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 48310619  64 TFNSFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLW 143
Cdd:COG3118   6 TDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90       100
                ....*....|....*....|
gi 48310619 144 DRFEGALPANQLVERIENSL 163
Cdd:COG3118  86 DRFVGALPKEQLREFLDKVL 105

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 48310619  64 TFNSFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLW 143
Cdd:COG3118   6 TDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90       100
                ....*....|....*....|
gi 48310619 144 DRFEGALPANQLVERIENSL 163
Cdd:COG3118  86 DRFVGALPKEQLREFLDKVL 105

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 48310619  67 SFDDLLQNSdKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIaVVKIDTEKYPSLANKYQIEALPTFILFKDGKLWDRF 146
Cdd:cd02947   2 EFEELIKSA-KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVK-FVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                        90
                ....*....|....
gi 48310619 147 EGALPANQLVERIE 160
Cdd:cd02947  80 VGADPKEELEEFLE 93

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619   64 TFNSFDDLLQnSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLW 143
Cdd:PRK10996  41 TGETLDKLLQ-DDLPVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVV 119

                         90
                 ....*....|.
gi 48310619  144 DRFEGALPANQ 154
Cdd:PRK10996 120 DMLNGAVPKAP 130

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 48310619  64 TFNSFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLW 143
Cdd:COG3118   6 TDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90       100
                ....*....|....*....|
gi 48310619 144 DRFEGALPANQLVERIENSL 163
Cdd:COG3118  86 DRFVGALPKEQLREFLDKVL 105

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 48310619  67 SFDDLLQNSdKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIaVVKIDTEKYPSLANKYQIEALPTFILFKDGKLWDRF 146
Cdd:cd02947   2 EFEELIKSA-KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVK-FVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                        90
                ....*....|....
gi 48310619 147 EGALPANQLVERIE 160
Cdd:cd02947  80 VGADPKEELEEFLE 93

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619   64 TFNSFDDLLQnSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLW 143
Cdd:PRK10996  41 TGETLDKLLQ-DDLPVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVV 119

                         90
                 ....*....|.
gi 48310619  144 DRFEGALPANQ 154
Cdd:PRK10996 120 DMLNGAVPKAP 130

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  70 DLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDiIAVVKIDTEK---------------YPS-------LANKYQ 127
Cdd:COG0526  22 SLADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGG-VVFVGVDVDEnpeavkaflkelglpYPVlldpdgeLAKAYG 100

                        90       100       110
                ....*....|....*....|....*....|....
gi 48310619 128 IEALPTFILF-KDGKLWDRFEGALPANQLVERIE 160
Cdd:COG0526 101 VRGIPTTVLIdKDGKIVARHVGPLSPEELEEALE 134

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 48310619  67 SFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGK 141
Cdd:cd03004  10 DFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYPGNA 84

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  67 SFDDLLQNSD-KPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLWDR 145
Cdd:cd02956   2 NFQQVLQESTqVPVVVDFWAPRSPPSKELLPLLERLAEEYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDG 81

                        90
                ....*....|....*
gi 48310619 146 FEGALPANQLVERIE 160
Cdd:cd02956  82 FQGAQPEEQLRQMLD 96

PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the endoplasmic reticulum (ER) and displays both isomerase and chaperone activities, which are independent of each other. Compared to PDI, the isomerase and chaperone activities of P5 are lower. The first cysteine in the CXXC motif of both redox active domains in P5 is necessary for isomerase activity. The P5 gene was first isolated as an amplified gene from a hydroxyurea-resistant hamster cell line. The zebrafish P5 homolog has been implicated to play a critical role in establishing left/right asymmetries in the embryonic midline. Some members of this subfamily are P5-like proteins containing only one redox active TRX domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 48310619  64 TFNSFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGK 141
Cdd:cd03001   6 TDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGAGK 83

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 48310619  80 LVDFYATWCGPCQLMVPILNEVSETLKDI---IAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLWDrFEGALPANQLV 156
Cdd:cd03000  19 LVDFYAPWCGHCKKLEPVWNEVGAELKSSgspVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAYN-YRGPRTKDDIV 97

                .
gi 48310619 157 E 157
Cdd:cd03000  98 E 98

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 48310619  61 KKQTFNSFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDI--IAVVKIDtekypSLAN----KYQIEALPTF 134
Cdd:cd02995   3 KVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDdnVVIAKMD-----ATANdvpsEFVVDGFPTI 77

