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 612908862   8 QQFESLKQGA--TVFEFTAGWCPDCRVIEPDLPELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYI 85
Cdd:cd02947    1 EEFEELIKSAkpVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 612908862  86 GKERKsiEQIDAFLA 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 612908862   8 QQFESLKQGA--TVFEFTAGWCPDCRVIEPDLPELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYI 85
Cdd:cd02947    1 EEFEELIKSAkpVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 612908862  86 GKERKsiEQIDAFLA 100
Cdd:cd02947   81 GADPK--EELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862   1 MKQLESEQQFESLKQG--ATVFEFTAGWCPDCRVIEPDLPELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNG 78
Cdd:PTZ00051   2 VHIVTSQAEFESTLSQneLVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNG 81

                         90
                 ....*....|....*..
gi 612908862  79 ELLGSYIGKERKSIEQI 95
Cdd:PTZ00051  82 SVVDTLLGANDEALKQL 98

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 612908862   21 EFTAGWCPDCRVIEPDL----PELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGE 79
Cdd:TIGR01130  24 EFYAPWCGHCKSLAPEYekaaDELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRNGE 86

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 612908862   8 QQFESLKQGA--TVFEFTAGWCPDCRVIEPDLPELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYI 85
Cdd:cd02947    1 EEFEELIKSAkpVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|....*
gi 612908862  86 GKERKsiEQIDAFLA 100
Cdd:cd02947   81 GADPK--EELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862   1 MKQLESEQQFESLKQG--ATVFEFTAGWCPDCRVIEPDLPELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNG 78
Cdd:PTZ00051   2 VHIVTSQAEFESTLSQneLVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNG 81

                         90
                 ....*....|....*..
gi 612908862  79 ELLGSYIGKERKSIEQI 95
Cdd:PTZ00051  82 SVVDTLLGANDEALKQL 98

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 612908862   19 VFEFTAGWCPDCRVIEPDLPELEARYPM-FDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYIGkeRKSIEQIDA 97
Cdd:pfam00085  22 LVDFYAPWCGPCKMLAPEYEELAQEYKGnVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVG--ARPKDALAA 99

                  ...
gi 612908862   98 FLA 100
Cdd:pfam00085 100 FLK 102

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862  16 GATVFEFTAGWCPDCRVIEPDLPELEARYP-MFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYIGKERKSieQ 94
Cdd:PRK09381  22 GAILVDFWAEWCGPCKMIAPILDEIADEYQgKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGALSKG--Q 99

                 ....*
gi 612908862  95 IDAFL 99
Cdd:PRK09381 100 LKEFL 104

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 612908862   7 EQQFESLKQGATVFEFTAGWCPDCRVIEPDLPELEARYP-MFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYI 85
Cdd:cd02956    4 QQVLQESTQVPVVVDFWAPRSPPSKELLPLLERLAEEYQgQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDGFQ 83

                         90
                 ....*....|....*
gi 612908862  86 GKerKSIEQIDAFLA 100
Cdd:cd02956   84 GA--QPEEQLRQMLD 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862   6 SEQQFESLKQGA----TVFEFTAGWCPDCRVIEPDLPEL-EARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGEL 80
Cdd:cd02984    1 SEEEFEELLKSDasklLVLHFWAPWAEPCKQMNQVFEELaKEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTI 80

                 .
gi 612908862  81 L 81
Cdd:cd02984   81 V 81

Phosducin (Phd)-like family, Viral inhibitor of apoptosis (IAP)-associated factor (VIAF) subfamily; VIAF is a Phd-like protein that functions in caspase activation during apoptosis. It was identified as an IAP binding protein through a screen of a human B-cell library using a prototype IAP. VIAF lacks a consensus IAP binding motif and while it does not function as an IAP antagonist, it still plays a regulatory role in the complete activation of caspases. VIAF itself is a substrate for IAP-mediated ubiquitination, suggesting that it may be a target of IAPs in the prevention of cell death. The similarity of VIAF to Phd points to a potential role distinct from apoptosis regulation. Phd functions as a cytosolic regulator of G protein by specifically binding to G protein betagamma (Gbg)-subunits. 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862  28 PDCRVIEPDLPELEARYPMFDFVSVDRDKfmdiCIEN-GIMGIPSFLVYKNGELLGSYIGKE-----RKSIEQIDAFLAQ 101
Cdd:cd02988  115 PLCRLLNQHLSELARKFPDTKFVKIISTQ----CIPNyPDKNLPTILVYRNGDIVKQFIGLLefggmNTTMEDLEWLLVQ 190

