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 15226610  28 LTDDSFEKEVGKDK-GALVEFYAPWCGHCKKLAPEYEKLGASFKKAKSVLIAKVDCDE-QKSVCTKYGVSGYPTIQWFPK 105
Cdd:cd02998   5 LTDSNFDKVVGDDKkDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLKFFPK 84

                        90       100
                ....*....|....*....|.
gi 15226610 106 GSLEPQKYEGPRNAEALAEYV 126
Cdd:cd02998  85 GSTEPVKYEGGRDLEDLVKFV 105

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 15226610  28 LTDDSFEKEVGKDK-GALVEFYAPWCGHCKKLAPEYEKLGASFKKAKSVLIAKVDCDE-QKSVCTKYGVSGYPTIQWFPK 105
Cdd:cd02998   5 LTDSNFDKVVGDDKkDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLKFFPK 84

                        90       100
                ....*....|....*....|.
gi 15226610 106 GSLEPQKYEGPRNAEALAEYV 126
Cdd:cd02998  85 GSTEPVKYEGGRDLEDLVKFV 105

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 15226610    28 LTDDSFEKEVGKDKGALVEFYAPWCGHCKKLAPEYEKLGASFKKAKSVLIAKVDCDEQKSVCTKYGVSGYPTIQWFPKGS 107
Cdd:TIGR01126   1 LTASNFDEIVLSNKDVLVEFYAPWCGHCKNLAPEYEKLAKELKKDPKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKGS 80

                          90       100
                  ....*....|....*....|..
gi 15226610   108 lEPQKYEGPRNAEALAEYVNKE 129
Cdd:TIGR01126  81 -KPVDYEGGRDLEAIVEFVNEK 101

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610    28 LTDDSFEKEVGKDKG-ALVEFYAPWCGHCKKLAPEYEKLGAsfKKAKSVLIAKVDCDEQKSVCTKYGVSGYPTIQWFPKG 106
Cdd:pfam00085   5 LTDANFDEVVQKSSKpVLVDFYAPWCGPCKMLAPEYEELAQ--EYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                          90       100
                  ....*....|....*....|..
gi 15226610   107 SlEPQKYEGPRNAEALAEYVNK 128
Cdd:pfam00085  83 Q-PVDDYVGARPKDALAAFLKA 103

Endoplasmic reticulum protein ERp29, C-terminal domain; ERp29 is a ubiquitously expressed endoplasmic reticulum protein found in mammals. ERp29 is comprised of two domains. This domain, the C-terminal domain, has an all helical fold. ERp29 is thought to form part of the thyroglobulin folding complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610   264 GIVESLDALVKELVAASEDEKKAVLSRIEEEASTLKGSTTRYGKLYLKLAKSYIEKGSDYASKETERLGRVLGK-SISPV 342
Cdd:pfam07749   1 GRIEELDALAAEFVAAAKDERKELLEEAKKAAEKLKEAEKKYAKYYVKVMEKILEKGEEYVEKELARLEKLLAKgKLSPE 80

                          90
                  ....*....|....*
gi 15226610   343 KADELTLKRNILTTF 357
Cdd:pfam07749  81 KKDELQIRLNILRSF 95

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 15226610 142 NVVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATvfKQEEGVVIANLDADAHKALGEKYGVSGFPTLKF 221
Cdd:COG3118   1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAA--EYGGKVKFVKVDVDENPELAAQFGVRSIPTLLL 78

                        90       100
                ....*....|....*....|....*.
gi 15226610 222 FpKDNKAGHDYDGGRDLDDFVSFINE 247
Cdd:COG3118  79 F-KDGQPVDRFVGALPKEQLREFLDK 103

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610   28 LTDDSFEKEVGKDKGA-----LVEFYAPWCGHCKKLAPEYEKLGASFKKAksVLIAKVDCDEQKSVCTKYGVSGYPTIQW 102
Cdd:PTZ00443  35 LNDKNFEKLTQASTGAttgpwFVKFYAPWCSHCRKMAPAWERLAKALKGQ--VNVADLDATRALNLAKRFAIKGYPTLLL 112

