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 24664269    17 FDKLIddAGTNKYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKNrvtliq 96
Cdd:TIGR01068   6 FDETI--ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKN------ 77

                          90
                  ....*....|....*
gi 24664269    97 fvGGNVERVVSTVEK 111
Cdd:TIGR01068  78 --GKEVDRSVGALPK 90

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 24664269  17 FDKLIDDagtNKYVLVEFFATWCGPCAMIGPRLEQLASDYfGRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKNRVTLIQ 96
Cdd:cd02947   3 FEELIKS---AKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                ....*
gi 24664269  97 FVGGN 101
Cdd:cd02947  79 VVGAD 83

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 24664269    17 FDKLIddAGTNKYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKNrvtliq 96
Cdd:TIGR01068   6 FDETI--ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKN------ 77

                          90
                  ....*....|....*
gi 24664269    97 fvGGNVERVVSTVEK 111
Cdd:TIGR01068  78 --GKEVDRSVGALPK 90

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 24664269  17 FDKLIDDagtNKYVLVEFFATWCGPCAMIGPRLEQLASDYfGRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKNRVTLIQ 96
Cdd:cd02947   3 FEELIKS---AKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                ....*
gi 24664269  97 FVGGN 101
Cdd:cd02947  79 VVGAD 83

Protein Disulfide Isomerase (PDIa) family, redox active TRX domains; composed of eukaryotic proteins involved in oxidative protein folding in the endoplasmic reticulum (ER) by acting as catalysts and folding assistants. Members of this family include PDI and PDI-related proteins like ERp72, ERp57 (or ERp60), ERp44, P5, PDIR, ERp46 and the transmembrane PDIs. PDI, ERp57, ERp72, P5, PDIR and ERp46 are all oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. These proteins usually contain multiple copies of a redox active TRX (a) domain containing a CXXC motif, and may also contain one or more redox inactive TRX-like (b) domains. Only one a domain is required for the oxidase function but multiple copies are necessary for the isomerase function. The different types of PDIs may show different substrate specificities and tissue-specific expression, or may be induced by stress. PDIs are in their reduced form at steady state and are oxidized to the active form by Ero1, which is localized in the ER through ERp44. Some members of this family also contain a DnaJ domain in addition to the redox active a domains; examples are ERdj5 and Pfj2. Also included in the family is the redox inactive N-terminal TRX-like domain of ERp29.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  17 FDKLIDDagtNKYVLVEFFATWCGPCAMIGPRLEQLASDYF--GRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKN-RVT 93
Cdd:cd02961   8 FDELVKD---SKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNgSKE 84

                        90       100
                ....*....|....*....|
gi 24664269  94 LIQFVGgnvERVVSTVEKFV 113
Cdd:cd02961  85 PVKYEG---PRTLESLVEFI 101

PDIa family, endoplasmic reticulum protein 38 (ERp38) subfamily; composed of proteins similar to the P5-like protein first isolated from alfalfa, which contains two redox active TRX (a) domains at the N-terminus, like human P5, and a C-terminal domain with homology to the C-terminal domain of ERp29, unlike human P5. The cDNA clone of this protein (named G1) was isolated from an alfalfa cDNA library by screening with human protein disulfide isomerase (PDI) cDNA. The G1 protein is constitutively expressed in all major organs of the plant and its expression is induced by treatment with tunicamycin, indicating that it may be a glucose-regulated protein. The G1 homolog in the eukaryotic social amoeba Dictyostelium discoideum is also described as a P5-like protein, which is located in the endoplasmic reticulum (ER) despite the absence of an ER-retrieval signal. G1 homologs from Aspergillus niger and Neurospora crassa have also been characterized, and are named TIGA and ERp38, respectively. Also included in the alignment is an atypical PDI from Leishmania donovani containing a single a domain, and the C-terminal a domain of a P5-like protein from Entamoeba histolytica.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269   8 VIIVDSKSyFDKLIDDAGtnKYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVL--KIDVDE-NEDLAVQYEVNSMPT 84
Cdd:cd02998   2 VVELTDSN-FDKVVGDDK--KDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVViaKVDADEaNKDLAKKYGVSGFPT 78