                 .
gi 612908862 102 Y 102
Cdd:cd02988  191 V 191

TlpA-like family, suppressor for copper sensitivity D protein (ScsD) and actinobacterial DsbE homolog subfamily; composed of ScsD, the DsbE homolog of Mycobacterium tuberculosis (MtbDsbE) and similar proteins, all containing a redox-active CXXC motif. The Salmonella typhimurium ScsD is a thioredoxin-like protein which confers copper tolerance to copper-sensitive mutants of E. coli. MtbDsbE has been characterized as an oxidase in vitro, catalyzing the disulfide bond formation of substrates like hirudin. The reduced form of MtbDsbE is more stable than its oxidized form, consistent with an oxidase function. This is in contrast to the function of DsbE from gram-negative bacteria which is a specific reductase of apocytochrome c.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862   8 QQF--ESLKQGATVFEFTAGWCPDCRVIEPDLPELEARYPmfdFVSV------DRD--KFM---------------DICI 62
Cdd:cd03011   11 EQFdlESLSGKPVLVYFWATWCPVCRFTSPTVNQLAADYP---VVSValrsgdDGAvaRFMqkkgygfpvindpdgVISA 87

                         90
                 ....*....|....*..
gi 612908862  63 ENGIMGIPSFLVYKNGE 79
Cdd:cd03011   88 RWGVSVTPAIVIVDPGG 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862  17 ATVFEFTAGWCPDCRVIEPDLPELEARY-PMFDFVSV--DRDKFMDICIENGIMGIPSFLVYKNGELLGS-----YIG-K 87
Cdd:cd03002   20 TTLVEFYAPWCGHCKNLKPEYAKAAKELdGLVQVAAVdcDEDKNKPLCGKYGVQGFPTLKVFRPPKKASKhavedYNGeR 99

                 ....*
gi 612908862  88 ERKSI 92
Cdd:cd03002  100 SAKAI 104

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 612908862  22 FTAGWCPDCRVIEPDLPELEARYP-MFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLGSYIGKERKS 91
Cdd:cd02949   20 YTSPTCGPCRTLKPILNKVIDEFDgAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKS 90

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 612908862   21 EFTAGWCPDCRVIEPDL----PELEARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGE 79
Cdd:TIGR01130  24 EFYAPWCGHCKSLAPEYekaaDELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRNGE 86

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 612908862  27 CPDCRVIEPDLPELEARYPMFDFVSVdRDKFMDICIENGIMGIPSFLVYKNGELLGSYIG 86
Cdd:cd02987   95 IPGCAALNSSLLCLAAEYPAVKFCKI-RASATGASDEFDTDALPALLVYKGGELIGNFVR 153

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862   6 SEQQFESLKQ---GATV----FEFTAGWCPDCRVIEPDLPEL-EARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKN 77
Cdd:PTZ00443  36 NDKNFEKLTQastGATTgpwfVKFYAPWCSHCRKMAPAWERLaKALKGQVNVADLDATRALNLAKRFAIKGYPTLLLFDK 115

                         90       100
                 ....*....|....*....|.
gi 612908862  78 GELLgSYIGKERkSIEQIDAF 98
Cdd:PTZ00443 116 GKMY-QYEGGDR-STEKLAAF 134

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 612908862   6 SEQQFESLKQGAT--VFEFTAGWCPDCRVIEPDLPEL-EARYPMFDFVSVDRDKFMDICIENGIMGIPSFLVYKNGELLG 82
Cdd:PRK10996  41 TGETLDKLLQDDLpvVIDFWAPWCGPCRNFAPIFEDVaAERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVD 120

                         90
                 ....*....|....*....
gi 612908862  83 SYIGKERKSieQIDAFLAQ 101
Cdd:PRK10996 121 MLNGAVPKA--PFDSWLNE 137

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 612908862   8 QQFESL-KQGAT--VFEFTAGWCPDCRVIepdLPELE--AR--YPMFDFVSVDRDKFMDICIENGIMGIPSFLVYK 76
Cdd:cd03004    9 EDFPELvLNRKEpwLVDFYAPWCGPCQAL---LPELRkaARalKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYP 81