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 544186046 323 PPELLEIINEDIAKRTCEEHQLCVVAVLPHILDTGAAGRNSYLEVLLKLADKYKKKMWGWLWTEAGAQSELETALGIGGF 402
Cdd:cd02983    1 APEIIELTSEDVFEETCEEKQLCIIAFLPHILDCQASCRNKYLEILKSVAEKFKKKPWGWLWTEAGAQLDLEEALNIGGF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 544186046 403 GYPAMAAINARKMKFALLKGSFSEQGINEFLRELSFGRGSTAPVGGGAFP 452
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 544186046 209 DVIELTDDSFDKNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVkeqtKGKVKLAAVDATVNQVLASRYGIRGFPTI 288
Cdd:cd03001    1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKAL----KGIVKVGAVDADVHQSLAQQYGVRGFPTI 76

                         90       100
                 ....*....|....*....|....*..
gi 544186046 289 KIFQKG-ESPVDYDGGRTRSDIVSRAL 314
Cdd:cd03001   77 KVFGAGkNSPQDYQGGRTAKAIVSAAL 103

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 544186046 323 PPELLEIINEDIAKRTCEEHQLCVVAVLPHILDTGAAGRNSYLEVLLKLADKYKKKMWGWLWTEAGAQSELETALGIGGF 402
Cdd:cd02983    1 APEIIELTSEDVFEETCEEKQLCIIAFLPHILDCQASCRNKYLEILKSVAEKFKKKPWGWLWTEAGAQLDLEEALNIGGF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 544186046 403 GYPAMAAINARKMKFALLKGSFSEQGINEFLRELSFGRGSTAPVGGGAFP 452
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 544186046 209 DVIELTDDSFDKNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVkeqtKGKVKLAAVDATVNQVLASRYGIRGFPTI 288
Cdd:cd03001    1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKAL----KGIVKVGAVDADVHQSLAQQYGVRGFPTI 76

                         90       100
                 ....*....|....*....|....*..
gi 544186046 289 KIFQKG-ESPVDYDGGRTRSDIVSRAL 314
Cdd:cd03001   77 KVFGAGkNSPQDYQGGRTAKAIVSAAL 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 544186046   78 LTPSNFNrEVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKD--VVKVGAVDADKHHSLGGQYGVQGFPTIKIFGSN 155
Cdd:TIGR01126   1 LTASNFD-EIVLSNKDVLVEFYAPWCGHCKNLAPEYEKLAKELKKdpKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKG 79

                          90
                  ....*....|....*...
gi 544186046  156 KnRPEDYQGGRTGEAIVD 173
Cdd:TIGR01126  80 S-KPVDYEGGRDLEAIVE 96

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 544186046   75 VIELTPSNFNREVIQSDSLW-LVEFYAPWCGHCQRLTPEWKKAATALKDVVKVGAVDADKHHSLGGQYGVQGFPTIKIFg 153
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPvLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFF- 79

                          90       100
                  ....*....|....*....|....*
gi 544186046  154 sNKNRPEDYQGGRTGEAIVDAALSA 178
Cdd:pfam00085  80 -KNGQPVDDYVGARPKDALAAFLKA 103

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046 209 DVIELTDDSFDKNVLDSEDVwMVEFYAPWCGHCKNLEPEWAAAASEVKEQtKGKVKLAAVDATVNQVLASRYGIRGFPTI 288
Cdd:PTZ00102  33 HVTVLTDSTFDKFITENEIV-LVKFYAPWCGHCKRLAPEYKKAAKMLKEK-KSEIVLASVDATEEMELAQEFGVRGYPTI 110

                         90       100
                 ....*....|....*....|....*...
gi 544186046 289 KIFQKGEsPVDYDGGRTRSDIVSRALDL 316
Cdd:PTZ00102 111 KFFNKGN-PVNYSGGRTADGIVSWIKKL 137

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 544186046 210 VIELTDDSFDKNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVkeqtKGKVKLAAVDATVNQVLASRYGIRGFPTIK 289
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEY----GGKVKFVKVDVDENPELAAQFGVRSIPTLL 77

                         90
                 ....*....|
gi 544186046 290 IFQKGEsPVD 299
Cdd:COG3118   78 LFKDGQ-PVD 86

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  276 LASRYGIRgFPTIKIFQK-GESPVDYDGGRTRSDIVSRaldlFSDNAPPPeLLEIINEDIAKRTCEEHQLCVVAVlphIL 354
Cdd:pfam13848  33 VADKYNIK-EPAILLFRKfDEETVHYPGDSINFEDLKK----FIQKNCLP-LVREFTPENAEELFEEGIPPLLLL---FL 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  355 DTGAAGRNSYLEVLLKLADKYKKKMwGWLWTEAGA-QSELETaLGIGGFGYPAMAAIN-ARKMKFALLKGSFSEQGINEF 432
Cdd:pfam13848 104 KKDDESTEEFKKALEKVAKKFRGKI-NFALVDAKSfGRPLEY-FGLSESDLPVIVIVDsFSHMYKYFPSDEFSPESLKEF 181

