PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  35 GQLRVLTDGDWQEVLTGEWMIEFFAPWCPACQQLEPVWTEFAGWGDDLGVNIAKVDVTEHPGLSGRFIIMALPTIYHCKD 114
Cdd:cd02994   1 SNVVELTDSNWTLVLEGEWMIEFYAPWCPACQQLQPEWEEFADWSDDLGINVAKVDVTQEPGLSGRFFVTALPTIYHAKD 80

                        90       100
                ....*....|....*....|.
gi 34784530 115 GVFRRYQGDRSKEDFLSFIEE 135
Cdd:cd02994  81 GVFRRYQGPRDKEDLISFIEE 101

PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  35 GQLRVLTDGDWQEVLTGEWMIEFFAPWCPACQQLEPVWTEFAGWGDDLGVNIAKVDVTEHPGLSGRFIIMALPTIYHCKD 114
Cdd:cd02994   1 SNVVELTDSNWTLVLEGEWMIEFYAPWCPACQQLQPEWEEFADWSDDLGINVAKVDVTQEPGLSGRFFVTALPTIYHAKD 80

                        90       100
                ....*....|....*....|.
gi 34784530 115 GVFRRYQGDRSKEDFLSFIEE 135
Cdd:cd02994  81 GVFRRYQGPRDKEDLISFIEE 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 34784530    39 VLTDGDWQEVL--TGEWM-IEFFAPWCPACQQLEPVWTEFAgwgDDLGVNI--AKVDVTEHPGLSGRFIIMALPTIYHCK 113
Cdd:pfam00085   4 VLTDANFDEVVqkSSKPVlVDFYAPWCGPCKMLAPEYEELA---QEYKGNVvfAKVDVDENPDLASKYGVRGYPTLIFFK 80

                          90       100
                  ....*....|....*....|...
gi 34784530   114 DG-VFRRYQGDRSKEDFLSFIEE 135
Cdd:pfam00085  81 NGqPVDDYVGARPKDALAAFLKA 103

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530   20 ILAACVVAQPEAPKAGQLRV----------LTDGDWQEVL-------TGEWMIEFFAPWCPACQQLEPVWTEFAGWGDDL 82
Cdd:PTZ00443   5 ILACCILFGLIADEATNVKLdaedanalvlLNDKNFEKLTqastgatTGPWFVKFYAPWCSHCRKMAPAWERLAKALKGQ 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 34784530   83 gVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDGVFRRYQ-GDRSKEDFLSF 132
Cdd:PTZ00443  85 -VNVADLDATRALNLAKRFAIKGYPTLLLFDKGKMYQYEgGDRSTEKLAAF 134

PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  35 GQLRVLTDGDWQEVLTGEWMIEFFAPWCPACQQLEPVWTEFAGWGDDLGVNIAKVDVTEHPGLSGRFIIMALPTIYHCKD 114
Cdd:cd02994   1 SNVVELTDSNWTLVLEGEWMIEFYAPWCPACQQLQPEWEEFADWSDDLGINVAKVDVTQEPGLSGRFFVTALPTIYHAKD 80

                        90       100
                ....*....|....*....|.
gi 34784530 115 GVFRRYQGDRSKEDFLSFIEE 135
Cdd:cd02994  81 GVFRRYQGPRDKEDLISFIEE 101

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 34784530  51 GEWMIEFFAPWCPACQQLEPVWTEFAGWGDDLG--VNIAKVDVTEHPGLSGRFIIMALPTIYHCKDGVFRRYQGDRSKED 128
Cdd:cd03000  16 DIWLVDFYAPWCGHCKKLEPVWNEVGAELKSSGspVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAYNYRGPRTKDD 95

                ....
gi 34784530 129 FLSF 132
Cdd:cd03000  96 IVEF 99

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 34784530    39 VLTDGDWQEVL--TGEWM-IEFFAPWCPACQQLEPVWTEFAgwgDDLGVNI--AKVDVTEHPGLSGRFIIMALPTIYHCK 113
Cdd:pfam00085   4 VLTDANFDEVVqkSSKPVlVDFYAPWCGPCKMLAPEYEELA---QEYKGNVvfAKVDVDENPDLASKYGVRGYPTLIFFK 80

