Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   66 DGPDFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVV 145
Cdd:COG3118   6 TDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90       100
                ....*....|....*....|
gi 9903609  146 DKFVGIKDEDQLEAFLKKLI 165
Cdd:COG3118  86 DRFVGALPKEQLREFLDKVL 105

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   66 DGPDFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVV 145
Cdd:COG3118   6 TDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90       100
                ....*....|....*....|
gi 9903609  146 DKFVGIKDEDQLEAFLKKLI 165
Cdd:COG3118  86 DRFVGALPKEQLREFLDKVL 105

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 9903609     69 DFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVDKF 148
Cdd:TIGR01068   5 NFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
gi 9903609    149 VGIKDEDQLEAFLKKLI 165
Cdd:TIGR01068  85 VGALPKAALKQLINKNL 101

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609    72 DRVVNSETPVVVDFHAQWCGPCKILGPRLEKMvAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVDKFVGI 151
Cdd:PTZ00051  12 ESTLSQNELVIVDFYAEWCGPCKRIAPFYEEC-SKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVVDTLLGA 90

                 ...
gi 9903609   152 KDE 154
Cdd:PTZ00051  91 NDE 93

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   66 DGPDFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVV 145
Cdd:COG3118   6 TDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90       100
                ....*....|....*....|
gi 9903609  146 DKFVGIKDEDQLEAFLKKLI 165
Cdd:COG3118  86 DRFVGALPKEQLREFLDKVL 105

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 9903609     69 DFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVDKF 148
Cdd:TIGR01068   5 NFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
gi 9903609    149 VGIKDEDQLEAFLKKLI 165
Cdd:TIGR01068  85 VGALPKAALKQLINKNL 101

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 9903609   69 DFQDRVVNS-ETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVDK 147
Cdd:cd02956   2 NFQQVLQEStQVPVVVDFWAPRSPPSKELLPLLERLAEEYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDG 81

                        90
                ....*....|....
gi 9903609  148 FVGIKDEDQLEAFL 161
Cdd:cd02956  82 FQGAQPEEQLRQML 95

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 9903609   72 DRVVNSETPVVVDFHAQWCGPCKILGPRLEKM--VAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDV-VDKF 148
Cdd:cd02961   9 DELVKDSKDVLVEFYAPWCGHCKALAPEYEKLakELKGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGSKePVKY 88

                        90
                ....*....|...
gi 9903609  149 VGIKDEDQLEAFL 161
Cdd:cd02961  89 EGPRTLESLVEFI 101

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609    70 FQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVDKFV 149
Cdd:PRK09381  13 FDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKV 92

                         90
                 ....*....|..
gi 9903609   150 GIKDEDQLEAFL 161
Cdd:PRK09381  93 GALSKGQLKEFL 104

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 9903609   69 DFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKM--VAKQHGKVVMAKVDIDD-HTDLAIEYEVSAVPTVLAI-KNGDV 144
Cdd:cd02998   9 NFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLaaVFANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLKFFpKGSTE 88

                        90
                ....*....|....*..
gi 9903609  145 VDKFVGIKDEDQLEAFL 161
Cdd:cd02998  89 PVKYEGGRDLEDLVKFV 105

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 9903609     69 DFQDRVVNSETpVVVDFHAQWCGPCKILGPRLEK---MVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVV 145
Cdd:TIGR01130  10 NFDDFIKSHEF-VLVEFYAPWCGHCKSLAPEYEKaadELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRNGEDS 88

                          90       100
                  ....*....|....*....|..
gi 9903609    146 DK-FVGIKDEDQLEAFLKKLIG 166
Cdd:TIGR01130  89 VSdYNGPRDADGIVKYMKKQSG 110

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 9903609   69 DFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTV 136
Cdd:cd03004  10 DFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTI 77

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 9903609   66 DGPDFqDRVVNSETPVVVDFHAQWCGPCKILGPRLEKM--VAKQHGKVVMAKVDI--DDHTDLAIEYEVSAVPTVLAIKN 141
Cdd:cd02997   6 TDEDF-RKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAatELKEDGKGVLAAVDCtkPEHDALKEEYNVKGFPTFKYFEN 84

                        90       100
                ....*....|....*....|
gi 9903609  142 GDVVDKFVGIKDEDQLEAFL 161
Cdd:cd02997  85 GKFVEKYEGERTAEDIIEFM 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 9903609   72 DRVV-NSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVVMAKVDIDD--HTDLAIEYEVSAVPTV 136
Cdd:cd03002  11 DKVVhNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEdkNKPLCGKYGVQGFPTL 78

