P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (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. The C-terminal domain is likely involved in substrate binding, similar to the b and b' domains of PDI.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275 271 APELIEIINESTFETACEGKPLCVVSVLPHILDCDAKCRNKFLDTLRTLGEKFKQKQWGWAWAEGGQQLALEESLEVGGF 350
Cdd:cd02983    1 APEIIELTSEDVFEETCEEKQLCIIAFLPHILDCQASCRNKYLEILKSVAEKFKKKPWGWLWTEAGAQLDLEEALNIGGF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 665408275 351 GYPAMAVVNFKKMKFSVLKGSFSKDGINEFLRDISYGRGHTAPVRGAKKP 400
Cdd:cd02983   81 GYPAMVAINFRKMKFATLKGSFSEDGINEFLRELSYGRGPTLPVNGLPKV 130

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 665408275  26 GVVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGVVKVGSVNADADSTLSGQFGVRGFPTIKIFG 105
Cdd:cd03001    1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                         90
                 ....*....|....
gi 665408275 106 ANKKSPTDYNGQRT 119
Cdd:cd03001   81 AGKNSPQDYQGGRT 94

P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (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. The C-terminal domain is likely involved in substrate binding, similar to the b and b' domains of PDI.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275 271 APELIEIINESTFETACEGKPLCVVSVLPHILDCDAKCRNKFLDTLRTLGEKFKQKQWGWAWAEGGQQLALEESLEVGGF 350
Cdd:cd02983    1 APEIIELTSEDVFEETCEEKQLCIIAFLPHILDCQASCRNKYLEILKSVAEKFKKKPWGWLWTEAGAQLDLEEALNIGGF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 665408275 351 GYPAMAVVNFKKMKFSVLKGSFSKDGINEFLRDISYGRGHTAPVRGAKKP 400
Cdd:cd02983   81 GYPAMVAINFRKMKFATLKGSFSEDGINEFLRELSYGRGPTLPVNGLPKV 130

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 665408275  26 GVVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGVVKVGSVNADADSTLSGQFGVRGFPTIKIFG 105
Cdd:cd03001    1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                         90
                 ....*....|....
gi 665408275 106 ANKKSPTDYNGQRT 119
Cdd:cd03001   81 AGKNSPQDYQGGRT 94

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 665408275  158 VIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKAAEYNVRGYPTIKFFPA 237
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|....*.
gi 665408275  238 GSKRAsdaqEYDGGRTASDIVSWASD 263
Cdd:pfam00085  82 GQPVD----DYVGARPKDALAAFLKA 103

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 665408275   30 LTPSNFDREVLKDDaIWVVEFYAPWCGHCQSLVPEYKKLAKALKG--VVKVGSVNADADSTLSGQFGVRGFPTIKIFGaN 107
Cdd:TIGR01126   1 LTASNFDEIVLSNK-DVLVEFYAPWCGHCKNLAPEYEKLAKELKKdpKIVLAKVDATAEKDLASRFGVSGFPTIKFFP-K 78

                          90
                  ....*....|..
gi 665408275  108 KKSPTDYNGQRT 119
Cdd:TIGR01126  79 GSKPVDYEGGRD 90

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 665408275   26 GVVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGVVKVGSVNADADSTLSGQFGVRGFPTIKIFg 105
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFF- 79

                          90
                  ....*....|....
gi 665408275  106 ANKKSPTDYNGQRT 119
Cdd:pfam00085  80 KNGQPVDDYVGARP 93

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 665408275 158 VIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKAAEYNVRGYPTIKFFPA 237
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                         90       100
                 ....*....|....*....|....*.
gi 665408275 238 GskrasdaQEYD---GGRTASDIVSW 260
Cdd:COG3118   82 G-------QPVDrfvGALPKEQLREF 100

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275  198 KAAKELKGKVKLGAldaTAHQSKAAEYNVRgYPTIKFFPAGSKRAsdaQEYDGG-RTASDIVSWASDKHVANVPapelie 276
Cdd:pfam13848  14 KAAKELKGDVRFGI---TFSKEVADKYNIK-EPAILLFRKFDEET---VHYPGDsINFEDLKKFIQKNCLPLVR------ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275  277 IINESTFETACE-GKPLCVVSVLPHildcDAKCRNKFLDTLRTLGEKFKqKQWGWAWAEGGQQLALEESLEVGGFGYPAM 355
Cdd:pfam13848  81 EFTPENAEELFEeGIPPLLLLFLKK----DDESTEEFKKALEKVAKKFR-GKINFALVDAKSFGRPLEYFGLSESDLPVI 155

                         170       180
                  ....*....|....*....|....*....
gi 665408275  356 AVVN-FKKMKFSVLKGSFSKDGINEFLRD 383
Cdd:pfam13848 156 VIVDsFSHMYKYFPSDEFSPESLKEFIND 184

