*....|....*....|...
gi 319406426  84 KVSSNKVGATSKGHLVEWIKNSL 106
Cdd:COG3118   83 QPVDRFVGALPKEQLREFLDKVL 105

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 319406426    4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:pfam00085   3 VVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                          90       100
                  ....*....|....*....|
gi 319406426   84 KVSSNKVGATSKGHLVEWIK 103
Cdd:pfam00085  83 QPVDDYVGARPKDALAAFLK 102

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:PRK09381   6 IHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNG 85

                         90       100
                 ....*....|....*....|....
gi 319406426  84 KVSSNKVGATSKGHLVEWIKNSLG 107
Cdd:PRK09381  86 EVAATKVGALSKGQLKEFLDANLA 109

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 319406426   4 IKIDSSNFENEVLTSPlPVVVDFWAEWCGPCKSIAPILDEIATEMQ--SQIKVAKINIDENPDLATQYGIRSIPTLLMFT 81
Cdd:cd02961    1 VELTDDNFDELVKDSK-DVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                         90       100
                 ....*....|....*....|..
gi 319406426  82 NGKVSSNK-VGATSKGHLVEWI 102
Cdd:cd02961   80 NGSKEPVKyEGPRTLESLVEFI 101

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 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:cd03001    3 VELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGAG 82

                 ...
gi 319406426  84 KVS 86
Cdd:cd03001   83 KNS 85

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426  21 PVVVDFWAEWCGPCKSIAPILDEIATEMQsQIKVAKINIDENPD----------------------LATQYGIRSIPTLL 78
Cdd:COG0526   30 PVLVNFWATWCPPCRAEMPVLKELAEEYG-GVVFVGVDVDENPEavkaflkelglpypvlldpdgeLAKAYGVRGIPTTV 108

                         90       100       110
                 ....*....|....*....|....*....|
gi 319406426  79 MFT-NGKVSSNKVGATSKGHLVEWIKNSLG 107
Cdd:COG0526  109 LIDkDGKIVARHVGPLSPEELEEALEKLLA 138

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426    5 KIDSSNFENEVLTSPLpVVVDFWAEWCGPCKSIAPILDEIATEMQSQ---IKVAKINIDENPDLATQYGIRSIPTLLMFT 81
Cdd:TIGR01130   5 VLTKDNFDDFIKSHEF-VLVEFYAPWCGHCKSLAPEYEKAADELKKKgppIKLAKVDATEEKDLAQKYGVSGYPTLKIFR 83

                          90       100
                  ....*....|....*....|....*..
gi 319406426   82 NGKVS-SNKVGATSKGHLVEWIKNSLG 107
Cdd:TIGR01130  84 NGEDSvSDYNGPRDADGIVKYMKKQSG 110

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 319406426   7 DSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKV--AKINIDE-NPDLATQYGIRSIPTLLMFTNG 83
Cdd:cd02998    6 TDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVviAKVDADEaNKDLAKKYGVSGFPTLKFFPKG 85

                         90       100
                 ....*....|....*....|..
gi 319406426  84 kvSSNKV---GATSKGHLVEWI 102
Cdd:cd02998   86 --STEPVkyeGGRDLEDLVKFV 105

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 319406426  10 NFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQ--IKVAKINIDENpDLATQYGIRSIPTLLMFTNGKVS 86
Cdd:cd02995    9 NFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDdnVVIAKMDATAN-DVPSEFVVDGFPTILFFPAGDKS 86

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426   4 IKIDSSNFENEVLTSPL----PVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLM 79
Cdd:PTZ00443  33 VLLNDKNFEKLTQASTGattgPWFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPTLLL 112

                         90       100       110
                 ....*....|....*....|....*....|..
gi 319406426  80 FTNGKVSSNKVGATSKGHLVEW----IKNSLG 107
Cdd:PTZ00443 113 FDKGKMYQYEGGDRSTEKLAAFalgdFKKALG 144

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 319406426   6 IDSSNFEnEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKV--AKINI--DENPDLATQYGIRSIPTLLMFT 81
Cdd:cd02997    5 LTDEDFR-KFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGvlAAVDCtkPEHDALKEEYNVKGFPTFKYFE 83

                         90       100
                 ....*....|....*....|.
gi 319406426  82 NGKVSSNKVGATSKGHLVEWI 102
Cdd:cd02997   84 NGKFVEKYEGERTAEDIIEFM 104

