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 328771660  5 AEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVNEVV 84
Cdd:cd02947   1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
gi 328771660 85 GAD-INKVEQLVK 96
Cdd:cd02947  81 GADpKEELEEFLE 93

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 328771660  5 AEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVNEVV 84
Cdd:cd02947   1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
gi 328771660 85 GAD-INKVEQLVK 96
Cdd:cd02947  81 GADpKEELEEFLE 93

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 328771660    3 SVAEFDKLI-ESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPN-VQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKV 80
Cdd:TIGR01068   2 TDANFDETIaSSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90
                  ....*....|....*..
gi 328771660   81 NEVVGA-DINKVEQLVK 96
Cdd:TIGR01068  82 DRSVGAlPKAALKQLIN 98

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 328771660    3 SVAEFDKLI-ESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTP-NVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKV 80
Cdd:pfam00085   6 TDANFDEVVqKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKgNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPV 85

                  ....*.
gi 328771660   81 NEVVGA 86
Cdd:pfam00085  86 DDYVGA 91

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 328771660  5 AEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVNEVV 84
Cdd:cd02947   1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
gi 328771660 85 GAD-INKVEQLVK 96
Cdd:cd02947  81 GADpKEELEEFLE 93

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 328771660    3 SVAEFDKLI-ESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPN-VQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKV 80
Cdd:TIGR01068   2 TDANFDETIaSSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90
                  ....*....|....*..
gi 328771660   81 NEVVGA-DINKVEQLVK 96
Cdd:TIGR01068  82 DRSVGAlPKAALKQLIN 98

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 328771660    3 SVAEFDKLI-ESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTP-NVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKV 80
Cdd:pfam00085   6 TDANFDEVVqKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKgNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPV 85

                  ....*.
gi 328771660   81 NEVVGA 86
Cdd:pfam00085  86 DDYVGA 91

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 328771660   5 AEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKK---TPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSK 79
Cdd:cd02961    6 DNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKElkgDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGSK 83

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   6 EFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEA----LAKKTPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVN 81
Cdd:PTZ00102  41 TFDKFITENEIVLVKFYAPWCGHCKRLAPEYKKaakmLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNPVN 120

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 328771660   8 DKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKT-PNVQFLKVDVDQLQAISSKHGVRAMPTFQFFK-KGSKVNEVVG 85
Cdd:cd03004   13 ELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALkGKVKVGSVDCQKYESLCQQANIRAYPTIRLYPgNASKYHSYNG 92

thioredoxin TrxA;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 328771660  10 LIESNKLTVVDFFAEWCGPCKMVAPRFEALAKK-TPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVNEVVGA 86
Cdd:PRK09381  17 VLKADGAILVDFWAEWCGPCKMIAPILDEIADEyQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGA 94

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660  13 SNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKVDV----------------------DQLQAISSKHGVRAMPT 70
Cdd:COG0526   27 KGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVdenpeavkaflkelglpypvllDPDGELAKAYGVRGIPT 106

                         90       100
                 ....*....|....*....|....*...
gi 328771660  71 FQFF-KKGSKVNEVVGA-DINKVEQLVK 96
Cdd:COG0526  107 TVLIdKDGKIVARHVGPlSPEELEEALE 134

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 328771660   1 ISSVAEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKK--TPNVQFLKVDVDQLQAISSKHGvRAMPTFQFFKKGS 78
Cdd:cd02948    4 INNQEEWEELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNElgDDLLHFATAEADTIDTLKRYRG-KCEPTFLFYKNGE 82

                         90
                 ....*....|....*..
gi 328771660  79 KVNEVVGADINKVEQLV 95
Cdd:cd02948   83 LVAVIRGANAPLLNKTI 99

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 328771660 12 ESNKLTVVDFFAEWCGPCKMVAPRFEALAKK-TPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVNEVVG 85
Cdd:cd02949  11 ESDRLILVLYTSPTCGPCRTLKPILNKVIDEfDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISG 85