                          90       100
                  ....*....|....*....|...
gi 34784530   114 DG-VFRRYQGDRSKEDFLSFIEE 135
Cdd:pfam00085  81 NGqPVDDYVGARPKDALAAFLKA 103

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 34784530  54 MIEFFAPWCPACQQLEPVWTEFAGWGDDlgVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDG-VFRRYQGDRSKEDFLSF 132
Cdd:cd02947  14 VVDFWAPWCGPCKAIAPVLEELAEEYPK--VKFVKVDVDENPELAEEYGVRSIPTFLFFKNGkEVDRVVGADPKEELEEF 91

                ..
gi 34784530 133 IE 134
Cdd:cd02947  92 LE 93

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530   20 ILAACVVAQPEAPKAGQLRV----------LTDGDWQEVL-------TGEWMIEFFAPWCPACQQLEPVWTEFAGWGDDL 82
Cdd:PTZ00443   5 ILACCILFGLIADEATNVKLdaedanalvlLNDKNFEKLTqastgatTGPWFVKFYAPWCSHCRKMAPAWERLAKALKGQ 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 34784530   83 gVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDGVFRRYQ-GDRSKEDFLSF 132
Cdd:PTZ00443  85 -VNVADLDATRALNLAKRFAIKGYPTLLLFDKGKMYQYEgGDRSTEKLAAF 134

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530   10 GMTAGACVLSILAACVVAQPEAPKAGQ-LRVLTDGDWQEVLTGE--WMIEFFAPWCPACQQLEPVWTEFAGWGDDLG--V 84
Cdd:PTZ00102   6 ILSSLFLLLILLAFAVFGSAEEHFISEhVTVLTDSTFDKFITENeiVLVKFYAPWCGHCKRLAPEYKKAAKMLKEKKseI 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 34784530   85 NIAKVDVTEHPGLSGRFIIMALPTIYHCKDGVFRRYQGDRSKEDFLSFIEE 135
Cdd:PTZ00102  86 VLASVDATEEMELAQEFGVRGYPTIKFFNKGNPVNYSGGRTADGIVSWIKK 136

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 34784530  46 QEVLTGEWMIEFFAPWCPACQQLEPVWTEFAG--WGDDLGVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDGV-FRRYQG 122
Cdd:cd03005  12 HHIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKkfNNENPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDGEkVDKYKG 91

                        90
                ....*....|.
gi 34784530 123 DRSKEDFLSFI 133
Cdd:cd03005  92 TRDLDSLKEFV 102

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 34784530  39 VLTDGDWQEVLTGE---WMIEFFAPWCPACQQLEPVWTEFAG-WGDDLGVNIAKVDVTE-HPGLSGRFIIMALPTI--YH 111
Cdd:cd02998   4 ELTDSNFDKVVGDDkkdVLVEFYAPWCGHCKNLAPEYEKLAAvFANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLkfFP 83

                        90       100
                ....*....|....*....|..
gi 34784530 112 CKDGVFRRYQGDRSKEDFLSFI 133
Cdd:cd02998  84 KGSTEPVKYEGGRDLEDLVKFV 105

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 34784530  40 LTDGDWQEVLTGE--WMIEFFAPWCPACQQLEPVWTEFA-GWGDDLGVNIAKVDVT--EHPGLSGRFIIMALPTIYHCKD 114
Cdd:cd02997   5 LTDEDFRKFLKKEkhVLVMFYAPWCGHCKKMKPEFTKAAtELKEDGKGVLAAVDCTkpEHDALKEEYNVKGFPTFKYFEN 84

                        90       100
                ....*....|....*....|
gi 34784530 115 GVFRR-YQGDRSKEDFLSFI 133
Cdd:cd02997  85 GKFVEkYEGERTAEDIIEFM 104

