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 262118377    6 EGPVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYAKSEfkDRVVIAKVDATANDVPD-EIQGFPT 84
Cdd:TIGR01130 345 EGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAE--SDVVIAKMDATANDVPPfEVEGFPT 422

                          90       100       110
                  ....*....|....*....|....*....|....
gi 262118377   85 IKLYPAGAKGQPVTYSGSRTVEDLIKFIAENGKY 118
Cdd:TIGR01130 423 IKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATF 456

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 262118377    6 EGPVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYAKSEfkDRVVIAKVDATANDVPD-EIQGFPT 84
Cdd:TIGR01130 345 EGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAE--SDVVIAKMDATANDVPPfEVEGFPT 422

                          90       100       110
                  ....*....|....*....|....*....|....
gi 262118377   85 IKLYPAGAKGQPVTYSGSRTVEDLIKFIAENGKY 118
Cdd:TIGR01130 423 IKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATF 456

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377   2 PLGSEGPVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYAKSefkDRVVIAKVDATANDVP-DEIQ 80
Cdd:PTZ00102 352 PEEQDGPVKVVVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGEKYKDN---DSIIVAKMNGTANETPlEEFS 428

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 262118377  81 --GFPTIKLYPAGAKgQPVTYSGSRTVEDLIKFIAENG 116
Cdd:PTZ00102 429 wsAFPTILFVKAGER-TPIPYEGERTVEGFKEFVNKHA 465

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 262118377  14 AKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGAlyaksEFKDRVVIAKVDATAN-DVPDE--IQGFPTIKLYpa 90
Cdd:COG3118    7 DENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAA-----EYGGKVKFVKVDVDENpELAAQfgVRSIPTLLLF-- 79

                         90       100
                 ....*....|....*....|....*.
gi 262118377  91 gAKGQPV-TYSGSRTVEDLIKFIAEN 115
Cdd:COG3118   80 -KDGQPVdRFVGALPKEQLREFLDKV 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 262118377    6 EGPVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYAKSEfkDRVVIAKVDATANDVPD-EIQGFPT 84
Cdd:TIGR01130 345 EGPVKVLVGKNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAE--SDVVIAKMDATANDVPPfEVEGFPT 422

                          90       100       110
                  ....*....|....*....|....*....|....
gi 262118377   85 IKLYPAGAKGQPVTYSGSRTVEDLIKFIAENGKY 118
Cdd:TIGR01130 423 IKFVPAGKKSEPVPYDGDRTLEDFSKFIAKHATF 456

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 262118377   9 VTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYAKsefKDRVVIAKVDATAN--DVPD--EIQGFPT 84
Cdd:cd02998    2 VVELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFAN---EDDVVIAKVDADEAnkDLAKkyGVSGFPT 78

                         90       100
                 ....*....|....*....|....*...
gi 262118377  85 IKLYPAGAKgQPVTYSGSRTVEDLIKFI 112
Cdd:cd02998   79 LKFFPKGST-EPVKYEGGRDLEDLVKFV 105

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 262118377  10 TVVVAKNYNEIVLDDtKDVLIEFYAPWCGHCKALAPKYEELGALYAKsefKDRVVIAKVDATAN-DVPDE--IQGFPTIK 86
Cdd:cd02961    1 VELTDDNFDELVKDS-KDVLVEFYAPWCGHCKALAPEYEKLAKELKG---DGKVVVAKVDCTANnDLCSEygVRGYPTIK 76

                         90       100
                 ....*....|....*....|....*.
gi 262118377  87 LYPAGAKgQPVTYSGSRTVEDLIKFI 112
Cdd:cd02961   77 LFPNGSK-EPVKYEGPRTLESLVEFI 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 262118377    8 PVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGAlyaksEFKDRVVIAKVDATAN-DVPD--EIQGFPT 84
Cdd:pfam00085   1 VVVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQ-----EYKGNVVFAKVDVDENpDLASkyGVRGYPT 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 262118377   85 IKLYPAGAKgqPVTYSGSRTVEDLIKFIAE 114
Cdd:pfam00085  76 LIFFKNGQP--VDDYVGARPKDALAAFLKA 103

