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 26341328    30 NVRVLTDENWTSLL--EGEWM-IEFYAPWCPACQNLQPEWESFAEwgE-DLEVKVAKVDVTEQTGLSGRFIITALPSIYH 105
Cdd:pfam00085   1 VVVVLTDANFDEVVqkSSKPVlVDFYAPWCGPCKMLAPEYEELAQ--EyKGNVVFAKVDVDENPDLASKYGVRGYPTLIF 78

                          90       100
                  ....*....|....*....|....*
gi 26341328   106 CKDG-EFRRYVGPRTKKDFINFVSD 129
Cdd:pfam00085  79 FKNGqPVDDYVGARPKDALAAFLKA 103

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 26341328  30 NVRVLTDENW-TSLLEGE--WMIEFYAPWCPACQNLQPEWESFA-EWGEDleVKVAKVDVTEQTGLSGRFIITALPSIYH 105
Cdd:COG3118   1 AVVELTDENFeEEVLESDkpVLVDFWAPWCGPCKMLAPVLEELAaEYGGK--VKFVKVDVDENPELAAQFGVRSIPTLLL 78

                        90       100
                ....*....|....*....|...
gi 26341328 106 CKDGEFR-RYVGPRTKKDFINFV 127
Cdd:COG3118  79 FKDGQPVdRFVGALPKEQLREFL 101

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 26341328  33 VLTDENWTSLLEGE--WMIEFYAPWCPACQNLQPEWESFAEW-GEDLEVKVAKVDVTEQTGLSGRFIITALPSIYHCKDG 109
Cdd:cd02961   2 ELTDDNFDELVKDSkdVLVEFYAPWCGHCKALAPEYEKLAKElKGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

                        90       100
                ....*....|....*....|
gi 26341328 110 --EFRRYVGPRTKKDFINFV 127
Cdd:cd02961  82 skEPVKYEGPRTLESLVEFI 101

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 26341328    30 NVRVLTDENWTSLLEGE--WMIEFYAPWCPACQNLQPEWESFAEW--GEDLEVKVAKVDVTEQTGLSGRFIITALPSIYH 105
Cdd:TIGR01130   2 DVLVLTKDNFDDFIKSHefVLVEFYAPWCGHCKSLAPEYEKAADElkKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKI 81

                          90       100
                  ....*....|....*....|....*..
gi 26341328   106 CKDGEFRR--YVGPRTKKDFINFVSDK 130
Cdd:TIGR01130  82 FRNGEDSVsdYNGPRDADGIVKYMKKQ 108

PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in vivo. It has been detected in many tissues, however, transcript and protein levels do not correlate in all tissues, suggesting regulation at a posttranscriptional level. An identical protein, named endoPDI, has been identified as an endothelial PDI that is highly expressed in the endothelium of tumors and hypoxic lesions. It has a protective effect on cells exposed to hypoxia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26341328  30 NVRVLTDENW-TSLLEGEWMIEFYAPWCPACQNLQPEWESFA--EWGEDLEVKVAKVDVTEQTGLSGRFIITALPSIYHC 106
Cdd:cd03005   1 GVLELTEDNFdHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAkkFNNENPSVKIAKVDCTQHRELCSEFQVRGYPTLLLF 80

                        90       100
                ....*....|....*....|..
gi 26341328 107 KDGE-FRRYVGPRTKKDFINFV 127
Cdd:cd03005  81 KDGEkVDKYKGTRDLDSLKEFV 102

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 26341328  30 NVRVLTDENW-TSLLEGE--WMIEFYAPWCPACQNLQPEWESFA-EWGEDleVKVAKVDVTEQTGLSGRFIITALPSIYH 105
Cdd:COG3118   1 AVVELTDENFeEEVLESDkpVLVDFWAPWCGPCKMLAPVLEELAaEYGGK--VKFVKVDVDENPELAAQFGVRSIPTLLL 78

                        90       100
                ....*....|....*....|...
gi 26341328 106 CKDGEFR-RYVGPRTKKDFINFV 127
Cdd:COG3118  79 FKDGQPVdRFVGALPKEQLREFL 101

