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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVK-VHSFPTLKFF 86
Cdd:cd02995   1 PVKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSEFvVDGFPTILFF 80

                        90       100
                ....*....|....*....|....
1X5C_A       87 PASADRTVIDYNGERTLDGFKKFL 110
Cdd:cd02995  81 PAGDKSNPIKYEGDRTLEDLIKFI 104

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVK-VHSFPTLKFF 86
Cdd:cd02995   1 PVKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSEFvVDGFPTILFF 80

                        90       100
                ....*....|....*....|....
1X5C_A       87 PASADRTVIDYNGERTLDGFKKFL 110
Cdd:cd02995  81 PAGDKSNPIKYEGDRTLEDLIKFI 104

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A         6 SGPVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANE--VEAVKVHSFPTL 83
Cdd:PTZ00102 356 DGPVKVVVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKDNDSIIVAKMNGTANEtpLEEFSWSAFPTI 435

                         90       100
                 ....*....|....*....|....*...
1X5C_A        84 KFFPAsADRTVIDYNGERTLDGFKKFLE 111
Cdd:PTZ00102 436 LFVKA-GERTPIPYEGERTVEGFKEFVN 462

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        9 VKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDheNIVIAKMDSTANE--VEAVKVHSFPTLKFF 86
Cdd:COG3118   2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGG--KVKFVKVDVDENPelAAQFGVRSIPTLLLF 79

                        90       100
                ....*....|....*....|....*
1X5C_A       87 paSADRTVIDYNGERTLDGFKKFLE 111
Cdd:COG3118  80 --KDGQPVDRFVGALPKEQLREFLD 102

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVK-VHSFPTLKFF 86
Cdd:cd02995   1 PVKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSEFvVDGFPTILFF 80

                        90       100
                ....*....|....*....|....
1X5C_A       87 PASADRTVIDYNGERTLDGFKKFL 110
Cdd:cd02995  81 PAGDKSNPIKYEGDRTLEDLIKFI 104

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       10 KVLVGKNFEDVAFDEKkNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVK--VHSFPTLKFFP 87
Cdd:cd02961   1 VELTDDNFDELVKDSK-DVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVVVAKVDCTANNDLCSEygVRGYPTIKLFP 79

                        90       100
                ....*....|....*....|...
1X5C_A       88 ASaDRTVIDYNGERTLDGFKKFL 110
Cdd:cd02961  80 NG-SKEPVKYEGPRTLESLVEFI 101

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A         6 SGPVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANE--VEAVKVHSFPTL 83
Cdd:PTZ00102 356 DGPVKVVVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKDNDSIIVAKMNGTANEtpLEEFSWSAFPTI 435

                         90       100
                 ....*....|....*....|....*...
1X5C_A        84 KFFPAsADRTVIDYNGERTLDGFKKFLE 111
Cdd:PTZ00102 436 LFVKA-GERTPIPYEGERTVEGFKEFVN 462

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A          8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDheNIVIAKMDSTANEVEAVK--VHSFPTLKF 85
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKG--NVVFAKVDVDENPDLASKygVRGYPTLIF 78

                          90       100
                  ....*....|....*....|....*.
1X5C_A         86 FPASadRTVIDYNGERTLDGFKKFLE 111
Cdd:pfam00085  79 FKNG--QPVDDYVGARPKDALAAFLK 102

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDhenIV-IAKMDSTANEVEAVK--VHSFPTLK 84
Cdd:cd03001   1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKG---IVkVGAVDADVHQSLAQQygVRGFPTIK 77

                        90
                ....*....|....*...
1X5C_A       85 FFPASADRTViDYNGERT 102
Cdd:cd03001  78 VFGAGKNSPQ-DYQGGRT 94

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       12 LVGKNFEDvAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVK----VHSFPTLKFFp 87
Cdd:cd02997   5 LTDEDFRK-FLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGVLAAVDCTKPEHDALKeeynVKGFPTFKYF- 82