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269   1 MAAMQKKVIIVDSKSYFDKLID-DAGTNKYVLVEFFATWCGPCAMIGPRLEQLASDYfGRMLVLKIDVDENED------- 72
Cdd:COG0526   1 MKAVGKPAPDFTLTDLDGKPLSlADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEY-GGVVFVGVDVDENPEavkaflk 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  73 ---------------LAVQYEVNSMPTFLII-KNRVTLIQFVGG-NVERVVSTVEKFVGK 115
Cdd:COG0526  80 elglpypvlldpdgeLAKAYGVRGIPTTVLIdKDGKIVARHVGPlSPEELEEALEKLLAK 139

PDI family, MPD1-like subfamily; composed of eukaryotic proteins similar to Saccharomyces cerevisiae MPD1 protein, which contains a single redox active TRX domain located at the N-terminus, and an ER retention signal at the C-terminus indicative of an ER-resident protein. MPD1 has been shown to suppress the maturation defect of carboxypeptidase Y caused by deletion of the yeast PDI1 gene. Other characterized members of this subfamily include the Aspergillus niger prpA protein and Giardia PDI-1. PrpA is non-essential to strain viability, however, its transcript level is induced by heterologous protein expression suggesting a possible role in oxidative protein folding during high protein production. Giardia PDI-1 has the ability to refold scrambled RNase and exhibits transglutaminase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269   7 KVIIVDSKSyFDKLIddAGTNKYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDE--NEDLAVQYEVNSMPT 84
Cdd:cd03002   1 PVYELTPKN-FDKVV--HNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEdkNKPLCGKYGVQGFPT 77

                ....*
gi 24664269  85 FLIIK 89
Cdd:cd03002  78 LKVFR 82

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24664269  30 VLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKN 90
Cdd:cd02956  15 VVVDFWAPRSPPSKELLPLLERLAEEYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAA 75

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24664269   6 KKVIIVDSKSYFDKLIDdaGTNKYVlVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDENEDLAVQYEVNSMPT 84
Cdd:cd03004   1 PSVITLTPEDFPELVLN--RKEPWL-VDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPT 76

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24664269  17 FDKLIDDagTNKYVLVEFFATWCGPCAMIGPRLEQLASDYFGR--MLVLKIDVDENeDLAVQYEVNSMPTFL 86
Cdd:cd02995  10 FDEVVLD--SDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDdnVVIAKMDATAN-DVPSEFVVDGFPTIL 78

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24664269  27 NKYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDEN--EDLAVQYEVNSMPTFLIIKNRVTLI-QFVG 99
Cdd:cd02950  20 GKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPkwLPEIDRYRVDGIPHFVFLDREGNEEgQSIG 95

protein disulfide isomerase, eukaryotic; This model represents eukaryotic protein disulfide isomerases retained in the endoplasmic reticulum (ER) and closely related forms. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase and dolichyl-diphosphooligosaccharide-protein glycotransferase. Members of this family have at least two protein-disulfide domains, each similar to thioredoxin but with the redox-active disulfide in the motif PWCGHCK, and an ER retention signal at the extreme C-terminus (KDEL, HDEL, and similar motifs).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269    17 FDKLIDDAGtnKYVLVEFFATWCGPCAMIGPRLEQLASDYFGR---MLVLKIDVDENEdlAVQYEVNSMPTFLIIK--NR 91
Cdd:TIGR01130 356 FDEIVLDET--KDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAesdVVIAKMDATAND--VPPFEVEGFPTIKFVPagKK 431

                          90       100
                  ....*....|....*....|....
gi 24664269    92 VTLIQFVGGnveRVVSTVEKFVGK 115
Cdd:TIGR01130 432 SEPVPYDGD---RTLEDFSKFIAK 452

