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 135773    11 FQEALDAAgdKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEFS 90
Cdd:cd02947   3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
gi 135773    91 GAN-KEKLEATIN 102
Cdd:cd02947  81 GADpKEELEEFLE 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 135773    11 FQEALDAAgdKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEFS 90
Cdd:cd02947   3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
gi 135773    91 GAN-KEKLEATIN 102
Cdd:cd02947  81 GADpKEELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773      1 MVKQIESKTAFQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFF 80
Cdd:PTZ00051   1 MVHIVTSQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVF 78

                         90       100
                 ....*....|....*....|
gi 135773     81 KKGQKVGEFSGANKEKLEAT 100
Cdd:PTZ00051  79 KNGSVVDTLLGANDEALKQL 98

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 135773      11 FQEALdAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSN-VIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEF 89
Cdd:TIGR01068   6 FDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
gi 135773      90 SGAN-KEKLEATINELV 105
Cdd:TIGR01068  85 VGALpKAALKQLINKNL 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 135773    11 FQEALDAAgdKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEFS 90
Cdd:cd02947   3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                        90
                ....*....|...
gi 135773    91 GAN-KEKLEATIN 102
Cdd:cd02947  81 GADpKEELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773      1 MVKQIESKTAFQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFF 80
Cdd:PTZ00051   1 MVHIVTSQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVF 78

                         90       100
                 ....*....|....*....|
gi 135773     81 KKGQKVGEFSGANKEKLEAT 100
Cdd:PTZ00051  79 KNGSVVDTLLGANDEALKQL 98

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 135773      11 FQEALdAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSN-VIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEF 89
Cdd:TIGR01068   6 FDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
gi 135773      90 SGAN-KEKLEATINELV 105
Cdd:TIGR01068  85 VGALpKAALKQLINKNL 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773    14 ALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDD----------------------CQDVASECEV 71
Cdd:COG0526  22 SLADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDEnpeavkaflkelglpypvlldpDGELAKAYGV 101

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 135773    72 KCMPTFQFF-KKGQKVGEFSGA-NKEKLEATINELV 105
Cdd:COG0526 102 RGIPTTVLIdKDGKIVARHVGPlSPEELEEALEKLL 137

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773     20 DKLVVVDFSATWCGPCKMIKPFFHSLS-EKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEFSGA-NKEKL 97
Cdd:PRK10996  52 DLPVVIDFWAPWCGPCRNFAPIFEDVAaERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAvPKAPF 131

                 ....*.
gi 135773     98 EATINE 103
Cdd:PRK10996 132 DSWLNE 137

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        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773    11 FQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKY---SNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKG-QKV 86
Cdd:cd02961   8 FDELV--KDSKDVLVEFYAPWCGHCKALAPEYEKLAKELkgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGsKEP 85

                        90
                ....*....|
gi 135773    87 GEFSGANKEK 96
Cdd:cd02961  86 VKYEGPRTLE 95

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 135773    25 VDFSATWCGPCKMIKPFFHSLSEKY----SNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGEFSGA 92
Cdd:cd03005  21 VKFFAPWCGHCKRLAPTWEQLAKKFnnenPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDGEKVDKYKGT 92

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 135773     20 DKLVVVDFSATWCGPCKMIKPFFHS----LSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVgEFSGA 92
Cdd:PTZ00102  49 NEIVLVKFYAPWCGHCKRLAPEYKKaakmLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNPV-NYSGG 124

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773    12 QEALDA--AGDKLVVVDFSATWCGPCKMIKPFFHSL-SEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKVGE 88
Cdd:cd02948   7 QEEWEEllSNKGLTVVDVYQEWCGPCKAVVSLFKKIkNELGDDLLHFATAEADTIDTLKRYRGKCEPTFLFYKNGELVAV 86

                        90
                ....*....|....*.
gi 135773    89 FSGANKEKLEATINEL 104
Cdd:cd02948  87 IRGANAPLLNKTITEL 102

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773     3 KQIESKTAFQEALdaAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYS---NVIFLEVDVDDCQDVASECEVKCMPTFQF 79
Cdd:cd02950   5 QLAASSTPPEVAL--SNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGdqvNFVMLNVDNPKWLPEIDRYRVDGIPHFVF 82

                        90       100
                ....*....|....*....|....*...
gi 135773    80 F-KKGQKVGEFSGA-NKEKLEATINELV 105
Cdd:cd02950  83 LdREGNEEGQSIGLqPKQVLAQNLDALV 110

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 135773    24 VVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDC---QDVASECEVKCMPTFQFFKKGQKV 86
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDpalEKELKRYGVGGVPTLVVFGPGIGV 66

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773    10 AFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYS--NVIFLEVDVDDCQDVASECEV------KCMPTFQFFK 81
Cdd:cd02962  37 TLEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNnnNLKFGKIDIGRFPNVAEKFRVstsplsKQLPTIILFQ 116

