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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   1 KVLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANELENIKIS-SFPTIKYFRK 79
Cdd:cd02995     3 KVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSEFVVdGFPTILFFPA 82

                          90       100
                  ....*....|....*....|..
gi 2079606953  80 DD-NKVIDFNLDRTLDDFVKFL 100
Cdd:cd02995    83 GDkSNPIKYEGDRTLEDLIKFI 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   1 KVLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANELENIKIS-SFPTIKYFRK 79
Cdd:cd02995     3 KVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSEFVVdGFPTILFFPA 82

                          90       100
                  ....*....|....*....|..
gi 2079606953  80 DD-NKVIDFNLDRTLDDFVKFL 100
Cdd:cd02995    83 GDkSNPIKYEGDRTLEDLIKFI 104

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   1 KVLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANE--LENIKISSFPTIKYFR 78
Cdd:PTZ00102  360 KVVVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKDNDSIIVAKMNGTANEtpLEEFSWSAFPTILFVK 439

                          90       100
                  ....*....|....*....|....*.
gi 2079606953  79 KDDNKVIDFNLDRTLDDFVKFLDANG 104
Cdd:PTZ00102  440 AGERTPIPYEGERTVEGFKEFVNKHA 465

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   5 SSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDnaDIVIAKMD-----STANELeniKISSFPTIKYFRk 79
Cdd:COG3118     7 DENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGG--KVKFVKVDvdenpELAAQF---GVRSIPTLLLFK- 80

                          90       100
                  ....*....|....*....|....*
gi 2079606953  80 dDNKVID-FNLDRTLDDFVKFLDAN 103
Cdd:COG3118    81 -DGQPVDrFVGALPKEQLREFLDKV 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   1 KVLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANELENIKIS-SFPTIKYFRK 79
Cdd:cd02995     3 KVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSEFVVdGFPTILFFPA 82

                          90       100
                  ....*....|....*....|..
gi 2079606953  80 DD-NKVIDFNLDRTLDDFVKFL 100
Cdd:cd02995    83 GDkSNPIKYEGDRTLEDLIKFI 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   1 KVLVSSNFESVaLDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTAN-ELENI-KISSFPTIKYFR 78
Cdd:cd02961     1 VELTDDNFDEL-VKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVVVAKVDCTANnDLCSEyGVRGYPTIKLFP 79

                          90       100
                  ....*....|....*....|..
gi 2079606953  79 KDDNKVIDFNLDRTLDDFVKFL 100
Cdd:cd02961    80 NGSKEPVKYEGPRTLESLVEFI 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 2079606953   2 VLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANE---LENIKISSFPTIKYFR 78
Cdd:cd02998     4 ELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIAKVDADEANkdlAKKYGVSGFPTLKFFP 83

                          90       100
                  ....*....|....*....|..
gi 2079606953  79 KDDNKVIDFNLDRTLDDFVKFL 100
Cdd:cd02998    84 KGSTEPVKYEGGRDLEDLVKFV 105

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 2079606953   1 KVLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNadIVIAKMDSTANELENIK--ISSFPTIKYFr 78
Cdd:pfam00085   3 VVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGN--VVFAKVDVDENPDLASKygVRGYPTLIFF- 79

                          90       100
                  ....*....|....*....|....
gi 2079606953  79 KDDNKVIDFNLDRTLDDFVKFLDA 102
Cdd:pfam00085  80 KNGQPVDDYVGARPKDALAAFLKA 103

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 2079606953   2 VLVSSNFESVaLDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYK-DNADIVIAKMDSTAN-EL-ENIKISSFPTIKYFR 78
Cdd:TIGR01130   5 VLTKDNFDDF-IKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKkKGPPIKLAKVDATEEkDLaQKYGVSGYPTLKIFR 83

                          90       100
                  ....*....|....*....|..
gi 2079606953  79 KDDNKVIDFNLDRTLDDFVKFL 100
Cdd:TIGR01130  84 NGEDSVSDYNGPRDADGIVKYM 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   1 KVLVSSNF-ESVAldkSKSVLVEFYAPWCGHCKQLAPIYDQLAEKY-KDNADIVIAKMDSTA-NEL-ENIKISSFPTIKY 76
Cdd:cd03005     3 LELTEDNFdHHIA---EGNHFVKFFAPWCGHCKRLAPTWEQLAKKFnNENPSVKIAKVDCTQhRELcSEFQVRGYPTLLL 79

                          90       100
                  ....*....|....*....|....
gi 2079606953  77 FRkDDNKVIDFNLDRTLDDFVKFL 100
Cdd:cd03005    80 FK-DGEKVDKYKGTRDLDSLKEFV 102

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 2079606953  20 LVEFYAPWCGHCKQLAPIYDQLAEKYKD-NADIVIAKMDST-----ANELeniKISSFPTIKYFRKDdnKVIDFNLDRTL 93
Cdd:cd03000    19 LVDFYAPWCGHCKKLEPVWNEVGAELKSsGSPVRVGKLDATayssiASEF---GVRGYPTIKLLKGD--LAYNYRGPRTK 93