                ....*..
gi 48310619 135 ILFKDGK 141
Cdd:cd02995  78 LFFPAGD 84

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  71 LLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKIDTEKYPSLANKYQIEALPTFILFKDGKLWDRFEGAL 150
Cdd:cd02949   8 LYHESDRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVK 87

                        90
                ....*....|
gi 48310619 151 PANQLVERIE 160
Cdd:cd02949  88 MKSEYREFIE 97

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  52 FAPLTVRAAKKQTFNSFDDLLQNS---DKPVLVDFYATWCGPCQLMVP-ILN--EVSETLKDIIAVVKID---------- 115
Cdd:COG2143  13 LLAAAAAAQEISFLLDLEEDLALAkaeGKPILLFFESDWCPYCKKLHKeVFSdpEVAAYLKENFVVVQLDaegdkevtdf 92

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 48310619 116 -----TEKypSLANKYQIEALPTFILF-KDGKLWDRFEGALPANQLV 156
Cdd:COG2143  93 dgetlTEK--ELARKYGVRGTPTLVFFdAEGKEIARIPGYLKPETFL 137

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  53 AP-LTVRAAKKQTFnSFDDLLqnsDKPVLVDFYATWCGPCQLMVPILNEVSETLKD----IIAVVK---------IDTEK 118
Cdd:COG1225   1 APdFTLPDLDGKTV-SLSDLR---GKPVVLYFYATWCPGCTAELPELRDLYEEFKDkgveVLGVSSdsdeahkkfAEKYG 76

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 48310619 119 YP---------SLANKYQIEALPTFILF-KDGKLWDRFEGALPANQLVERI 159
Cdd:COG1225  77 LPfpllsdpdgEVAKAYGVRGTPTTFLIdPDGKIRYVWVGPVDPRPHLEEV 127

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 48310619  64 TFNSFDDLLQNsdKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVVKI---DTEKYPSLANKYQIEALPTFILFKDG 140
Cdd:cd03005   6 TEDNFDHHIAE--GNHFVKFFAPWCGHCKRLAPTWEQLAKKFNNENPSVKIakvDCTQHRELCSEFQVRGYPTLLLFKDG 83

                ....*....
gi 48310619 141 KLWDRFEGA 149
Cdd:cd03005  84 EKVDKYKGT 92

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  66 NSFDDLLQNS-DKPVLVDFYATWCGPCQLMVPILNEVSETLKDI-IAVVKIDTEKYPSLANKYQIEA------LPTFILF 137
Cdd:cd02962  36 KTLEEELERDkRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNNnLKFGKIDIGRFPNVAEKFRVSTsplskqLPTIILF 115

                ....*....
gi 48310619 138 KDGKLWDRF 146
Cdd:cd02962 116 QGGKEVARR 124

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  70 DLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAVV--KIDTEKYPSLANKYQIEALPTFILF-KDGKLWDRF 146
Cdd:cd02950  14 EVALSNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVmlNVDNPKWLPEIDRYRVDGIPHFVFLdREGNEEGQS 93

                        90
                ....*....|....*
gi 48310619 147 EGALPANQLVERIEN 161
Cdd:cd02950  94 IGLQPKQVLAQNLDA 108

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 48310619  70 DLLQNSDKPVLVDFYATWCGPCQLMVPIL---NEVSETLKDIIAVVKID-TEKYPS---LANKYQIEALPTFILFKDGKL 142
Cdd:cd02953   5 AQALAQGKPVFVDFTADWCVTCKVNEKVVfsdPEVQAALKKDVVLLRADwTKNDPEitaLLKRFGVFGPPTYLFYGPGGE 84

                        90       100
                ....*....|....*....|
gi 48310619 143 WD--RFEGALPANQLVERIE 160
Cdd:cd02953  85 PEplRLPGFLTADEFLEALE 104

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 48310619  67 SFDDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDII--AVVKIDTEKYPSLANKYQIEALPTFILFKDGK 141
Cdd:cd03002   9 NFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVqvAAVDCDEDKNKPLCGKYGVQGFPTLKVFRPPK 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  68 FDDLLQNSDKpVLVDFYATWCGPCQLMVPILNEVSETLK----DIIAVV--KIDTEKYPSLANKYQIEALPTFILFKDGK 141
Cdd:cd02996  11 IDDILQSAEL-VLVNFYADWCRFSQMLHPIFEEAAAKIKeefpDAGKVVwgKVDCDKESDIADRYRINKYPTLKLFRNGM 89

