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 392920292  20 EDFtEKVIQSSVPVIVDFHAEWCGPCQALGPRLEEkVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGEKISG 99
Cdd:cd02947    1 EEF-EELIKSAKPVVVDFWAPWCGPCKAIAPVLEE-LAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                         90
                 ....*....|....*
gi 392920292 100 FSGVLDDEQLDDFIE 114
Cdd:cd02947   79 VVGADPKEELEEFLE 93

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 392920292   18 SVEDFTEKVIQSSVPVIVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGEKI 97
Cdd:pfam00085   6 TDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPV 85

                          90
                  ....*....|....*...
gi 392920292   98 SGFSGVLDDEQLDDFIED 115
Cdd:pfam00085  86 DDYVGARPKDALAAFLKA 103

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 392920292  20 EDFtEKVIQSSVPVIVDFHAEWCGPCQALGPRLEEkVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGEKISG 99
Cdd:cd02947    1 EEF-EELIKSAKPVVVDFWAPWCGPCKAIAPVLEE-LAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDR 78

                         90
                 ....*....|....*
gi 392920292 100 FSGVLDDEQLDDFIE 114
Cdd:cd02947   79 VVGADPKEELEEFLE 93

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 392920292   18 SVEDFTEKVIQSSVPVIVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGEKI 97
Cdd:pfam00085   6 TDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPV 85

                          90
                  ....*....|....*...
gi 392920292   98 SGFSGVLDDEQLDDFIED 115
Cdd:pfam00085  86 DDYVGARPKDALAAFLKA 103

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  10 GASVFD---IDSVEDFTEKVIQSSVPVIVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAGELAMDYGISAVP 86
Cdd:PRK10996  29 GHDLFDgevINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAERELSARFRIRSIP 108

                         90       100       110
                 ....*....|....*....|....*....|.
gi 392920292  87 TVFAFKNGEKISGFSGVLDDEQLDDFIEDVL 117
Cdd:PRK10996 109 TIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

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 392920292  20 EDFtEKVIQSSVPVIVDFHAEWCGPCQALGPRLEE---KVNGrQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNG-E 95
Cdd:cd02961    6 DNF-DELVKDSKDVLVEFYAPWCGHCKALAPEYEKlakELKG-DGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGsK 83

                         90
                 ....*....|....*...
gi 392920292  96 KISGFSGVLDDEQLDDFI 113
Cdd:cd02961   84 EPVKYEGPRTLESLVEFI 101

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  18 SVEDFTEKviqssvPVIVDFHAEWCGPCQALGPRLEEkVNGRQGSVLLAKINV----------------------DHAGE 75
Cdd:COG0526   22 SLADLKGK------PVLVNFWATWCPPCRAEMPVLKE-LAEEYGGVVFVGVDVdenpeavkaflkelglpypvllDPDGE 94

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 392920292  76 LAMDYGISAVPTVFAF-KNGEKISGFSGVLDDEQLDDFIEDVLAA 119
Cdd:COG0526   95 LAKAYGVRGIPTTVLIdKDGKIVARHVGPLSPEELEEALEKLLAK 139

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292   7 FSHGASVFDIDSVEDFT----EKVIQSSVPVIVDFHAEWCGPCQALGPRLEEKVN--GRQGS-VLLAKINVDHAGELAMD 79
Cdd:PTZ00102  22 FGSAEEHFISEHVTVLTdstfDKFITENEIVLVKFYAPWCGHCKRLAPEYKKAAKmlKEKKSeIVLASVDATEEMELAQE 101

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 392920292  80 YGISAVPTVFAFKNGEKISgFSGVLDDEQLDDFIEDVL 117
Cdd:PTZ00102 102 FGVRGYPTIKFFNKGNPVN-YSGGRTADGIVSWIKKLT 138

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  17 DSVE----DFTEKVIQSSVPVIVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFK 92
Cdd:cd03001    1 DVVEltdsNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                 ....
gi 392920292  93 NGEK 96
Cdd:cd03001   81 AGKN 84

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 392920292  20 EDFTEKViqSSVPVIVDFHAEWCGPCQALGPRLEE---KVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGEK 96
Cdd:cd03005    8 DNFDHHI--AEGNHFVKFFAPWCGHCKRLAPTWEQlakKFNNENPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDGEK 85