                  ....*.
gi 2079606953  94 DDFVKF 99
Cdd:cd03000    94 DDIVEF 99

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 2079606953   3 LVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANE--LENIKISSFPTIKYFR-- 78
Cdd:cd03002     5 LTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKNKplCGKYGVQGFPTLKVFRpp 84

                          90       100
                  ....*....|....*....|...
gi 2079606953  79 KDDNK--VIDFNLDRTLDDFVKF 99
Cdd:cd03002    85 KKASKhaVEDYNGERSAKAIVDF 107

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 2079606953   6 SNFESvALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKdnaDIVIAKMDSTANE--LENIKISSFPTIKYFRkdDNK 83
Cdd:cd02947     1 EEFEE-LIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYP---KVKFVKVDVDENPelAEEYGVRSIPTFLFFK--NGK 74

                  ...
gi 2079606953  84 VID 86
Cdd:cd02947    75 EVD 77

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 2079606953   2 VLVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNadIVIAKMDSTANEL----ENIKisSFPTIKYF 77
Cdd:cd03004     5 TLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGK--VKVGSVDCQKYESlcqqANIR--AYPTIRLY 80

                          90
                  ....*....|.
gi 2079606953  78 RKDDNKVIDFN 88
Cdd:cd03004    81 PGNASKYHSYN 91

5'-adenylylsulfate reductase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953  15 KSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKdNADIVIAKM----DSTANELENIKISSFPTIKYFRKDDNKVIDFNLD 90
Cdd:PLN02309  364 RKEPWLVVLYAPWCPFCQAMEASYEELAEKLA-GSGVKVAKFradgDQKEFAKQELQLGSFPTILLFPKNSSRPIKYPSE 442

                          90
                  ....*....|....
gi 2079606953  91 R----TLDDFVKFL 100
Cdd:PLN02309  443 KrdvdSLLSFVNSL 456

thioredoxin; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2079606953   2 VLVSSNFESVaLDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYkdnADIVIAKM--DSTANELENIKISSFPTIKYFR 78
Cdd:PTZ00051    5 VTSQAEFEST-LSQNELVIVDFYAEWCGPCKRIAPFYEECSKEY---TKMVFVKVdvDELSEVAEKENITSMPTFKVFK 79

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953   3 LVSSNFESVALDKSKSV----LVEFYAPWCGHCKQLAPIYDQLAEKYKDNADivIAKMDST--ANELENIKISSFPTIKY 76
Cdd:PTZ00443   35 LNDKNFEKLTQASTGATtgpwFVKFYAPWCSHCRKMAPAWERLAKALKGQVN--VADLDATraLNLAKRFAIKGYPTLLL 112

                          90       100
                  ....*....|....*....|....
gi 2079606953  77 FRKddNKVIDF-NLDRTLDDFVKF 99
Cdd:PTZ00443  113 FDK--GKMYQYeGGDRSTEKLAAF 134

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 2079606953   3 LVSSNFESVaLDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYK----DNADIVIAKMDSTANE--LENIKISSFPTIKY 76
Cdd:cd02996     6 LTSGNIDDI-LQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKeefpDAGKVVWGKVDCDKESdiADRYRINKYPTLKL 84

                  ..
gi 2079606953  77 FR 78
Cdd:cd02996    85 FR 86

thioredoxin TrxA;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2079606953   3 LVSSNFESVALDKSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANELENIKISSFPTIKYFR 78
Cdd:PRK09381    8 LTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK 83

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2079606953   6 SNFESVaLDKSKS--VLVEFYAPWCGHCKQLAPIYDQLAEKYKDNadIVIAKMDSTAN 61
Cdd:cd02956     1 QNFQQV-LQESTQvpVVVDFWAPRSPPSKELLPLLERLAEEYQGQ--FVLAKVNCDAQ 55

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2079606953  20 LVEFYAPWCGHCKQLAPIYDQLAEKYKdnaDIVIAKMDSTANELENIK-----ISSFPTIKYFRKDDNKVID 86
Cdd:cd01659     1 LVLFYAPWCPFCQALRPVLAELALLNK---GVKFEAVDVDEDPALEKElkrygVGGVPTLVVFGPGIGVKYG 69

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 2079606953  20 LVEFYAPWCGHCKQLAPIYDQLAEKYkdNADIVIAKMDSTANEL--ENIKISSFPTIKYFRKDDNKVIDFNlDRTLDDFV 97
Cdd:cd03003    22 FVNFYSPRCSHCHDLAPTWREFAKEM--DGVIRIGAVNCGDDRMlcRSQGVNSYPSLYVFPSGMNPEKYYG-DRSKESLV 98

