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 569001520   45 DGILVLNHRTLSLALQEHSALMVEFYAPWCGHCKELAPEYSKAAALLAAESAVVTLAKVDGPAEPELTKEFEVVGYPTLK 124
Cdd:TIGR01130   1 EDVLVLTKDNFDDFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  125 FFQNGNRtNPEEYAGPKTAEGIAEWLRRRVGPSATHLEDEEGVQALMAKWDMVVIGFFQDLQGKDMATFLALAKDALDMT 204
Cdd:TIGR01130  81 IFRNGED-SVSDYNGPRDADGIVKYMKKQSGPAVKEIETVADLEAFLADDDVVVIGFFKDLDSELNDTFLSVAEKLRDVY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  205 FGF--TDQPQLFEKFGLTKDTVVLFK---------------------------------------KTSPKIFAAKILNHL 243
Cdd:TIGR01130 160 FFFahSSDVAAFAKLGAFPDSVVLFKpkdedekfskvdgemdtdvsdlekfiraeslplvgeftqETAAKYFESGPLVVL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  244 LLFVNQTLAQHRELLTDFREAAPPFRGQVLFVMVDVAADNSHVLNYFGLKAEEAPTLRLINVETTKKYAPTGViAITAAS 323
Cdd:TIGR01130 240 YYNVDESLDPFEELRNRFLEAAKKFRGKFVNFAVADEEDFGRELEYFGLKAEKFPAVAIQDLEGNKKYPMDQE-EFSSEN 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  324 VAAFCQAVLHGEIKHYLLSQEIPPDwDQGPVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDRE 403
Cdd:TIGR01130 319 LEAFVKDFLDGKLKPYLKSEPIPED-DEGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAE 397

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569001520  404 -DIVIAELDATANELEAFSVLGYPTLKFFPAGPDRKVIDYKSTRDLETFSKFLDSGGHLPKEEPK 467
Cdd:TIGR01130 398 sDVVIAKMDATANDVPPFEVEGFPTIKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATFPLEGKA 462

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 569001520   45 DGILVLNHRTLSLALQEHSALMVEFYAPWCGHCKELAPEYSKAAALLAAESAVVTLAKVDGPAEPELTKEFEVVGYPTLK 124
Cdd:TIGR01130   1 EDVLVLTKDNFDDFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  125 FFQNGNRtNPEEYAGPKTAEGIAEWLRRRVGPSATHLEDEEGVQALMAKWDMVVIGFFQDLQGKDMATFLALAKDALDMT 204
Cdd:TIGR01130  81 IFRNGED-SVSDYNGPRDADGIVKYMKKQSGPAVKEIETVADLEAFLADDDVVVIGFFKDLDSELNDTFLSVAEKLRDVY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  205 FGF--TDQPQLFEKFGLTKDTVVLFK---------------------------------------KTSPKIFAAKILNHL 243
Cdd:TIGR01130 160 FFFahSSDVAAFAKLGAFPDSVVLFKpkdedekfskvdgemdtdvsdlekfiraeslplvgeftqETAAKYFESGPLVVL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  244 LLFVNQTLAQHRELLTDFREAAPPFRGQVLFVMVDVAADNSHVLNYFGLKAEEAPTLRLINVETTKKYAPTGViAITAAS 323
Cdd:TIGR01130 240 YYNVDESLDPFEELRNRFLEAAKKFRGKFVNFAVADEEDFGRELEYFGLKAEKFPAVAIQDLEGNKKYPMDQE-EFSSEN 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  324 VAAFCQAVLHGEIKHYLLSQEIPPDwDQGPVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDRE 403
Cdd:TIGR01130 319 LEAFVKDFLDGKLKPYLKSEPIPED-DEGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAE 397

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569001520  404 -DIVIAELDATANELEAFSVLGYPTLKFFPAGPDRKVIDYKSTRDLETFSKFLDSGGHLPKEEPK 467
Cdd:TIGR01130 398 sDVVIAKMDATANDVPPFEVEGFPTIKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATFPLEGKA 462

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 569001520 353 PVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDREDIVIAELDATANELE-AFSVLGYPTLKFF 431
Cdd:cd02995    1 PVKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPsEFVVDGFPTILFF 80

                         90       100
                 ....*....|....*....|....
gi 569001520 432 PAGPDRKVIDYKSTRDLETFSKFL 455
Cdd:cd02995   81 PAGDKSNPIKYEGDRTLEDLIKFI 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 569001520 354 VKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDRedIVIAELDATAN-EL-EAFSVLGYPTLKFF 431
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGK--VKFVKVDVDENpELaAQFGVRSIPTLLLF 79

