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 446817898  11 AEKTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYkGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEVGeRLVEP 90
Cdd:cd02947    5 ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVD-RVVGA 82

                         90
                 ....*....|.
gi 446817898  91 SSQKPIEDAIK 101
Cdd:cd02947   83 DPKEELEEFLE 93

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 446817898  11 AEKTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYkGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEVGeRLVEP 90
Cdd:cd02947    5 ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVD-RVVGA 82

                         90
                 ....*....|.
gi 446817898  91 SSQKPIEDAIK 101
Cdd:cd02947   83 DPKEELEEFLE 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 446817898    5 INGKNYAE--KTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKE 82
Cdd:TIGR01068   1 LTDANFDEtiASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|..
gi 446817898   83 VgERLVEPSSQKPIEDAIKTLL 104
Cdd:TIGR01068  81 V-DRSVGALPKAALKQLINKNL 101

thioredoxin 2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 446817898  17 QAVVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEV 83
Cdd:PRK10996  53 LPVVIDFWAPWCGPCRNFAPIFEDVAAERSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVV 119

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 446817898  11 AEKTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYkGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEVGeRLVEP 90
Cdd:cd02947    5 ELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVD-RVVGA 82

                         90
                 ....*....|.
gi 446817898  91 SSQKPIEDAIK 101
Cdd:cd02947   83 DPKEELEEFLE 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 446817898    5 INGKNYAE--KTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKE 82
Cdd:TIGR01068   1 LTDANFDEtiASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|..
gi 446817898   83 VgERLVEPSSQKPIEDAIKTLL 104
Cdd:TIGR01068  81 V-DRSVGALPKAALKQLINKNL 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 446817898    3 EVINGKNYAE--KTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNA 80
Cdd:pfam00085   3 VVLTDANFDEvvQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                  ....*
gi 446817898   81 KEVGE 85
Cdd:pfam00085  83 QPVDD 87

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446817898   1 MLEVINGKNYAEKTAHQ--AVVVNVGASWCPDCRKIEPIMENLAKTYKgKVEFFKVSFDESQDLKESLGIRKIPTLIFYK 78
Cdd:PTZ00051   1 MVHIVTSQAEFESTLSQneLVIVDFYAEWCGPCKRIAPFYEECSKEYT-KMVFVKVDVDELSEVAEKENITSMPTFKVFK 79

                 ....*....
gi 446817898  79 NAKEVGERL 87
Cdd:PTZ00051  80 NGSVVDTLL 88

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446817898  12 EKTAHQAVVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEVgerlvePS 91
Cdd:cd02956    8 QESTQVPVVVDFWAPRSPPSKELLPLLERLAEEYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPV------DG 81

                         90
                 ....*....|....
gi 446817898  92 SQKPI-EDAIKTLL 104
Cdd:cd02956   82 FQGAQpEEQLRQML 95

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446817898  17 QAVVVNVGASWCPDCRKIEPIMENLAKTYKGK-VEF-----------------------FKVSFDESQDLKESLGIRKIP 72
Cdd:cd02966   20 KVVLVNFWASWCPPCRAEMPELEALAKEYKDDgVEVvgvnvddddpaavkaflkkygitFPVLLDPDGELAKAYGVRGLP 99

                 ....*
gi 446817898  73 TLIFY 77
Cdd:cd02966  100 TTFLI 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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 446817898  20 VVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYK 78
Cdd:cd03004   23 LVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYP 81