PDIa family, endoplasmic reticulum protein 44 (ERp44) subfamily; ERp44 is an ER-resident protein, induced during stress, involved in thiol-mediated ER retention. It contains an N-terminal TRX domain, similar to that of PDIa, with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. The CXFS motif in the N-terminal domain allows ERp44 to form stable reversible mixed disulfides with its substrates. Through this activity, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. It also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   57 VCLTTFNVQDgpdfqdrVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAK------QHGKVVMAKVDIDDHTDLAIEYEV 130
Cdd:cd02996   4 VSLTSGNIDD-------ILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKikeefpDAGKVVWGKVDCDKESDIADRYRI 76

                        90
                ....*....|....*..
gi 9903609  131 SAVPTVLAIKNGDVVDK 147
Cdd:cd02996  77 NKYPTLKLFRNGMMMKR 93

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 9903609     67 GPDFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAK---QHGKVVMAKVD--IDDHTDlaieYEVSAVPTVLAIKN 141
Cdd:TIGR01130 353 GKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKykdAESDVVIAKMDatANDVPP----FEVEGFPTIKFVPA 428

                          90       100
                  ....*....|....*....|....
gi 9903609    142 GDVVD--KFVGIKDEDQLEAFLKK 163
Cdd:TIGR01130 429 GKKSEpvPYDGDRTLEDFSKFIAK 452

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609    65 QDGP-------DFQDRVVNSETPVVVDFHAQWCGPCKILGPRLEKM--VAKQHGKVVMAKVDiDDHTDLAIE-YEVSAVP 134
Cdd:PTZ00102 355 QDGPvkvvvgnTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELgeKYKDNDSIIVAKMN-GTANETPLEeFSWSAFP 433

                         90       100       110
                 ....*....|....*....|....*....|
gi 9903609   135 TVLAIKNGD-VVDKFVGIKDEDQLEAFLKK 163
Cdd:PTZ00102 434 TILFVKAGErTPIPYEGERTVEGFKEFVNK 463

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   80 PVVVDFHAQWCGPCKILGPRLEKMVAKQHGK---VV-------------MAKVDI------DDHTDLAIEYEVSAVPTVL 137
Cdd:COG1225  23 PVVLYFYATWCPGCTAELPELRDLYEEFKDKgveVLgvssdsdeahkkfAEKYGLpfpllsDPDGEVAKAYGVRGTPTTF 102

                        90       100       110
                ....*....|....*....|....*....|
gi 9903609  138 AI-KNGDVVDKFVG-IKDEDQLEAFLKKLI 165
Cdd:COG1225 103 LIdPDGKIRYVWVGpVDPRPHLEEVLEALL 132

Thioredoxin-related protein SoxW [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   80 PVVVDFHAQWCGPCKilgpRLEKMV---------AKQHgkVVMAKVDIDDHT-------------DLAIEYEVSAVPTVL 137
Cdd:COG2143  42 PILLFFESDWCPYCK----KLHKEVfsdpevaayLKEN--FVVVQLDAEGDKevtdfdgetltekELARKYGVRGTPTLV 115

                        90       100
                ....*....|....*....|....*...
gi 9903609  138 AI-KNGDVVDKFVGIKDEDQLEAFLKKL 164
Cdd:COG2143 116 FFdAEGKEIARIPGYLKPETFLALLKYV 143

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   83 VDFHAQWCGPCKILGPRLEKMVA--KQHGKVV-MAKVDIDDHTDLAIEYEVSAVPTVLAIKnGDVVDKFVGIKDEDQLEA 159
Cdd:cd03000  20 VDFYAPWCGHCKKLEPVWNEVGAelKSSGSPVrVGKLDATAYSSIASEFGVRGYPTIKLLK-GDLAYNYRGPRTKDDIVE 98

                ....*
gi 9903609  160 FLKKL 164
Cdd:cd03000  99 FANRV 103

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 9903609   83 VDFHAQWCGPCKILGPRLEKMVAK-QHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGdVVDKFVGIKDEDQLEAFL 161
Cdd:cd02994  21 IEFYAPWCPACQQLQPEWEEFADWsDDLGINVAKVDVTQEPGLSGRFFVTALPTIYHAKDG-VFRRYQGPRDKEDLISFI 99

