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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  26 VFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFGA 105
Cdd:cd03001   2 VVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGA 81

                        90       100
                ....*....|....*....|..
gi 17556044 106 TeKSKPIDYNGPRTAKGIADAV 127
Cdd:cd03001  82 G-KNSPQDYQGGRTAKAIVSAA 102

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  26 VFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFGA 105
Cdd:cd03001   2 VVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGA 81

                        90       100
                ....*....|....*....|..
gi 17556044 106 TeKSKPIDYNGPRTAKGIADAV 127
Cdd:cd03001  82 G-KNSPQDYQGGRTAKAIVSAA 102

protein disulfide-isomerase domain; This model describes a domain of eukaryotic protein disulfide isomerases, generally found in two copies. The high cutoff for total score reflects the expectation of finding both copies. The domain is similar to thioredoxin but the redox-active disulfide region motif is APWCGHCK. [Protein fate, Protein folding and stabilization]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044   159 LTDSNFDKLVLnSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMGGR--VKFGALDATAHESIAQKFGIRGFPTIKFFAPG 236
Cdd:TIGR01126   1 LTASNFDEIVL-SNKDVLVEFYAPWCGHCKNLAPEYEKLAKELKKDpkIVLAKVDATAEKDLASRFGVSGFPTIKFFPKG 79

                          90       100
                  ....*....|....*....|....*.
gi 17556044   237 tssaSDAEDYQGGRTSTDLISYAESK 262
Cdd:TIGR01126  80 ----SKPVDYEGGRDLEAIVEFVNEK 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 17556044    26 VFELTDSNFDaKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLK---GIAEIGAIDATVHQKIPLKYSIKGYPTIKI 102
Cdd:TIGR01130   3 VLVLTKDNFD-DFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKkkgPPIKLAKVDATEEKDLAQKYGVSGYPTLKI 81

                          90       100
                  ....*....|....*....|....*..
gi 17556044   103 FGATEKSkPIDYNGPRTAKGIADAVKK 129
Cdd:TIGR01130  82 FRNGEDS-VSDYNGPRDADGIVKYMKK 107

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  156 VVVLTDSNFDKLvLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEM---GGRVKFGALDATAHESIAQKFGIRGFPTIKF 232
Cdd:PTZ00102  34 VTVLTDSTFDKF-ITENEIVLVKFYAPWCGHCKRLAPEYKKAAKMLkekKSEIVLASVDATEEMELAQEFGVRGYPTIKF 112

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 17556044  233 FAPGTSsasdaEDYQGGRTSTDLISYAEskyDDFGAAPEVVEGTGKAVVE 282
Cdd:PTZ00102 113 FNKGNP-----VNYSGGRTADGIVSWIK---KLTGPAVTEVESASEIKLI 154

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 17556044    25 SVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFg 104
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFF- 79

                          90       100
                  ....*....|....*....|....*
gi 17556044   105 aTEKSKPIDYNGPRTAKGIADAVKK 129
Cdd:pfam00085  80 -KNGQPVDDYVGARPKDALAAFLKA 103

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 17556044  25 SVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFg 104
Cdd:COG3118   1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLF- 79

                        90       100
                ....*....|....*....|....*...
gi 17556044 105 atEKSKPID-YNGPRTAKGIADAVKKSI 131
Cdd:COG3118  80 --KDGQPVDrFVGALPKEQLREFLDKVL 105

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  26 VFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFGA 105
Cdd:cd03001   2 VVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGA 81

                        90       100
                ....*....|....*....|..
gi 17556044 106 TeKSKPIDYNGPRTAKGIADAV 127
Cdd:cd03001  82 G-KNSPQDYQGGRTAKAIVSAA 102

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 17556044 157 VVLTDSNFDKLVLNSKePWMVEFFAPWCGHCQKLEPEWKKAAEEM--GGRVKFGALDATAHESIAQKFGIRGFPTIKFFA 234
Cdd:cd02961   1 VELTDDNFDELVKDSK-DVLVEFYAPWCGHCKALAPEYEKLAKELkgDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                        90       100
                ....*....|....*....|....*
gi 17556044 235 PGTssaSDAEDYQGGRTSTDLISYA 259
Cdd:cd02961  80 NGS---KEPVKYEGPRTLESLVEFI 101