                         90       100
                 ....*....|....*....|....*..
gi 569001520 432 PAGpdrKVIDYKS-TRDLETFSKFLDS 457
Cdd:COG3118   80 KDG---QPVDRFVgALPKEQLREFLDK 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 569001520   45 DGILVLNHRTLSLALQEHSALMVEFYAPWCGHCKELAPEYSKAAALLAAESAVVTLAKVDGPAEPELTKEFEVVGYPTLK 124
Cdd:TIGR01130   1 EDVLVLTKDNFDDFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  125 FFQNGNRtNPEEYAGPKTAEGIAEWLRRRVGPSATHLEDEEGVQALMAKWDMVVIGFFQDLQGKDMATFLALAKDALDMT 204
Cdd:TIGR01130  81 IFRNGED-SVSDYNGPRDADGIVKYMKKQSGPAVKEIETVADLEAFLADDDVVVIGFFKDLDSELNDTFLSVAEKLRDVY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  205 FGF--TDQPQLFEKFGLTKDTVVLFK---------------------------------------KTSPKIFAAKILNHL 243
Cdd:TIGR01130 160 FFFahSSDVAAFAKLGAFPDSVVLFKpkdedekfskvdgemdtdvsdlekfiraeslplvgeftqETAAKYFESGPLVVL 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  244 LLFVNQTLAQHRELLTDFREAAPPFRGQVLFVMVDVAADNSHVLNYFGLKAEEAPTLRLINVETTKKYAPTGViAITAAS 323
Cdd:TIGR01130 240 YYNVDESLDPFEELRNRFLEAAKKFRGKFVNFAVADEEDFGRELEYFGLKAEKFPAVAIQDLEGNKKYPMDQE-EFSSEN 318

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  324 VAAFCQAVLHGEIKHYLLSQEIPPDwDQGPVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDRE 403
Cdd:TIGR01130 319 LEAFVKDFLDGKLKPYLKSEPIPED-DEGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAE 397

                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569001520  404 -DIVIAELDATANELEAFSVLGYPTLKFFPAGPDRKVIDYKSTRDLETFSKFLDSGGHLPKEEPK 467
Cdd:TIGR01130 398 sDVVIAKMDATANDVPPFEVEGFPTIKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATFPLEGKA 462

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 569001520 353 PVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDREDIVIAELDATANELE-AFSVLGYPTLKFF 431
Cdd:cd02995    1 PVKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPsEFVVDGFPTILFF 80

                         90       100
                 ....*....|....*....|....
gi 569001520 432 PAGPDRKVIDYKSTRDLETFSKFL 455
Cdd:cd02995   81 PAGDKSNPIKYEGDRTLEDLIKFI 104

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 569001520 355 KTLVSKNFEQVAFDEtKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDREDIVIAELDATANE--LEAFSVLGYPTLKFFP 432
Cdd:cd02961    1 VELTDDNFDELVKDS-KDVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVVVAKVDCTANNdlCSEYGVRGYPTIKLFP 79

                         90       100
                 ....*....|....*....|...
gi 569001520 433 AGpDRKVIDYKSTRDLETFSKFL 455
Cdd:cd02961   80 NG-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 569001520  48 LVLNHRTLSLALQEHSALMVEFYAPWCGHCKELAPEYSKAAALLAAESAVVtLAKVDGPAEPELTKEFEVVGYPTLKFFQ 127
Cdd:cd02961    1 VELTDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVV-VAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                         90       100
                 ....*....|....*....|...
gi 569001520 128 NGNRtNPEEYAGPKTAEGIAEWL 150
Cdd:cd02961   80 NGSK-EPVKYEGPRTLESLVEFI 101

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 569001520 354 VKTLVSKNFEQ-VAfdeTKNVFVKFYAPWCSHCKEMAPAWEALAEKY-KDREDIVIAELDATA-NEL-EAFSVLGYPTLK 429
Cdd:cd03005    2 VLELTEDNFDHhIA---EGNHFVKFFAPWCGHCKRLAPTWEQLAKKFnNENPSVKIAKVDCTQhRELcSEFQVRGYPTLL 78

                         90       100
                 ....*....|....*....|....*.
gi 569001520 430 FFPAGpdRKVIDYKSTRDLETFSKFL 455
Cdd:cd03005   79 LFKDG--EKVDKYKGTRDLDSLKEFV 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 569001520  353 PVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDreDIVIAELDATANELEA--FSVLGYPTLKF 430
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKG--NVVFAKVDVDENPDLAskYGVRGYPTLIF 78

                          90       100
                  ....*....|....*....|....*..
gi 569001520  431 FPAGpdRKVIDYKSTRDLETFSKFLDS 457
Cdd:pfam00085  79 FKNG--QPVDDYVGARPKDALAAFLKA 103