TRX family, chloroplastic drought-induced stress protein of 32 kD (CDSP32); CDSP32 is composed of two TRX domains, a C-terminal TRX domain which contains a redox active CXXC motif and an N-terminal TRX-like domain which contains an SXXS sequence instead of the redox active motif. CDSP32 is a stress-inducible TRX, i.e., it acts as a TRX by reducing protein disulfides and is induced by environmental and oxidative stress conditions. It plays a critical role in plastid defense against oxidative damage, a role related to its function as a physiological electron donor to BAS1, a plastidic 2-cys peroxiredoxin. Plants lacking CDSP32 exhibit decreased photosystem II photochemical efficiencies and chlorophyll retention compared to WT controls, as well as an increased proportion of BAS1 in its overoxidized monomeric form.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446817898  19 VVVNVGASWCPDCRKIEPIMENLAKTYkGKVEFFKVSFDESQDLKESL---GIRKIPTLIFYKNAKEVGE 85
Cdd:cd02985   18 VVLEFALKHSGPSVKIYPTMVKLSRTC-NDVVFLLVNGDENDSTMELCrreKIIEVPHFLFYKDGEKIHE 86

TRX domain, novel NADPH thioredoxin reductase (NTR) family; composed of fusion proteins found only in oxygenic photosynthetic organisms containing both TRX and NTR domains. The TRX domain functions as a protein disulfide reductase via the reversible oxidation of an active center dithiol present in a CXXC motif, while the NTR domain functions as a reductant to oxidized TRX. The fusion protein is bifunctional, showing both TRX and NTR activities, but it is not an independent NTR/TRX system. In plants, the protein is found exclusively in shoots and mature leaves and is localized in the chloroplast. It is involved in plant protection against oxidative stress.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 446817898  28 CPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEVGE 85
Cdd:cd02949   25 CGPCRTLKPILNKVIDEFDGAVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKE 82

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 446817898   1 MLEVINGKNYAEKTAHQAVVVNVgASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQ--DLKESLGIRKIPTLIFYK 78
Cdd:cd03002    4 ELTPKNFDKVVHNTNYTTLVEFY-APWCGHCKNLKPEYAKAAKELDGLVQVAAVDCDEDKnkPLCGKYGVQGFPTLKVFR 82

                         90       100
                 ....*....|....*....|....*..
gi 446817898  79 NAKEVGERLVE----PSSQKPIEDAIK 101
Cdd:cd03002   83 PPKKASKHAVEdyngERSAKAIVDFVL 109

OST3 / OST6 family, transporter family; The proteins in this family are part of a complex of eight ER proteins that transfers core oligosaccharide from dolichol carrier to Asn-X-Ser/Thr motifs. This family includes both OST3 and OST6, each of which contains four predicted transmembrane helices. Disruption of OST3 and OST6 leads to a defect in the assembly of the complex. Hence, the function of these genes seems to be essential for recruiting a fully active complex necessary for efficient N-glycosylation. These proteins are also thought to be novel Mg2+ transporters.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 446817898   28 CPDCRKIEPIMENLAKTY-------KGKVEFFKVSFDESQDLKESLGIRKIPTLIFY 77
Cdd:pfam04756  46 CQLCREFQPEFELVAKSWfkdhkagSSKLFFATLDFDDGKDVFQSLGLQTAPHLLLF 102

Phosducin (Phd)-like family, Thioredoxin (TRX) domain containing protein 9 (TxnDC9) subfamily; composed of predominantly uncharacterized eukaryotic proteins, containing a TRX-like domain without the redox active CXXC motif. The gene name for the human protein is TxnDC9. The two characterized members are described as Phd-like proteins, PLP1 of Saccharomyces cerevisiae and PhLP3 of Dictyostelium discoideum. Gene disruption experiments show that both PLP1 and PhLP3 are non-essential proteins. Unlike Phd and most Phd-like proteins, members of this group do not contain the Phd N-terminal helical domain which is implicated in binding to the G protein betagamma subunit.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 446817898  31 CRKIEPIMENLAKTYKGkVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEVgERLV 88
Cdd:cd02989   37 CKIMDKHLEILAKKHLE-TKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTV-DRIV 92

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 446817898  16 HQAVVVNVGASWCPDCRKIEPIMENLAKTYKG--KVEFFKVSFDES-QDLKESLGIRKIPTLIFY-KNAKE 82
Cdd:cd02998   18 KKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANedDVVIAKVDADEAnKDLAKKYGVSGFPTLKFFpKGSTE 88