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 328771660   4 VAEFDKLIESNKLTVVDFFAEWCGPCKMvaprFEALAKKTPNVQ--------FLKVDV----DQLQAISSKHGVRAMPTF 71
Cdd:cd02953    1 EAALAQALAQGKPVFVDFTADWCVTCKV----NEKVVFSDPEVQaalkkdvvLLRADWtkndPEITALLKRFGVFGPPTY 76

                         90
                 ....*....|...
gi 328771660  72 QFFKKGSKVNEVV 84
Cdd:cd02953   77 LFYGPGGEPEPLR 89

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 328771660   5 AEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALA---KKTPNVQFLKVDV--DQLQAISSKHGVRAMPTFQFFKKG 77
Cdd:cd02997    8 EDFRKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAAtelKEDGKGVLAAVDCtkPEHDALKEEYNVKGFPTFKYFENG 85

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   4 VAEFDKLIESNK--LTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKVDV-DQLQAISSKHGVRAMPTFQFFKKGSKV 80
Cdd:cd02999    6 LNIALDLMAFNRedYTAVLFYASWCPFSASFRPHFNALSSMFPQIRHLAIEEsSIKPSLLSRYGVVGFPTILLFNSTPRV 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   8 DKLIESNK--LTVVDFFAEWCGPCKMVAPRFE----ALAKKTPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKVN 81
Cdd:cd03000    7 DSFKDVRKedIWLVDFYAPWCGHCKKLEPVWNevgaELKSSGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAYN 86

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   5 AEFDKLIESNKLTVVDFFAEWCGPCKmvapRFEALAKKTPNVQ--------FLKVDVD----QLQAISSKHGVRAMPTFQ 72
Cdd:COG4232  311 AALAEARAEGKPVFVDFTADWCVTCK----ENERTVFSDPEVQaaladdvvLLKADVTdndpEITALLKRFGRFGVPTYV 386

                         90
                 ....*....|....*...
gi 328771660  73 FFKKGSKVNEVVGADINK 90
Cdd:COG4232  387 FYDPDGEELPRLGFMLTA 404

TRX family, chloroplastic drought-induced stress protein of 32 kD (CDSP32); CDSP32 is composed of two TRX domains, a C-terminal TRX domain which contains a redox active CXXC motif and an N-terminal TRX-like domain which contains an SXXS sequence instead of the redox active motif. CDSP32 is a stress-inducible TRX, i.e., it acts as a TRX by reducing protein disulfides and is induced by environmental and oxidative stress conditions. It plays a critical role in plastid defense against oxidative damage, a role related to its function as a physiological electron donor to BAS1, a plastidic 2-cys peroxiredoxin. Plants lacking CDSP32 exhibit decreased photosystem II photochemical efficiencies and chlorophyll retention compared to WT controls, as well as an increased proportion of BAS1 in its overoxidized monomeric form.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   3 SVAEFDKL--IESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKV---DVDQLQAISSKHGVRAMPTFQFFKKG 77
Cdd:cd02985    2 SVEELDEAlkKAKGRLVVLEFALKHSGPSVKIYPTMVKLSRTCNDVVFLLVngdENDSTMELCRREKIIEVPHFLFYKDG 81

                 ....*...
gi 328771660  78 SKVNEVVG 85
Cdd:cd02985   82 EKIHEEEG 89

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 328771660   7 FDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPN-------VQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSK 79
Cdd:cd02996   11 IDDILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKEefpdagkVVWGKVDCDKESDIADRYRINKYPTLKLFRNGMM 90

                 ..
gi 328771660  80 VN 81
Cdd:cd02996   91 MK 92

Phosducin (Phd)-like family, Thioredoxin (TRX) domain containing protein 9 (TxnDC9) subfamily; composed of predominantly uncharacterized eukaryotic proteins, containing a TRX-like domain without the redox active CXXC motif. The gene name for the human protein is TxnDC9. The two characterized members are described as Phd-like proteins, PLP1 of Saccharomyces cerevisiae and PhLP3 of Dictyostelium discoideum. Gene disruption experiments show that both PLP1 and PhLP3 are non-essential proteins. Unlike Phd and most Phd-like proteins, members of this group do not contain the Phd N-terminal helical domain which is implicated in binding to the G protein betagamma subunit.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   1 ISSVAEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVQFLKVDVDQLQAISSKHGVRAMPTFQFFKKGSKV 80
Cdd:cd02989    9 VSDEKEFFEIVKSSERVVCHFYHPEFFRCKIMDKHLEILAKKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTV 88