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 15226610  103 FPKGSLepQKYE-GPRNAEALAEYVNKEGGTNVKlAAVPQ--NVVVLTPDNF 151
Cdd:PTZ00443 113 FDKGKM--YQYEgGDRSTEKLAAFALGDFKKALG-APVPAplSFFALTIDFF 161

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 15226610  28 LTDDSFEKEVGKDK-GALVEFYAPWCGHCKKLAPEYEKLGASFKKAKSVLIAKVDCDE-QKSVCTKYGVSGYPTIQWFPK 105
Cdd:cd02998   5 LTDSNFDKVVGDDKkDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLKFFPK 84

                        90       100
                ....*....|....*....|.
gi 15226610 106 GSLEPQKYEGPRNAEALAEYV 126
Cdd:cd02998  85 GSTEPVKYEGGRDLEDLVKFV 105

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 15226610    28 LTDDSFEKEVGKDKGALVEFYAPWCGHCKKLAPEYEKLGASFKKAKSVLIAKVDCDEQKSVCTKYGVSGYPTIQWFPKGS 107
Cdd:TIGR01126   1 LTASNFDEIVLSNKDVLVEFYAPWCGHCKNLAPEYEKLAKELKKDPKIVLAKVDATAEKDLASRFGVSGFPTIKFFPKGS 80

                          90       100
                  ....*....|....*....|..
gi 15226610   108 lEPQKYEGPRNAEALAEYVNKE 129
Cdd:TIGR01126  81 -KPVDYEGGRDLEAIVEFVNEK 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 15226610 144 VVLTPDNFDEIVLDqNKDVLVEFYAPWCGHCKSLAPTYEKVATVFKQEEGVVIANLDADAHKALGEKYGVSGFPTLKFFP 223
Cdd:cd02961   1 VELTDDNFDELVKD-SKDVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                        90       100
                ....*....|....*....|..
gi 15226610 224 KDNKAGHDYDGGRDLDDFVSFI 245
Cdd:cd02961  80 NGSKEPVKYEGPRTLESLVEFI 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610 143 VVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATVFKQEEGVVIANLDADAHKALGEkYGVSGFPTLKFF 222
Cdd:cd02995   2 VKVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATANDVPSE-FVVDGFPTILFF 80

                        90       100
                ....*....|....*....|....
gi 15226610 223 PKDNKA-GHDYDGGRDLDDFVSFI 245
Cdd:cd02995  81 PAGDKSnPIKYEGDRTLEDLIKFI 104

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 15226610    71 KAKSVLIAKVDCDEQKSVCTKYGV--SGYPTIQWFPKGslEPQKY---EGPRNAEALAEYVNK--EGGTN--VKLAAVPQ 141
Cdd:TIGR01130 265 RGKFVNFAVADEEDFGRELEYFGLkaEKFPAVAIQDLE--GNKKYpmdQEEFSSENLEAFVKDflDGKLKpyLKSEPIPE 342

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610   142 N----VVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATVFK-QEEGVVIANLDADAHKAlgEKYGVSGF 216
Cdd:TIGR01130 343 DdegpVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKdAESDVVIAKMDATANDV--PPFEVEGF 420

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 15226610   217 PTLKFFPKDNKAGH-DYDGGRDLDDFVSFINEKSGTS 252
Cdd:TIGR01130 421 PTIKFVPAGKKSEPvPYDGDRTLEDFSKFIAKHATFP 457

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 15226610   142 NVVVLTPDNFDEiVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATVFKQE-EGVVIANLDADAHKALGEKYGVSGFPTLK 220
Cdd:TIGR01130   2 DVLVLTKDNFDD-FIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADELKKKgPPIKLAKVDATEEKDLAQKYGVSGYPTLK 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 15226610   221 FFPKDNKAGHDYDGGRDLDDFVSFINEKSG 250
Cdd:TIGR01130  81 IFRNGEDSVSDYNGPRDADGIVKYMKKQSG 110

