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 42794771 190 GLYELSASNFELHVAQGDHFIKFFAPWCGHCKALAPTWEQLALGLEH-SETVKIGKVDCTQHYELCSGNQVRGYPTLLWF 268
Cdd:cd03005   1 GVLELTEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNNeNPSVKIAKVDCTQHRELCSEFQVRGYPTLLLF 80

                        90       100
                ....*....|....*....|..
gi 42794771 269 RDGKKVDQYKGKRDLESLREYV 290
Cdd:cd03005  81 KDGEKVDKYKGTRDLDSLKEFV 102

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 42794771  61 HSKHLyTADMFTHGIQSAAHFVMFFAPWCGHCQRLQPTWNDLGDKYNSmEDAKVYVAKVDCTAHSDVCSAQGVRGYPTLK 140
Cdd:cd03005   1 GVLEL-TEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNN-ENPSVKIAKVDCTQHRELCSEFQVRGYPTLL 78

                        90       100
                ....*....|....*....|....
gi 42794771 141 LFKPGQEAVKYQGPRDFQTLENWM 164
Cdd:cd03005  79 LFKDGEKVDKYKGTRDLDSLKEFV 102

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 42794771 190 GLYELSASNFELHVAQGDHFIKFFAPWCGHCKALAPTWEQLALGLEH-SETVKIGKVDCTQHYELCSGNQVRGYPTLLWF 268
Cdd:cd03005   1 GVLELTEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNNeNPSVKIAKVDCTQHRELCSEFQVRGYPTLLLF 80

                        90       100
                ....*....|....*....|..
gi 42794771 269 RDGKKVDQYKGKRDLESLREYV 290
Cdd:cd03005  81 KDGEKVDKYKGTRDLDSLKEFV 102

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 42794771  61 HSKHLyTADMFTHGIQSAAHFVMFFAPWCGHCQRLQPTWNDLGDKYNSmEDAKVYVAKVDCTAHSDVCSAQGVRGYPTLK 140
Cdd:cd03005   1 GVLEL-TEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNN-ENPSVKIAKVDCTQHRELCSEFQVRGYPTLL 78

                        90       100
                ....*....|....*....|....
gi 42794771 141 LFKPGQEAVKYQGPRDFQTLENWM 164
Cdd:cd03005  79 LFKDGEKVDKYKGTRDLDSLKEFV 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 42794771   327 LTENNFDDTIAEG-ITFIKFYAPWCGHCKTLAPTWEELSkKEFPGLAGVKIAEVDCTAERNICSKYSVRGYPTLLLFRGG 405
Cdd:TIGR01126   1 LTASNFDEIVLSNkDVLVEFYAPWCGHCKNLAPEYEKLA-KELKKDPKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKG 79

                          90       100
                  ....*....|....*....|...
gi 42794771   406 KKVSEHSGGRDLDSLHRFVLSQA 428
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 42794771   324 VLALTENNFDDTIA--EGITFIKFYAPWCGHCKTLAPTWEELSKkEFPGlaGVKIAEVDCTAERNICSKYSVRGYPTLLL 401
Cdd:pfam00085   2 VVVLTDANFDEVVQksSKPVLVDFYAPWCGPCKMLAPEYEELAQ-EYKG--NVVFAKVDVDENPDLASKYGVRGYPTLIF 78

                          90       100
                  ....*....|....*....|...
gi 42794771   402 FRGGKKVSEHSGGRDLDSLHRFV 424
Cdd:pfam00085  79 FKNGQPVDDYVGARPKDALAAFL 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 42794771    82 VMFFAPWCGHCQRLQPTWNDLGDKYnsmeDAKVYVAKVDCTAHSDVCSAQGVRGYPTLKLFKPGQEAVKYQGPRDFQTLE 161
Cdd:pfam00085  23 VDFYAPWCGPCKMLAPEYEELAQEY----KGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVGARPKDALA 98

                  ...
gi 42794771   162 NWM 164
Cdd:pfam00085  99 AFL 101

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771   82 VMFFAPWCGHCQRLQPTWNDLGdKYNSMEDAKVYVAKVDCTAHSDVCSAQGVRGYPTLKLFKPGQEaVKYQGPRDFQTLE 161
Cdd:PTZ00102  54 VKFYAPWCGHCKRLAPEYKKAA-KMLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNP-VNYSGGRTADGIV 131