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 569001520   59 LQEHSALMVEFYAPWCGHCKELAPEYSKAAALLaaeSAVVTLAKVDGPAEPELTKEFEVVGYPTLKFFQNGNrtNPEEYA 138
Cdd:pfam00085  15 QKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEY---KGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQ--PVDDYV 89

                          90
                  ....*....|....
gi 569001520  139 GPKTAEGIAEWLRR 152
Cdd:pfam00085  90 GARPKDALAAFLKA 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 569001520  66 MVEFYAPWCGHCKELAPEYSKAAALLAAESAVVtLAKVDGPAEpELTKEFEVVGYPTLKFFQNGNRTNPEEYAGPKTAEG 145
Cdd:cd02995   22 LVEFYAPWCGHCKALAPIYEELAEKLKGDDNVV-IAKMDATAN-DVPSEFVVDGFPTILFFPAGDKSNPIKYEGDRTLED 99

                 ....*
gi 569001520 146 IAEWL 150
Cdd:cd02995  100 LIKFI 104

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520 350 DQGPVKTLVSKNFEQVAFDETKNV----FVKFYAPWCSHCKEMAPAWEALAEKYKDRedIVIAELDAT--ANELEAFSVL 423
Cdd:PTZ00443  28 DANALVLLNDKNFEKLTQASTGATtgpwFVKFYAPWCSHCRKMAPAWERLAKALKGQ--VNVADLDATraLNLAKRFAIK 105

                         90       100       110
                 ....*....|....*....|....*....|..
gi 569001520 424 GYPTLKFFPAGpdrKVIDYKS-TRDLETFSKF 454
Cdd:PTZ00443 106 GYPTLLLFDKG---KMYQYEGgDRSTEKLAAF 134

Protein Disulfide Isomerase (PDIb') family, redox inactive TRX-like domain b'; 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, calsequestrin and other PDI-related proteins like ERp72, ERp57 (or ERp60), ERp44, P5 and PDIR. PDI, ERp57, ERp72, P5 and PDIR 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 contain multiple copies of a redox active TRX (a) domain containing a CXXC motif, and one or more redox inactive TRX-like (b) domains. The molecular structure of PDI is abb'a'. Also included in this family is the PDI-related protein ERp27, which contains only redox-inactive TRX-like (b and b') domains. The redox inactive domains are implicated in substrate recognition with the b' domain serving as the primary substrate binding site. Only the b' domain is necessary for the binding of small peptide substrates. In addition to the b' domain, other domains are required for the binding of larger polypeptide substrates. The b' domain is also implicated in chaperone activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520 230 TSPKIFAAKI--LNHLLLFVNQTLAQHRELLTDFREAAPPFRGQVLFVMVDvAADNSHVLNYFGLKAEEAPTLRLINVET 307
Cdd:cd02982    1 NAETFFNYEEsgKPLLVLFYNKDDSESEELRERFKEVAKKFKGKLLFVVVD-ADDFGRHLEYFGLKEEDLPVIAIINLSD 79

                         90       100
                 ....*....|....*....|....*
gi 569001520 308 TKKYAPTGViAITAASVAAFCQAVL 332
Cdd:cd02982   80 GKKYLMPEE-ELTAESLEEFVEDFL 103

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 569001520  66 MVEFYAPWCGHCKELAPEYSKAAALLAAESAVVTLAKVDGPAEPELTKEFEVVGYPTLKFFQNGNRTNpeeYAGPKTAEG 145
Cdd:cd03000   19 LVDFYAPWCGHCKKLEPVWNEVGAELKSSGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAYN---YRGPRTKDD 95

                 ....*..
gi 569001520 146 IAEWLRR 152
Cdd:cd03000   96 IVEFANR 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 569001520 354 VKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDRedIVIAELDATAN-EL-EAFSVLGYPTLKFF 431
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGK--VKFVKVDVDENpELaAQFGVRSIPTLLLF 79

                         90       100
                 ....*....|....*....|....*..
gi 569001520 432 PAGpdrKVIDYKS-TRDLETFSKFLDS 457
Cdd:COG3118   80 KDG---QPVDRFVgALPKEQLREFLDK 103

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  182 FQDLQGKDMATFLALAKD-ALDMTFGFTDQPQLFEKFGLTKDTVVLFKKTS----------------------------- 231
Cdd:pfam13848   1 FEDKDSPLYEIFRKAAKElKGDVRFGITFSKEVADKYNIKEPAILLFRKFDeetvhypgdsinfedlkkfiqknclplvr 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520  232 -------PKIFAAKILNHLLLFVNQTLAQHRELLTDFREAAPPFRGQVLFVMVDvAADNSHVLNYFGLKAEEAPTLRLIN 304
Cdd:pfam13848  81 eftpenaEELFEEGIPPLLLLFLKKDDESTEEFKKALEKVAKKFRGKINFALVD-AKSFGRPLEYFGLSESDLPVIVIVD 159