P5 family, C-terminal redox inactive TRX-like domain; P5 is a protein disulfide isomerase (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. The C-terminal domain is likely involved in substrate binding, similar to the b and b' domains of PDI.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275 271 APELIEIINESTFETACEGKPLCVVSVLPHILDCDAKCRNKFLDTLRTLGEKFKQKQWGWAWAEGGQQLALEESLEVGGF 350
Cdd:cd02983    1 APEIIELTSEDVFEETCEEKQLCIIAFLPHILDCQASCRNKYLEILKSVAEKFKKKPWGWLWTEAGAQLDLEEALNIGGF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 665408275 351 GYPAMAVVNFKKMKFSVLKGSFSKDGINEFLRDISYGRGHTAPVRGAKKP 400
Cdd:cd02983   81 GYPAMVAINFRKMKFATLKGSFSEDGINEFLRELSYGRGPTLPVNGLPKV 130

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 665408275  26 GVVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGVVKVGSVNADADSTLSGQFGVRGFPTIKIFG 105
Cdd:cd03001    1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                         90
                 ....*....|....
gi 665408275 106 ANKKSPTDYNGQRT 119
Cdd:cd03001   81 AGKNSPQDYQGGRT 94

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 665408275 159 IELTEDNFDKLVLNSDDiWLVEFFAPWCGHCKNLAPEWAKAAKELK--GKVKLGALDATAHQSKAAEYNVRGYPTIKFFP 236
Cdd:cd02961    1 VELTDDNFDELVKDSKD-VLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                         90       100
                 ....*....|....*....|....*
gi 665408275 237 AGSKrasDAQEYDGGRTASDIVSWA 261
Cdd:cd02961   80 NGSK---EPVKYEGPRTLESLVEFI 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 665408275  156 DDVIELTEDNFDkLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGK---VKLGALDATAHQSKAAEYNVRGYPTI 232
Cdd:TIGR01130   1 EDVLVLTKDNFD-DFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKgppIKLAKVDATEEKDLAQKYGVSGYPTL 79

                          90       100
                  ....*....|....*....|....*...
gi 665408275  233 KFFPAGSKrasDAQEYDGGRTASDIVSW 260
Cdd:TIGR01130  80 KIFRNGED---SVSDYNGPRDADGIVKY 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 665408275 158 VIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKAAEYNVRGYPTIKFFPA 237
Cdd:cd03004    3 VITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYPG 82

                         90       100
                 ....*....|....*....|....*
gi 665408275 238 GskrASDAQEYDG-GRTASDIVSWA 261
Cdd:cd03004   83 N---ASKYHSYNGwHRDADSILEFI 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 665408275  158 VIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKAAEYNVRGYPTIKFFPA 237
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|....*.
gi 665408275  238 GSKRAsdaqEYDGGRTASDIVSWASD 263
Cdd:pfam00085  82 GQPVD----DYVGARPKDALAAFLKA 103

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 665408275 158 VIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKA--AEYNVRGYPTIKFF 235
Cdd:cd03002    2 VYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKNKPlcGKYGVQGFPTLKVF 81

                         90       100
                 ....*....|....*....|....*...
gi 665408275 236 PAGSKRASDAQE-YDGGRTASDIVSWAS 262
Cdd:cd03002   82 RPPKKASKHAVEdYNGERSAKAIVDFVL 109

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275 156 DDVIELTEDNFDKLvLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELK---GKVKLGALDATAHQSKAAEYNVRGYPTI 232
Cdd:PTZ00102  32 EHVTVLTDSTFDKF-ITENEIVLVKFYAPWCGHCKRLAPEYKKAAKMLKekkSEIVLASVDATEEMELAQEFGVRGYPTI 110

                         90       100       110
                 ....*....|....*....|....*....|.
gi 665408275 233 KFFPAGSKRasdaqEYDGGRTASDIVSWASD 263
Cdd:PTZ00102 111 KFFNKGNPV-----NYSGGRTADGIVSWIKK 136

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 665408275  27 VVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGVVKVGSVNADADSTLSGQFGVRGFPTIKIFGA 106
Cdd:cd03004    3 VITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYPG 82

                         90
                 ....*....|
gi 665408275 107 NKKSPTDYNG 116
Cdd:cd03004   83 NASKYHSYNG 92

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 665408275 157 DVIELTEDNFDKLvLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELK--GKVKLGALDAT--AHQSKAAEYNVRGYPTI 232
Cdd:cd02997    1 DVVHLTDEDFRKF-LKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKedGKGVLAAVDCTkpEHDALKEEYNVKGFPTF 79

                         90       100
                 ....*....|....*....|....*...
gi 665408275 233 KFFPAGSKRasdaQEYDGGRTASDIVSW 260
Cdd:cd02997   80 KYFENGKFV----EKYEGERTAEDIIEF 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 665408275   27 VVELTPSN----FDREVLKDDAIWVVEFYAPWcghcQSLVPEYKKLAKALKG-VVKVGSVNADADSTLSGQFGV--RGFP 99
Cdd:TIGR01130 219 VGEFTQETaakyFESGPLVVLYYNVDESLDPF----EELRNRFLEAAKKFRGkFVNFAVADEEDFGRELEYFGLkaEKFP 294

