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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 752820168  1 MSKVLDDFSAQYGDqVRVERVDVMQNSELAQKYEVRYVPTLVFEDgNGNILGKEVGYLSLEEIIIKLE 68
Cdd:cd02947  28 IAPVLEELAEEYPK-VKFVKVDVDENPELAEEYGVRSIPTFLFFK-NGKEVDRVVGADPKEELEEFLE 93

thioredoxin TrxA;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 752820168   1 MSKVLDDFSAQYGDQVRVERVDVMQNSELAQKYEVRYVPTLVFEDgNGNILGKEVGYLS 59
Cdd:PRK09381  39 IAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFK-NGEVAATKVGALS 96

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 752820168  1 MSKVLDDFSAQYGDqVRVERVDVMQNSELAQKYEVRYVPTLVFEDgNGNILGKEVGYLSLEEIIIKLE 68
Cdd:cd02947  28 IAPVLEELAEEYPK-VKFVKVDVDENPELAEEYGVRSIPTFLFFK-NGKEVDRVVGADPKEELEEFLE 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 752820168    1 MSKVLDDFSAQYGDQVRVERVDVMQNSELAQKYEVRYVPTLVFEDgNGNILGKEVGYLSLEEIIIKLEE 69
Cdd:pfam00085  36 LAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFK-NGQPVDDYVGARPKDALAAFLKA 103

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 752820168  25 QNSELAQKYEVRYVPTLVFEDGNGNILGKEVGYLSLEEIIIKLEEY 70
Cdd:COG0526   91 PDGELAKAYGVRGIPTTVLIDKDGKIVARHVGPLSPEELEEALEKL 136

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 752820168  11 QYGDQVRVERVDVMQNSELAQKYEVRYVPTL-VFEDGNGNILgKEVGYLSLEEII 64
Cdd:cd02961   45 KGDGKVVVAKVDCTANNDLCSEYGVRGYPTIkLFPNGSKEPV-KYEGPRTLESLV 98

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 752820168   1 MSKVLDDFSAQYGDQVRVervdVMQNSE------LAQKYEVRYVPTLVFEDGNGNILGKEVGYLSLEEI 63
Cdd:cd02950   38 MAPDVAKLKQKYGDQVNF----VMLNVDnpkwlpEIDRYRVDGIPHFVFLDREGNEEGQSIGLQPKQVL 102

Thioredoxin (TRX)-Glutaredoxin (GRX)-like family; composed of archaeal and bacterial proteins that show similarity to both TRX and GRX, including the C-terminal TRX-fold subdomain of Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO). All members contain a redox-active CXXC motif and may function as PDOs. The archaeal proteins Mj0307 and Mt807 show structures more similar to GRX, but activities more similar to TRX. Some members of the family are similar to PfPDO in that they contain a second CXXC motif located in a second TRX-fold subdomain at the N-terminus; the superimposable N- and C-terminal TRX subdomains form a compact structure. PfPDO is postulated to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI). The C-terminal CXXC motif of PfPDO is required for its oxidase, reductase and isomerase activities. Also included in the family is the C-terminal TRX-fold subdomain of the N-terminal domain (NTD) of bacterial AhpF, which has a similar fold as PfPDO with two TRX-fold subdomains but without the second CXXC motif.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 752820168 10 AQYGDQVRVERVDVMQNSELAQKYEVRYVPTLVFED 45
Cdd:cd02973  25 AALNPNISAEMIDAAEFPDLADEYGVMSVPAIVING 60

SoxW family; SoxW is a bacterial periplasmic TRX, containing a redox active CXXC motif, encoded by a genetic locus (sox operon) involved in thiosulfate oxidation. Sulfur bacteria oxidize sulfur compounds to provide reducing equivalents for carbon dioxide fixation during autotrophic growth and the respiratory electron transport chain. It is unclear what the role of SoxW is, since it has been found to be dispensable in the oxidation of thiosulfate to sulfate. SoxW is specifically kept in the reduced state by SoxV, which is essential in thiosulfate oxidation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 752820168  24 MQNSELAQKYEVRYVPTLVFEDGN-GNILGKEVGYLSLEE 62
Cdd:cd02951   71 LSEKELARKYRVRFTPTVIFLDPEgGKEIARLPGYLPPDE 110

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
                  ....*....|....*....|....*....|.
gi 752820168   21 VDVMQNSELAQKYEVRYVPTL-VFEDGNGNI 50
Cdd:TIGR01130  59 VDATEEKDLAQKYGVSGYPTLkIFRNGEDSV 89