                         170       180
                  ....*....|....*....|....*.
gi 569001520  305 VET-TKKYAPTGViaITAASVAAFCQ 329
Cdd:pfam13848 160 SFShMYKYFPSDE--FSPESLKEFIN 183

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 569001520 353 PVKTLVSKNFEQVAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDREDIVIAELDATAN-ELEA-FSVLGYPTLKF 430
Cdd:cd03002    1 PVYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKNkPLCGkYGVQGFPTLKV 80

                         90       100
                 ....*....|....*....|....*..
gi 569001520 431 FPAGPD---RKVIDYKSTRDLETFSKF 454
Cdd:cd03002   81 FRPPKKaskHAVEDYNGERSAKAIVDF 107

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 569001520  45 DGILVLNHRTLSLALQEH-SALMVEFYAPWCGHCKELAPEYSKAAALLAAESAVVTLAKVDGpAEPE---LTKEFEVVGY 120
Cdd:cd02992    1 DPVIVLDAASFNSALLGSpSAWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDC-ADEEnvaLCRDFGVTGY 79

                 ....*.
gi 569001520 121 PTLKFF 126
Cdd:cd02992   80 PTLRYF 85

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 569001520 374 FVKFYAPWCSHCKEMAPAWEALAEKYKDR-EDIVIAELDATANELEA--FSVLGYPTLKFFPAGpdrKVIDYKSTRDLET 450
Cdd:cd03000   19 LVDFYAPWCGHCKKLEPVWNEVGAELKSSgSPVRVGKLDATAYSSIAseFGVRGYPTIKLLKGD---LAYNYRGPRTKDD 95

                 ....
gi 569001520 451 FSKF 454
Cdd:cd03000   96 IVEF 99

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569001520 365 VAFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYKDREDIVIAELDATA--NELEAFSVLGYPTLKFF 431
Cdd:cd02950   15 VALSNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPKwlPEIDRYRVDGIPHFVFL 83

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 569001520 356 TLVSKNFEQVaFDETKNVFVKFYAPWCSHCKEMAPAWEALAEKYK----DREDIVIAELDATANELEA--FSVLGYPTLK 429
Cdd:cd02996    5 SLTSGNIDDI-LQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKeefpDAGKVVWGKVDCDKESDIAdrYRINKYPTLK 83

                         90       100
                 ....*....|....*....|....*.
gi 569001520 430 FFPAGPDRKViDYKSTRDLETFSKFL 455
Cdd:cd02996   84 LFRNGMMMKR-EYRGQRSVEALAEFV 108

thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520   66 MVEFYAPWCGHCKELAPEYSKAAALLAAEsavVTLAKVDGPAEPELTKEFEVVGYPTLKFFQNGNRTNPEEYAGPKTAeg 145
Cdd:TIGR01068  18 LVDFWAPWCGPCKMIAPILEELAKEYEGK---VKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRSVGALPKAA-- 92

                  ....*
gi 569001520  146 IAEWL 150
Cdd:TIGR01068  93 LKQLI 97

PDIa family, 5'-Adenylylsulfate (APS) reductase subfamily; composed of plant-type APS reductases containing a C-terminal redox active TRX domain and an N-terminal reductase domain which is part of a superfamily that includes N type ATP PPases. APS reductase catalyzes the reduction of activated sulfate to sulfite, a key step in the biosynthesis of sulfur-containing metabolites. Sulfate is first activated by ATP sulfurylase, forming APS, which can be phosphorylated to 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Depending on the organism, either APS or PAPS can be used for sulfate reduction. Prokaryotes and fungi use PAPS, whereas plants use both APS and PAPS. Since plant-type APS reductase uses glutathione (GSH) as its electron donor, the C-terminal domain may function like glutaredoxin, a GSH-dependent member of the TRX superfamily. The flow of reducing equivalents goes from GSH -> C-terminal TRX domain -> N-terminal reductase domain -> APS. Plant-type APS reductase shows no homology to that of dissimilatory sulfate-reducing bacteria, which is an iron-sulfur flavoenzyme. Also included in the alignment is EYE2 from Chlamydomonas reinhardtii, a protein required for eyespot assembly.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569001520 371 KNVFVKFYAPWCSHCKEMAPAWEALAEKYKDrEDIVIAELDATANELE-AFSVLG---YPTLKFFPAGpDRKVIDYKS-T 445
Cdd:cd02993   22 QSTLVVLYAPWCPFCQAMEASYEELAEKLAG-SNVKVAKFNADGEQREfAKEELQlksFPTILFFPKN-SRQPIKYPSeQ 99

                         90
                 ....*....|
gi 569001520 446 RDLETFSKFL 455
Cdd:cd02993  100 RDVDSLLMFV 109