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275  100 TIKIFG--ANKKSPtdYNGQRTAKAIAEAALAEVKK-KVQGVLGGGGGSSSGGsgsssgDDVIELTEDNFDKLVLNSDDI 176
Cdd:TIGR01130 295 AVAIQDleGNKKYP--MDQEEFSSENLEAFVKDFLDgKLKPYLKSEPIPEDDE------GPVKVLVGKNFDEIVLDETKD 366

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275  177 WLVEFFAPWCGHCKNLAPEWAKAAKELKG---KVKLGALDATAHQskAAEYNVRGYPTIKFFPAGSKRASdaQEYDGGRT 253
Cdd:TIGR01130 367 VLVEFYAPWCGHCKNLAPIYEELAEKYKDaesDVVIAKMDATAND--VPPFEVEGFPTIKFVPAGKKSEP--VPYDGDRT 442

                  ....*
gi 665408275  254 ASDIV 258
Cdd:TIGR01130 443 LEDFS 447

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 665408275 174 DDIWLVEFFAPWCGHCKNLAPEWAKAAKELKG---KVKLGALDATAHQSKAAEYNVRGYPTIKFFpagskRASDAQEYDG 250
Cdd:cd03000   15 EDIWLVDFYAPWCGHCKKLEPVWNEVGAELKSsgsPVRVGKLDATAYSSIASEFGVRGYPTIKLL-----KGDLAYNYRG 89

                         90
                 ....*....|.
gi 665408275 251 GRTASDIVSWA 261
Cdd:cd03000   90 PRTKDDIVEFA 100

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 665408275 158 VIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKAAEYNVRGYPTIKFFPA 237
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                         90       100
                 ....*....|....*....|....*.
gi 665408275 238 GskrasdaQEYD---GGRTASDIVSW 260
Cdd:COG3118   82 G-------QPVDrfvGALPKEQLREF 100

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 665408275 156 DDVIELTEDNFDKLVLNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELK---GKVKLGALDATAHQSKAA--EYNVRGYP 230
Cdd:cd02992    1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRkwrPVVRVAAVDCADEENVALcrDFGVTGYP 80

                         90       100       110
                 ....*....|....*....|....*....|
gi 665408275 231 TIKFFPAGSKRASDAQEYDG-GRTASDIVS 259
Cdd:cd02992   81 TLRYFPPFSKEATDGLKQEGpERDVNELRE 110

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 665408275  26 GVVELTPSNFDREVLKddAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGV---VKVGSVNADADSTLSGQFGVRGFPTIK 102
Cdd:cd03005    1 GVLELTEDNFDHHIAE--GNHFVKFFAPWCGHCKRLAPTWEQLAKKFNNEnpsVKIAKVDCTQHRELCSEFQVRGYPTLL 78

                         90
                 ....*....|....*..
gi 665408275 103 IFGANKKsPTDYNGQRT 119
Cdd:cd03005   79 LFKDGEK-VDKYKGTRD 94

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 665408275  25 DGVVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALK---GVVKVGSVN--ADADSTLSGQFGVRGFP 99
Cdd:cd02992    1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRkwrPVVRVAAVDcaDEENVALCRDFGVTGYP 80

                         90       100
                 ....*....|....*....|
gi 665408275 100 TIKIFGANKKSPTDYNGQRT 119
Cdd:cd02992   81 TLRYFPPFSKEATDGLKQEG 100

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 665408275   24 SDGVVELTPSNFDREVLKDDAIWVVEFYAPWCGHCQSLVPEYKKLAKALKGvVKVGSVNADADSTLSG--QFGVRGFPTI 101
Cdd:TIGR01130 345 EGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKD-AESDVVIAKMDATANDvpPFEVEGFPTI 423

                          90
                  ....*....|....*....
gi 665408275  102 KIFGANKKS-PTDYNGQRT 119
Cdd:TIGR01130 424 KFVPAGKKSePVPYDGDRT 442

PDIa family, N-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 comprised of the first TRX domain of ERdj5 located after the DnaJ domain at the N-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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665408275 157 DVIELTEDNFDKLVlNSDDIWLVEFFAPWCGHCKNLAPEWAKAAKELKGKVKLGALDATAHQSKAAEYNVRGYPTIKFFP 236
Cdd:cd03003    2 EIVTLDRGDFDAAV-NSGEIWFVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFP 80

                         90       100
                 ....*....|....*....|....*
gi 665408275 237 AGSKrasdAQEYDGGRTASDIVSWA 261
Cdd:cd03003   81 SGMN----PEKYYGDRSKESLVKFA 101