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319406426  18 SPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTN 82
Cdd:cd02949   12 SDRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKD 76

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426  21 PVVVDFWAEWCGPCKSIAPILDEIATEMQSQ-IKVAKINIDENP-----------------------DLATQYGIRSIPT 76
Cdd:cd02966   21 VVLVNFWASWCPPCRAEMPELEALAKEYKDDgVEVVGVNVDDDDpaavkaflkkygitfpvlldpdgELAKAYGVRGLPT 100

                         90
                 ....*....|
gi 319406426  77 LLMF-TNGKV 85
Cdd:cd02966  101 TFLIdRDGRI 110

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 319406426    9 SNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQ---IKVAKINIDENpDLAtQYGIRSIPTLLMFTNGK 84
Cdd:TIGR01130 354 KNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAesdVVIAKMDATAN-DVP-PFEVEGFPTIKFVPAGK 430

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 319406426   4 IKIDSSNFENEVLTSPLpVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:cd03003    4 VTLDRGDFDAAVNSGEI-WFVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSG 82

                         90
                 ....*....|....*...
gi 319406426  84 KVSSNKVGATSKGHLVEW 101
Cdd:cd03003   83 MNPEKYYGDRSKESLVKF 100

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319406426  10 NFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQS--QIKVAKINIDENPDLATQYGIRSIPTLLMFTNG 83
Cdd:PTZ00102 366 TFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKDndSIIVAKMNGTANETPLEEFSWSAFPTILFVKAG 441

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 319406426   4 IKIDSSNFeNEVLTSPLpvVVDFWAEWCGPCKSIAPILDEIATEMQS-QIKVAKINIDENPDLATQYGIRSIPTLLMFTN 82
Cdd:cd02994    4 VELTDSNW-TLVLEGEW--MIEFYAPWCPACQQLQPEWEEFADWSDDlGINVAKVDVTQEPGLSGRFFVTALPTIYHAKD 80

                 .
gi 319406426  83 G 83
Cdd:cd02994   81 G 81

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426   4 IKIDSSNFENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIAT---EMQSQIKVAKIN--IDENPDLATQYGIRSIPTLL 78
Cdd:cd02992    4 IVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARdlrKWRPVVRVAAVDcaDEENVALCRDFGVTGYPTLR 83

                 ..
gi 319406426  79 MF 80
Cdd:cd02992   84 YF 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 319406426  14 EVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDeNP---DLATQYGIRSIPTLLMFTN 82
Cdd:cd02950   15 VALSNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVD-NPkwlPEIDRYRVDGIPHFVFLDR 85

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426   11 FENEVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEM------------QSQIKVAK--------INIDENPDLATQYG 70
Cdd:TIGR00385  55 YTADVLTQGKPVLLNVWASWCPPCRAEHPYLNELAKQGlpivgvdykddrQNAIKFLKelgnpyqlSLFDPDGMLGLDLG 134

                          90       100
                  ....*....|....*....|..
gi 319406426   71 IRSIP-TLLMFTNGKVSSNKVG 91
Cdd:TIGR00385 135 VYGAPeTFLVDGNGVIRYRHAG 156

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426  21 PVVVDFWAEWCGPCKsiapILD-------EIATEMQSQIKVAKINIDENP-------------DLATQYGIRSIPTLLMF 80
Cdd:COG2143   42 PILLFFESDWCPYCK----KLHkevfsdpEVAAYLKENFVVVQLDAEGDKevtdfdgetltekELARKYGVRGTPTLVFF 117

                         90       100
                 ....*....|....*....|....
gi 319406426  81 T-NGKVSSNKVGATSKGHLVEWIK 103
Cdd:COG2143  118 DaEGKEIARIPGYLKPETFLALLK 141

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 319406426  22 VVVDFWAEWCGPCKSIAPILDEIATeMQSQIKVakINIDEN---PDLATQYGIRSIPTLLMF 80
Cdd:cd02999   21 TAVLFYASWCPFSASFRPHFNALSS-MFPQIRH--LAIEESsikPSLLSRYGVVGFPTILLF 79

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426  21 PVVVdFWAEWCGPCKSIAPILDEIatemqsQIKVAKINIDENPD----LATQYGIRSIPTLlmFTNGKVssnkVGATSKG 96
Cdd:COG0695    1 KVTL-YTTPGCPYCARAKRLLDEK------GIPYEEIDVDEDPEareeLRERSGRRTVPVI--FIGGEH----LGGFDEG 67