                        90       100
                ....*....|....*....|...
1X5C_A       88 aSADRTVIDYNGERTLDGFKKFL 110
Cdd:cd02997  83 -ENGKFVEKYEGERTAEDIIEFM 104

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYkdHENIVIAKMDSTANEVEAV----KVHSFPTL 83
Cdd:cd03002   1 PVYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKEL--DGLVQVAAVDCDEDKNKPLcgkyGVQGFPTL 78

                        90       100
                ....*....|....*....|...
1X5C_A       84 KFFPASAD---RTVIDYNGERTL 103
Cdd:cd03002  79 KVFRPPKKaskHAVEDYNGERSA 101

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        9 VKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDheNIVIAKMDSTANE--VEAVKVHSFPTLKFF 86
Cdd:COG3118   2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGG--KVKFVKVDVDENPelAAQFGVRSIPTLLLF 79

                        90       100
                ....*....|....*....|....*
1X5C_A       87 paSADRTVIDYNGERTLDGFKKFLE 111
Cdd:COG3118  80 --KDGQPVDRFVGALPKEQLREFLD 102

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
1X5C_A         15 KNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYkdHENIVIAKMDSTANEVEAVK--VHSFPTLKFFP 87
Cdd:TIGR01068   4 ANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEY--EGKVKFVKLNVDENPDIAAKygIRSIPTLLLFK 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       15 KNFEDvAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDhenIVIAKMDSTANE--VEAVKVHSFPTLKFFpasADR 92
Cdd:cd02947   1 EEFEE-LIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPK---VKFVKVDVDENPelAEEYGVRSIPTFLFF---KNG 73

                        90       100
                ....*....|....*....|
1X5C_A       93 TVID-YNGERTLDGFKKFLE 111
Cdd:cd02947  74 KEVDrVVGADPKEELEEFLE 93

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       30 VEFYAPWCGHCKQLAPIWDKLGEtYKDHENIVIAKMDSTANEVEAVK--VHSFPTlkFFPASaDRTVIDYNGERTLDGFK 107
Cdd:cd02994  21 IEFYAPWCPACQQLQPEWEEFAD-WSDDLGINVAKVDVTQEPGLSGRffVTALPT--IYHAK-DGVFRRYQGPRDKEDLI 96

                ....
1X5C_A      108 KFLE 111
Cdd:cd02994  97 SFIE 100

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       25 KKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHeNIVIAKMDSTANEVEAVK----VHSFPTLKFFPASAdRTVIDYNGE 100
Cdd:cd02993  21 NQSTLVVLYAPWCPFCQAMEASYEELAEKLAGS-NVKVAKFNADGEQREFAKeelqLKSFPTILFFPKNS-RQPIKYPSE 98

                        90
                ....*....|.
1X5C_A      101 -RTLDGFKKFL 110
Cdd:cd02993  99 qRDVDSLLMFV 109

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A         8 PVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKdheNIVIAKM--DSTANEVEAVKVHSFPTLKF 85
Cdd:PTZ00051   1 MVHIVTSQAEFESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYT---KMVFVKVdvDELSEVAEKENITSMPTFKV 77

                         90
                 ....*....|....*..
1X5C_A        86 FP-ASADRTVIDYNGER 101
Cdd:PTZ00051  78 FKnGSVVDTLLGANDEA 94

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        7 GPVKVLvGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENIVIAKMDSTANEVEAVKVHSFPTLKFF 86
Cdd:cd02999   1 PPEEVL-NIALDLMAFNREDYTAVLFYASWCPFSASFRPHFNALSSMFPQIRHLAIEESSIKPSLLSRYGVVGFPTILLF 79

                        90       100
                ....*....|....*....|...
1X5C_A       87 PASadrTVIDYNGERTLDGFKKF 109
Cdd:cd02999  80 NST---PRVRYNGTRTLDSLAAF 99