                  ...
gi 544186046  433 LRE 435
Cdd:pfam13848 182 IND 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 544186046 323 PPELLEIINEDIAKRTCEEHQLCVVAVLPHILDTGAAGRNSYLEVLLKLADKYKKKMWGWLWTEAGAQSELETALGIGGF 402
Cdd:cd02983    1 APEIIELTSEDVFEETCEEKQLCIIAFLPHILDCQASCRNKYLEILKSVAEKFKKKPWGWLWTEAGAQLDLEEALNIGGF 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 544186046 403 GYPAMAAINARKMKFALLKGSFSEQGINEFLRELSFGRGSTAPVGGGAFP 452
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 544186046 209 DVIELTDDSFDKNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVkeqtKGKVKLAAVDATVNQVLASRYGIRGFPTI 288
Cdd:cd03001    1 DVVELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKAL----KGIVKVGAVDADVHQSLAQQYGVRGFPTI 76

                         90       100
                 ....*....|....*....|....*..
gi 544186046 289 KIFQKG-ESPVDYDGGRTRSDIVSRAL 314
Cdd:cd03001   77 KVFGAGkNSPQDYQGGRTAKAIVSAAL 103

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 544186046  76 IELTPSNFNrEVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALK--DVVKVGAVDADKHHSLGGQYGVQGFPTIKIFG 153
Cdd:cd02961    1 VELTDDNFD-ELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                         90       100
                 ....*....|....*....|
gi 544186046 154 SNKNRPEDYQGGRTGEAIVD 173
Cdd:cd02961   80 NGSKEPVKYEGPRTLESLVE 99

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 544186046   78 LTPSNFNrEVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKD--VVKVGAVDADKHHSLGGQYGVQGFPTIKIFGSN 155
Cdd:TIGR01126   1 LTASNFD-EIVLSNKDVLVEFYAPWCGHCKNLAPEYEKLAKELKKdpKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKG 79

                          90
                  ....*....|....*...
gi 544186046  156 KnRPEDYQGGRTGEAIVD 173
Cdd:TIGR01126  80 S-KPVDYEGGRDLEAIVE 96

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 544186046  208 KDVIELTDDSFDkNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVKEQTKgKVKLAAVDATVNQVLASRYGIRGFPT 287
Cdd:TIGR01130   1 EDVLVLTKDNFD-DFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKGP-PIKLAKVDATEEKDLAQKYGVSGYPT 78

                          90       100
                  ....*....|....*....|....*
gi 544186046  288 IKIFQKGE-SPVDYDGGRTRSDIVS 311
Cdd:TIGR01130  79 LKIFRNGEdSVSDYNGPRDADGIVK 103

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 544186046  74 DVIELTPSNFNREVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALK--DVVKVGAVDADK-HHSLGGQYGVQGFPTIK 150
Cdd:cd02998    1 NVVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFAneDDVVIAKVDADEaNKDLAKKYGVSGFPTLK 80

                         90       100
                 ....*....|....*....|..
gi 544186046 151 IFGSNKNRPEDYQGGRTGEAIV 172
Cdd:cd02998   81 FFPKGSTEPVKYEGGRDLEDLV 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 544186046   75 VIELTPSNFNREVIQSDSLW-LVEFYAPWCGHCQRLTPEWKKAATALKDVVKVGAVDADKHHSLGGQYGVQGFPTIKIFg 153
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPvLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFF- 79

                          90       100
                  ....*....|....*....|....*
gi 544186046  154 sNKNRPEDYQGGRTGEAIVDAALSA 178
Cdd:pfam00085  80 -KNGQPVDDYVGARPKDALAAFLKA 103

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 544186046 209 DVIELTDDSFDKNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVKEqtKGKVKLAAVDAT-VNQVLASRYGIRGFPT 287
Cdd:cd02998    1 NVVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFAN--EDDVVIAKVDADeANKDLAKKYGVSGFPT 78

                         90       100
                 ....*....|....*....|....*
gi 544186046 288 IKIFQKGES-PVDYDGGRTRSDIVS 311
Cdd:cd02998   79 LKFFPKGSTePVKYEGGRDLEDLVK 103

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 544186046 209 DVIELTDDSFDKNVLDSEDVwMVEFYAPWCGHCKNLEPEWAAAASEVKEqtKGKVKLAAVDATV--NQVLASRYGIRGFP 286
Cdd:cd02997    1 DVVHLTDEDFRKFLKKEKHV-LVMFYAPWCGHCKKMKPEFTKAATELKE--DGKGVLAAVDCTKpeHDALKEEYNVKGFP 77

                         90       100
                 ....*....|....*....|....*
gi 544186046 287 TIKIFQKGESPVDYDGGRTRSDIVS 311
Cdd:cd02997   78 TFKYFENGKFVEKYEGERTAEDIIE 102

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 544186046   75 VIELTPSN----FNREVIQSDSLWLVEFYAPWcghcQRLTPEWKKAATALKD-VVKVGAVDADKHHSLGGQYGV--QGFP 147
Cdd:TIGR01130 219 VGEFTQETaakyFESGPLVVLYYNVDESLDPF----EELRNRFLEAAKKFRGkFVNFAVADEEDFGRELEYFGLkaEKFP 294

