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 186478272  17 AGDKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRGSQ--GRVCSFSctna 94
Cdd:cd02947    8 KSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKevDRVVGAD---- 83

                         90
                 ....*....|
gi 186478272  95 TIKKFRDALA 104
Cdd:cd02947   84 PKEELEEFLE 93

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 186478272  17 AGDKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRGSQ--GRVCSFSctna 94
Cdd:cd02947    8 KSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKevDRVVGAD---- 83

                         90
                 ....*....|
gi 186478272  95 TIKKFRDALA 104
Cdd:cd02947   84 PKEELEEFLE 93

thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478272    4 ISSAQelVDSLTNAGDKLVVVDFFSPGCGGCKALHPKICQFA-EMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRGS 82
Cdd:TIGR01068   1 LTDAN--FDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAkEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNG 78

                  .
gi 186478272   83 Q 83
Cdd:TIGR01068  79 K 79

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478272   1 MREISSAQELVDSLTnAGDKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYR 80
Cdd:PTZ00051   1 MVHIVTSQAEFESTL-SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFK 79

                 ...
gi 186478272  81 GSQ 83
Cdd:PTZ00051  80 NGS 82

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 186478272  17 AGDKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRGSQ--GRVCSFSctna 94
Cdd:cd02947    8 KSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKevDRVVGAD---- 83

                         90
                 ....*....|
gi 186478272  95 TIKKFRDALA 104
Cdd:cd02947   84 PKEELEEFLE 93

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 186478272  13 SLTNAGDKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHK 62
Cdd:COG0526   22 SLADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDENP 71

thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186478272    4 ISSAQelVDSLTNAGDKLVVVDFFSPGCGGCKALHPKICQFA-EMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRGS 82
Cdd:TIGR01068   1 LTDAN--FDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAkEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNG 78

                  .
gi 186478272   83 Q 83
Cdd:TIGR01068  79 K 79

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 186478272   6 SAQELVDSLTNAGDKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHKS---MCYSLGVHVLPFFRFYRGS 82
Cdd:cd02985    2 SVEELDEALKKAKGRLVVLEFALKHSGPSVKIYPTMVKLSRTCNDVVFLLVNGDENDStmeLCRREKIIEVPHFLFYKDG 81

                 .
gi 186478272  83 Q 83
Cdd:cd02985   82 E 82

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 186478272   2 REISSaQELVDSLTNAG-DKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEhKSMCYSLGVHVLPFFRFYR 80
Cdd:cd02957    7 REISS-KEFLEEVTKASkGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEK-AFLVNYLDIKVLPTLLVYK 84

                         90
                 ....*....|..
gi 186478272  81 GSQ--GRVCSFS 90
Cdd:cd02957   85 NGEliDNIVGFE 96

TRX domain, PICOT (for PKC-interacting cousin of TRX) subfamily; PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT contains an N-terminal TRX-like domain, which does not contain the catalytic CXXC motif, followed by one to three glutaredoxin domains. The TRX-like domain is required for interaction with PKC theta. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 186478272   6 SAQELVDSLTNAGDKLVVVDFFSPGCGGCKALHPKICQFA-EMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRGSQ 83
Cdd:cd02984    1 SEEEFEELLKSDASKLLVLHFWAPWAEPCKQMNQVFEELAkEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGT 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 186478272   2 REISSAQELVDSLTNAgdKLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFY 79
Cdd:cd02989    7 REVSDEKEFFEIVKSS--ERVVCHFYHPEFFRCKIMDKHLEILAKKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILF 82

disulphide isomerase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 186478272  19 DKLVVVDFFSPGCGGCKALHP---KIC-QFAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYRG 81
Cdd:PTZ00102  49 NEIVLVKFYAPWCGHCKRLAPeykKAAkMLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNK 115

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 186478272   18 GDKLVVVDFFSPGCGGCKALHP---KICQ-FAEMNPDVQFLQVNYEEHKSMCYSLGVHVLPFFRFYR 80
Cdd:TIGR01130  17 SHEFVLVEFYAPWCGHCKSLAPeyeKAADeLKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFR 83

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 186478272  12 DSLTNAGDKLVVVDFFSPGCGGCKALHP---KICQFAEMNPDVQFLQVNY-EEHKSMCYSLGVHVLPFFRFY 79
Cdd:cd02998   11 DKVVGDDKKDVLVEFYAPWCGHCKNLAPeyeKLAAVFANEDDVVIAKVDAdEANKDLAKKYGVSGFPTLKFF 82

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
                 ....*....|....*....|....*....|....*....|....*....|
gi 186478272  13 SLTNAGDKLVVVDFFSPGCGGCKALHPKICQFAEM--NPDVQFLQVNYEE 60
Cdd:cd02966   13 SLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEykDDGVEVVGVNVDD 62

DsbA family, Com1-like subfamily; composed of proteins similar to Com1, a 27-kDa outer membrane-associated immunoreactive protein originally found in both acute and chronic disease strains of the pathogenic bacteria Coxiella burnetti. It contains a CXXC motif, assumed to be imbedded in a DsbA-like structure. Its homology to DsbA suggests that the protein is a protein disulfide oxidoreductase. The role of such a protein in pathogenesis is unknown.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 186478272  20 KLVVVDFFSPGCGGCKALHPKICQFAEMNPDVQF 53
Cdd:cd03023    6 DVTIVEFFDYNCGYCKKLAPELEKLLKEDPDVRV 39

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
                  ....*....|....*....|....*....|....*....|...
gi 186478272   19 DKLVVVDFFSPGCGGCKALHPKICQFAEM---NPDVQFLQVNY 58
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKlkkKKNVEIVFVSL 43