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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       11 FQEALDAAgdKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEFS 90
Cdd:cd02947   3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
1TRS_A       91 GAN-KEKLEATIN 102
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       11 FQEALDAAgdKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEFS 90
Cdd:cd02947   3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
1TRS_A       91 GAN-KEKLEATIN 102
Cdd:cd02947  81 GADpKEELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A         1 MVKQIESKTAFQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFF 80
Cdd:PTZ00051   1 MVHIVTSQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVF 78

                         90       100
                 ....*....|....*....|
1TRS_A        81 KKGQKVGEFSGANKEKLEAT 100
Cdd:PTZ00051  79 KNGSVVDTLLGANDEALKQL 98

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A         11 FQEALdAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSN-VIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEF 89
Cdd:TIGR01068   6 FDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
1TRS_A         90 SGAN-KEKLEATINELV 105
Cdd:TIGR01068  85 VGALpKAALKQLINKNL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       11 FQEALDAAgdKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEFS 90
Cdd:cd02947   3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
1TRS_A       91 GAN-KEKLEATIN 102
Cdd:cd02947  81 GADpKEELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A         1 MVKQIESKTAFQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFF 80
Cdd:PTZ00051   1 MVHIVTSQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVF 78

                         90       100
                 ....*....|....*....|
1TRS_A        81 KKGQKVGEFSGANKEKLEAT 100
Cdd:PTZ00051  79 KNGSVVDTLLGANDEALKQL 98

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A         11 FQEALdAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSN-VIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEF 89
Cdd:TIGR01068   6 FDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
1TRS_A         90 SGAN-KEKLEATINELV 105
Cdd:TIGR01068  85 VGALpKAALKQLINKNL 101

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A        7 SKTAFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLS-EKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQK 85
Cdd:cd02984   1 SEEEFEELLKSDASKLLVLHFWAPWAEPCKQMNQVFEELAkEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTI 80

                        90
                ....*....|....*..
1TRS_A       86 VGEFSGANKEKLEATIN 102
Cdd:cd02984  81 VDRVSGADPKELAKKVE 97

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       11 FQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKY---SNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKG-QKV 86
Cdd:cd02961   8 FDELV--KDSKDVLVEFYAPWCGHCKALAPEYEKLAKELkgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGsKEP 85

                        90
                ....*....|
1TRS_A       87 GEFSGANKEK 96
Cdd:cd02961  86 VKYEGPRTLE 95

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A        20 DKLVVVDFSATWCGPCKMIKPFFHSLS-EKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEFSGA-NKEKL 97
Cdd:PRK10996  52 DLPVVIDFWAPWCGPCRNFAPIFEDVAaERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAvPKAPF 131

                 ....*.
1TRS_A        98 EATINE 103
Cdd:PRK10996 132 DSWLNE 137

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
1TRS_A       25 VDFSATWCGPCKMIKPFFHSLSEKY----SNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEFSGA 92
Cdd:cd03005  21 VKFFAPWCGHCKRLAPTWEQLAKKFnnenPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDGEKVDKYKGT 92

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
1TRS_A        20 DKLVVVDFSATWCGPCKMIKPFFHS----LSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQKVgEFSGA 92
Cdd:PTZ00102  49 NEIVLVKFYAPWCGHCKRLAPEYKKaakmLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNPV-NYSGG 124

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A        2 VKQIESKTAFQEALDaaGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYS---NVIFLEVDVdDAQDVASEAEVKATPTFQ 78
Cdd:cd02995   2 VKVVVGKNFDEVVLD--SDKDVLVEFYAPWCGHCKALAPIYEELAEKLKgddNVVIAKMDA-TANDVPSEFVVDGFPTIL 78

                ....*..
1TRS_A       79 FFKKGQK 85
Cdd:cd02995  79 FFPAGDK 85

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A          7 SKTAFQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHS----LSEKYSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKK 82
Cdd:TIGR01130   7 TKDNFDDFI--KSHEFVLVEFYAPWCGHCKSLAPEYEKaadeLKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRN 84