                        90
                ....*....|....*
gi 135773    82 KGQKVGEFSGANKEK 96
Cdd:cd02962 117 GGKEVARRPYYNDSK 131

PDIa family, TMX3 subfamily; composed of eukaryotic proteins similar to human TMX3, a TRX related transmembrane protein containing one redox active TRX domain at the N-terminus and a classical ER retrieval sequence for type I transmembrane proteins at the C-terminus. The TMX3 transcript is found in a variety of tissues with the highest levels detected in skeletal muscle and the heart. In vitro, TMX3 showed oxidase activity albeit slightly lower than that of protein disulfide isomerase.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 135773    15 LDAAGDKLVVVDFSATWCGPCKMIKPFF----HSLSEKYSNVIFLEVDVDDCQDVASECEVKCMPTFQFFKKG 83
Cdd:cd03000  10 KDVRKEDIWLVDFYAPWCGHCKKLEPVWnevgAELKSSGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGD 82

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773    24 VVDFSATWCGPCKMIKPFFHSLSE---KYSNVifLEVDVDDC-----QDVASECEVKCMPTFQFFK---KGQKVGEfsga 92
Cdd:cd02992  23 LVEFYASWCGHCRAFAPTWKKLARdlrKWRPV--VRVAAVDCadeenVALCRDFGVTGYPTLRYFPpfsKEATDGL---- 96

                        90
                ....*....|..
gi 135773    93 NKEKLEATINEL 104
Cdd:cd02992  97 KQEGPERDVNEL 108

PDIa family, PDIR subfamily; composed of proteins similar to human PDIR (for Protein Disulfide Isomerase Related). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress. Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773    20 DKLVVVDFSATWCGPCKMIKPFFHSLSE---KYSNVIFLEVDVD-DCQD-VASECEVKCMPTFQFFKKGQKVGEFSGANK 94
Cdd:cd02997  17 EKHVLVMFYAPWCGHCKKMKPEFTKAATelkEDGKGVLAAVDCTkPEHDaLKEEYNVKGFPTFKYFENGKFVEKYEGERT 96

                ..
gi 135773    95 EK 96
Cdd:cd02997  97 AE 98

PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the endoplasmic reticulum (ER) and displays both isomerase and chaperone activities, which are independent of each other. Compared to PDI, the isomerase and chaperone activities of P5 are lower. The first cysteine in the CXXC motif of both redox active domains in P5 is necessary for isomerase activity. The P5 gene was first isolated as an amplified gene from a hydroxyurea-resistant hamster cell line. The zebrafish P5 homolog has been implicated to play a critical role in establishing left/right asymmetries in the embryonic midline. Some members of this subfamily are P5-like proteins containing only one redox active TRX domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 135773    20 DKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFL-EVDVDDCQDVASECEVKCMPTFQFFKKGQK 85
Cdd:cd03001  18 DDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVgAVDADVHQSLAQQYGVRGFPTIKVFGAGKN 84

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 135773     25 VDFSATWCGPCKMIKPFFHSLSEKYSNVIFL-EVDVDDCQDVASECEVKCMPTFQFFKKGqKVGEFSGANK--EKLEA 99
Cdd:PTZ00443  57 VKFYAPWCSHCRKMAPAWERLAKALKGQVNVaDLDATRALNLAKRFAIKGYPTLLLFDKG-KMYQYEGGDRstEKLAA 133

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 135773     27 FSATWCGPCKMIKPFFHSLSEKYsnvifLEVDVDDCQDVASECEVKCMPT 76
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANVEYTY-----VDVDTDEGVELTAKHHIRSLPT 49

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 135773     2 VKQIESKTAFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVDDCqDVASECEVKCMPTFQFFK 81
Cdd:cd02957   6 VREISSKEFLEEVTKASKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYK 84

                        90
                ....*....|
gi 135773    82 KGQKVGEFSG 91
Cdd:cd02957  85 NGELIDNIVG 94

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 135773      20 DKLVVVDFSATWCGPCKMIKPFFHSLSEKYS-----NVIFLEVDVD 60
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKLKkkknvEIVFVSLDRD 46

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 135773     20 DKLVVVDFSATWCGPCKMIKPFFHSLSEKYS---NVIFLEVDVDDCQDVASECEVKCMPTFQFFKKGQKV 86
Cdd:PTZ00102 375 DKDVLLEIYAPWCGHCKNLEPVYNELGEKYKdndSIIVAKMNGTANETPLEEFSWSAFPTILFVKAGERT 444

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 135773       8 KTAFQEALDAA--GDKLVVVDFSATWCGPCKMIKPFFHS-------LSEkysNVIFLEVDVDD 61
Cdd:pfam13899   3 LSDLEEALAAAaeRGKPVLVDFGADWCFTCQVLERDFLSheevkaaLAK---NFVLLRLDWTS 62