                  ..
gi 2079606953  98 KF 99
Cdd:cd03003    99 KF 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953  12 ALDKSKSVLVEFYAPWCGHCKQL-------APIYDQLAEkykdnaDIVIAKMDSTANE------LENIKISSFPTIKYFR 78
Cdd:COG4232   316 ARAEGKPVFVDFTADWCVTCKENertvfsdPEVQAALAD------DVVLLKADVTDNDpeitalLKRFGRFGVPTYVFYD 389

                          90       100
                  ....*....|....*....|....*.
gi 2079606953  79 KDDN--KVIDFNLDRtlDDFVKFLDA 102
Cdd:COG4232   390 PDGEelPRLGFMLTA--DEFLAALEK 413

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2079606953   3 LVSSNFESVALD--KSKSVLVEFYAPWCGHCKQLAPIYDQLAEKYKD-NADIV 52
Cdd:COG1225     6 LPDLDGKTVSLSdlRGKPVVLYFYATWCPGCTAELPELRDLYEEFKDkGVEVL 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2079606953  17 KSVLVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVIAKMDSTANELENIKISSFPTIKYFR 78
Cdd:cd02949    14 RLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFK 75

Protein thiol-disulfide isomerase DsbC [Posttranslational modification, protein turnover, chaperones];

                          10        20        30
                  ....*....|....*....|....*....|
gi 2079606953  19 VLVEFYAPWCGHCKQLAPIYDQLAEKYKDN 48
Cdd:COG1651     3 TVVEFFDYQCPYCARFHPELPELLKKYVDG 32

DsbA family; consists of DsbA and DsbA-like proteins, including DsbC, DsbG, glutathione (GSH) S-transferase kappa (GSTK), 2-hydroxychromene-2-carboxylate (HCCA) isomerase, an oxidoreductase (FrnE) presumed to be involved in frenolicin biosynthesis, a 27-kDa outer membrane protein, and similar proteins. Members of this family contain a redox active CXXC motif (except GSTK and HCCA isomerase) imbedded in a TRX fold, and an alpha helical insert of about 75 residues (shorter in DsbC and DsbG) relative to TRX. DsbA is involved in the oxidative protein folding pathway in prokaryotes, catalyzing disulfide bond formation of proteins secreted into the bacterial periplasm. DsbC and DsbG function as protein disulfide isomerases and chaperones to correct non-native disulfide bonds formed by DsbA and prevent aggregation of incorrectly folded proteins.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 2079606953  20 LVEFYAPWCGHCKQLAPIYDQLAEKYKDNADIVI 53
Cdd:cd02972     1 IVEFFDPLCPYCYLFEPELEKLLYADDGGVRVVY 34

Thioredoxin-related protein SoxW [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2079606953  12 ALDKSKSVLVEFYAPWCGHCKQL-----APiyDQLAEKYKDNADIVIAKMDS------------TANEL-ENIKISSFPT 73
Cdd:COG2143    36 AKAEGKPILLFFESDWCPYCKKLhkevfSD--PEVAAYLKENFVVVQLDAEGdkevtdfdgetlTEKELaRKYGVRGTPT 113

                          90
                  ....*....|.
gi 2079606953  74 IKYFRKDDNKV 84
Cdd:COG2143   114 LVFFDAEGKEI 124

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2079606953  17 KSVLVEFYAPWCGHCKQLAPI----YDQLAEKYKdNADIVIAKMDSTANELE 64
Cdd:cd02964    18 KTVGLYFSASWCPPCRAFTPKlvefYEKLKEEGK-NFEIVFVSRDRSEESFN 68

PDIa family, N-terminal EFP1 subfamily; EFP1 is a binding partner protein of thyroid oxidase (ThOX), also called Duox. ThOX proteins are responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones. EFP1 was isolated through a yeast two-hybrid method using the EF-hand fragment of dog Duox1 as a bait. It could be one of the partners in the assembly of a multiprotein complex constituting the thyroid hydrogen peroxide generating system. EFP1 contains two TRX domains related to the redox active TRX domains of protein disulfide isomerase (PDI). This subfamily is composed of the N-terminal TRX domain of EFP1, which contains a CXXS sequence in place of the typical CXXC motif, similar to ERp44. The CXXS motif allows the formation of stable mixed disulfides, crucial for the ER-retention function of ERp44.

                          10        20
                  ....*....|....*....|....*....
gi 2079606953  19 VLVEFYAPWCGHCKQLAPIYDQLAEKYKD 47
Cdd:cd03006    32 SLVMYYAPWDAQSQAARQEFEQVAQKLSD 60

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
                  ....*....|....*....|....*....|....*....|....*
gi 2079606953  15 KSKSVLVEFYAPWCGHCKQLAPIYDQLAEK---------YKDNAD 50
Cdd:cd03010    24 KGKPYLLNVWASWCAPCREEHPVLMALARQgrvpiyginYKDNPE 68