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 15226610    28 LTDDSFEKEVGKDKG-ALVEFYAPWCGHCKKLAPEYEKLGAsfKKAKSVLIAKVDCDEQKSVCTKYGVSGYPTIQWFPKG 106
Cdd:pfam00085   5 LTDANFDEVVQKSSKpVLVDFYAPWCGPCKMLAPEYEELAQ--EYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                          90       100
                  ....*....|....*....|..
gi 15226610   107 SlEPQKYEGPRNAEALAEYVNK 128
Cdd:pfam00085  83 Q-PVDDYVGARPKDALAAFLKA 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 15226610 142 NVVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVAtvfKQEEGVVI---ANLDADAHKALGEKYGVSGFPT 218
Cdd:cd03002   1 PVYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAA---KELDGLVQvaaVDCDEDKNKPLCGKYGVQGFPT 77

                        90       100       110
                ....*....|....*....|....*....|.
gi 15226610 219 LKFFPKDNKAG----HDYDGGRDLDDFVSFI 245
Cdd:cd03002  78 LKVFRPPKKASkhavEDYNGERSAKAIVDFV 108

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 15226610  28 LTDDSFEKEVG-KDKGALVEFYAPWCGHCKKLAPEYEKLGASFKKAKSVLIAKVDCDEQkSVCTKYGVSGYPTIQWFPKG 106
Cdd:cd02995   5 VVGKNFDEVVLdSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIAKMDATAN-DVPSEFVVDGFPTILFFPAG 83

                        90       100
                ....*....|....*....|.
gi 15226610 107 SL-EPQKYEGPRNAEALAEYV 126
Cdd:cd02995  84 DKsNPIKYEGDRTLEDLIKFI 104

Endoplasmic reticulum protein ERp29, C-terminal domain; ERp29 is a ubiquitously expressed endoplasmic reticulum protein found in mammals. ERp29 is comprised of two domains. This domain, the C-terminal domain, has an all helical fold. ERp29 is thought to form part of the thyroglobulin folding complex.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610   264 GIVESLDALVKELVAASEDEKKAVLSRIEEEASTLKGSTTRYGKLYLKLAKSYIEKGSDYASKETERLGRVLGK-SISPV 342
Cdd:pfam07749   1 GRIEELDALAAEFVAAAKDERKELLEEAKKAAEKLKEAEKKYAKYYVKVMEKILEKGEEYVEKELARLEKLLAKgKLSPE 80

                          90
                  ....*....|....*
gi 15226610   343 KADELTLKRNILTTF 357
Cdd:pfam07749  81 KKDELQIRLNILRSF 95

ERp29 and ERp38, C-terminal domain; composed of the protein disulfide isomerase (PDI)-like proteins ERp29 and ERp38. ERp29 (also called ERp28) is a ubiquitous endoplasmic reticulum (ER)-resident protein expressed in high levels in secretory cells. It contains a redox inactive TRX-like domain at the N-terminus. The expression profile of ERp29 suggests a role in secretory protein production, distinct from that of PDI. It has also been identified as a member of the thyroglobulin folding complex and is essential in regulating the secretion of thyroglobulin. The Drosophila homolog, Wind, is the product of windbeutel, an essential gene in the development of dorsal-ventral patterning. Wind is required for correct targeting of Pipe, a Golgi-resident type II transmembrane protein with homology to 2-O-sulfotransferase. ERp38 is a P5-like protein, first isolated from alfalfa (the cDNA clone was named G1), which contains two redox active TRX domains at the N-terminus, like human P5. However, unlike human P5, ERp38 also contains a C-terminal domain with homology to the C-terminal domain of ERp29. It may be a glucose-regulated protein. The function of the all-helical C-terminal domain of ERp29 and ERp38 remains unclear. The C-terminal domain of Wind is thought to provide a distinct site required for interaction with its substrate, Pipe.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610 266 VESLDALVKELVAASEDEKKAVLSRIEEEASTLKGSTTRYGKLYLKLAKSYIEKGSDYASKETERLGRVLGKSI-SPVKA 344
Cdd:cd00238   1 IEELDELAKEFVDASDEERKELLEKVKEAVEKLKEAEAKYAKYYVKVMEKILEKGEDYVEKELARLERLLEKKGlAPEKA 80