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 262118377  14 AKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGAlyaksEFKDRVVIAKVDATAN-DVPDE--IQGFPTIKLYpa 90
Cdd:COG3118    7 DENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAA-----EYGGKVKFVKVDVDENpELAAQfgVRSIPTLLLF-- 79

                         90       100
                 ....*....|....*....|....*.
gi 262118377  91 gAKGQPV-TYSGSRTVEDLIKFIAEN 115
Cdd:COG3118   80 -KDGQPVdRFVGALPKEQLREFLDKV 104

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 262118377  25 TKDVLIEFYAPWCGHCKALAPKYEELgalyAKSEFKD--RVVIAKVDATA-NDVPDEIQ--GFPTIKLYPAGAKGqpVTY 99
Cdd:cd03005   16 EGNHFVKFFAPWCGHCKRLAPTWEQL----AKKFNNEnpSVKIAKVDCTQhRELCSEFQvrGYPTLLLFKDGEKV--DKY 89

                         90
                 ....*....|...
gi 262118377 100 SGSRTVEDLIKFI 112
Cdd:cd03005   90 KGTRDLDSLKEFV 102

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 262118377   8 PVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGAlyaksEFKDRVVIAKVDATANDVPD-----EIQGF 82
Cdd:cd03002    1 PVYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAK-----ELDGLVQVAAVDCDEDKNKPlcgkyGVQGF 75

                         90       100       110
                 ....*....|....*....|....*....|...
gi 262118377  83 PTIKLYPAGAKGQ---PVTYSGSRTVEDLIKFI 112
Cdd:cd03002   76 PTLKVFRPPKKASkhaVEDYNGERSAKAIVDFV 108

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 262118377   14 AKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGalyakSEFKDRVVIAKVDATAN-DVPDE--IQGFPTIKLYPa 90
Cdd:TIGR01068   3 DANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELA-----KEYEGKVKFVKLNVDENpDIAAKygIRSIPTLLLFK- 76

                          90       100
                  ....*....|....*....|....*.
gi 262118377   91 gaKGQPVTYS-GSRTVEDLIKFIAEN 115
Cdd:TIGR01068  77 --NGKEVDRSvGALPKAALKQLINKN 100

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 262118377  15 KNYNEIVLDDtKDVLIEFYAPWCGHCKALAPKYEELgalyakSEFKDRVVIAKVDATAN-DVPDE--IQGFPTIKLYpag 91
Cdd:cd02947    1 EEFEELIKSA-KPVVVDFWAPWCGPCKAIAPVLEEL------AEEYPKVKFVKVDVDENpELAEEygVRSIPTFLFF--- 70

                         90       100
                 ....*....|....*....|...
gi 262118377  92 AKGQPV-TYSGSRTVEDLIKFIA 113
Cdd:cd02947   71 KNGKEVdRVVGADPKEELEEFLE 93

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 262118377   8 PVTVVVAKNYNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYAKseFKDRVVIAKVDAtANDVPD------EIQG 81
Cdd:cd02992    2 PVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRK--WRPVVRVAAVDC-ADEENValcrdfGVTG 78

                         90       100       110
                 ....*....|....*....|....*....|....
gi 262118377  82 FPTIKLYPAGAKGQPVTYsGSRTVEDLIKFIAEN 115
Cdd:cd02992   79 YPTLRYFPPFSKEATDGL-KQEGPERDVNELREA 111

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 262118377   9 VTVVVAKNYNEIvLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYaKSEFKD--RVVIAKVDA-TANDVPD--EIQGFP 83
Cdd:cd02996    3 IVSLTSGNIDDI-LQSAELVLVNFYADWCRFSQMLHPIFEEAAAKI-KEEFPDagKVVWGKVDCdKESDIADryRINKYP 80

                         90       100
                 ....*....|....*....|....*....
gi 262118377  84 TIKLYPAGAKGQpVTYSGSRTVEDLIKFI 112
Cdd:cd02996   81 TLKLFRNGMMMK-REYRGQRSVEALAEFV 108

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377  24 DTKDVLIEFYAPWCGHCKALAPKYEELGALYAKSEFKdrvvIAKVDATANDVP-----DEIQGFPTIKLYPAGAKgQPVT 98
Cdd:cd02993   20 RNQSTLVVLYAPWCPFCQAMEASYEELAEKLAGSNVK----VAKFNADGEQREfakeeLQLKSFPTILFFPKNSR-QPIK 94