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446817898  17 QAVVVNVGASWCPDCRKIEPIMENLAKTYKGK-VEFFKVSFDESQDLKE---------------------SLGIRKIPTL 74
Cdd:COG1225   22 KPVVLYFYATWCPGCTAELPELRDLYEEFKDKgVEVLGVSSDSDEAHKKfaekyglpfpllsdpdgevakAYGVRGTPTT 101

                         90       100       110
                 ....*....|....*....|....*....|.
gi 446817898  75 IFY-KNAKEVGERLVEPSSQKPIEDAIKTLL 104
Cdd:COG1225  102 FLIdPDGKIRYVWVGPVDPRPHLEEVLEALL 132

PDIa family, P5 subfamily; composed of eukaryotic proteins similar to human P5, a PDI-related protein with a domain structure of aa'b (where a and a' are redox active TRX domains and b is a redox inactive TRX-like domain). Like PDI, P5 is located in the endoplasmic reticulum (ER) and displays both isomerase and chaperone activities, which are independent of each other. Compared to PDI, the isomerase and chaperone activities of P5 are lower. The first cysteine in the CXXC motif of both redox active domains in P5 is necessary for isomerase activity. The P5 gene was first isolated as an amplified gene from a hydroxyurea-resistant hamster cell line. The zebrafish P5 homolog has been implicated to play a critical role in establishing left/right asymmetries in the embryonic midline. Some members of this subfamily are P5-like proteins containing only one redox active TRX domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 446817898  19 VVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTL-IFYKNAKE 82
Cdd:cd03001   21 WLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIkVFGAGKNS 85

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 446817898  25 ASWCPDCRKIEPIMENLAKTYKGK-VEFFKVSFDESQDLKESLGI------RKIPTLIFYKNAKEVGER 86
Cdd:cd02962   56 TTWSPECVNFAPVFAELSLKYNNNnLKFGKIDIGRFPNVAEKFRVstsplsKQLPTIILFQGGKEVARR 124

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 446817898  24 GASWCPDCRKIEPIMENLAKTYkgkvefFKVSFDESQDLKESLGIRKIPTLI 75
Cdd:PHA02125   6 GAEWCANCKMVKPMLANVEYTY------VDVDTDEGVELTAKHHIRSLPTLV 51

thiol-disulfide oxidoreductase ResA;

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 446817898  17 QAVVVNVGASWCPDCRKIEPIMENLAKTYKGK-VEFFKVSFDESQ 60
Cdd:PRK03147  62 KGVFLNFWGTWCKPCEKEMPYMNELYPKYKEKgVEIIAVNVDETE 106

Thioredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 446817898   24 GASWCPDCRKIEPIMENLAKTYKG-KVEFFkvSFDESQDLKESL---GIRKIPTLIFY-KNAKEVG 84
Cdd:pfam14595  49 TEDWCGDAAQNVPVLAKIAELNPNiELRIL--LRDENLELMDQYltgGGRAIPTFIFLdEDGEELG 112

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 446817898   17 QAVVVNVGASWCPDCRKIEPIMENLAKTYKG---KVEFFKVSFDESQDLKESLGIRKIPTLIFYknAKEVGERLVEPSSQ 93
Cdd:TIGR00424 372 EAWLVVLYAPWCPFCQAMEASYLELAEKLAGsgvKVAKFRADGDQKEFAKQELQLGSFPTILFF--PKHSSRPIKYPSEK 449

                  ....
gi 446817898   94 KPIE 97
Cdd:TIGR00424 450 RDVD 453

Dim1 family; Dim1 is also referred to as U5 small nuclear ribonucleoprotein particle (snRNP)-specific 15kD protein. It is a component of U5 snRNP, which pre-assembles with U4/U6 snRNPs to form a [U4/U6:U5] tri-snRNP complex required for pre-mRNA splicing. Dim1 interacts with multiple splicing-associated proteins, suggesting that it functions at multiple control points in the splicing of pre-mRNA as part of a large spliceosomal complex involving many protein-protein interactions. U5 snRNP contains seven core proteins (common to all snRNPs) and nine U5-specific proteins, one of which is Dim1. Dim1 adopts a thioredoxin fold but does not contain the redox active CXXC motif. It is essential for G2/M phase transition, as a consequence to its role in pre-mRNA splicing.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 446817898  14 TAHQAVVVNVGASWCPDCRKIEPIMENLAKTYKGKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAK 81
Cdd:cd02954   12 EEEKVVVIRFGRDWDPVCMQMDEVLAKIAEDVSNFAVIYLVDIDEVPDFNKMYELYDPPTVMFFFRNK 79