                ....
gi 48310619 142 LWDR 145
Cdd:cd02996  90 MMKR 93

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  63 QTFNSFDDLLQ---NSDKpVLVDFYATWCGPCQLMVPILNEVSETLKDIiAVVKIDTEKYPSLANKYQIEALPTFILFKD 139
Cdd:cd02989   7 REVSDEKEFFEivkSSER-VVCHFYHPEFFRCKIMDKHLEILAKKHLET-KFIKVNAEKAPFLVEKLNIKVLPTVILFKN 84

                ....*....
gi 48310619 140 GKLWDRFEG 148
Cdd:cd02989  85 GKTVDRIVG 93

TRX domain, DnaJ domain containing protein family; composed of uncharacterized proteins of about 500-800 amino acids, containing an N-terminal DnaJ domain followed by one redox active TRX domain. DnaJ is a member of the 40 kDa heat-shock protein (Hsp40) family of molecular chaperones, which regulate the activity of Hsp70s. TRX is involved in the redox regulation of many protein substrates through the reduction of disulfide bonds. TRX has been implicated to catalyse the reduction of Hsp33, a chaperone holdase that binds to unfolded protein intermediates. The presence of DnaJ and TRX domains in members of this family suggests that they could be involved in a redox-regulated chaperone network.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  64 TFNSFDD--LLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDI---IAVVKIDTEKypSLANKYQIEALPTFILFK 138
Cdd:cd02963  10 TFSQYENeiVPKSFKKPYLIKITSDWCFSCIHIEPVWKEVIQELEPLgvgIATVNAGHER--RLARKLGAHSVPAIVGII 87

                        90       100
                ....*....|....*....|...
gi 48310619 139 DGKLWDRFEGALPANQLVERIEN 161
Cdd:cd02963  88 NGQVTFYHDSSFTKQHVVDFVRK 110

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619    76 DKPVLVDFYATWCGPCQLMVPILNEVSETLKD-----IIAVVKIDTE--------KYPS--------------LANKYQI 128
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKLKKkknveIVFVSLDRDLeefkdylkKMPKdwlsvpfddderneLKRKYGV 80

                          90
                  ....*....|....
gi 48310619   129 EALPTFILF-KDGK 141
Cdd:pfam13905  81 NAIPTLVLLdPNGE 94

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 48310619    54 PLTVRAAKKQTFNSfdDLLQNSdKPVLVDFYATWCGPCQLMVPILNEVSETLKDIIAV 111
Cdd:TIGR00385  44 RLASLDEPGQFYTA--DVLTQG-KPVLLNVWASWCPPCRAEHPYLNELAKQGLPIVGV 98

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  69 DDLLQNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDII-AVVKID-TEKYPSLANKYQIEALPTFILFKDGKLWDRF 146
Cdd:cd02985   8 EALKKAKGRLVVLEFALKHSGPSVKIYPTMVKLSRTCNDVVfLLVNGDeNDSTMELCRREKIIEVPHFLFYKDGEKIHEE 87

