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 516234300   8 QQFEELKQGN--TVFEFTAGWCPDCKIIEPELPQLEEKYQSFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELLGSYI 85
Cdd:cd02947    1 EEFEELIKSAkpVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 516234300  86 GKERKsiEQIDQFLA 100
Cdd:cd02947   81 GADPK--EELEEFLE 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 516234300   8 QQFEELKQGN--TVFEFTAGWCPDCKIIEPELPQLEEKYQSFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELLGSYI 85
Cdd:cd02947    1 EEFEELIKSAkpVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 516234300  86 GKERKsiEQIDQFLA 100
Cdd:cd02947   81 GADPK--EELEEFLE 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 516234300    2 IQLETEQQFEE-LKQGNT--VFEFTAGWCPDCKIIEPELPQLEEKYQS-FKFVSVDRDQFLDICIENGIMGIPSFLVYRD 77
Cdd:pfam00085   2 VVVLTDANFDEvVQKSSKpvLVDFYAPWCGPCKMLAPEYEELAQEYKGnVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|...
gi 516234300   78 GELLGSYIGkeRKSIEQIDQFLA 100
Cdd:pfam00085  82 GQPVDDYVG--ARPKDALAAFLK 102

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 516234300    6 TEQQFEE-LKQGNT--VFEFTAGWCPDCKIIEPELPQLEEKYQS-FKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELL 81
Cdd:TIGR01068   2 TDANFDEtIASSDKpvLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90       100
                  ....*....|....*....|..
gi 516234300   82 GSYIGKERKSieQIDQFLAQYI 103
Cdd:TIGR01068  82 DRSVGALPKA--ALKQLINKNL 101

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 516234300   8 QQFEELKQGN--TVFEFTAGWCPDCKIIEPELPQLEEKYQSFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELLGSYI 85
Cdd:cd02947    1 EEFEELIKSAkpVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 516234300  86 GKERKsiEQIDQFLA 100
Cdd:cd02947   81 GADPK--EELEEFLE 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 516234300    2 IQLETEQQFEE-LKQGNT--VFEFTAGWCPDCKIIEPELPQLEEKYQS-FKFVSVDRDQFLDICIENGIMGIPSFLVYRD 77
Cdd:pfam00085   2 VVVLTDANFDEvVQKSSKpvLVDFYAPWCGPCKMLAPEYEELAQEYKGnVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|...
gi 516234300   78 GELLGSYIGkeRKSIEQIDQFLA 100
Cdd:pfam00085  82 GQPVDDYVG--ARPKDALAAFLK 102

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516234300   6 TEQQFEELKQGNT--VFEFTAGWCPDCKIIEPELPQLEEKYQSFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELLGS 83
Cdd:PTZ00051   7 SQAEFESTLSQNElvIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVVDT 86

                         90
                 ....*....|..
gi 516234300  84 YIGKERKSIEQI 95
Cdd:PTZ00051  87 LLGANDEALKQL 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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 516234300  18 TVFEFTAGWCPDCKIIEPELPQLEEKYQ---SFKFVSVDRDQFLDICIENGIMGIPSF-LVYRDGELLGSYIGKERKSI 92
Cdd:cd02950   23 TLVEFYADWCTVCQEMAPDVAKLKQKYGdqvNFVMLNVDNPKWLPEIDRYRVDGIPHFvFLDREGNEEGQSIGLQPKQV 101

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 516234300   6 TEQQF-EELKQGNTVFEFTAGWCPDCKIIEPELPQLEEKYQ----SFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGEL 80
Cdd:cd03005    6 TEDNFdHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNnenpSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDGEK 85

                 ....*..
gi 516234300  81 LGSYIGK 87
Cdd:cd03005   86 VDKYKGT 92

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516234300   6 TEQQFEELKQGN----TVFEFTAGWCPDCKIIEPELPQL-EEKYQSFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGEL 80
Cdd:cd02984    1 SEEEFEELLKSDasklLVLHFWAPWAEPCKQMNQVFEELaKEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTI 80

                 .
gi 516234300  81 L 81
Cdd:cd02984   81 V 81

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 516234300   7 EQQFEELKQGNTVFEFTAGWCPDCKIIEPELPQLEEKYQ-SFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELLGSYI 85
Cdd:cd02956    4 QQVLQESTQVPVVVDFWAPRSPPSKELLPLLERLAEEYQgQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDGFQ 83