                         90
                 ....*....|....*..
gi 392920292  97 ISGFSGVLDDEQLDDFI 113
Cdd:cd03005   86 VDKYKGTRDLDSLKEFV 102

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  22 FTEKVIQSSVPVIVDFHAEWCGPCQALGPRLEE--KVNGRQGSVLLAKINVDhAGELAM-DYGISAVPTVFAFKNGEKIS 98
Cdd:PTZ00102 367 FEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNElgEKYKDNDSIIVAKMNGT-ANETPLeEFSWSAFPTILFVKAGERTP 445

                         90
                 ....*....|....*..
gi 392920292  99 -GFSGVLDDEQLDDFIE 114
Cdd:PTZ00102 446 iPYEGERTVEGFKEFVN 462

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 392920292  20 EDFTEKVIQSSVPVIVDFHAEWCGPCQALGPRLEE--KVNGRQGSVLLAKINVDhAGELAMDYGISAVPTVFAFKNGEK- 96
Cdd:cd02995    8 KNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEElaEKLKGDDNVVIAKMDAT-ANDVPSEFVVDGFPTILFFPAGDKs 86

                         90
                 ....*....|....*....
gi 392920292  97 --ISgFSGVLDDEQLDDFI 113
Cdd:cd02995   87 npIK-YEGDRTLEDLIKFI 104

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 392920292  24 EKVIQSSVPVIVDFHAEWCGPCQALGPRLEE---KVNGR---QGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGE 95
Cdd:cd02996   12 DDILQSAELVLVNFYADWCRFSQMLHPIFEEaaaKIKEEfpdAGKVVWGKVDCDKESDIADRYRINKYPTLKLFRNGM 89

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  32 PVIVDFHAEWCGPCQALGPRLEE--KVNGRQGSVLLAkINV-----------------------DHAGELAMDYGISAVP 86
Cdd:cd02966   21 VVLVNFWASWCPPCRAEMPELEAlaKEYKDDGVEVVG-VNVddddpaavkaflkkygitfpvllDPDGELAKAYGVRGLP 99

                         90
                 ....*....|....*..
gi 392920292  87 TVFAF-KNGEKISGFSG 102
Cdd:cd02966  100 TTFLIdRDGRIRARHVG 116

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 392920292  32 PVIVDFHAEWCGPCQALGPRLEEKvnGRQGSVLLAKIN-----------------------VDHAGELAMDYGISAVPTV 88
Cdd:cd03010   27 PYLLNVWASWCAPCREEHPVLMAL--ARQGRVPIYGINykdnpenalawlarhgnpyaavgFDPDGRVGIDLGVYGVPET 104

                         90       100
                 ....*....|....*....|...
gi 392920292  89 FAF-KNGEKISGFSGVLDDEQLD 110
Cdd:cd03010  105 FLIdGDGIIRYKHVGPLTPEVWE 127

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 392920292  25 KVIQSS-VPVIVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAG--ELAMDYGISAVPTVFAFKNGEKIS 98
Cdd:cd03002   12 KVVHNTnYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKnkPLCGKYGVQGFPTLKVFRPPKKAS 88

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  34 IVDFHAEWCGPCQALGPRLEEKvnGRQGSVL---LAKINVDHAGELAMDYGISAVPTVFAFKNGEkISGFSGVLDDEQLD 110
Cdd:cd02994   20 MIEFYAPWCPACQQLQPEWEEF--ADWSDDLginVAKVDVTQEPGLSGRFFVTALPTIYHAKDGV-FRRYQGPRDKEDLI 96

                 ....*
gi 392920292 111 DFIED 115
Cdd:cd02994   97 SFIEE 101

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 392920292  32 PVIVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAG--ELAMDYGISAVPTvFAF--KNGEKISGFSGVLDDE 107
Cdd:cd02950   22 PTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPKwlPEIDRYRVDGIPH-FVFldREGNEEGQSIGLQPKQ 100

                 ....*..
gi 392920292 108 QLDDFIE 114
Cdd:cd02950  101 VLAQNLD 107

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 392920292  32 PVIVDFHAEWCGPCQALGPRL---EEKVNGRQGSVLLAKINVDHAG----ELAMDYGISAVPTVFAFKNGEKISGF--SG 102
Cdd:cd02953   13 PVFVDFTADWCVTCKVNEKVVfsdPEVQAALKKDVVLLRADWTKNDpeitALLKRFGVFGPPTYLFYGPGGEPEPLrlPG 92

                         90
                 ....*....|..
gi 392920292 103 VLDdeqLDDFIE 114
Cdd:cd02953   93 FLT---ADEFLE 101

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 392920292   9 HGaSVFDIDSvEDFTEKVIQSS--VPVIVDFHAEWCGPCQALGPRLEEKVNgRQGSVLLAKINVDHAGeLAMDYGISAVP 86
Cdd:cd02957    3 FG-EVREISS-KEFLEEVTKASkgTRVVVHFYEPGFPRCKILDSHLEELAA-KYPETKFVKINAEKAF-LVNYLDIKVLP 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 392920292  87 TVFAFKNGEKISGFSGVLDDEQlDDFIEDVL 117
Cdd:cd02957   79 TLLVYKNGELIDNIVGFEELGG-DDFTTEDL 108

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  32 PVIVdFHAEWCGPCQALGPRLEEKvngrqgSVLLAKINVDH----AGELAMDYGISAVPTVFAfkNGEKISGFsgvlDDE 107
Cdd:COG0695    1 KVTL-YTTPGCPYCARAKRLLDEK------GIPYEEIDVDEdpeaREELRERSGRRTVPVIFI--GGEHLGGF----DEG 67

                 ....*..
gi 392920292 108 QLDDFIE 114
Cdd:COG0695   68 ELDALLA 74

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292   32 PVIVDFHAEWCGPCQALGPRLEEKVNGR---QGSVLLAKINVDHAG-------------ELAMDYGISAVPTVFAFKNGE 95
Cdd:pfam13098   6 PVLVVFTDPDCPYCKKLKKELLEDPDVTvylGPNFVFIAVNIWCAKevakaftdilenkELGRKYGVRGTPTIVFFDGKG 85

                          90
                  ....*....|....*...
gi 392920292   96 KISGFSGVLDDEQLDDFI 113
Cdd:pfam13098  86 ELLRLPGYVPAEEFLALL 103

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392920292  20 EDFTEKVIQSSV----PVIVDFHAEWCGPCQAL------GPRLEEKVngrQGSVLLAKINVDH----AGELAMDYGISAV 85
Cdd:COG4232  306 QADLEAALAEARaegkPVFVDFTADWCVTCKENertvfsDPEVQAAL---ADDVVLLKADVTDndpeITALLKRFGRFGV 382

                         90       100       110
                 ....*....|....*....|....*....|....
gi 392920292  86 PTVFAF-KNGEKISGFSGVLDDEQLDDFIEDVLA 118
Cdd:COG4232  383 PTYVFYdPDGEELPRLGFMLTADEFLAALEKAKG 416

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 392920292  32 PVIVDFHAEWCGPCQALGPRLEEKVNGRQG-SVLLAKINVDHAGELAMDYGISAVPTVFAFKNGeKISGF-SGVLDDEQL 109
Cdd:cd02963   26 PYLIKITSDWCFSCIHIEPVWKEVIQELEPlGVGIATVNAGHERRLARKLGAHSVPAIVGIING-QVTFYhDSSFTKQHV 104

                 ....*..
gi 392920292 110 DDFIEDV 116
Cdd:cd02963  105 VDFVRKL 111

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392920292  34 IVDFHAEWCGPCQALGPRLEEKVNGRQGSVLLAKINVDHAGELAMDYGISAVPTVFAFKNGEKISGFSGVLDDEQLDDF 112
Cdd:cd03003   22 FVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSGMNPEKYYGDRSKESLVKF 100

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 392920292  70 VDHAGELAMDYGISAVPTVFAfkNGEKISGFsgvLDDEQLDDFIEDVL 117
Cdd:COG1651  110 VEADTALAQALGVTGTPTFVV--NGKLVSGA---VPYEELEAALDAAL 152

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 392920292  33 VIVDFHAEWCGPCQALGPRLEeKVNGRQGSVLLAKINVDHAG---ELAMDYGISAVPTVFAFKNGEKISGFSGVLDDEQL 109
Cdd:cd02985   18 VVLEFALKHSGPSVKIYPTMV-KLSRTCNDVVFLLVNGDENDstmELCRREKIIEVPHFLFYKDGEKIHEEEGIGPDELI 96

                 ..
gi 392920292 110 DD 111
Cdd:cd02985   97 GD 98