                ....*
gi 48310619 147 EGALP 151
Cdd:cd02985  88 EGIGP 92

PDIa family, 5'-Adenylylsulfate (APS) reductase subfamily; composed of plant-type APS reductases containing a C-terminal redox active TRX domain and an N-terminal reductase domain which is part of a superfamily that includes N type ATP PPases. APS reductase catalyzes the reduction of activated sulfate to sulfite, a key step in the biosynthesis of sulfur-containing metabolites. Sulfate is first activated by ATP sulfurylase, forming APS, which can be phosphorylated to 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Depending on the organism, either APS or PAPS can be used for sulfate reduction. Prokaryotes and fungi use PAPS, whereas plants use both APS and PAPS. Since plant-type APS reductase uses glutathione (GSH) as its electron donor, the C-terminal domain may function like glutaredoxin, a GSH-dependent member of the TRX superfamily. The flow of reducing equivalents goes from GSH -> C-terminal TRX domain -> N-terminal reductase domain -> APS. Plant-type APS reductase shows no homology to that of dissimilatory sulfate-reducing bacteria, which is an iron-sulfur flavoenzyme. Also included in the alignment is EYE2 from Chlamydomonas reinhardtii, a protein required for eyespot assembly.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 48310619  72 LQNSDKPVLVDFYATWCGPCQLMVPILNEVSETL---KDIIAVVKIDTEKYPSLANKYQIEALPTFILF 137
Cdd:cd02993  17 GERRNQSTLVVLYAPWCPFCQAMEASYEELAEKLagsNVKVAKFNADGEQREFAKEELQLKSFPTILFF 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  38 RRFGSVQSPSSSTRFAplTVRAAKKQTFnsfddllqnsdkpVLVDFYATWCGPCQLMVPILNEVSETLKDIiAVVKIDTE 117
Cdd:cd02957   1 KGFGEVREISSKEFLE--EVTKASKGTR-------------VVVHFYEPGFPRCKILDSHLEELAAKYPET-KFVKINAE 64

                        90       100
                ....*....|....*....|....*....
gi 48310619 118 KyPSLANKYQIEALPTFILFKDGKLWDRF 146
Cdd:cd02957  65 K-AFLVNYLDIKVLPTLLVYKNGELIDNI 92

PDIa family, endoplasmic reticulum protein 44 (ERp44)-like subfamily; composed of uncharacterized PDI-like eukaryotic proteins containing only one redox active TRX (a) domain with a CXXS motif, similar to ERp44. CXXS is still a redox active motif; however, the mixed disulfide formed with the substrate is more stable than those formed by CXXC motif proteins. PDI-related proteins are usually involved in the oxidative protein folding in the ER by acting as catalysts and folding assistants. ERp44 is involved in thiol-mediated retention in the ER.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619  63 QTFNSFDDLL-QNSDKPVLVDFYATWCGPCQLMVPILNEVSETLKDiIAVVKID-TEKYPSLANKYQIEALPTFILFKDG 140
Cdd:cd02999   4 EVLNIALDLMaFNREDYTAVLFYASWCPFSASFRPHFNALSSMFPQ-IRHLAIEeSSIKPSLLSRYGVVGFPTILLFNST 82

                        90
                ....*....|....*..
gi 48310619 141 KLWdRFEGALPANQLVE 157
Cdd:cd02999  83 PRV-RYNGTRTLDSLAA 98

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
                ....*....|....*....|....*....|....*.
gi 48310619  72 LQNsdKPVLVDFYATWCGPCQLMVPILNEVSETLKD 107
Cdd:cd02964  15 LEG--KTVGLYFSASWCPPCRAFTPKLVEFYEKLKE 48

thiol:disulfide interchange protein precursor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619   63 QTFNSFDDLLQ------NSDKPVLVDFYATWCGPCQLMvpilnEVsETLKDI--------IAVVKID-TEKYP---SLAN 124
Cdd:PRK00293 455 QRIKTVAELDQalaeakGKGKPVMLDLYADWCVACKEF-----EK-YTFSDPqvqqaladTVLLQADvTANNAedvALLK 528

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 48310619  125 KYQIEALPTFILF-KDGKLWD--RFEGALPANQLVERIEN 161
Cdd:PRK00293 529 HYNVLGLPTILFFdAQGQEIPdaRVTGFMDAAAFAAHLRQ 568

Redoxin; This family of redoxins includes peroxiredoxin, thioredoxin and glutaredoxin proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 48310619    70 DLLQNSDKPVLVDFYAT-WCGPCQLMVPILNEVSETLK----DIIAVV 112
Cdd:pfam08534  22 SLSDFKGKKVVLNFWPGaFCPTCSAEHPYLEKLNELYKekgvDVVAVN 69

AhpC/TSA family; This family contains proteins related to alkyl hydroperoxide reductase (AhpC) and thiol specific antioxidant (TSA).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48310619    60 AKKQTFNSFDdLLQNSDKPVLVDFYAT-WCGPCQLMVPILNEVSETLKD----IIAVVKIDTEKYPSLANKYQIealpTF 134
Cdd:pfam00578  10 LPDGDGGTVS-LSDYRGKWVVLFFYPAdWTPVCTTELPALADLYEEFKKlgveVLGVSVDSPESHKAFAEKYGL----PF 84