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26341328  48 MIEFYAPWCPACQNLQPEWESFAEwgEDLEVKVAKVDVTEQTGLSGRFIITALPSIYHCKDG-EFRRYVGPRTKKDFINF 126
Cdd:cd02947  14 VVDFWAPWCGPCKAIAPVLEELAE--EYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGkEVDRVVGADPKEELEEF 91

                .
gi 26341328 127 V 127
Cdd:cd02947  92 L 92

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26341328   24 AHGRRNNVRVLTDENWTSLL-EGEW-MIEFYAPWCPACQNLQPEWESFAEWGEDL--EVKVAKVDVTEQTGLSGRFIITA 99
Cdd:PTZ00102  27 EHFISEHVTVLTDSTFDKFItENEIvLVKFYAPWCGHCKRLAPEYKKAAKMLKEKksEIVLASVDATEEMELAQEFGVRG 106

                         90       100       110
                 ....*....|....*....|....*....|
gi 26341328  100 LPSIYHCKDGEFRRYVGPRTKKDFINFVSD 129
Cdd:PTZ00102 107 YPTIKFFNKGNPVNYSGGRTADGIVSWIKK 136

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 26341328  30 NVRVLTDENWTSLLEGE---WMIEFYAPWCPACQNLQPEWESFAE-WGEDLEVKVAKVDVTE-QTGLSGRFIITALPSI- 103
Cdd:cd02998   1 NVVELTDSNFDKVVGDDkkdVLVEFYAPWCGHCKNLAPEYEKLAAvFANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLk 80

                        90       100
                ....*....|....*....|....*
gi 26341328 104 -YHCKDGEFRRYVGPRTKKDFINFV 127
Cdd:cd02998  81 fFPKGSTEPVKYEGGRDLEDLVKFV 105

PDIa family, C-terminal ERdj5 subfamily; ERdj5, also known as JPDI and macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox active TRX domains. This subfamily is composed of the three TRX domains located at the C-terminal half of the protein. ERdj5 is a ubiquitous protein localized in the endoplasmic reticulum (ER) and is abundant in secretory cells. It's transcription is induced during ER stress. It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation. Also included in the alignment is the single complete TRX domain of an uncharacterized protein from Tetraodon nigroviridis, which also contains a DnaJ domain at its N-terminus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26341328  31 VRVLTDENWTSL-LEGE--WMIEFYAPWCPACQNLQPEWESFAEWGEDLeVKVAKVDVTEQTGLSGRFIITALPSI--YH 105
Cdd:cd03004   3 VITLTPEDFPELvLNRKepWLVDFYAPWCGPCQALLPELRKAARALKGK-VKVGSVDCQKYESLCQQANIRAYPTIrlYP 81

                        90
                ....*....|.
gi 26341328 106 CKDGEFRRYVG 116
Cdd:cd03004  82 GNASKYHSYNG 92

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 26341328  32 RVLTDENWTSllegewMIEFYAPWCPACQNLQPEWESFAEwGEDLEVKVAKVDVTEQTG--LSGRFIITALPSI------ 103
Cdd:cd03002  12 KVVHNTNYTT------LVEFYAPWCGHCKNLKPEYAKAAK-ELDGLVQVAAVDCDEDKNkpLCGKYGVQGFPTLkvfrpp 84

                        90       100
                ....*....|....*....|....*.
gi 26341328 104 -YHCKDGEfRRYVGPRTKKDFINFVS 128
Cdd:cd03002  85 kKASKHAV-EDYNGERSAKAIVDFVL 109

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 26341328   35 TDENWTSLLEGEW--MIEFYAPWCPACQNLQPEWESFAEWGEDlEVKVAKVDVTEQTGLSGRFIITALPSIYHCKDGE 110
Cdd:PRK10996  41 TGETLDKLLQDDLpvVIDFWAPWCGPCRNFAPIFEDVAAERSG-KVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQ 117