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771  162 NWMLQTL---------NEEPVTPEPEVEPPSAPELKQGLYELsASNFELHVAQGDHFIKFFA-PWCGHCKA-LAPTWEQL 230
Cdd:PTZ00102 132 SWIKKLTgpavtevesASEIKLIAKKIFVAFYGEYTSKDSEL-YKKFEEVADKHREHAKFFVkKHEGKNKIyVLHKDEEG 210

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771  231 ALGLEHSETVKIGKVDCTQHYEL---CSGNQVRGYPT----LLWFRDGKK-VDQYKG-----KRDLESLREYVESQLQRT 297
Cdd:PTZ00102 211 VELFMGKTKEELEEFVSTESFPLfaeINAENYRRYISsgkdLVWFCGTTEdYDKYKSvvrkvARKLREKYAFVWLDTEQF 290

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771  298 ETGATETVTPSEAPVLA------------------------------------------AEPEADKGTVLALTENNFDDT 335
Cdd:PTZ00102 291 GSHAKEHLLIEEFPGLAyqspagryllppakesfdsvealieffkdveagkveksiksePIPEEQDGPVKVVVGNTFEEI 370

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771  336 I--AEGITFIKFYAPWCGHCKTLAPTWEELSKKeFPGLAGVKIAEVDCTAERNICSKYSVRGYPTLLLFRGGKKVS-EHS 412
Cdd:PTZ00102 371 VfkSDKDVLLEIYAPWCGHCKNLEPVYNELGEK-YKDNDSIIVAKMNGTANETPLEEFSWSAFPTILFVKAGERTPiPYE 449

                        410
                 ....*....|..
gi 42794771  413 GGRDLDSLHRFV 424
Cdd:PTZ00102 450 GERTVEGFKEFV 461

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 42794771 193 ELSASNFELHVAQGDH--FIKFFAPWCGHCKALAPTWEQLALglEHSETVKIGKVDCTQHYELCSGNQVRGYPTLLWFRD 270
Cdd:COG3118   4 ELTDENFEEEVLESDKpvLVDFWAPWCGPCKMLAPVLEELAA--EYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                        90       100
                ....*....|....*....|....
gi 42794771 271 GKKVDQYKGKRDLESLREYVESQL 294
Cdd:COG3118  82 GQPVDRFVGALPKEQLREFLDKVL 105

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771   74 GIQSAAHFVMFFAPWCGHCQRLQPTWNDLGDKYNsmedAKVYVAKVDCTAHSDVCSAQGVRGYPTLKLFKPGQEAVKYQG 153
Cdd:PTZ00443  49 GATTGPWFVKFYAPWCSHCRKMAPAWERLAKALK----GQVNVADLDATRALNLAKRFAIKGYPTLLLFDKGKMYQYEGG 124

                         90       100
                 ....*....|....*....|....*
gi 42794771  154 PRDFQTLENWMLQTLNEEPVTPEPE 178
Cdd:PTZ00443 125 DRSTEKLAAFALGDFKKALGAPVPA 149

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 42794771 190 GLYELSASNFELHVAQGDHFIKFFAPWCGHCKALAPTWEQLALGLEH-SETVKIGKVDCTQHYELCSGNQVRGYPTLLWF 268
Cdd:cd03005   1 GVLELTEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNNeNPSVKIAKVDCTQHRELCSEFQVRGYPTLLLF 80

                        90       100
                ....*....|....*....|..
gi 42794771 269 RDGKKVDQYKGKRDLESLREYV 290
Cdd:cd03005  81 KDGEKVDKYKGTRDLDSLKEFV 102

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 42794771  61 HSKHLyTADMFTHGIQSAAHFVMFFAPWCGHCQRLQPTWNDLGDKYNSmEDAKVYVAKVDCTAHSDVCSAQGVRGYPTLK 140
Cdd:cd03005   1 GVLEL-TEDNFDHHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFNN-ENPSVKIAKVDCTQHRELCSEFQVRGYPTLL 78

