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 2545657638  64 DAEKVVLLDFTATWCPPCHMLAPHLKSVVNRKGT-DLLVVDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEAQ 142
Cdd:cd02947     8 KSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKvKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGADPKEE 87

                  ....*.
gi 2545657638 143 VEQFVD 148
Cdd:cd02947    88 LEEFLE 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 2545657638  63 ADAEKVVLLDFTATWCPPCHMLAPHLKSVVNRKGTD--LLVVDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSE 140
Cdd:pfam00085  15 QKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNvvFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVGARPK 94

                  ....*...
gi 2545657638 141 AQVEQFVD 148
Cdd:pfam00085  95 DALAAFLK 102

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 2545657638  64 DAEKVVLLDFTATWCPPCHMLAPHLKSVVNRKGT-DLLVVDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEAQ 142
Cdd:cd02947     8 KSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKvKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGADPKEE 87

                  ....*.
gi 2545657638 143 VEQFVD 148
Cdd:cd02947    88 LEEFLE 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 2545657638  63 ADAEKVVLLDFTATWCPPCHMLAPHLKSVVNRKGTD--LLVVDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSE 140
Cdd:pfam00085  15 QKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNvvFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVGARPK 94

                  ....*...
gi 2545657638 141 AQVEQFVD 148
Cdd:pfam00085  95 DALAAFLK 102

thioredoxin 2; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  66 EKVVLLDFTATWCPPCHMLAPHLKSVV-NRKGTDLLV-VDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEAQV 143
Cdd:PRK10996   52 DLPVVIDFWAPWCGPCRNFAPIFEDVAaERSGKVRFVkVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPF 131

                  ....*..
gi 2545657638 144 EQFVDQA 150
Cdd:PRK10996  132 DSWLNEA 138

thioredoxin TrxA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  65 AEKVVLLDFTATWCPPCHMLAPHLKSVVNRKGTDLLV--VDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEAQ 142
Cdd:PRK09381   20 ADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVakLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGALSKGQ 99

                  ....*.
gi 2545657638 143 VEQFVD 148
Cdd:PRK09381  100 LKEFLD 105

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 2545657638  66 EKVVLLDFTATWCPPCHMLAPHLKSVVN--RKGTDLLV--VDVDKEPELSQRFKVRAMPTVVAYRRG-QEVSRFVGAQSE 140
Cdd:cd02961    15 SKDVLVEFYAPWCGHCKALAPEYEKLAKelKGDGKVVVakVDCTANNDLCSEYGVRGYPTIKLFPNGsKEPVKYEGPRTL 94

                  ....*..
gi 2545657638 141 AQVEQFV 147
Cdd:cd02961    95 ESLVEFI 101

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 2545657638  67 KVVLLDFTATWCPPCHMLAPHL---------------------------KSVVNRKGTDLLVVdVDKEPELSQRFKVRAM 119
Cdd:cd02966    20 KVVLVNFWASWCPPCRAEMPELealakeykddgvevvgvnvddddpaavKAFLKKYGITFPVL-LDPDGELAKAYGVRGL 98

                          90
                  ....*....|....*...
gi 2545657638 120 PTVVAY-RRGQEVSRFVG 136
Cdd:cd02966    99 PTTFLIdRDGRIRARHVG 116

PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  70 LLDFTATWCPPCHMLAPHLKSVvNRKGTDLLV----VDVDKEPELSQRFKVRAMPTVVAYRRGqEVSRFVGAQSEAQVEQ 145
Cdd:cd02994    20 MIEFYAPWCPACQQLQPEWEEF-ADWSDDLGInvakVDVTQEPGLSGRFFVTALPTIYHAKDG-VFRRYQGPRDKEDLIS 97

                  ..
gi 2545657638 146 FV 147
Cdd:cd02994    98 FI 99

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 2545657638  64 DAEKVVLLDFTATWCPPCHMLAP---HLKSVVNRKGTDLLVVDVDKEPELSQRFKV------RAMPTVVAYRRGQEVSRF 134
Cdd:cd02962    45 DKRVTWLVEFFTTWSPECVNFAPvfaELSLKYNNNNLKFGKIDIGRFPNVAEKFRVstsplsKQLPTIILFQGGKEVARR 124

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKSV---VNRKGTDLLV--VDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEA 141
Cdd:PTZ00102   50 EIVLVKFYAPWCGHCKRLAPEYKKAakmLKEKKSEIVLasVDATEEMELAQEFGVRGYPTIKFFNKGNPVNYSGGRTADG 129