                         90
                 ....*....|....*
gi 262118377  99 Y-SGSRTVEDLIKFI 112
Cdd:cd02993   95 YpSEQRDVDSLLMFV 109

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 262118377  29 LIEFYAPWCGHCKALAPKYEElgalYAKsEFKDRVVIAKVDATANDVPDEIQG---FPTIKLYPAGAKgqPVTYSGSRTV 105
Cdd:cd03003   22 FVNFYSPRCSHCHDLAPTWRE----FAK-EMDGVIRIGAVNCGDDRMLCRSQGvnsYPSLYVFPSGMN--PEKYYGDRSK 94

                 ....*.
gi 262118377 106 EDLIKF 111
Cdd:cd03003   95 ESLVKF 100

5'-adenylylsulfate reductase, thioredoxin-independent; This enzyme, involved in the assimilation of inorganic sulfate, is closely related to the thioredoxin-dependent PAPS reductase of Bacteria (CysH) and Saccharomyces cerevisiae. However, it has its own C-terminal thioredoxin-like domain and is not thioredoxin-dependent. Also, it has a substrate preference for 5'-adenylylsulfate (APS) over 3'-phosphoadenylylsulfate (PAPS) so the pathway does not require an APS kinase (CysC) to convert APS to PAPS. Arabidopsis thaliana appears to have three isozymes, all able to complement E. coli CysH mutants (even in backgrounds lacking thioredoxin or APS kinase) but likely localized to different compartments in Arabidopsis. [Central intermediary metabolism, Sulfur metabolism]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377   18 NEIVLDDTKDV-LIEFYAPWCGHCKALAPKYEELGALYAKSEFKdrvvIAKVDATAND---VPDEIQ--GFPTIKLYPAG 91
Cdd:TIGR00424 363 NLLKLEERKEAwLVVLYAPWCPFCQAMEASYLELAEKLAGSGVK----VAKFRADGDQkefAKQELQlgSFPTILFFPKH 438

                          90       100
                  ....*....|....*....|..
gi 262118377   92 AKgQPVTY-SGSRTVEDLIKFI 112
Cdd:TIGR00424 439 SS-RPIKYpSEKRDVDSLMSFV 459

DsbD gamma family; DsbD gamma is the C-terminal periplasmic domain of the bacterial protein DsbD. It contains a CXXC motif in a TRX fold and shuttles the reducing potential from the membrane domain (DsbD beta) to the N-terminal periplasmic domain (DsbD alpha). DsbD beta, a transmembrane domain comprising of eight helices, acquires its reducing potential from the cytoplasmic thioredoxin. DsbD alpha transfers the acquired reducing potential from DsbD gamma to target proteins such as the periplasmic protein disulphide isomerases, DsbC and DsbG. This flow of reducing potential from the cytoplasm through DsbD allows DsbC and DsbG to act as isomerases in the oxidizing environment of the bacterial periplasm. DsbD also transfers reducing potential from the cytoplasm to specific reductases in the periplasm which are involved in the maturation of cytochromes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377  26 KDVLIEFYAPWCGHCKALapKYEELGALYAKSEFKDRVVIAKVDATANDvpDEIQGF---------PTIKLYPAGAKGQP 96
Cdd:cd02953   12 KPVFVDFTADWCVTCKVN--EKVVFSDPEVQAALKKDVVLLRADWTKND--PEITALlkrfgvfgpPTYLFYGPGGEPEP 87

                         90
                 ....*....|....
gi 262118377  97 VTYSGSRTVEDLIK 110
Cdd:cd02953   88 LRLPGFLTADEFLE 101

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 262118377  19 EIVLDDTKDVLIEFYAPWCGHCKALAPKYEELgalyaKSEFKDRV--VIAKVD 69
Cdd:cd02950   14 EVALSNGKPTLVEFYADWCTVCQEMAPDVAKL-----KQKYGDQVnfVMLNVD 61