                        90       100
                ....*....|....*....|....
gi 42794771 141 LFKPGQEAVKYQGPRDFQTLENWM 164
Cdd:cd03005  79 LFKDGEKVDKYKGTRDLDSLKEFV 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 42794771 193 ELSASNFELHVAQG-DHFIKFFAPWCGHCKALAPTWEQLALGLEHSETVKIGKVDCTQHYELCSGNQVRGYPTLLWFRDG 271
Cdd:cd02961   2 ELTDDNFDELVKDSkDVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

                        90       100
                ....*....|....*....|
gi 42794771 272 -KKVDQYKGKRDLESLREYV 290
Cdd:cd02961  82 sKEPVKYEGPRTLESLVEFI 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 42794771 327 LTENNFDDTIAEG-ITFIKFYAPWCGHCKTLAPTWEELSKKeFPGLAGVKIAEVDCTAERNICSKYSVRGYPTLLLFRGG 405
Cdd:cd02961   3 LTDDNFDELVKDSkDVLVEFYAPWCGHCKALAPEYEKLAKE-LKGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

                        90       100
                ....*....|....*....|
gi 42794771 406 -KKVSEHSGGRDLDSLHRFV 424
Cdd:cd02961  82 sKEPVKYEGPRTLESLVEFI 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 42794771  67 TADMFTHGIQ-SAAHFVMFFAPWCGHCQRLQPTWNDLGDKYNsmEDAKVYVAKVDCTAHSDVCSAQGVRGYPTLKLFKPG 145
Cdd:cd02961   4 TDDNFDELVKdSKDVLVEFYAPWCGHCKALAPEYEKLAKELK--GDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNG 81

                        90       100
                ....*....|....*....|
gi 42794771 146 -QEAVKYQGPRDFQTLENWM 164
Cdd:cd02961  82 sKEPVKYEGPRTLESLVEFI 101

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 42794771    81 FVMFFAPWCGHCQRLQPTWNDLGDKYNsmEDAKVYVAKVDCTAHSDVCSAQGVRGYPTLKLFKPGQEAVKYQGPRDFQTL 160
Cdd:TIGR01126  17 LVEFYAPWCGHCKNLAPEYEKLAKELK--KDPKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKGSKPVDYEGGRDLEAI 94

                  ....
gi 42794771   161 ENWM 164
Cdd:TIGR01126  95 VEFV 98

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 42794771   193 ELSASNFELHVAQGDHFI-KFFAPWCGHCKALAPTWEQLALGL-EHSETVKIGKVDCTQHYELCSGNQVRGYPTLLWFRD 270
Cdd:TIGR01130   5 VLTKDNFDDFIKSHEFVLvEFYAPWCGHCKSLAPEYEKAADELkKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFRN 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 42794771   271 GKKVDQ-YKGKRDLESLREYVESQLQRTetgATETVTPSEAP------------VLAAEPEADKGTVLALTENNFDDT 335
Cdd:TIGR01130  85 GEDSVSdYNGPRDADGIVKYMKKQSGPA---VKEIETVADLEafladddvvvigFFKDLDSELNDTFLSVAEKLRDVY 159

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 42794771   324 VLALTENNFDDTIA--EGITFIKFYAPWCGHCKTLAPTWEELSKkEFPGlaGVKIAEVDCTAERNICSKYSVRGYPTLLL 401
Cdd:pfam00085   2 VVVLTDANFDEVVQksSKPVLVDFYAPWCGPCKMLAPEYEELAQ-EYKG--NVVFAKVDVDENPDLASKYGVRGYPTLIF 78

                          90       100
                  ....*....|....*....|...
gi 42794771   402 FRGGKKVSEHSGGRDLDSLHRFV 424
Cdd:pfam00085  79 FKNGQPVDDYVGARPKDALAAFL 101

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 42794771 327 LTENNFDDTIAEGI--TFIKFYAPWCGHCKTLAPTWEELSKKeFPGLAGVKIAEVDCTAerN-ICSKYSVRGYPTLLLFR 403
Cdd:cd02995   5 VVGKNFDEVVLDSDkdVLVEFYAPWCGHCKALAPIYEELAEK-LKGDDNVVIAKMDATA--NdVPSEFVVDGFPTILFFP 81

                        90       100
                ....*....|....*....|...
gi 42794771 404 GGKK--VSEHSGGRDLDSLHRFV 424
Cdd:cd02995  82 AGDKsnPIKYEGDRTLEDLIKFI 104

