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 21355839  40 DNVIMLDIESLRPALNLKNS-KLVQFLNSFCGDCHRFAPVFKTLSRDLYKWRRILRIYAVDCAQERNAQLCREFNIRQTP 118
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSaWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADEENVALCRDFGVTGYP 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 21355839 119 SLRFFGPDMRKNDDVLGAVIPGQDPEFISSTLAE 152
Cdd:cd02992  81 TLRYFPPFSKEATDGLKQEGPERDVNELREALIL 114

Flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidase; This is a flavin adenine dinucleotide (FAD) binding domain found in Quiescin sulfhydryl oxidases (QSOX) (EC:1.8.3.2). QSOX is a multi-domain disulfide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention due to its over-production in tumors. Structural studies indicate that the closure of the Trx1 domain over the FAD-binding site may enhance the active-site chemistry for disulfide formation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21355839   307 QVYRADLEQAIDKLLHIELRKWVLLEGNSLNALKNIIKIFRYLNPLNKDGKLLLTDLDNSLSS--KQSIKGADFGDLVDS 384
Cdd:pfam18371   4 KVYMADLESALHYSLRVELAKHSVLEGEELKALKDYVTVLAKYFPGRPSVKNLLQSLDSWLQSqpETKISYSALLDALDN 83

                          90       100
                  ....*....|....*....|.
gi 21355839   385 LENGRRVF--KARRYVGCIGS 403
Cdd:pfam18371  84 KKEAPGAVlpEEVRWVGCQGS 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 21355839  40 DNVIMLDIESLRPALNLKNS-KLVQFLNSFCGDCHRFAPVFKTLSRDLYKWRRILRIYAVDCAQERNAQLCREFNIRQTP 118
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSaWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADEENVALCRDFGVTGYP 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 21355839 119 SLRFFGPDMRKNDDVLGAVIPGQDPEFISSTLAE 152
Cdd:cd02992  81 TLRYFPPFSKEATDGLKQEGPERDVNELREALIL 114

Flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidase; This is a flavin adenine dinucleotide (FAD) binding domain found in Quiescin sulfhydryl oxidases (QSOX) (EC:1.8.3.2). QSOX is a multi-domain disulfide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention due to its over-production in tumors. Structural studies indicate that the closure of the Trx1 domain over the FAD-binding site may enhance the active-site chemistry for disulfide formation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21355839   307 QVYRADLEQAIDKLLHIELRKWVLLEGNSLNALKNIIKIFRYLNPLNKDGKLLLTDLDNSLSS--KQSIKGADFGDLVDS 384
Cdd:pfam18371   4 KVYMADLESALHYSLRVELAKHSVLEGEELKALKDYVTVLAKYFPGRPSVKNLLQSLDSWLQSqpETKISYSALLDALDN 83

                          90       100
                  ....*....|....*....|.
gi 21355839   385 LENGRRVF--KARRYVGCIGS 403
Cdd:pfam18371  84 KKEAPGAVlpEEVRWVGCQGS 104

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21355839  61 LVQFLNSFCGDCHRFAPVFKTLSRDlYKWRriLRIYAVDCaqERNAQLCREFNIRQTPSLRFF 123
Cdd:COG3118  22 LVDFWAPWCGPCKMLAPVLEELAAE-YGGK--VKFVKVDV--DENPELAAQFGVRSIPTLLLF 79

type-F conjugative transfer system pilin assembly thiol-disulfide isomerase TrbB; This protein is part of a large group of proteins involved in conjugative transfer of plasmid DNA, specifically the F-type system. This protein has been predicted to contain a thioredoxin fold, contains a conserved pair of cysteines and has been shown to function as a thiol disulfide isomerase by complementation of an Ecoli DsbA defect. The protein is believed to be involved in pilin assembly. The protein is closely related to TraF (TIGR02739) which is somewhat longer, lacks the cysteine motif and is apparently not functional as a disulfide bond isomerase.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 21355839    30 ANEASLYSDTDNvimldiESLRPALNLKNSKLVQFLNSFCGDCHRFAPVFKTLS 83
Cdd:TIGR02738  29 APPQGLTAATDN------APQGRHANQDDYALVFFYQSTCPYCHQFAPVLKRFS 76

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 21355839  40 DNVIMLDIESLRPALNLKNS-KLVQFLNSFCGDCHRFAPVFKTLSRDLYKWRRILRIYAVDCAQERNAQLCREFNIRQTP 118
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSaWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADEENVALCRDFGVTGYP 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 21355839 119 SLRFFGPDMRKNDDVLGAVIPGQDPEFISSTLAE 152
Cdd:cd02992  81 TLRYFPPFSKEATDGLKQEGPERDVNELREALIL 114

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 21355839  43 IMLDIESLRPALNLKNSKLVQFLNSFCGDCHRFAPVFKTLSRDLyKWRRILRIYAVDCAQerNAQLCREFNIRQTPSLRF 122
Cdd:cd02961   1 VELTDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKEL-KGDGKVVVAKVDCTA--NNDLCSEYGVRGYPTIKL 77

