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 22326600  85 SHFDQVMEDAQKlgesVVIVWMAAWCRKCIYLKPKLEKLAAEfYPRLRFYHVDVNAVPyRLVSRAGVTKMPTIQLWRDGQ 164
Cdd:cd02947   1 EEFEELIKSAKP----VVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENP-ELAEEYGVRSIPTFLFFKNGK 74

                        90       100
                ....*....|....*....|...
gi 22326600 165 KQAEVIGGHKAhfvvNEVREMIE 187
Cdd:cd02947  75 EVDRVVGADPK----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 22326600  85 SHFDQVMEDAQKlgesVVIVWMAAWCRKCIYLKPKLEKLAAEfYPRLRFYHVDVNAVPyRLVSRAGVTKMPTIQLWRDGQ 164
Cdd:cd02947   1 EEFEELIKSAKP----VVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENP-ELAEEYGVRSIPTFLFFKNGK 74

                        90       100
                ....*....|....*....|...
gi 22326600 165 KQAEVIGGHKAhfvvNEVREMIE 187
Cdd:cd02947  75 EVDRVVGADPK----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 22326600    87 FDQVMEDAQKLgesVVIVWMAAWCRKCIYLKPKLEKLAAEFYPRLRFYHVDVNAVPyRLVSRAGVTKMPTIQLWRDGQKQ 166
Cdd:pfam00085  10 FDEVVQKSSKP---VLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENP-DLASKYGVRGYPTLIFFKNGQPV 85

                  ....*.
gi 22326600   167 AEVIGG 172
Cdd:pfam00085  86 DDYVGA 91

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326600    49 LAAERIRAVDIQKQDGGLQ---------ELDDSPVSVELGpicgeSHFDQVMEDAQKlgeSVVIVWMAAWCRKCIYLKPK 119
Cdd:TIGR01130 314 FSSENLEAFVKDFLDGKLKpylksepipEDDEGPVKVLVG-----KNFDEIVLDETK---DVLVEFYAPWCGHCKNLAPI 385

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 22326600   120 LEKLAAEF---YPRLRFYHVD--VNAVPYrlvsrAGVTKMPTIQLWRDGQK 165
Cdd:TIGR01130 386 YEELAEKYkdaESDVVIAKMDatANDVPP-----FEVEGFPTIKFVPAGKK 431

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 22326600  85 SHFDQVMEDAQKlgesVVIVWMAAWCRKCIYLKPKLEKLAAEfYPRLRFYHVDVNAVPyRLVSRAGVTKMPTIQLWRDGQ 164
Cdd:cd02947   1 EEFEELIKSAKP----VVVDFWAPWCGPCKAIAPVLEELAEE-YPKVKFVKVDVDENP-ELAEEYGVRSIPTFLFFKNGK 74

                        90       100
                ....*....|....*....|...
gi 22326600 165 KQAEVIGGHKAhfvvNEVREMIE 187
Cdd:cd02947  75 EVDRVVGADPK----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 22326600    87 FDQVMEDAQKLgesVVIVWMAAWCRKCIYLKPKLEKLAAEFYPRLRFYHVDVNAVPyRLVSRAGVTKMPTIQLWRDGQKQ 166
Cdd:pfam00085  10 FDEVVQKSSKP---VLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENP-DLASKYGVRGYPTLIFFKNGQPV 85

                  ....*.
gi 22326600   167 AEVIGG 172
Cdd:pfam00085  86 DDYVGA 91

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326600   82 CGESHFD-QVMEDAQ----KLGES---VVIVWMAAWCRKCIYLKPKLEKLAAEFYPRLRFYHVDVNAVPyRLVSRAGVTK 153
Cdd:PRK10996  28 CGHDLFDgEVINATGetldKLLQDdlpVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAER-ELSARFRIRS 106

                         90       100
                 ....*....|....*....|....*.
gi 22326600  154 MPTIQLWRDGQKqAEVIGGH--KAHF 177
Cdd:PRK10996 107 IPTIMIFKNGQV-VDMLNGAvpKAPF 131

PDIa family, endoplasmic reticulum protein 44 (ERp44)-like subfamily; composed of uncharacterized PDI-like eukaryotic proteins containing only one redox active TRX (a) domain with a CXXS motif, similar to ERp44. CXXS is still a redox active motif; however, the mixed disulfide formed with the substrate is more stable than those formed by CXXC motif proteins. PDI-related proteins are usually involved in the oxidative protein folding in the ER by acting as catalysts and folding assistants. ERp44 is involved in thiol-mediated retention in the ER.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326600  79 GPICGESHFDQVMedAQKLGESVVIVWMAAWCRKCIYLKPKLEKLAAeFYPRLRFYHVDVNAVPYRLVSRAGVTKMPTIQ 158
Cdd:cd02999   1 PPEEVLNIALDLM--AFNREDYTAVLFYASWCPFSASFRPHFNALSS-MFPQIRHLAIEESSIKPSLLSRYGVVGFPTIL 77

                ....*
gi 22326600 159 LWRDG 163
Cdd:cd02999  78 LFNST 82

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 22326600  76 VELGPicgeSHFDQVMEDAqklGESVVIVWMAAWCRKCIYLKPKLEKLAAEFYPRLRFYHVDVNAVPYR-LVSRAGVTKM 154
Cdd:cd03002   3 YELTP----KNFDKVVHNT---NYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKNKpLCGKYGVQGF 75

                        90
                ....*....|.
gi 22326600 155 PTIQLWRDGQK 165
Cdd:cd03002  76 PTLKVFRPPKK 86

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326600  84 ESHFDQVMEDAQKlgeSVVIVWMAAWCRKCIYLKPKLEKLAAEFY--PRLRFYHVDVNAVPYRLVSRAGVTKMPTIQLWR 161
Cdd:cd02998   7 DSNFDKVVGDDKK---DVLVEFYAPWCGHCKNLAPEYEKLAAVFAneDDVVIAKVDADEANKDLAKKYGVSGFPTLKFFP 83

                ....*..
gi 22326600 162 DGQKQAE 168
Cdd:cd02998  84 KGSTEPV 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326600    49 LAAERIRAVDIQKQDGGLQ---------ELDDSPVSVELGpicgeSHFDQVMEDAQKlgeSVVIVWMAAWCRKCIYLKPK 119
Cdd:TIGR01130 314 FSSENLEAFVKDFLDGKLKpylksepipEDDEGPVKVLVG-----KNFDEIVLDETK---DVLVEFYAPWCGHCKNLAPI 385

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 22326600   120 LEKLAAEF---YPRLRFYHVD--VNAVPYrlvsrAGVTKMPTIQLWRDGQK 165
Cdd:TIGR01130 386 YEELAEKYkdaESDVVIAKMDatANDVPP-----FEVEGFPTIKFVPAGKK 431

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 22326600 112 KCIYLKPKLEKLAAEfYPRLRFYHVDVNAVPYrLVSRAGVTKMPTIQLWRDGQKQAEVIG 171
Cdd:cd02989  36 RCKIMDKHLEILAKK-HLETKFIKVNAEKAPF-LVEKLNIKVLPTVILFKNGKTVDRIVG 93