PDIa family, endoplasmic reticulum protein 44 (ERp44)-like subfamily; composed of uncharacterized PDI-like eukaryotic proteins containing only one redox active TRX (a) domain with a CXXS motif, similar to ERp44. CXXS is still a redox active motif; however, the mixed disulfide formed with the substrate is more stable than those formed by CXXC motif proteins. PDI-related proteins are usually involved in the oxidative protein folding in the ER by acting as catalysts and folding assistants. ERp44 is involved in thiol-mediated retention in the ER.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377  28 VLIEFYAPWCGHCKALAPKYEELGALYAksefkdRVVIAKVDATANdVPD-----EIQGFPTIKLYPAGAKgqpVTYSGS 102
Cdd:cd02999   21 TAVLFYASWCPFSASFRPHFNALSSMFP------QIRHLAIEESSI-KPSllsryGVVGFPTILLFNSTPR---VRYNGT 90

                         90
                 ....*....|
gi 262118377 103 RTVEDLIKFI 112
Cdd:cd02999   91 RTLDSLAAFY 100

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377   2 PLGSEGPVTVVVAKNYNEIVLDDTKD--VLIEFYAPWCGHCKALAPKYEELGALYAKSEF-------KDRVVIAKVDATA 72
Cdd:COG0526    3 AVGKPAPDFTLTDLDGKPLSLADLKGkpVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFvgvdvdeNPEAVKAFLKELG 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 262118377  73 NDVP---DE---------IQGFPTIKLYpaGAKGQPV-TYSGSRTVEDLIKFIAE 114
Cdd:COG0526   83 LPYPvllDPdgelakaygVRGIPTTVLI--DKDGKIVaRHVGPLSPEELEEALEK 135

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 262118377  28 VLIEFYAPWCGHCKALAPkyeELGALYAKSEFKDRVVIAkVdATANDVPDEIQGF 82
Cdd:cd02966   22 VLVNFWASWCPPCRAEMP---ELEALAKEYKDDGVEVVG-V-NVDDDDPAAVKAF 71

Thioredoxin-related protein SoxW [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118377  26 KDVLIEFYAPWCGHCKALapKYEELGALYAKSEFKDRVVIAKVDATAN----DVPDE------------IQGFPTIKLYP 89
Cdd:COG2143   41 KPILLFFESDWCPYCKKL--HKEVFSDPEVAAYLKENFVVVQLDAEGDkevtDFDGEtltekelarkygVRGTPTLVFFD 118

                         90       100       110
                 ....*....|....*....|....*....|
gi 262118377  90 agAKGQPVT----YSGSRTVEDLIKFIAEN 115
Cdd:COG2143  119 --AEGKEIAripgYLKPETFLALLKYVAEG 146

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 262118377   26 KDVLIEFYAPWCGHCKALAP---KYEELGALyakseFKDRVVIAKVDATAND-----VPDEiQGFPTIKLYPA 90
Cdd:pfam13899  18 KPVLVDFGADWCFTCQVLERdflSHEEVKAA-----LAKNFVLLRLDWTSRDanitrAFDG-QGVPHIAFLDP 84

PDIa family, N-terminal EFP1 subfamily; EFP1 is a binding partner protein of thyroid oxidase (ThOX), also called Duox. ThOX proteins are responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones. EFP1 was isolated through a yeast two-hybrid method using the EF-hand fragment of dog Duox1 as a bait. It could be one of the partners in the assembly of a multiprotein complex constituting the thyroid hydrogen peroxide generating system. EFP1 contains two TRX domains related to the redox active TRX domains of protein disulfide isomerase (PDI). This subfamily is composed of the N-terminal TRX domain of EFP1, which contains a CXXS sequence in place of the typical CXXC motif, similar to ERp44. The CXXS motif allows the formation of stable mixed disulfides, crucial for the ER-retention function of ERp44.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 262118377  17 YNEIVLDDTKDVLIEFYAPWCGHCKALAPKYEELGALYA 55
Cdd:cd03006   21 YAEELRTDAEVSLVMYYAPWDAQSQAARQEFEQVAQKLS 59

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 262118377   28 VLIEFYAPWCGHCKALAPKYEElgaLYAKSEFKDRVVIAKV--DATANDVPDEIQGFP 83
Cdd:pfam13905   4 VLLYFGASWCKPCRRFTPLLKE---LYEKLKKKKNVEIVFVslDRDLEEFKDYLKKMP 58