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 17556044  28 ELTDSNFDaKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLK--GIAEIGAIDATVHQKIPLKYSIKGYPTIKIFGA 105
Cdd:cd02961   2 ELTDDNFD-ELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPN 80

                        90       100
                ....*....|....*....|..
gi 17556044 106 TEKsKPIDYNGPRTAKGIADAV 127
Cdd:cd02961  81 GSK-EPVKYEGPRTLESLVEFI 101

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 17556044   156 VVVLTDSNFDKLVLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMGGRVKFGALDATAHESIAQKFGIRGFPTIKFFAP 235
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|...
gi 17556044   236 GtssaSDAEDYQGGRTSTDLISY 258
Cdd:pfam00085  82 G----QPVDDYVGARPKDALAAF 100

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 17556044 156 VVVLTDSNFDKLVLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMGGR--VKFGALDAT-AHESIAQKFGIRGFPTIKF 232
Cdd:cd02998   2 VVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEddVVIAKVDADeANKDLAKKYGVSGFPTLKF 81

                        90       100
                ....*....|....*....|....*.
gi 17556044 233 FAPGTssaSDAEDYQGGRTSTDLISY 258
Cdd:cd02998  82 FPKGS---TEPVKYEGGRDLEDLVKF 104

PDI family, MPD1-like subfamily; composed of eukaryotic proteins similar to Saccharomyces cerevisiae MPD1 protein, which contains a single redox active TRX domain located at the N-terminus, and an ER retention signal at the C-terminus indicative of an ER-resident protein. MPD1 has been shown to suppress the maturation defect of carboxypeptidase Y caused by deletion of the yeast PDI1 gene. Other characterized members of this subfamily include the Aspergillus niger prpA protein and Giardia PDI-1. PrpA is non-essential to strain viability, however, its transcript level is induced by heterologous protein expression suggesting a possible role in oxidative protein folding during high protein production. Giardia PDI-1 has the ability to refold scrambled RNase and exhibits transglutaminase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044 156 VVVLTDSNFDKLVLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMGGRVKFGAL--DATAHESIAQKFGIRGFPTIKFF 233
Cdd:cd03002   2 VYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVdcDEDKNKPLCGKYGVQGFPTLKVF 81

                        90       100
                ....*....|....*....|....*..
gi 17556044 234 APGTSSASDA-EDYQGGRTSTDLISYA 259
Cdd:cd03002  82 RPPKKASKHAvEDYNGERSAKAIVDFV 108

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  156 VVVLTDSNFDKLvLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEM---GGRVKFGALDATAHESIAQKFGIRGFPTIKF 232
Cdd:PTZ00102  34 VTVLTDSTFDKF-ITENEIVLVKFYAPWCGHCKRLAPEYKKAAKMLkekKSEIVLASVDATEEMELAQEFGVRGYPTIKF 112

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 17556044  233 FAPGTSsasdaEDYQGGRTSTDLISYAEskyDDFGAAPEVVEGTGKAVVE 282
Cdd:PTZ00102 113 FNKGNP-----VNYSGGRTADGIVSWIK---KLTGPAVTEVESASEIKLI 154

PDIa family, C-terminal ERdj5 subfamily; ERdj5, also known as JPDI and macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox active TRX domains. This subfamily is composed of the three TRX domains located at the C-terminal half of the protein. ERdj5 is a ubiquitous protein localized in the endoplasmic reticulum (ER) and is abundant in secretory cells. It's transcription is induced during ER stress. It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation. Also included in the alignment is the single complete TRX domain of an uncharacterized protein from Tetraodon nigroviridis, which also contains a DnaJ domain at its N-terminus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  25 SVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFG 104
Cdd:cd03004   2 SVITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYP 81

                        90       100
                ....*....|....*....|..
gi 17556044 105 ATEkSKPIDYNG-PRTAKGIAD 125
Cdd:cd03004  82 GNA-SKYHSYNGwHRDADSILE 102

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 17556044    25 SVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAEIGAIDATVHQKIPLKYSIKGYPTIKIFg 104
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFF- 79

                          90       100
                  ....*....|....*....|....*
gi 17556044   105 aTEKSKPIDYNGPRTAKGIADAVKK 129
Cdd:pfam00085  80 -KNGQPVDDYVGARPKDALAAFLKA 103

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are 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. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  25 SVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKG-----IAEigaIDATVHQkIPLKYSIKGYPT 99
Cdd:cd02995   1 PVKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGddnvvIAK---MDATAND-VPSEFVVDGFPT 76

                        90       100
                ....*....|....*....|....*.
gi 17556044 100 IKIFGATEKSKPIDYNGPRTAKGIAD 125
Cdd:cd02995  77 ILFFPAGDKSNPIKYEGDRTLEDLIK 102

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 17556044 156 VVVLTDSNFDKLvLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEM--GGRVKFGALDAT--AHESIAQKFGIRGFPTIK 231
Cdd:cd02997   2 VVHLTDEDFRKF-LKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELkeDGKGVLAAVDCTkpEHDALKEEYNVKGFPTFK 80

                        90       100
                ....*....|....*....|....*..
gi 17556044 232 FFAPGTSSasdaEDYQGGRTSTDLISY 258
Cdd:cd02997  81 YFENGKFV----EKYEGERTAEDIIEF 103

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are 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. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044 156 VVVLTDSNFDKLVLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMGGR--VKFGALDATAHEsIAQKFGIRGFPTIKFF 233
Cdd:cd02995   2 VKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDdnVVIAKMDATAND-VPSEFVVDGFPTILFF 80

                        90       100
                ....*....|....*....|....*
gi 17556044 234 APGtsSASDAEDYQGGRTSTDLISY 258
Cdd:cd02995  81 PAG--DKSNPIKYEGDRTLEDLIKF 103

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 17556044    23 KDSVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLKGIAE---IGAIDATVHQkIPlKYSIKGYPT 99
Cdd:TIGR01130 345 EGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAESdvvIAKMDATAND-VP-PFEVEGFPT 422

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 17556044   100 IKIFGATEKSKPIDYNGPRTAKGIADAVKKSIEKSLE 136
Cdd:TIGR01130 423 IKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATFPLE 459

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  156 VVVLTDSNFDKLVLNSKE----PWMVEFFAPWCGHCQKLEPEWKKAAEEMGGRVKFGALDATAHESIAQKFGIRGFPTIK 231
Cdd:PTZ00443  32 LVLLNDKNFEKLTQASTGattgPWFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPTLL 111

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 17556044  232 FFAPGTssasdAEDYQGG-RTSTDLISYAESKYDDFGAAP 270
Cdd:PTZ00443 112 LFDKGK-----MYQYEGGdRSTEKLAAFALGDFKKALGAP 146

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17556044   159 LTDSNFDKLVLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMGGRVKFGALDATAHESIAQKFGIRGFPTIKFFAPG 236
Cdd:TIGR01068   1 LTDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNG 78

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 17556044  24 DSVFELTDSNFDAKVLKSDRIWIVEFYAPYCGHCKSLVPEYKKAAKLLK---GIAEIGAID--ATVHQKIPLKYSIKGYP 98
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRkwrPVVRVAAVDcaDEENVALCRDFGVTGYP 80

                        90
                ....*....|....*..
gi 17556044  99 TIKIFGATEKSKPIDYN 115
Cdd:cd02992  81 TLRYFPPFSKEATDGLK 97

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17556044  156 VVVLTDSNFDKLVLNSKEPWMVEFFAPWCGHCQKLEPEWKKAAEEMG--GRVKFGALDATAHESIAQKFGIRGFPTIKFF 233
Cdd:PTZ00102 359 VKVVVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKdnDSIIVAKMNGTANETPLEEFSWSAFPTILFV 438

                         90       100
                 ....*....|....*....|....*..
gi 17556044  234 APGTssaSDAEDYQGGRTSTDLISYAE 260
Cdd:PTZ00102 439 KAGE---RTPIPYEGERTVEGFKEFVN 462

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 17556044 156 VVVLTDSNFDKLVlnsKEPWMVEFFAPWCGHCQKLEPEWKKAA---EEMGgrVKFGALDATAHESIAQKFGIRGFPTIkf 232
Cdd:cd02994   3 VVELTDSNWTLVL---EGEWMIEFYAPWCPACQQLQPEWEEFAdwsDDLG--INVAKVDVTQEPGLSGRFFVTALPTI-- 75

                        90       100       110
                ....*....|....*....|....*....|
gi 17556044 233 fapgtSSASDAE--DYQGGRTSTDLISYAE 260
Cdd:cd02994  76 -----YHAKDGVfrRYQGPRDKEDLISFIE 100