                 ....*
gi 328771660  81 NEVVG 85
Cdd:cd02989   89 DRIVG 93

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 328771660   7 FDKLIESNKLT--VVDFFAEWCGPCKMVAPRFEALAKK--TPNVQFLKVDVDQLQAISSKHGV------RAMPTFQFFKK 76
Cdd:cd02962   38 LEEELERDKRVtwLVEFFTTWSPECVNFAPVFAELSLKynNNNLKFGKIDIGRFPNVAEKFRVstsplsKQLPTIILFQG 117

                 ....
gi 328771660  77 GSKV 80
Cdd:cd02962  118 GKEV 121

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660  19 VDFFAEWCGPCKMVAPRFEALAKKTPN-VQFLKVDVDQLQAISSKHGVRAMPTFQFFKKG 77
Cdd:PTZ00443  57 VKFYAPWCSHCRKMAPAWERLAKALKGqVNVADLDATRALNLAKRFAIKGYPTLLLFDKG 116

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 328771660  15 KLTVVDFFAEWCGPCKMVAPRFEALAK--KTPNVQFLKV---DVDQLQAISSKHGV 65
Cdd:COG1225   22 KPVVLYFYATWCPGCTAELPELRDLYEefKDKGVEVLGVssdSDEAHKKFAEKYGL 77

thiol:disulfide interchange protein precursor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   1 ISSVAEFD-KLIESN---KLTVVDFFAEWCGPCKmvapRFEALAKKTPNVQ-------FLKVDV----DQLQAISSKHGV 65
Cdd:PRK00293 457 IKTVAELDqALAEAKgkgKPVMLDLYADWCVACK----EFEKYTFSDPQVQqaladtvLLQADVtannAEDVALLKHYNV 532

                 ....*....
gi 328771660  66 RAMPTFQFF 74
Cdd:PRK00293 533 LGLPTILFF 541

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   12 ESNKLTVVDFFAEWCGPCKMVAPRFEALAKKT----PNVQFLKVDVDQ-------------LQAISSKHGVRAMPTFQFF 74
Cdd:pfam13098   2 GNGKPVLVVFTDPDCPYCKKLKKELLEDPDVTvylgPNFVFIAVNIWCakevakaftdileNKELGRKYGVRGTPTIVFF 81

                          90
                  ....*....|..
gi 328771660   75 KKGSKVNEVVGA 86
Cdd:pfam13098  82 DGKGELLRLPGY 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328771660   5 AEFDKLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNVqfLKVDV----DQLQAISSKhGVRAMPTFQFFKKGSKV 80
Cdd:cd03003    9 GDFDAAVNSGEIWFVNFYSPRCSHCHDLAPTWREFAKEMDGV--IRIGAvncgDDRMLCRSQ-GVNSYPSLYVFPSGMNP 85

                         90
                 ....*....|....*.
gi 328771660  81 NEVVGAdiNKVEQLVK 96
Cdd:cd03003   86 EKYYGD--RSKESLVK 99

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 328771660 24 EWCGPCKMVAprfEALAKKtpNVQFLKVDVDQ----LQAISSKHGVRAMPTfqfFKKGSKVneVVGADINKVEQLV 95
Cdd:cd02976   8 PDCPYCKATK---RFLDER--GIPFEEVDVDEdpeaLEELKKLNGYRSVPV---VVIGDEH--LSGFRPDKLRALL 73

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
                 ....*....|....*....|....*....
gi 328771660  14 NKLTVVDFFAEWCGPCKMVAPRFEALAKK 42
Cdd:cd03010   25 GKPYLLNVWASWCAPCREEHPVLMALARQ 53

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
                  ....*....|....*....|....*....|....*...
gi 328771660    9 KLIESNKLTVVDFFAEWCGPCKMVAPRFEALAKKTPNV 46
Cdd:TIGR00385  58 DVLTQGKPVLLNVWASWCPPCRAEHPYLNELAKQGLPI 95