TlpA-like family, DsbE (also known as CcmG and CycY) subfamily; DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c.

                         10        20
                 ....*....|....*....|....*....
gi 446817898  15 AHQAVVVNVGASWCPDCRKIEPIMENLAK 43
Cdd:cd03010   24 KGKPYLLNVWASWCAPCREEHPVLMALAR 52

Phosducin (Phd)-like family; composed of Phd and Phd-like proteins (PhLP), characterized as cytosolic regulators of G protein functions. Phd and PhLPs specifically bind G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane and impeding G protein-mediated signal transduction by inhibiting the formation of a functional G protein trimer (G protein alphabetagamma). Phd also inhibits the GTPase activity of G protein alpha. Phd can be phosphorylated by protein kinase A and G protein-coupled receptor kinase 2, leading to its inactivation. Phd was originally isolated from the retina, where it is highly expressed and has been implicated to play an important role in light adaptation. It is also found in the pineal gland, liver, spleen, striated muscle and the brain. The C-terminal domain of Phd adopts a thioredoxin fold, but it does not contain a CXXC motif. Phd interacts with G protein beta mostly through the N-terminal helical domain. Also included in this family is a PhLP characterized as a viral inhibitor of apoptosis (IAP)-associated factor, named VIAF, that functions in caspase activation during apoptosis.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 446817898  19 VVVNVGASWCPDCRKIEPIMENLAKTYKGkVEFFKVSFDESqDLKESLGIRKIPTLIFYKNAKEVG 84
Cdd:cd02957   27 VVVHFYEPGFPRCKILDSHLEELAAKYPE-TKFVKINAEKA-FLVNYLDIKVLPTLLVYKNGELID 90

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 446817898  25 ASWCPDCRKIEPIMENLAKTYKGKVEFFKV-----SFDESQDLKESLGIRKIPTLIFYK 78
Cdd:cd02992   28 ASWCGHCRAFAPTWKKLARDLRKWRPVVRVaavdcADEENVALCRDFGVTGYPTLRYFP 86

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 446817898  19 VVVNVGASWCPDCRKIEPIMENLAKTYK--GKVEFFKVSFDESQDLKESLGIRKIPTLIFYKNAKEV-----GERLVE 89
Cdd:PTZ00102 378 VLLEIYAPWCGHCKNLEPVYNELGEKYKdnDSIIVAKMNGTANETPLEEFSWSAFPTILFVKAGERTpipyeGERTVE 455

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

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 446817898  13 KTAHQAVVVNVGASWCPDCRKI-EPIMEN--LAKTYKGKVEFFKVSFDES-------------QDLKESLGIRKIPTLIF 76
Cdd:COG2143   37 KAEGKPILLFFESDWCPYCKKLhKEVFSDpeVAAYLKENFVVVQLDAEGDkevtdfdgetlteKELARKYGVRGTPTLVF 116

                         90
                 ....*....|
gi 446817898  77 Y-KNAKEVGE 85
Cdd:COG2143  117 FdAEGKEIAR 126

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
                 ....*....|....*....|....*....|....*....|....*....|....
gi 446817898  25 ASWCPDCRKIEPIMENLAKTYKgKVEFFkvSFDESQDLKESL---GIRKIPTLI 75
Cdd:cd02999   27 ASWCPFSASFRPHFNALSSMFP-QIRHL--AIEESSIKPSLLsryGVVGFPTIL 77