                  ...
gi 2545657638 142 QVE 144
Cdd:PTZ00102  130 IVS 132

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2545657638  70 LLDFTATWCPPCHMLAPHLKSVVNR-KGTdLLV--VDVDKEPELSQRFKVRAMPTVVAY 125
Cdd:cd03004    23 LVDFYAPWCGPCQALLPELRKAARAlKGK-VKVgsVDCQKYESLCQQANIRAYPTIRLY 80

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 2545657638  70 LLDFTATWCPPCHMLAPHLKSVVNRKGTDL----LVVDVDK-EPELsQRFKVRAMPTVVAY-RRGQEVSRFVGAQSEAQV 143
Cdd:cd02950    24 LVEFYADWCTVCQEMAPDVAKLKQKYGDQVnfvmLNVDNPKwLPEI-DRYRVDGIPHFVFLdREGNEEGQSIGLQPKQVL 102

                  ....*
gi 2545657638 144 EQFVD 148
Cdd:cd02950   103 AQNLD 107

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKSVVNR---KGTDLLVVDV---------------------DKEPELSQRFKVRAMPTV 122
Cdd:COG1225    22 KPVVLYFYATWCPGCTAELPELRDLYEEfkdKGVEVLGVSSdsdeahkkfaekyglpfpllsDPDGEVAKAYGVRGTPTT 101

                          90       100       110
                  ....*....|....*....|....*....|
gi 2545657638 123 VAYRR-GQEVSRFVGA-QSEAQVEQFVDQA 150
Cdd:COG1225   102 FLIDPdGKIRYVWVGPvDPRPHLEEVLEAL 131

thiol-disulfide oxidoreductase ResA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKS---VVNRKGTDLLVVDVDkEPELS-QRF----------------------KVRAMP 120
Cdd:PRK03147   62 KGVFLNFWGTWCKPCEKEMPYMNElypKYKEKGVEIIAVNVD-ETELAvKNFvnrygltfpvaidkgrqvidayGVGPLP 140

                          90       100
                  ....*....|....*....|....*..
gi 2545657638 121 TVVAYRRGQEVSRFV-GAQSEAQVEQF 146
Cdd:PRK03147  141 TTFLIDKDGKVVKVItGEMTEEQLEEY 167

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2545657638  68 VVLLDFTATWCPPCHMLAPHLKSVV-NRKGT-DLLVVDVDKEPELSQRFKVRAMPTV 122
Cdd:cd03001    20 VWLVEFYAPWCGHCKNLAPEWKKAAkALKGIvKVGAVDADVHQSLAQQYGVRGFPTI 76

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 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKS---VVNR--KGTDLLVVDV-DKEPE---LSQRFKVRAMPTVVAYRRGQEVS--RFV 135
Cdd:cd02953    12 KPVFVDFTADWCVTCKVNEKVVFSdpeVQAAlkKDVVLLRADWtKNDPEitaLLKRFGVFGPPTYLFYGPGGEPEplRLP 91

                          90
                  ....*....|
gi 2545657638 136 GAQSEAQVEQ 145
Cdd:cd02953    92 GFLTADEFLE 101

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  73 FTATWCPPCHMLAP-------HLKSVVNrkgtdLLVVDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEAQVEQ 145
Cdd:PTZ00443   59 FYAPWCSHCRKMAPawerlakALKGQVN-----VADLDATRALNLAKRFAIKGYPTLLLFDKGKMYQYEGGDRSTEKLAA 133

                  .
gi 2545657638 146 F 146
Cdd:PTZ00443  134 F 134

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 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKSVVNR-KGTDLLV---VDVDKE-PELSQRFKVRAMPTVVAYRRG-QEVSRFVGAQSE 140
Cdd:cd02998    19 KDVLVEFYAPWCGHCKNLAPEYEKLAAVfANEDDVViakVDADEAnKDLAKKYGVSGFPTLKFFPKGsTEPVKYEGGRDL 98

                  ....*..
gi 2545657638 141 AQVEQFV 147
Cdd:cd02998    99 EDLVKFV 105

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 2545657638  52 EVVAKRLDVGHADAEKVVLLDFTATWCPPCHMLAPHLKSvVNRKGTDLLVVDVDKE---PELSQRFKVRAMPTVVAYRRG 128
Cdd:cd02999     4 EVLNIALDLMAFNREDYTAVLFYASWCPFSASFRPHFNA-LSSMFPQIRHLAIEESsikPSLLSRYGVVGFPTILLFNST 82

                  ....*...
gi 2545657638 129 QEVsRFVG 136
Cdd:cd02999    83 PRV-RYNG 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  78 CPPCHMLAPHLKSVVNR-KGTDLLVVDVDKePELSQRFKVRAMPTVVAYRRGQEVSRFVG 136
Cdd:cd02957    36 FPRCKILDSHLEELAAKyPETKFVKINAEK-AFLVNYLDIKVLPTLLVYKNGELIDNIVG 94