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 26341328  48 MIEFYAPWCPACQNLQPEWESFAEwgEDLEVKVAKVDVTEQTGL---SGRFIITALPSIYHCKDGEFRRYV 115
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAELAL--LNKGVKFEAVDVDEDPALekeLKRYGVGGVPTLVVFGPGIGVKYG 69

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 26341328  30 NVRVLTDENWTSLLEGE-----WMIEFYAPWCPACQNLQPEWESFAEWGEDLEVKVAKV 83
Cdd:cd02993   2 AVVTLSRAEIEALAKGErrnqsTLVVLYAPWCPFCQAMEASYEELAEKLAGSNVKVAKF 60

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 26341328  51 FYAPWCPACQNLQPEWESFA-----EWGEDLEVKVAKVDVTEQTGLSGRFIITALPSIYHCKDGEF--RRYVGPRTKKDF 123
Cdd:cd02996  25 FYADWCRFSQMLHPIFEEAAakikeEFPDAGKVVWGKVDCDKESDIADRYRINKYPTLKLFRNGMMmkREYRGQRSVEAL 104

                ....
gi 26341328 124 INFV 127
Cdd:cd02996 105 AEFV 108

5'-adenylylsulfate reductase, thioredoxin-independent; This enzyme, involved in the assimilation of inorganic sulfate, is closely related to the thioredoxin-dependent PAPS reductase of Bacteria (CysH) and Saccharomyces cerevisiae. However, it has its own C-terminal thioredoxin-like domain and is not thioredoxin-dependent. Also, it has a substrate preference for 5'-adenylylsulfate (APS) over 3'-phosphoadenylylsulfate (PAPS) so the pathway does not require an APS kinase (CysC) to convert APS to PAPS. Arabidopsis thaliana appears to have three isozymes, all able to complement E. coli CysH mutants (even in backgrounds lacking thioredoxin or APS kinase) but likely localized to different compartments in Arabidopsis. [Central intermediary metabolism, Sulfur metabolism]

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 26341328    29 NNVRVLTDENWTSLLEGE-----WMIEFYAPWCPACQNLQPEWESFAEWGEDLEVKVAK 82
Cdd:TIGR00424 351 NNVVSLSRPGIENLLKLEerkeaWLVVLYAPWCPFCQAMEASYLELAEKLAGSGVKVAK 409

5'-adenylylsulfate reductase

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 26341328   29 NNVRVLTDENWTSLLEGE-----WMIEFYAPWCPACQNLQPEWESFAEWGEDLEVKVAK 82
Cdd:PLN02309 345 QNVVALSRAGIENLLKLEnrkepWLVVLYAPWCPFCQAMEASYEELAEKLAGSGVKVAK 403

ybbN protein family; ybbN is a hypothetical protein containing a redox-inactive TRX-like domain. Its gene has been sequenced from several gammaproteobacteria and actinobacteria.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 26341328  49 IEFYAPWCPACQNLQPEWESFAEwGEDLEVKVAKVDVTEQTGLSGRFIITALPSIYHCKDG 109
Cdd:cd02956  17 VDFWAPRSPPSKELLPLLERLAE-EYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAG 76

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
                ....*....|....*....|....*....|....*...
gi 26341328  48 MIEFYAPWCPACQNLQPEWESFAE-WGEDLEVKVAKVD 84
Cdd:cd02950  24 LVEFYADWCTVCQEMAPDVAKLKQkYGDQVNFVMLNVD 61

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26341328  29 NNVRVLTDENWTSLLEGE----WMIEFYAPWCPACQNLQPeweSFAEWGEDLE---VKVAKVDVTEQTGLSGRFIITA-- 99
Cdd:cd02962  28 EHIKYFTPKTLEEELERDkrvtWLVEFFTTWSPECVNFAP---VFAELSLKYNnnnLKFGKIDIGRFPNVAEKFRVSTsp 104

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 26341328 100 ----LPSIYHCKDGE--FRR--YVGPRTKKDFINFVSD 129
Cdd:cd02962 105 lskqLPTIILFQGGKevARRpyYNDSKGRAVPFTFSKE 142