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 767988336  46 LVLTPAGLTQMLNQTRFLMVLFHNPSSKQSRNLAEELGKAVEIMgKGKNGIGFGKVDITIEKELQQEFGITKAPELKlFF 125
Cdd:cd02961    1 VELTDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKEL-KGDGKVVVAKVDCTANNDLCSEYGVRGYPTIK-LF 78

                         90       100
                 ....*....|....*....|...
gi 767988336 126 EGNRSEPISCKGVVESAALVVWL 148
Cdd:cd02961   79 PNGSKEPVKYEGPRTLESLVEFI 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 767988336   46 LVLTPAGLTQMLNQTRFLMVLFHNPSSKQSRNLAEELGKAVEIMGKGKNGIGFGKVDITIEKELQQEFGITKAPELKLFF 125
Cdd:TIGR01130   4 LVLTKDNFDDFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767988336  126 EGNRSePISCKGVVESAALVVWLRRQISQKAFLFNSSEQVAEFVISRPLVIVGFFQDLEEEVAELFYDVIKDFPELTFGV 205
Cdd:TIGR01130  84 NGEDS-VSDYNGPRDADGIVKYMKKQSGPAVKEIETVADLEAFLADDDVVVIGFFKDLDSELNDTFLSVAEKLRDVYFFF 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767988336  206 ITIGNV--IGRFHVTLDSVLVFKKGKIVNRQKLINDS--TNKQELNRVIKQHLTDFVIEYNTENKDLISELHIMSHMLLF 281
Cdd:TIGR01130 163 AHSSDVaaFAKLGAFPDSVVLFKPKDEDEKFSKVDGEmdTDVSDLEKFIRAESLPLVGEFTQETAAKYFESGPLVVLYYN 242

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767988336  282 VSKSSESYGIIIQHYKLASKEFQNKilFILVD-ADEPRNGRVFKYFRVTEVDIPSVQILNLSSD 344
Cdd:TIGR01130 243 VDESLDPFEELRNRFLEAAKKFRGK--FVNFAvADEEDFGRELEYFGLKAEKFPAVAIQDLEGN 304

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 767988336  46 LVLTPAGLTQMLNQTRFLMVLFHNPSSKQSRNLAEELGKAVEIMgKGKNGIGFGKVDITIEKELQQEFGITKAPELKlFF 125
Cdd:cd02961    1 VELTDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKEL-KGDGKVVVAKVDCTANNDLCSEYGVRGYPTIK-LF 78

                         90       100
                 ....*....|....*....|...
gi 767988336 126 EGNRSEPISCKGVVESAALVVWL 148
Cdd:cd02961   79 PNGSKEPVKYEGPRTLESLVEFI 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767988336   76 RNLAEELGKAVEIMgkgKNGIGFGKVDITIEKELQQEFGITKAPELKLFFEGNrsEPISCKGVVESAALVVWLRR 150
Cdd:pfam00085  34 KMLAPEYEELAQEY---KGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQ--PVDDYVGARPKDALAAFLKA 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 767988336   46 LVLTPAGLTQMLNQTRFLMVLFHNPSSKQSRNLAEELGKAVEIMGKGKNGIGFGKVDITIEKELQQEFGITKAPELKLFF 125
Cdd:TIGR01130   4 LVLTKDNFDDFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKIFR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767988336  126 EGNRSePISCKGVVESAALVVWLRRQISQKAFLFNSSEQVAEFVISRPLVIVGFFQDLEEEVAELFYDVIKDFPELTFGV 205
Cdd:TIGR01130  84 NGEDS-VSDYNGPRDADGIVKYMKKQSGPAVKEIETVADLEAFLADDDVVVIGFFKDLDSELNDTFLSVAEKLRDVYFFF 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767988336  206 ITIGNV--IGRFHVTLDSVLVFKKGKIVNRQKLINDS--TNKQELNRVIKQHLTDFVIEYNTENKDLISELHIMSHMLLF 281
Cdd:TIGR01130 163 AHSSDVaaFAKLGAFPDSVVLFKPKDEDEKFSKVDGEmdTDVSDLEKFIRAESLPLVGEFTQETAAKYFESGPLVVLYYN 242

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767988336  282 VSKSSESYGIIIQHYKLASKEFQNKilFILVD-ADEPRNGRVFKYFRVTEVDIPSVQILNLSSD 344
Cdd:TIGR01130 243 VDESLDPFEELRNRFLEAAKKFRGK--FVNFAvADEEDFGRELEYFGLKAEKFPAVAIQDLEGN 304

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 767988336  46 LVLTPAGLTQMLNQTRFLMVLFHNPSSKQSRNLAEELGKAVEIMgKGKNGIGFGKVDITIEKELQQEFGITKAPELKlFF 125
Cdd:cd02961    1 VELTDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKEL-KGDGKVVVAKVDCTANNDLCSEYGVRGYPTIK-LF 78

                         90       100
                 ....*....|....*....|...
gi 767988336 126 EGNRSEPISCKGVVESAALVVWL 148
Cdd:cd02961   79 PNGSKEPVKYEGPRTLESLVEFI 101

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, ERp44 and PDIR. PDI, ERp57 (or ERp60), ERp72 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 b domains are implicated in substrate recognition.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767988336 159 FNSSEQVAEFVISRPLVIVGFFQDLEEEVAELFYDVIKDFPE-LTFGVITIGNVIGRFHVTLDSVLVFKKGkiVNRQKLI 237
Cdd:cd02981    4 LTSKEELEKFLDKDDVVVVGFFKDEESEEYKTFEKVAESLRDdYGFGHTSDKEVAKKLKVKPGSVVLFKPF--EEEPVEY 81

                         90
                 ....*....|....*.
gi 767988336 238 NDSTNKQELNRVIKQH 253
Cdd:cd02981   82 DGEFTEESLVEFIKDN 97

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 767988336  48 LTPAGLTQ-MLNQTRFLMVLFHNPSSKQSRNLAEELGKAVEIMgKGKngIGFGKVDITIEKELQQEFGITKAPELKlFFE 126
Cdd:cd03001    5 LTDSNFDKkVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKAL-KGI--VKVGAVDADVHQSLAQQYGVRGFPTIK-VFG 80

                         90       100
                 ....*....|....*....|.
gi 767988336 127 GNRSEPISCKGVVESAALVVW 147
Cdd:cd03001   81 AGKNSPQDYQGGRTAKAIVSA 101