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 1735576498 137 AVVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVV-VAAVDATAARDISSRFEVRGYPTIK 215
Cdd:cd02998     1 NVVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVViAKVDADEANKDLAKKYGVSGFPTLK 80

                          90       100
                  ....*....|....*....|....*..
gi 1735576498 216 FFPRGTaaKEAEDYEGGRSVEDFVTFL 242
Cdd:cd02998    81 FFPKGS--TEPVKYEGGRDLEDLVKFV 105

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 1735576498  22 DLTPENFDSVVGGDK-PALVEFFAPWCGHCKQLAPEYDVVGSTFQANDGVVVAKVDAD-AHRDLGSRFGVSGFPTIKWFP 99
Cdd:cd02998     4 ELTDSNFDKVVGDDKkDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIAKVDADeANKDLAKKYGVSGFPTLKFFP 83

                          90       100
                  ....*....|....*....|..
gi 1735576498 100 ASSKSPEDYSGGRTASDIVNFI 121
Cdd:cd02998    84 KGSTEPVKYEGGRDLEDLVKFV 105

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 1735576498 141 LTDSNFDAVVMDPEaDVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVVVAAVDATAARDISSRFEVRGYPTIKFFPRG 220
Cdd:TIGR01126   1 LTASNFDEIVLSNK-DVLVEFYAPWCGHCKNLAPEYEKLAKELKKDPKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKG 79

                          90       100
                  ....*....|....*....|....*.
gi 1735576498 221 taaKEAEDYEGGRSVEDFVTFLNTKA 246
Cdd:TIGR01126  80 ---SKPVDYEGGRDLEAIVEFVNEKS 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 1735576498 138 VVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAerKVVVAAVDATAARDISSRFEVRGYPTIKFF 217
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKG--NVVFAKVDVDENPDLASKYGVRGYPTLIFF 79

                          90       100
                  ....*....|....*....|....*.
gi 1735576498 218 PRGtaaKEAEDYEGGRSVEDFVTFLN 243
Cdd:pfam00085  80 KNG---QPVDDYVGARPKDALAAFLK 102

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 1735576498  22 DLTPENFDS-VVGGDKPALVEFFAPWCGHCKQLAPEYDVVGSTFQanDGVVVAKVDADAHRDLGSRFGVSGFPTIKWFpA 100
Cdd:COG3118     4 ELTDENFEEeVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYG--GKVKFVKVDVDENPELAAQFGVRSIPTLLLF-K 80

                          90       100
                  ....*....|....*....|..
gi 1735576498 101 SSKSPEDYSGGRTASDIVNFIN 122
Cdd:COG3118    81 DGQPVDRFVGALPKEQLREFLD 102

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 1735576498 137 AVVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFS---------AERkvvvaavdataARDISSRFE 207
Cdd:COG3118     1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGgkvkfvkvdVDE-----------NPELAAQFG 69

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1735576498 208 VRGYPTIKFFPRGtaaKEAEDYEGGRSVEDFVTFLN 243
Cdd:COG3118    70 VRSIPTLLLFKDG---QPVDRFVGALPKEQLREFLD 102

ERp29 and ERp38, C-terminal domain; composed of the protein disulfide isomerase (PDI)-like proteins ERp29 and ERp38. ERp29 (also called ERp28) is a ubiquitous endoplasmic reticulum (ER)-resident protein expressed in high levels in secretory cells. It contains a redox inactive TRX-like domain at the N-terminus. The expression profile of ERp29 suggests a role in secretory protein production, distinct from that of PDI. It has also been identified as a member of the thyroglobulin folding complex and is essential in regulating the secretion of thyroglobulin. The Drosophila homolog, Wind, is the product of windbeutel, an essential gene in the development of dorsal-ventral patterning. Wind is required for correct targeting of Pipe, a Golgi-resident type II transmembrane protein with homology to 2-O-sulfotransferase. ERp38 is a P5-like protein, first isolated from alfalfa (the cDNA clone was named G1), which contains two redox active TRX domains at the N-terminus, like human P5. However, unlike human P5, ERp38 also contains a C-terminal domain with homology to the C-terminal domain of ERp29. It may be a glucose-regulated protein. The function of the all-helical C-terminal domain of ERp29 and ERp38 remains unclear. The C-terminal domain of Wind is thought to provide a distinct site required for interaction with its substrate, Pipe.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1735576498 263 VEALDEFVRAFVAAAEEEREAIIEQTASKVKELGESAKDTGAYYVKAMRRYTERGAGWVTKESARLSSMATSAAVAAARK 342
Cdd:cd00238     1 IEELDELAKEFVDASDEERKELLEKVKEAVEKLKEAEAKYAKYYVKVMEKILEKGEDYVEKELARLERLLEKKGLAPEKA 80