                ..
gi 9903609  162 KK 163
Cdd:cd02994 100 EE 101

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 9903609   76 NSETPVVVDFHAQWCGPCKILGPRLEKM--------VAKQHGKV-----VMAKVDI------DDHTDLAIEYEVSAVPTV 136
Cdd:cd03011  18 LSGKPVLVYFWATWCPVCRFTSPTVNQLaadypvvsVALRSGDDgavarFMQKKGYgfpvinDPDGVISARWGVSVTPAI 97

                        90       100
                ....*....|....*....|.
gi 9903609  137 LAIKNGDVVDKFVGIKDEDQL 157
Cdd:cd03011  98 VIVDPGGIVFVTTGVTSEWGL 118

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   69 DFQDRVVNSETPVVVDFHAQWcGPCKILGPRLEKMvAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVDKF 148
Cdd:cd02989  14 EFFEIVKSSERVVCHFYHPEF-FRCKIMDKHLEIL-AKKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTVDRI 91

                ..
gi 9903609  149 VG 150
Cdd:cd02989  92 VG 93

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 9903609   66 DGPDFQDRVVNSETPVVVDFHAQWCGPCKILGP---RLEKMVAKQHGKVVMAKVD--IDDHTDLAIEYEVSAVPTV 136
Cdd:cd02992   7 DAASFNSALLGSPSAWLVEFYASWCGHCRAFAPtwkKLARDLRKWRPVVRVAAVDcaDEENVALCRDFGVTGYPTL 82

TlpA-like family, DsbE (also known as CcmG and CycY) subfamily; DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 9903609   80 PVVVDFHAQWCGPCKILGPRLEKMvAKQHGKVVM----------------------AKVDIDDHTDLAIEYEVSAVPTVL 137
Cdd:cd03010  27 PYLLNVWASWCAPCREEHPVLMAL-ARQGRVPIYginykdnpenalawlarhgnpyAAVGFDPDGRVGIDLGVYGVPETF 105

                        90       100
                ....*....|....*....|..
gi 9903609  138 AI-KNGDVVDKFVGIKDEDQLE 158
Cdd:cd03010 106 LIdGDGIIRYKHVGPLTPEVWE 127

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 9903609   72 DRVVNSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHGKVV-MAKVDIDDHTDLAiEYEVSAVPTVLAIKNGDVVDKFVG 150
Cdd:cd02948  11 EELLSNKGLTVVDVYQEWCGPCKAVVSLFKKIKNELGDDLLhFATAEADTIDTLK-RYRGKCEPTFLFYKNGELVAVIRG 89

thioredoxin-like protein

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 9903609    85 FHAQWCGPCKILGPRLEKMVAKqhgkvvMAKVDIDDHTDLAIEYEVSAVPTVLaikNGDVVDKFVGI 151
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANVEYT------YVDVDTDEGVELTAKHHIRSLPTLV---NTSTLDRFTGV 62

Thioredoxin (TRX)-Glutaredoxin (GRX)-like family; composed of archaeal and bacterial proteins that show similarity to both TRX and GRX, including the C-terminal TRX-fold subdomain of Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO). All members contain a redox-active CXXC motif and may function as PDOs. The archaeal proteins Mj0307 and Mt807 show structures more similar to GRX, but activities more similar to TRX. Some members of the family are similar to PfPDO in that they contain a second CXXC motif located in a second TRX-fold subdomain at the N-terminus; the superimposable N- and C-terminal TRX subdomains form a compact structure. PfPDO is postulated to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI). The C-terminal CXXC motif of PfPDO is required for its oxidase, reductase and isomerase activities. Also included in the family is the C-terminal TRX-fold subdomain of the N-terminal domain (NTD) of bacterial AhpF, which has a similar fold as PfPDO with two TRX-fold subdomains but without the second CXXC motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 9903609  103 MVAKQHGKVVMAKVDIDDHTDLAIEYEVSAVPTVLAikNGDVVdkFVG 150
Cdd:cd02973  23 RIAALNPNISAEMIDAAEFPDLADEYGVMSVPAIVI--NGKVE--FVG 66

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 9903609   70 FQDRVV--NSETPVVVDFHAQWCGPCKILGPRLEKMVAKQHG-KVVMAKVDIDDHTDLAIEYEVSAVPTVLAIKNGDVVD 146
Cdd:cd02963  14 YENEIVpkSFKKPYLIKITSDWCFSCIHIEPVWKEVIQELEPlGVGIATVNAGHERRLARKLGAHSVPAIVGIINGQVTF 93

                        90
                ....*....|....*...
gi 9903609  147 KFVGIKDEDQLEAFLKKL 164
Cdd:cd02963  94 YHDSSFTKQHVVDFVRKL 111