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  148 TIKIFGSNKN---RPEDyqggrtGEAIVDAALSALRQLVKDRLGGRSggyssgkqgRSDSSSKKD---VIELTDDSFDKN 221
Cdd:TIGR01130 295 AVAIQDLEGNkkyPMDQ------EEFSSENLEAFVKDFLDGKLKPYL---------KSEPIPEDDegpVKVLVGKNFDEI 359

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  222 VLDSE-DVwMVEFYAPWCGHCKNLEPEWAAAASEVKEQTKgKVKLAAVDATVNQVlaSRYGIRGFPTIKIFQKGE--SPV 298
Cdd:TIGR01130 360 VLDETkDV-LVEFYAPWCGHCKNLAPIYEELAEKYKDAES-DVVIAKMDATANDV--PPFEVEGFPTIKFVPAGKksEPV 435

                         250
                  ....*....|..
gi 544186046  299 DYDGGRTRSDIV 310
Cdd:TIGR01130 436 PYDGDRTLEDFS 447

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  72 SDDVIELTPSNFNReVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKDV---VKVGAVDADKHHSLGGQYGVQGFPT 148
Cdd:PTZ00102  31 SEHVTVLTDSTFDK-FITENEIVLVKFYAPWCGHCKRLAPEYKKAAKMLKEKkseIVLASVDATEEMELAQEFGVRGYPT 109

                         90       100
                 ....*....|....*....|....*
gi 544186046 149 IKIFgsNKNRPEDYQGGRTGEAIVD 173
Cdd:PTZ00102 110 IKFF--NKGNPVNYSGGRTADGIVS 132

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 544186046 210 VIELTDDSFDKNVLDSEDVWMVEFYAPWCGHCKNLEPEWAAAASEVkeqtKGKVKLAAVDATVNQVLASRYGIRGFPTIK 289
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEY----GGKVKFVKVDVDENPELAAQFGVRSIPTLL 77

                         90
                 ....*....|
gi 544186046 290 IFQKGEsPVD 299
Cdd:COG3118   78 LFKDGQ-PVD 86

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 544186046  75 VIELTPSNFNREVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKDVVKVGAVDADKHHSLGGQYGVQGFPTIKIF 152
Cdd:COG3118    2 VVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLF 79

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 544186046  74 DVIELTPSNFnREVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKDVVKV--GAVDADK--HHSLGGQYGVQGFPTI 149
Cdd:cd02997    1 DVVHLTDEDF-RKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGvlAAVDCTKpeHDALKEEYNVKGFPTF 79

                         90       100
                 ....*....|....*....|....
gi 544186046 150 KIFgSNKNRPEDYQGGRTGEAIVD 173
Cdd:cd02997   80 KYF-ENGKFVEKYEGERTAEDIIE 102

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  75 VIELTPSNFNREVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKDV--VKVGAVDADK--HHSLggqYGVQGFPTIK 150
Cdd:cd02995    2 VKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDdnVVIAKMDATAndVPSE---FVVDGFPTIL 78

                         90       100
                 ....*....|....*....|....
gi 544186046 151 IF-GSNKNRPEDYQGGRTGEAIVD 173
Cdd:cd02995   79 FFpAGDKSNPIKYEGDRTLEDLIK 102

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 544186046  73 DDVIELTPSNFNREVIQSDSLWLVEFYAPWCGHCQRLTPEWKKAATALKD---VVKVGAVD--ADKHHSLGGQYGVQGFP 147
Cdd:cd02992    1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRKwrpVVRVAAVDcaDEENVALCRDFGVTGYP 80

                         90       100       110
                 ....*....|....*....|....*....|...
gi 544186046 148 TIKIFGSNKNRPEDYQGGRTGEAIVDAALSALR 180
Cdd:cd02992   81 TLRYFPPFSKEATDGLKQEGPERDVNELREALI 113

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046 203 DSSSKKDVIELTDDSFDKNVLDSEDV----WMVEFYAPWCGHCKNLEPEWAAAASEVkeqtKGKVKLAAVDATVNQVLAS 278
Cdd:PTZ00443  25 DAEDANALVLLNDKNFEKLTQASTGAttgpWFVKFYAPWCSHCRKMAPAWERLAKAL----KGQVNVADLDATRALNLAK 100

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 544186046 279 RYGIRGFPTIKIFQKGESpVDYDGG-RTRSDIVSRALDLFSD--NAPPPELLEII 330
Cdd:PTZ00443 101 RFAIKGYPTLLLFDKGKM-YQYEGGdRSTEKLAAFALGDFKKalGAPVPAPLSFF 154

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 544186046  75 VIELTPSNFNREVIQSDSL----WLVEFYAPWCGHCQRLTPEWKKAATALKDVVKVGAVDADKHHSLGGQYGVQGFPTIK 150
Cdd:PTZ00443  32 LVLLNDKNFEKLTQASTGAttgpWFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPTLL 111