                          90
                  ....*....|...
gi 1735576498 343 TNIMLRRNVLAAF 355
Cdd:cd00238    81 DELTRRLNILRSF 93

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 1735576498  22 DLTPENFDSVVGGDK-PALVEFFAPWCGHCKQLAPEYDVVGSTFQANDGVVVAKVDAD-AHRDLGSRFGVSGFPTIKWFP 99
Cdd:cd02998     4 ELTDSNFDKVVGDDKkDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIAKVDADeANKDLAKKYGVSGFPTLKFFP 83

                          90       100
                  ....*....|....*....|..
gi 1735576498 100 ASSKSPEDYSGGRTASDIVNFI 121
Cdd:cd02998    84 KGSTEPVKYEGGRDLEDLVKFV 105

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 1735576498 137 AVVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVV-VAAVDATAARDISSRFEVRGYPTIK 215
Cdd:cd02998     1 NVVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVViAKVDADEANKDLAKKYGVSGFPTLK 80

                          90       100
                  ....*....|....*....|....*..
gi 1735576498 216 FFPRGTaaKEAEDYEGGRSVEDFVTFL 242
Cdd:cd02998    81 FFPKGS--TEPVKYEGGRDLEDLVKFV 105

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 1735576498 141 LTDSNFDAVVMDPEaDVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVVVAAVDATAARDISSRFEVRGYPTIKFFPRG 220
Cdd:TIGR01126   1 LTASNFDEIVLSNK-DVLVEFYAPWCGHCKNLAPEYEKLAKELKKDPKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKG 79

                          90       100
                  ....*....|....*....|....*.
gi 1735576498 221 taaKEAEDYEGGRSVEDFVTFLNTKA 246
Cdd:TIGR01126  80 ---SKPVDYEGGRDLEAIVEFVNEKS 102

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 1735576498  26 ENFDSVVG-GDKPALVEFFAPWCGHCKQLAPEYDVVGSTFQANDGVVVAKVDADAHrDLGSRFGVSGFPTIKWFPASSKS 104
Cdd:cd02995     8 KNFDEVVLdSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATAN-DVPSEFVVDGFPTILFFPAGDKS 86

                          90
                  ....*....|....*...
gi 1735576498 105 -PEDYSGGRTASDIVNFI 121
Cdd:cd02995    87 nPIKYEGDRTLEDLIKFI 104

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 1735576498  23 LTPENFDSVV-GGDKPALVEFFAPWCGHCKQLAPEYDVVGSTFQANdgVVVAKVDADAHRDLGSRFGVSGFPTIKWFPAs 101
Cdd:pfam00085   5 LTDANFDEVVqKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGN--VVFAKVDVDENPDLASKYGVRGYPTLIFFKN- 81

                          90       100
                  ....*....|....*....|.
gi 1735576498 102 SKSPEDYSGGRTASDIVNFIN 122
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLK 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 1735576498 137 AVVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVVVAAVDATAArdISSRFEVRGYPTIKF 216
Cdd:cd03001     1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQS--LAQQYGVRGFPTIKV 78

                          90       100
                  ....*....|....*....|....*
gi 1735576498 217 FPRGtaAKEAEDYEGGRSVEDFVTF 241
Cdd:cd03001    79 FGAG--KNSPQDYQGGRTAKAIVSA 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 1735576498 120 FINGKtgLSRRVKKEP------TAVVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVVVAA 193
Cdd:TIGR01130 326 FLDGK--LKPYLKSEPipeddeGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAESDVVIA 403

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1735576498 194 VDATAARDISSrFEVRGYPTIKFFPRGtAAKEAEDYEGGRSVEDFVTFLNTKAGT 248
Cdd:TIGR01130 404 KMDATANDVPP-FEVEGFPTIKFVPAG-KKSEPVPYDGDRTLEDFSKFIAKHATF 456

PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in vivo. It has been detected in many tissues, however, transcript and protein levels do not correlate in all tissues, suggesting regulation at a posttranscriptional level. An identical protein, named endoPDI, has been identified as an endothelial PDI that is highly expressed in the endothelium of tumors and hypoxic lesions. It has a protective effect on cells exposed to hypoxia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1735576498  22 DLTPENFDSVVGGdKPALVEFFAPWCGHCKQLAPEYDVVG-STFQANDGVVVAKVDADAHRDLGSRFGVSGFPTIKWFPA 100
Cdd:cd03005     4 ELTEDNFDHHIAE-GNHFVKFFAPWCGHCKRLAPTWEQLAkKFNNENPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKD 82

                          90       100
                  ....*....|....*....|.
gi 1735576498 101 SSKsPEDYSGGRTASDIVNFI 121
Cdd:cd03005    83 GEK-VDKYKGTRDLDSLKEFV 102

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1735576498  22 DLTPENFDSVVGGDKPALVEFFAPWCGHCKQLAPEYDVVGSTF-QANDGVVVAKVDADAHRDLGSRFGVSGFPTIKWFpa 100
Cdd:PTZ00102   36 VLTDSTFDKFITENEIVLVKFYAPWCGHCKRLAPEYKKAAKMLkEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFF-- 113

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1735576498 101 SSKSPEDYSGGRTASDIVNFINGKTGLSRRVKKEPTAVVELTDSNFDAVVMD 152
Cdd:PTZ00102  114 NKGNPVNYSGGRTADGIVSWIKKLTGPAVTEVESASEIKLIAKKIFVAFYGE 165

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 1735576498  23 LTPENFDSVVGGDKPALVEFFAPWCGHCKQLAPEYDVVGSTFQANDGVVVAKVDA--DAHRDLGSRFGVSGFPTIKWFpA 100
Cdd:cd02997     5 LTDEDFRKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGVLAAVDCtkPEHDALKEEYNVKGFPTFKYF-E 83

                          90       100
                  ....*....|....*....|.
gi 1735576498 101 SSKSPEDYSGGRTASDIVNFI 121
Cdd:cd02997    84 NGKFVEKYEGERTAEDIIEFM 104

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 1735576498 137 AVVELTDSNFDAVVMDpEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAERKVVVAA--VDATAARDISSRFEVRGYPTI 214
Cdd:cd02997     1 DVVHLTDEDFRKFLKK-EKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGVLAAvdCTKPEHDALKEEYNVKGFPTF 79

                          90       100
                  ....*....|....*....|....*...
gi 1735576498 215 KFFPRGtaaKEAEDYEGGRSVEDFVTFL 242
Cdd:cd02997    80 KYFENG---KFVEKYEGERTAEDIIEFM 104

PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in vivo. It has been detected in many tissues, however, transcript and protein levels do not correlate in all tissues, suggesting regulation at a posttranscriptional level. An identical protein, named endoPDI, has been identified as an endothelial PDI that is highly expressed in the endothelium of tumors and hypoxic lesions. It has a protective effect on cells exposed to hypoxia.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1735576498 137 AVVELTDSNFDAVVmdPEADVLVEFFAPWCGHCKSLKPVYEKVANAF-SAERKVVVAAVDATAARDISSRFEVRGYPTIK 215
Cdd:cd03005     1 GVLELTEDNFDHHI--AEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFnNENPSVKIAKVDCTQHRELCSEFQVRGYPTLL 78

                          90       100
                  ....*....|....*....|....*..
gi 1735576498 216 FFPRGtaaKEAEDYEGGRSVEDFVTFL 242
Cdd:cd03005    79 LFKDG---EKVDKYKGTRDLDSLKEFV 102

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 1735576498  22 DLTPENFDS-VVGGDKPALVEFFAPWCGHCKQLAPEYDVVGStfQANDGVVVAKVDADAHRDLGSRFGVSGFPTIKWFPA 100
Cdd:cd03004     5 TLTPEDFPElVLNRKEPWLVDFYAPWCGPCQALLPELRKAAR--ALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYPG 82

                          90       100
                  ....*....|....*....|..
gi 1735576498 101 SSKSPEDYSG-GRTASDIVNFI 121
Cdd:cd03004    83 NASKYHSYNGwHRDADSILEFI 104

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 1735576498  23 LTPENFDSVV-GGDKPALVEFFAPWCGHCKQLAPEYDVVGSTFQanDGVVVAKVDADAHRDLGSRFGVSGFPTIKWFP 99
Cdd:TIGR01068   1 LTDANFDETIaSSDKPVLVDFWAPWCGPCKMIAPILEELAKEYE--GKVKFVKLNVDENPDIAAKYGIRSIPTLLLFK 76