                ....*..
gi 21355839 123 FGPDMRK 129
Cdd:cd02961  78 FPNGSKE 84

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 21355839  41 NVIMLDIESLRPAL-NLKNSKLVQFLNSFCGDCHRFAPVFKTLSRDLykwRRILRIYAVDCAQERNAQLCREFNIRQTPS 119
Cdd:cd03002   1 PVYELTPKNFDKVVhNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKEL---DGLVQVAAVDCDEDKNKPLCGKYGVQGFPT 77

                ....*.
gi 21355839 120 LRFFGP 125
Cdd:cd03002  78 LKVFRP 83

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 21355839  41 NVIMLDIESLRPALNLKNSKLVQFLNSFCGDCHRFAPVFKTLSRDLYKWRRIlRIYAVDCAQERNAQLCREFNIRQTPSL 120
Cdd:cd02997   1 DVVHLTDEDFRKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKG-VLAAVDCTKPEHDALKEEYNVKGFPTF 79

                ...
gi 21355839 121 RFF 123
Cdd:cd02997  80 KYF 82

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21355839  61 LVQFLNSFCGDCHRFAPVFKTLSRDLYKWRRILRIYAVDCAQERNaqLCREFNIRQTPSLRFF 123
Cdd:cd03005  20 FVKFFAPWCGHCKRLAPTWEQLAKKFNNENPSVKIAKVDCTQHRE--LCSEFQVRGYPTLLLF 80

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21355839  61 LVQFLNSFCGDCHRFAPVFKTLSRDlYKWRriLRIYAVDCaqERNAQLCREFNIRQTPSLRFF 123
Cdd:COG3118  22 LVDFWAPWCGPCKMLAPVLEELAAE-YGGK--VKFVKVDV--DENPELAAQFGVRSIPTLLLF 79

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 21355839  42 VIMLDIESLR-PALNLKNSKLVQFLNSFCGDCHRFAPVFKTLSRDLYKwrrILRIYAVDCAQerNAQLCREFNIRQTPSL 120
Cdd:cd03004   3 VITLTPEDFPeLVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKG---KVKVGSVDCQK--YESLCQQANIRAYPTI 77

                ....*....
gi 21355839 121 RFFGPDMRK 129
Cdd:cd03004  78 RLYPGNASK 86

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21355839    61 LVQFLNSFCGDCHRFAPVFKTLSrDLYKWRriLRIYAVDCAQerNAQLCREFNIRQTPSLRFFgPDMRKNDDVLGA 136
Cdd:pfam00085  22 LVDFYAPWCGPCKMLAPEYEELA-QEYKGN--VVFAKVDVDE--NPDLASKYGVRGYPTLIFF-KNGQPVDDYVGA 91

type-F conjugative transfer system pilin assembly thiol-disulfide isomerase TrbB; This protein is part of a large group of proteins involved in conjugative transfer of plasmid DNA, specifically the F-type system. This protein has been predicted to contain a thioredoxin fold, contains a conserved pair of cysteines and has been shown to function as a thiol disulfide isomerase by complementation of an Ecoli DsbA defect. The protein is believed to be involved in pilin assembly. The protein is closely related to TraF (TIGR02739) which is somewhat longer, lacks the cysteine motif and is apparently not functional as a disulfide bond isomerase.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 21355839    30 ANEASLYSDTDNvimldiESLRPALNLKNSKLVQFLNSFCGDCHRFAPVFKTLS 83
Cdd:TIGR02738  29 APPQGLTAATDN------APQGRHANQDDYALVFFYQSTCPYCHQFAPVLKRFS 76

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 21355839    61 LVQFLNSFCGDCHRFAPVFKTLSRDLykwRRILRIYAVDCAQERNaqLCREFNIRQTPSLRFFgpdmrKNDDVLGAVIPG 140
Cdd:TIGR01068  18 LVDFWAPWCGPCKMIAPILEELAKEY---EGKVKFVKLNVDENPD--IAAKYGIRSIPTLLLF-----KNGKEVDRSVGA 87

                          90
                  ....*....|....
gi 21355839   141 QDPEFISSTLAELV 154
Cdd:TIGR01068  88 LPKAALKQLINKNL 101

disulphide isomerase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21355839   61 LVQFLNSFCGDCHRFAPVFKTLSRDLYKWRRILRIYAVDCAQERNaqLCREFNIRQTPSLRFF 123
Cdd:PTZ00102  53 LVKFYAPWCGHCKRLAPEYKKAAKMLKEKKSEIVLASVDATEEME--LAQEFGVRGYPTIKFF 113

conjugal transfer protein TrbB; Provisional

                         10        20
                 ....*....|....*....|....*....
gi 21355839   55 NLKNSKLVQFLNSFCGDCHRFAPVFKTLS 83
Cdd:PRK13728  67 NLADWKVVLFMQGHCPYCHQFDPVLKQLA 95