                        90
                ....*....|...
gi 15226610 345 DELTLKRNILTTF 357
Cdd:cd00238  81 DELTRRLNILRSF 93

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 15226610 142 NVVVLTPDNFDEIvLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATVFKQEEGVVIANLDA--DAHKALGEKYGVSGFPTL 219
Cdd:cd02997   1 DVVHLTDEDFRKF-LKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGVLAAVDCtkPEHDALKEEYNVKGFPTF 79

                        90       100
                ....*....|....*....|....*.
gi 15226610 220 KFFPKDnKAGHDYDGGRDLDDFVSFI 245
Cdd:cd02997  80 KYFENG-KFVEKYEGERTAEDIIEFM 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 15226610 142 NVVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATvfKQEEGVVIANLDADAHKALGEKYGVSGFPTLKF 221
Cdd:COG3118   1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAA--EYGGKVKFVKVDVDENPELAAQFGVRSIPTLLL 78

                        90       100
                ....*....|....*....|....*.
gi 15226610 222 FpKDNKAGHDYDGGRDLDDFVSFINE 247
Cdd:COG3118  79 F-KDGQPVDRFVGALPKEQLREFLDK 103

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 15226610 143 VVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATVFKqeEGVVIANLDADAHKALGEKYGVSGFPTLKFF 222
Cdd:cd03004   3 VITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALK--GKVKVGSVDCQKYESLCQQANIRAYPTIRLY 80

                        90       100
                ....*....|....*....|....
gi 15226610 223 PKDNKAGHDYDG-GRDLDDFVSFI 245
Cdd:cd03004  81 PGNASKYHSYNGwHRDADSILEFI 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 15226610  28 LTDDSF-EKEVGKDKGALVEFYAPWCGHCKKLAPEYEKLgASFKKAKsVLIAKVDCDEQKSVCTKYGVSGYPTIQWFPKG 106
Cdd:cd03004   6 LTPEDFpELVLNRKEPWLVDFYAPWCGPCQALLPELRKA-ARALKGK-VKVGSVDCQKYESLCQQANIRAYPTIRLYPGN 83

                        90       100
                ....*....|....*....|.
gi 15226610 107 SLEPQKYEG-PRNAEALAEYV 126
Cdd:cd03004  84 ASKYHSYNGwHRDADSILEFI 104

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 15226610 142 NVVVLTPDNFDEIVLDQNKDVLVEFYAPWCGHCKSLAPTYEKVATVFKQEEGVV-IANLD--ADAHKALGEKYGVSGFPT 218
Cdd:cd02992   2 PVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVrVAAVDcaDEENVALCRDFGVTGYPT 81

                        90
                ....*....|...
gi 15226610 219 LKFFPKDNKAGHD 231
Cdd:cd02992  82 LRYFPPFSKEATD 94

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226610 149 DNFDEIVlDQNKDVLVEFYAPWCGHCKSLAPTYEKVAtvfKQEEGVVIANLDADAHKALGEKYGVSGFPTLKFFpKDNKA 228
Cdd:cd02947   1 EEFEELI-KSAKPVVVDFWAPWCGPCKAIAPVLEELA---EEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFF-KNGKE 75

                        90
                ....*....|....*...
gi 15226610 229 GHDYDGGRDLDDFVSFIN 246
Cdd:cd02947  76 VDRVVGADPKEELEEFLE 93

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 15226610    28 LTDDSFEKEV-GKDKGALVEFYAPWCGHCKKLAPEYEKLGAsfKKAKSVLIAKVDCDEQKSVCTKYGVSGYPTIQWFPKG 106
Cdd:TIGR01068   1 LTDANFDETIaSSDKPVLVDFWAPWCGPCKMIAPILEELAK--EYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNG 78