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 24664269  26 TNKYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKNRVTLIQFVG 99
Cdd:cd02949  12 SDRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISG 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24664269  21 IDDA-GTNKYVLVEFFATWCGPCAMIGPRLEQlASDYF-------GRMLVLKIDVDENEDLAVQYEVNSMPTFLIIKN 90
Cdd:cd02996  11 IDDIlQSAELVLVNFYADWCRFSQMLHPIFEE-AAAKIkeefpdaGKVVWGKVDCDKESDIADRYRINKYPTLKLFRN 87

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  24 AGTNKYVLVEFFATWCGPCAMIGPRLEQLASDY-----------FGRM--------LVLKIDVDENEDLAVQYEVNSMPT 84
Cdd:cd03011  17 SLSGKPVLVYFWATWCPVCRFTSPTVNQLAADYpvvsvalrsgdDGAVarfmqkkgYGFPVINDPDGVISARWGVSVTPA 96

                ....*.
gi 24664269  85 FLIIKN 90
Cdd:cd03011  97 IVIVDP 102

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  28 KYVLVEFFATWCGPCAMIGPRLEQLASDYFGRMLV--------------------LKIDV--DENEDLAVQYEVNSMPTF 85
Cdd:COG1225  22 KPVVLYFYATWCPGCTAELPELRDLYEEFKDKGVEvlgvssdsdeahkkfaekygLPFPLlsDPDGEVAKAYGVRGTPTT 101

                ...
gi 24664269  86 LII 88
Cdd:COG1225 102 FLI 104

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269    24 AGTNKYVLVEFFATWCGPCAMIGPRLEQLAS--DYFGRMLVLKI--------------DVDENEDLAVQYEVNSMPTFLI 87
Cdd:pfam13098   1 KGNGKPVLVVFTDPDCPYCKKLKKELLEDPDvtVYLGPNFVFIAvniwcakevakaftDILENKELGRKYGVRGTPTIVF 80

                          90
                  ....*....|..
gi 24664269    88 IKNRVTLIQFVG 99
Cdd:pfam13098  81 FDGKGELLRLPG 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24664269  31 LVEFFATWCGPCAMIGPRLEQLA--SDYFGrMLVLKIDVDENEDLAVQYEVNSMPTFLIIKN 90
Cdd:cd02994  20 MIEFYAPWCPACQQLQPEWEEFAdwSDDLG-INVAKVDVTQEPGLSGRFFVTALPTIYHAKD 80

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        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  18 DKLIDDAG-TNKYVLVEFFATWCGPCAMIGPRLEQLASDyfGRMLVLKID-----------------------VDENEDL 73
Cdd:cd03010  15 DKTLTSADlKGKPYLLNVWASWCAPCREEHPVLMALARQ--GRVPIYGINykdnpenalawlarhgnpyaavgFDPDGRV 92

                        90       100
                ....*....|....*....|....*..
gi 24664269  74 AVQYEVNSMP-TFLIIKNRVTLIQFVG 99
Cdd:cd03010  93 GIDLGVYGVPeTFLIDGDGIIRYKHVG 119

thioredoxin-like protein

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269   34 FFATWCGPCAMIGPRLEQLASDYfgrmlvLKIDVDENEDLAVQYEVNSMPTFLiikNRVTLIQFVGgnVERVVSTVEKFV 113
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANVEYTY------VDVDTDEGVELTAKHHIRSLPTLV---NTSTLDRFTG--VPRNVAELKEKL 73

                 .
gi 24664269  114 G 114
Cdd:PHA02125  74 G 74

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269    28 KYVLVEFFATWCGPCAMIGPRLEQLASD------------------YFGRM-----LVLKidvDENEDLAVQYEVNSMP- 83
Cdd:TIGR00385  64 KPVLLNVWASWCPPCRAEHPYLNELAKQglpivgvdykddrqnaikFLKELgnpyqLSLF---DPDGMLGLDLGVYGAPe 140