TRX domain, DnaJ domain containing protein family; composed of uncharacterized proteins of about 500-800 amino acids, containing an N-terminal DnaJ domain followed by one redox active TRX domain. DnaJ is a member of the 40 kDa heat-shock protein (Hsp40) family of molecular chaperones, which regulate the activity of Hsp70s. TRX is involved in the redox regulation of many protein substrates through the reduction of disulfide bonds. TRX has been implicated to catalyse the reduction of Hsp33, a chaperone holdase that binds to unfolded protein intermediates. The presence of DnaJ and TRX domains in members of this family suggests that they could be involved in a redox-regulated chaperone network.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  65 AEKVVLLDFTATWCPPCHMLAPHLKSVVNRK---GTDLLVVDVDKEPELSQRFKVRAMPTVVAYRRGQEVSRFVGAQSEA 141
Cdd:cd02963    23 FKKPYLIKITSDWCFSCIHIEPVWKEVIQELeplGVGIATVNAGHERRLARKLGAHSVPAIVGIINGQVTFYHDSSFTKQ 102

                  ....*...
gi 2545657638 142 QVEQFVDQ 149
Cdd:cd02963   103 HVVDFVRK 110

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 2545657638  66 EKVVLLDFTATWCPPCHMLAPHLKSV---VNRKGTDLLV--VDVDKEPELSQRFKVRAMPTVVAYRRGQE 130
Cdd:cd03000    15 EDIWLVDFYAPWCGHCKKLEPVWNEVgaeLKSSGSPVRVgkLDATAYSSIASEFGVRGYPTIKLLKGDLA 84

Tryparedoxin (TryX)-like family, TryX and nucleoredoxin (NRX) subfamily; TryX and NRX are thioredoxin (TRX)-like protein disulfide oxidoreductases that alter the redox state of target proteins via the reversible oxidation of an active center CXXC motif. TryX is involved in the regulation of oxidative stress in parasitic trypanosomatids by reducing TryX peroxidase, which in turn catalyzes the reduction of hydrogen peroxide and organic hydroperoxides. TryX derives reducing equivalents from reduced trypanothione, a polyamine peptide conjugate unique to trypanosomatids, which is regenerated by the NADPH-dependent flavoprotein trypanothione reductase. Vertebrate NRX is a 400-amino acid nuclear protein with one redox active TRX domain containing a CPPC active site motif followed by one redox inactive TRX-like domain. Mouse NRX transcripts are expressed in all adult tissues but is restricted to the nervous system and limb buds in embryos. Plant NRX, longer than the vertebrate NRX by about 100-200 amino acids, is a nuclear protein containing a redox inactive TRX-like domain between two redox active TRX domains. Both vertebrate and plant NRXs show thiol oxidoreductase activity in vitro. Their localization in the nucleus suggests a role in the redox regulation of nuclear proteins such as transcription factors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKSVVNR---KGTDLLVV----DVDKE--------------P--------ELSQRFKVR 117
Cdd:cd03009    19 KTVGLYFSASWCPPCRAFTPKLVEFYEKlkeSGKNFEIVfiswDRDEEsfndyfskmpwlavPfsdrerrsRLNRTFKIE 98

                          90
                  ....*....|....*..
gi 2545657638 118 AMPTVVA-YRRGQEVSR 133
Cdd:cd03009    99 GIPTLIIlDADGEVVTT 115

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2545657638  67 KVVLLDFTATWCPPCHMLAPHLKSVVNR----KGTDLLVVDVDKEPELSQRFkVRAMP 120
Cdd:pfam13905   2 KVVLLYFGASWCKPCRRFTPLLKELYEKlkkkKNVEIVFVSLDRDLEEFKDY-LKKMP 58

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2545657638  77 WCPPCHMLAPHLKSVVNRKGTDLL---VVDVDKEPELsQRFKVRAMPTVVAYRRGQEVSRFVGAQSeAQVEQFVDQ 149
Cdd:cd02948    28 WCGPCKAVVSLFKKIKNELGDDLLhfaTAEADTIDTL-KRYRGKCEPTFLFYKNGELVAVIRGANA-PLLNKTITE 101

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 2545657638  53 VVAKRLDVGHADAEKVVLLDFTATWCPPCHMLAP-------HLKSVvnrkGTDLLVVDVD-KEPELSQrFKVRAMPTVVA 124
Cdd:TIGR01130 351 LVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPiyeelaeKYKDA----ESDVVIAKMDaTANDVPP-FEVEGFPTIKF 425

                  ....
gi 2545657638 125 YRRG 128
Cdd:TIGR01130 426 VPAG 429