                          90
                  ....*....|.
1TRS_A         83 G-QKVGEFSGA 92
Cdd:TIGR01130  85 GeDSVSDYNGP 95

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
1TRS_A       24 VVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAQDVASEAE---VKATPTFQFFKKGQKV 86
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDPALEKELKrygVGGVPTLVVFGPGIGV 66

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
                ....*....|....*....|....*....|....*....|....*....|....*..
1TRS_A       15 LDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSN----VIFLEVDVDDAQDVAS 67
Cdd:cd02966  14 LSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKDdgveVVGVNVDDDDPAAVKA 70

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       24 VVDFSATWCGPCKMIKPFFHSLSE---KYSNVIFLEVdVDDA----QDVASEAEVKATPTFQFFK---KGQKVGEfsgaN 93
Cdd:cd02992  23 LVEFYASWCGHCRAFAPTWKKLARdlrKWRPVVRVAA-VDCAdeenVALCRDFGVTGYPTLRYFPpfsKEATDGL----K 97

                        90
                ....*....|.
1TRS_A       94 KEKLEATINEL 104
Cdd:cd02992  98 QEGPERDVNEL 108

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       10 AFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYS--NVIFLEVDVDDAQDVASEAEV------KATPTFQFFK 81
Cdd:cd02962  37 TLEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNnnNLKFGKIDIGRFPNVAEKFRVstsplsKQLPTIILFQ 116

                        90
                ....*....|....*
1TRS_A       82 KGQKVGEFSGANKEK 96
Cdd:cd02962 117 GGKEVARRPYYNDSK 131

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       20 DKLVVVDFSATWCGPCKMIKPFFHSLSE--KYSNVIFL---EVDVDDAQDVASEAEVKATPTFQFFKKGQKVGEFSGANK 94
Cdd:cd02997  17 EKHVLVMFYAPWCGHCKKMKPEFTKAATelKEDGKGVLaavDCTKPEHDALKEEYNVKGFPTFKYFENGKFVEKYEGERT 96

                ..
1TRS_A       95 EK 96
Cdd:cd02997  97 AE 98

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
1TRS_A       24 VVDFSATWCGPCKMIKPFFHSLSEK-YSNVIFLEVDVDDAQDVASEAEVKATPTFQFFKKGQK 85
Cdd:cd03004  23 LVDFYAPWCGPCQALLPELRKAARAlKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYPGNAS 85

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
1TRS_A        25 VDFSATWCGPCKMIKPFFHSLSEKYSNVIFL-EVDVDDAQDVASEAEVKATPTFQFFKKGqKVGEFSGANK--EKLEA 99
Cdd:PTZ00443  57 VKFYAPWCSHCRKMAPAWERLAKALKGQVNVaDLDATRALNLAKRFAIKGYPTLLLFDKG-KMYQYEGGDRstEKLAA 133

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A         21 KLVVVDFSATWCGPCKMIKP----------FFHSLSEKYSNVIFLEVDVDDA-QDVASEAE------VKATPTFQFFKKG 83
Cdd:pfam13098   5 KPVLVVFTDPDCPYCKKLKKelledpdvtvYLGPNFVFIAVNIWCAKEVAKAfTDILENKElgrkygVRGTPTIVFFDGK 84

                          90
                  ....*....|....*....
1TRS_A         84 QKVGEFSGA-NKEKLEATI 101
Cdd:pfam13098  85 GELLRLPGYvPAEEFLALL 103

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
1TRS_A        27 FSATWCGPCKMIKPFFHSLSEKYsnvifLEVDVDDAQDVASEAEVKATPT 76
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANVEYTY-----VDVDTDEGVELTAKHHIRSLPT 49

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       23 VVVdFSATWCGPCKMIKPFFHSLsekysNVIFLEVDVD----DAQDVASEAEVKATPtfQFFKKGQKVGEFSganKEKLE 98
Cdd:COG0695   2 VTL-YTTPGCPYCARAKRLLDEK-----GIPYEEIDVDedpeAREELRERSGRRTVP--VIFIGGEHLGGFD---EGELD 70

                .
1TRS_A       99 A 99
Cdd:COG0695  71 A 71

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
1TRS_A         20 DKLVVVDFSATWCGPCKMIKPFFHSLSEKYS-----NVIFLEVDVD 60
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKLKkkknvEIVFVSLDRD 46

TlpA-like family, suppressor for copper sensitivity D protein (ScsD) and actinobacterial DsbE homolog subfamily; composed of ScsD, the DsbE homolog of Mycobacterium tuberculosis (MtbDsbE) and similar proteins, all containing a redox-active CXXC motif. The Salmonella typhimurium ScsD is a thioredoxin-like protein which confers copper tolerance to copper-sensitive mutants of E. coli. MtbDsbE has been characterized as an oxidase in vitro, catalyzing the disulfide bond formation of substrates like hirudin. The reduced form of MtbDsbE is more stable than its oxidized form, consistent with an oxidase function. This is in contrast to the function of DsbE from gram-negative bacteria which is a specific reductase of apocytochrome c.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A       21 KLVVVDFSATWCGPCKMIKPFFHSLSEKYsNVIFLEVDVDDAQDVAS---------------------EAEVKATPTFQF 79
Cdd:cd03011  21 KPVLVYFWATWCPVCRFTSPTVNQLAADY-PVVSVALRSGDDGAVARfmqkkgygfpvindpdgvisaRWGVSVTPAIVI 99

                ....*..
1TRS_A       80 FKKGQKV 86
Cdd:cd03011 100 VDPGGIV 106

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
1TRS_A         23 VVVdFSATWCGPCKMIKPFFHSLsekysNVIFLEVDVDDAQDVASE-AEVKATPTF-QFFKKGQKV 86
Cdd:pfam00462   1 VVL-YTKPTCPFCKRAKRLLKSL-----GVDFEEIDVDEDPEIREElKELSGWPTVpQVFIDGEHI 60

Phosducin (Phd)-like family; composed of Phd and Phd-like proteins (PhLP), characterized as cytosolic regulators of G protein functions. Phd and PhLPs specifically bind G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane and impeding G protein-mediated signal transduction by inhibiting the formation of a functional G protein trimer (G protein alphabetagamma). Phd also inhibits the GTPase activity of G protein alpha. Phd can be phosphorylated by protein kinase A and G protein-coupled receptor kinase 2, leading to its inactivation. Phd was originally isolated from the retina, where it is highly expressed and has been implicated to play an important role in light adaptation. It is also found in the pineal gland, liver, spleen, striated muscle and the brain. The C-terminal domain of Phd adopts a thioredoxin fold, but it does not contain a CXXC motif. Phd interacts with G protein beta mostly through the N-terminal helical domain. Also included in this family is a PhLP characterized as a viral inhibitor of apoptosis (IAP)-associated factor, named VIAF, that functions in caspase activation during apoptosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A        2 VKQIESKTAFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDAqDVASEAEVKATPTFQFFK 81
Cdd:cd02957   6 VREISSKEFLEEVTKASKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYK 84

                        90
                ....*....|
1TRS_A       82 KGQKVGEFSG 91
Cdd:cd02957  85 NGELIDNIVG 94

thiol-disulfide oxidoreductase ResA;

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
1TRS_A        21 KLVVVDFSATWCGPCKMIKPFFHSLSEKYSN--VIFLEVDVDDAQ 63
Cdd:PRK03147  62 KGVFLNFWGTWCKPCEKEMPYMNELYPKYKEkgVEIIAVNVDETE 106

Glutaredoxin-like protein, YruB-family; This glutaredoxin-like protein family contains the conserved CxxC motif and includes the Clostridium pasteurianum protein YruB which has been cloned from a rubredoxin operon. Somewhat related to NrdH, it is unknown whether this protein actually interacts with glutathione/glutathione reducatase, or, like NrdH, some other reductant system.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
1TRS_A         24 VVDFSATWCGPCKMIKPFFHSLsekysNVIFLEVDVDD----AQDVASEAEVKATPTFQFfkkGQKVgeFSGANKEKLEA 99
Cdd:TIGR02196   2 VKVYTTPWCPPCVKAKEYLTSK-----GVAFEEIDVEKdaaaREELLKVYGQRGVPVIVI---GHKI--VVGFDPEKLDQ 71

                  ...
1TRS_A        100 TIN 102
Cdd:TIGR02196  72 LLN 74