                          90       100
                  ....*....|....*....|....*.
gi 24664269    84 TFLIIKNRVTLIQFVGGNVERVVSTV 109
Cdd:TIGR00385 141 TFLVDGNGVIRYRHAGPLNPEVWTEE 166

Tryparedoxin (TryX)-like family, TryX and nucleoredoxin (NRX) subfamily; TryX and NRX are thioredoxin (TRX)-like protein disulfide oxidoreductases that alter the redox state of target proteins via the reversible oxidation of an active center CXXC motif. TryX is involved in the regulation of oxidative stress in parasitic trypanosomatids by reducing TryX peroxidase, which in turn catalyzes the reduction of hydrogen peroxide and organic hydroperoxides. TryX derives reducing equivalents from reduced trypanothione, a polyamine peptide conjugate unique to trypanosomatids, which is regenerated by the NADPH-dependent flavoprotein trypanothione reductase. Vertebrate NRX is a 400-amino acid nuclear protein with one redox active TRX domain containing a CPPC active site motif followed by one redox inactive TRX-like domain. Mouse NRX transcripts are expressed in all adult tissues but is restricted to the nervous system and limb buds in embryos. Plant NRX, longer than the vertebrate NRX by about 100-200 amino acids, is a nuclear protein containing a redox inactive TRX-like domain between two redox active TRX domains. Both vertebrate and plant NRXs show thiol oxidoreductase activity in vitro. Their localization in the nucleus suggests a role in the redox regulation of nuclear proteins such as transcription factors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  28 KYVLVEFFATWCGPCAMIGPRL----EQLAS--------------------DYFGRMLVLKI---DVDENEDLAVQYEVN 80
Cdd:cd03009  19 KTVGLYFSASWCPPCRAFTPKLvefyEKLKEsgknfeivfiswdrdeesfnDYFSKMPWLAVpfsDRERRSRLNRTFKIE 98

                ....*...
gi 24664269  81 SMPTFLII 88
Cdd:cd03009  99 GIPTLIIL 106

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 24664269  27 NKYVLVEFFATWCGPCAMI------GPR-LEQLASDYfgrmLVLKIDV----DENEDLAVQYEVNSMPTFLIIKNR---- 91
Cdd:cd02953  11 GKPVFVDFTADWCVTCKVNekvvfsDPEvQAALKKDV----VLLRADWtkndPEITALLKRFGVFGPPTYLFYGPGgepe 86

                ....*...
gi 24664269  92 -VTLIQFV 98
Cdd:cd02953  87 pLRLPGFL 94

Tryparedoxin (TryX)-like family; composed of TryX and related proteins including nucleoredoxin (NRX), rod-derived cone viability factor (RdCVF) and the nematode homolog described as a 16-kD class of TRX. Most members of this family, except RdCVF, are protein disulfide oxidoreductases containing an active site CXXC motif, similar to TRX.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24664269  27 NKYVLVEFFATWCGPCAMIGPRL----EQLAS--------------------DYFGRM---LVLKI-DVDENEDLAVQYE 78
Cdd:cd02964  17 GKTVGLYFSASWCPPCRAFTPKLvefyEKLKEegknfeivfvsrdrseesfnEYFSEMppwLAVPFeDEELRELLEKQFK 96

                        90
                ....*....|.
gi 24664269  79 VNSMPTFLIIK 89
Cdd:cd02964  97 VEGIPTLVVLK 107

Thioredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24664269    30 VLVeFFATWCGPCAMIGPRLEQLASdyfgrmLVLKIDV-----DENEDLAVQYEVN---SMPTFLII 88
Cdd:pfam14595  45 ILV-ITEDWCGDAAQNVPVLAKIAE------LNPNIELrillrDENLELMDQYLTGggrAIPTFIFL 104