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 34784530  40 LTDGDWQEVLTGE--WMIEFFAPWCPACQQLEPVWTEFAGWGDDLgVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDGVF 117
Cdd:cd03003   6 LDRGDFDAAVNSGeiWFVNFYSPRCSHCHDLAPTWREFAKEMDGV-IRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSGMN 84

                        90
                ....*....|....*.
gi 34784530 118 -RRYQGDRSKEDFLSF 132
Cdd:cd03003  85 pEKYYGDRSKESLVKF 100

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  54 MIEFFAPWCPACQQLEPVWTEFAGWgdDLGVNIAKVDVTEHPGL---SGRFIIMALPTIYHCKDGVFRRY 120
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAELALL--NKGVKFEAVDVDEDPALekeLKRYGVGGVPTLVVFGPGIGVKY 68

PDIa family, endoplasmic reticulum protein 44 (ERp44) subfamily; ERp44 is an ER-resident protein, induced during stress, involved in thiol-mediated ER retention. It contains an N-terminal TRX domain, similar to that of PDIa, with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. The CXFS motif in the N-terminal domain allows ERp44 to form stable reversible mixed disulfides with its substrates. Through this activity, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. It also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  57 FFAPWCPACQQLEPVWTEFAG-----WGDDLGVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDG--VFRRYQGDRSKEDF 129
Cdd:cd02996  25 FYADWCRFSQMLHPIFEEAAAkikeeFPDAGKVVWGKVDCDKESDIADRYRINKYPTLKLFRNGmmMKREYRGQRSVEAL 104

                ....
gi 34784530 130 LSFI 133
Cdd:cd02996 105 AEFV 108

ybbN protein family; ybbN is a hypothetical protein containing a redox-inactive TRX-like domain. Its gene has been sequenced from several gammaproteobacteria and actinobacteria.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34784530  55 IEFFAPWCPACQQLEPVWT----EFAGWGDdlgvnIAKVDVTEHPGLSGRFIIMALPTIYHCKDG 115
Cdd:cd02956  17 VDFWAPRSPPSKELLPLLErlaeEYQGQFV-----LAKVNCDAQPQIAQQFGVQALPTVYLFAAG 76

TRX domain, PICOT (for PKC-interacting cousin of TRX) subfamily; PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT contains an N-terminal TRX-like domain, which does not contain the catalytic CXXC motif, followed by one to three glutaredoxin domains. The TRX-like domain is required for interaction with PKC theta. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 34784530  57 FFAPWCPACQQLEPVWTEFAGwGDDLGVNIAKVDVTEHPGLSGRFIIMALPTIYHCKDG 115
Cdd:cd02984  21 FWAPWAEPCKQMNQVFEELAK-EAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNG 78

Thiol-disulfide isomerase or thioredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  40 LTDGDWQEV----LTGEW-MIEFFAPWCPACQQLEPVWTEFAgwgDDL-GVNIAKVDVTEHPGLSGRFI----------- 102
Cdd:COG0526  13 LTDLDGKPLsladLKGKPvLVNFWATWCPPCRAEMPVLKELA---EEYgGVVFVGVDVDENPEAVKAFLkelglpypvll 89

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 34784530 103 -----------IMALPTIYH-CKDG-VFRRYQGDRSKEDFLSFIEE 135
Cdd:COG0526  90 dpdgelakaygVRGIPTTVLiDKDGkIVARHVGPLSPEELEEALEK 135

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784530  35 GQLRVLTDGDWQEVLTGE-----WMIEFFAPWCPACQQLEPVWTEFAGWGDDLGVNIAKV 89
Cdd:cd02993   1 EAVVTLSRAEIEALAKGErrnqsTLVVLYAPWCPFCQAMEASYEELAEKLAGSNVKVAKF 60

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
                ....*....|....*....|....
gi 34784530  53 WMIEFFAPWCPACQQLEPVWTEFA 76
Cdd:cd02992  22 WLVEFYASWCGHCRAFAPTWKKLA 45