5'-adenylylsulfate reductase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A        25 KKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHeNIVIAKM----DSTANEVEAVKVHSFPTLKFFPASADRtVIDYNGE 100
Cdd:PLN02309 365 KEPWLVVLYAPWCPFCQAMEASYEELAEKLAGS-GVKVAKFradgDQKEFAKQELQLGSFPTILLFPKNSSR-PIKYPSE 442

                 .
1X5C_A       101 R 101
Cdd:PLN02309 443 K 443

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A         30 VEFYAPWCGHCKQLAPIWDKLGETYKDhENIVIAKMDSTANEVEAVK----VHSFPTLKFFPASADRTvIDYNGE-RTLD 104
Cdd:TIGR00424 376 VVLYAPWCPFCQAMEASYLELAEKLAG-SGVKVAKFRADGDQKEFAKqelqLGSFPTILFFPKHSSRP-IKYPSEkRDVD 453

                  ....*.
1X5C_A        105 GFKKFL 110
Cdd:TIGR00424 454 SLMSFV 459

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
1X5C_A       29 FVEFYAPWCGHCKQLAPIWDKLgetYKDHENIVIAKMDSTANEVEAVK-----VHSFPTLKFFPASADRTV 94
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAEL---ALLNKGVKFEAVDVDEDPALEKElkrygVGGVPTLVVFGPGIGVKY 68

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A         24 EKKNVFVEFYAPWCGHCKQLAPI---WDKLGETYKDHENIVIAKMDSTANEVEAVK-------------VHSFPTLKFFP 87
Cdd:pfam13098   3 NGKPVLVVFTDPDCPYCKKLKKElleDPDVTVYLGPNFVFIAVNIWCAKEVAKAFTdilenkelgrkygVRGTPTIVFFD 82

                  ....*...
1X5C_A         88 ASADRTVI 95
Cdd:pfam13098  83 GKGELLRL 90

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       24 EKKNVFVEFYAPWCGHCKQLAPiwdklgETYKDHE-------NIVIAKMDSTANEVE------AVKVHSFPTLKFFPASA 90
Cdd:cd02953  10 QGKPVFVDFTADWCVTCKVNEK------VVFSDPEvqaalkkDVVLLRADWTKNDPEitallkRFGVFGPPTYLFYGPGG 83

                        90       100
                ....*....|....*....|.
1X5C_A       91 DRTVIDYNGERTLDGFKKFLE 111
Cdd:cd02953  84 EPEPLRLPGFLTADEFLEALE 104

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
                ....*....|....*....|....*....|.
1X5C_A       26 KNVFVEFYAPWCGHCKQLAPIWDKLGETYKD 56
Cdd:cd02966  20 KVVLVNFWASWCPPCRAEMPELEALAKEYKD 50

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
1X5C_A       23 DEKKNVFVEFYAPWCGHCKQLAPIWDKLGEtyKDHENIVIAKMDstANEV----EAVKVHSFPTLKFF 86
Cdd:cd02984  12 DASKLLVLHFWAPWAEPCKQMNQVFEELAK--EAFPSVLFLSIE--AEELpeisEKFEITAVPTFVFF 75

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
1X5C_A       30 VEFY-APWCGHCKQLAPIWDKLGETYkdhENIVIAKMDSTANEVEAV-KVHSFPTLKF 85
Cdd:COG0695   2 VTLYtTPGCPYCARAKRLLDEKGIPY---EEIDVDEDPEAREELRERsGRRTVPVIFI 56

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        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1X5C_A       18 EDVAFDEKKNVFVEFYAPWCGHCKQL-----APIwdKLGETYKDHENIVIAKMD-------------STANEVEAVKVHS 79
Cdd:cd02951   7 AEAAADGKKPLLLLFSQPGCPYCDKLkrdylNDP--AVQAYIRAHFVVVYINIDgdkevtdfdgealSEKELARKYRVRF 84

                        90       100       110
                ....*....|....*....|....*....|..
1X5C_A       80 FPTLKFFPASADRTVIDYNGERTLDGFKKFLE 111
Cdd:cd02951  85 TPTVIFLDPEGGKEIARLPGYLPPDEFLAYLE 116