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 42794771 323 TVLALTENNFDDTI--AEGITFIKFYAPWCGHCKTLAPTWEELSKkEFPGlaGVKIAEVDCTAERNICSKYSVRGYPTLL 400
Cdd:COG3118   1 AVVELTDENFEEEVleSDKPVLVDFWAPWCGPCKMLAPVLEELAA-EYGG--KVKFVKVDVDENPELAAQFGVRSIPTLL 77

                        90       100
                ....*....|....*....|....
gi 42794771 401 LFRGGKKVSEHSGGRDLDSLHRFV 424
Cdd:COG3118  78 LFKDGQPVDRFVGALPKEQLREFL 101

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 42794771  81 FVMFFAPWCGHCQRLQPTWNDLGDKYNSmeDAKVYVAKVDCT-AHSDVCSAQGVRGYPTLKLFKPG-QEAVKYQGPRDFQ 158
Cdd:cd02998  22 LVEFYAPWCGHCKNLAPEYEKLAAVFAN--EDDVVIAKVDADeANKDLAKKYGVSGFPTLKFFPKGsTEPVKYEGGRDLE 99

                ....*
gi 42794771 159 TLENW 163
Cdd:cd02998 100 DLVKF 104

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 42794771 324 VLALTENNFDDTIAE--GITFIKFYAPWCGHCKTLAPTWEELSkKEFPGLagVKIAEVDCTAERNICSKYSVRGYPTLLL 401
Cdd:cd03001   2 VVELTDSNFDKKVLNsdDVWLVEFYAPWCGHCKNLAPEWKKAA-KALKGI--VKVGAVDADVHQSLAQQYGVRGFPTIKV 78

                        90       100
                ....*....|....*....|....*
gi 42794771 402 FRGGKKVS-EHSGGRDLDSLHRFVL 425
Cdd:cd03001  79 FGAGKNSPqDYQGGRTAKAIVSAAL 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 42794771 193 ELSASNFELHVAQGDH--FIKFFAPWCGHCKALAPTWEQLALglEHSETVKIGKVDCTQHYELCSGNQVRGYPTLLWFRD 270
Cdd:COG3118   4 ELTDENFEEEVLESDKpvLVDFWAPWCGPCKMLAPVLEELAA--EYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                        90       100
                ....*....|....*....|....
gi 42794771 271 GKKVDQYKGKRDLESLREYVESQL 294
Cdd:COG3118  82 GQPVDRFVGALPKEQLREFLDKVL 105

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 42794771  81 FVMFFAPWCGHCQRLQPTWNDLGDKYNSMEDakVYVAKVDCTAhSDVCSAQGVRGYPTLKLFKPG--QEAVKYQGPRDFQ 158
Cdd:cd02995  22 LVEFYAPWCGHCKALAPIYEELAEKLKGDDN--VVIAKMDATA-NDVPSEFVVDGFPTILFFPAGdkSNPIKYEGDRTLE 98

                ....*.
gi 42794771 159 TLENWM 164
Cdd:cd02995  99 DLIKFI 104

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 42794771 193 ELSASNFELHVAQGDHF--IKFFAPWCGHCKALAPTWEQLALGLEHseTVKIGKVDCTQHYELCSGNQVRGYPTL-LWFR 269
Cdd:cd03004   5 TLTPEDFPELVLNRKEPwlVDFYAPWCGPCQALLPELRKAARALKG--KVKVGSVDCQKYESLCQQANIRAYPTIrLYPG 82

                        90       100
                ....*....|....*....|..
gi 42794771 270 DGKKVDQYKG-KRDLESLREYV 290
Cdd:cd03004  83 NASKYHSYNGwHRDADSILEFI 104

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 42794771  320 DKGTVLALTENNFDD-TIAE-----GITFIKFYAPWCGHCKTLAPTWEELSkKEFPGLagVKIAEVDCTAERNICSKYSV 393
Cdd:PTZ00443  28 DANALVLLNDKNFEKlTQAStgattGPWFVKFYAPWCSHCRKMAPAWERLA-KALKGQ--VNVADLDATRALNLAKRFAI 104

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 42794771  394 RGYPTLLLFRGGKKVSEHSGGRDLDSLHRFVLSQAKDEL 432
Cdd:PTZ00443 105 KGYPTLLLFDKGKMYQYEGGDRSTEKLAAFALGDFKKAL 143