                         90
                 ....*....|....*
gi 516234300  86 GKerKSIEQIDQFLA 100
Cdd:cd02956   84 GA--QPEEQLRQMLD 96

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 516234300  11 EELKQGNTVF-EFTAGWCPDCKIIEPEL---PQLEEKYQS-FKFVSVD---RD----QFLDiciENGIMGIPSFLVYRDG 78
Cdd:cd02953    6 QALAQGKPVFvDFTADWCVTCKVNEKVVfsdPEVQAALKKdVVLLRADwtkNDpeitALLK---RFGVFGPPTYLFYGPG 82

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 516234300  19 VFEFTAGWCPDCKIIEPELPQLEekyqsFKFVSVDRDQFLDICIENGIMGIPSFL 73
Cdd:PHA02125   2 IYLFGAEWCANCKMVKPMLANVE-----YTYVDVDTDEGVELTAKHHIRSLPTLV 51

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 516234300  19 VFEFTAGWCPDCKIIEPELPQLEEKYQSFKFVSVDRDQFLDIC---IENGIMGIPSFLVYRDGE 79
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDPALEkelKRYGVGGVPTLVVFGPGI 64

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 516234300  22 FTAGWCPDCKIIEPELPQLEEKYQS-FKFVSVDRDQFLDICIENGIMGIPSFLVYRDGELLGSYIGKERKS 91
Cdd:cd02949   20 YTSPTCGPCRTLKPILNKVIDEFDGaVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKS 90

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 516234300  18 TVFEFTAGWCPDCKIIEPELPQLEEKYQS-FKFVSVDRDQFL--DICIENGIMGIPSFLVYRDGELLGS-----YIG-KE 88
Cdd:cd03002   21 TLVEFYAPWCGHCKNLKPEYAKAAKELDGlVQVAAVDCDEDKnkPLCGKYGVQGFPTLKVFRPPKKASKhavedYNGeRS 100

                 ....
gi 516234300  89 RKSI 92
Cdd:cd03002  101 AKAI 104

disulphide isomerase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 516234300  22 FTAGWCPDCKIIEPEL----PQLEEKYQSFKFVSVDRDQFLDICIENGIMGIPSFLVYRDGE 79
Cdd:PTZ00102  56 FYAPWCGHCKRLAPEYkkaaKMLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGN 117

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 516234300  18 TVFEFTAGWCPDCKIIEPELPQLEEKYQS--FKFVSVDRD--------QFLD---------------ICIENGIMGIP-S 71
Cdd:cd02966   22 VLVNFWASWCPPCRAEMPELEALAKEYKDdgVEVVGVNVDdddpaavkAFLKkygitfpvlldpdgeLAKAYGVRGLPtT 101

                         90
                 ....*....|....*
gi 516234300  72 FLVYRDGELLGSYIG 86
Cdd:cd02966  102 FLIDRDGRIRARHVG 116

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 516234300   22 FTAGWCPDCKIIEPELPQLEEKYQSFK-----FVSVDRDQ-------------FLDICIEN----------GIMGIPSFL 73
Cdd:pfam13905   8 FGASWCKPCRRFTPLLKELYEKLKKKKnveivFVSLDRDLeefkdylkkmpkdWLSVPFDDdernelkrkyGVNAIPTLV 87

                  ....*..
gi 516234300   74 VY-RDGE 79
Cdd:pfam13905  88 LLdPNGE 94

Phosducin (Phd)-like family, Phd subfamily; Phd is a cytosolic regulator of G protein functions. It specifically binds G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane. This impedes the formation of a functional G protein trimer (G protein alphabetagamma), thereby inhibiting G protein-mediated signal transduction. 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 516234300  27 CPDCKIIEPELPQLEEKYQSFKFVSVdRDQFLDICIENGIMGIPSFLVYRDGELLGSYIG 86
Cdd:cd02987   95 IPGCAALNSSLLCLAAEYPAVKFCKI-RASATGASDEFDTDALPALLVYKGGELIGNFVR 153

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
                  ....*....|....*....|....*....|....*....|
gi 516234300   10 FEE--LKQGNTVF-EFTAGWCPDCKIIEPELPQLEEKYQS 46
Cdd:TIGR01130 356 FDEivLDETKDVLvEFYAPWCGHCKNLAPIYEELAEKYKD 395