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 1735576498  39 LVEFFAPWCGHCKQLAPEYDVVGSTFQA-NDGVVVAKVDADAHRDLGSRFGVSGFPTIKWFPASSKSpeDYSGGRTASDI 117
Cdd:cd03000    19 LVDFYAPWCGHCKKLEPVWNEVGAELKSsGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAY--NYRGPRTKDDI 96

                  ....*
gi 1735576498 118 VNFIN 122
Cdd:cd03000    97 VEFAN 101

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 1735576498  22 DLTPENFDSVVGGDKPA-LVEFFAPWCGHCKQLAPEYDVVGSTFQANDGVV-VAKVD--ADAHRDLGSRFGVSGFPTIKW 97
Cdd:cd02992     5 VLDAASFNSALLGSPSAwLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVrVAAVDcaDEENVALCRDFGVTGYPTLRY 84

                          90       100
                  ....*....|....*....|....
gi 1735576498  98 FPASSKSPEDYSGGRTASDIVNFI 121
Cdd:cd02992    85 FPPFSKEATDGLKQEGPERDVNEL 108

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 1735576498 137 AVVELTDSnFDAVVMDpeaDV-LVEFFAPWCGHCKSLKPVYEKVANAFSAE-RKVVVAAVDATAARDISSRFEVRGYPTI 214
Cdd:cd03000     1 LVLDLDDS-FKDVRKE---DIwLVDFYAPWCGHCKKLEPVWNEVGAELKSSgSPVRVGKLDATAYSSIASEFGVRGYPTI 76

                          90       100
                  ....*....|....*....|....*....
gi 1735576498 215 KFFPRGTAAkeaeDYEGGRSVEDFVTFLN 243
Cdd:cd03000    77 KLLKGDLAY----NYRGPRTKDDIVEFAN 101

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 1735576498  23 LTPENFDSVVGGDKPALVEFFAPWCGHCKQLAPEY----DVVGSTFQANDGVVVAKVDADAHRDLGSRFGVSGFPTIKWF 98
Cdd:cd02996     6 LTSGNIDDILQSAELVLVNFYADWCRFSQMLHPIFeeaaAKIKEEFPDAGKVVWGKVDCDKESDIADRYRINKYPTLKLF 85

                          90       100
                  ....*....|....*....|...
gi 1735576498  99 PASSKSPEDYSGGRTASDIVNFI 121
Cdd:cd02996    86 RNGMMMKREYRGQRSVEALAEFV 108

Endoplasmic reticulum protein ERp29, C-terminal domain; ERp29 is a ubiquitously expressed endoplasmic reticulum protein found in mammals. ERp29 is comprised of two domains. This domain, the C-terminal domain, has an all helical fold. ERp29 is thought to form part of the thyroglobulin folding complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1735576498 261 GRVEALDEFVRAFVAAAEEEREAIIEQTASKVKELGESAKDTGAYYVKAMRRYTERGAGWVTKESARLSSMATSAAVAAA 340
Cdd:pfam07749   1 GRIEELDALAAEFVAAAKDERKELLEEAKKAAEKLKEAEKKYAKYYVKVMEKILEKGEEYVEKELARLEKLLAKGKLSPE 80

                          90
                  ....*....|....*
gi 1735576498 341 RKTNIMLRRNVLAAF 355
Cdd:pfam07749  81 KKDELQIRLNILRSF 95

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 1735576498 136 TAVVELTDSNFDAVVMDPEADVLVEFFAPWCGHCKSLKPVYEKVANAFSAerKVVVAAVDATAARDISSRFEVRGYPTIK 215
Cdd:cd03004     1 PSVITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKG--KVKVGSVDCQKYESLCQQANIRAYPTIR 78

                  ...
gi 1735576498 216 FFP 218
Cdd:cd03004    79 LYP 81

thioredoxin; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1735576498  24 TPENFDSVVGGDKPALVEFFAPWCGHCKQLAPEYDVVGSTFQAndgVVVAKVDADAHRDLGSRFGVSGFPTIKWF 98
Cdd:PTZ00051    7 SQAEFESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTK---MVFVKVDVDELSEVAEKENITSMPTFKVF 78