                 ....*..
gi 319406426  97 HLVEWIK 103
Cdd:COG0695   68 ELDALLA 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 319406426  14 EVLTSPLPVVVDFWAEWCGPCKSIAPILDEIATEMQSQI-KVAKINIDeNPDLATQYGIRSIPTLLMFTNGK 84
Cdd:cd02948   12 ELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDDLlHFATAEAD-TIDTLKRYRGKCEPTFLFYKNGE 82

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 319406426  26 FWAEWCGPCKSIAPILDEIatemqsQIKVAKINIDENPDLATQYGIRSIPTLL 78
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANV------EYTYVDVDTDEGVELTAKHHIRSLPTLV 51

Thioredoxin;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 319406426   28 AEWCGPCKSIAPILDEIAtEMQSQIKVAKINIDENPDLATQY---GIRSIPTLLMF 80
Cdd:pfam14595  50 EDWCGDAAQNVPVLAKIA-ELNPNIELRILLRDENLELMDQYltgGGRAIPTFIFL 104

thiol-disulfide oxidoreductase ResA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319406426  22 VVVDFWAEWCGPCKSIAPILDEIATEMQSQ-IKVAKINIDEnPDLATQ-----------------------YGIRSIP-T 76
Cdd:PRK03147  64 VFLNFWGTWCKPCEKEMPYMNELYPKYKEKgVEIIAVNVDE-TELAVKnfvnrygltfpvaidkgrqvidaYGVGPLPtT 142

                 ....*....
gi 319406426  77 LLMFTNGKV 85
Cdd:PRK03147 143 FLIDKDGKV 151

Thioredoxin (TRX)-Glutaredoxin (GRX)-like family; composed of archaeal and bacterial proteins that show similarity to both TRX and GRX, including the C-terminal TRX-fold subdomain of Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO). All members contain a redox-active CXXC motif and may function as PDOs. The archaeal proteins Mj0307 and Mt807 show structures more similar to GRX, but activities more similar to TRX. Some members of the family are similar to PfPDO in that they contain a second CXXC motif located in a second TRX-fold subdomain at the N-terminus; the superimposable N- and C-terminal TRX subdomains form a compact structure. PfPDO is postulated to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI). The C-terminal CXXC motif of PfPDO is required for its oxidase, reductase and isomerase activities. Also included in the family is the C-terminal TRX-fold subdomain of the N-terminal domain (NTD) of bacterial AhpF, which has a similar fold as PfPDO with two TRX-fold subdomains but without the second CXXC motif.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 319406426  31 CGPCKSIAPILDEIAtEMQSQIKVAKINIDENPDLATQYGIRSIPTllMFTNGKV 85
Cdd:cd02973   11 CPYCPDAVQAANRIA-ALNPNISAEMIDAAEFPDLADEYGVMSVPA--IVINGKV 62

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319406426  21 PVVVDFWAEWCGPCKSIAPILDEIATEM-QSQIKVAKINID-ENPDLATQ-YGIRSIPTLLMF 80
Cdd:cd02993   23 STLVVLYAPWCPFCQAMEASYEELAEKLaGSNVKVAKFNADgEQREFAKEeLQLKSFPTILFF 85

Dim1 family; Dim1 is also referred to as U5 small nuclear ribonucleoprotein particle (snRNP)-specific 15kD protein. It is a component of U5 snRNP, which pre-assembles with U4/U6 snRNPs to form a [U4/U6:U5] tri-snRNP complex required for pre-mRNA splicing. Dim1 interacts with multiple splicing-associated proteins, suggesting that it functions at multiple control points in the splicing of pre-mRNA as part of a large spliceosomal complex involving many protein-protein interactions. U5 snRNP contains seven core proteins (common to all snRNPs) and nine U5-specific proteins, one of which is Dim1. Dim1 adopts a thioredoxin fold but does not contain the redox active CXXC motif. It is essential for G2/M phase transition, as a consequence to its role in pre-mRNA splicing.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319406426  22 VVVDFWAEWCGPCKSIAPILDEIATEMQSQIKVAKINIDENPDLATQYGIRSIPTLLMFTNGK 84
Cdd:cd02954   17 VVIRFGRDWDPVCMQMDEVLAKIAEDVSNFAVIYLVDIDEVPDFNKMYELYDPPTVMFFFRNK 79