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 1839420794   8 IINLNDKNFQQEINKTNL-VLVDFWAEWCNPCKIFSKVLEEVSLEYKN-IIFTKLNIENYKVITEKYNIRSVPTILLFKN 85
Cdd:COG3118     2 VVELTDENFEEEVLESDKpVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                          90       100
                  ....*....|....*....|....
gi 1839420794  86 GNIIDKIIGSITKIQLKNFLNKNL 109
Cdd:COG3118    82 GQPVDRFVGALPKEQLREFLDKVL 105

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 1839420794   8 IINLNDKNFQQEINKTNL-VLVDFWAEWCNPCKIFSKVLEEVSLEYKN-IIFTKLNIENYKVITEKYNIRSVPTILLFKN 85
Cdd:COG3118     2 VVELTDENFEEEVLESDKpVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                          90       100
                  ....*....|....*....|....
gi 1839420794  86 GNIIDKIIGSITKIQLKNFLNKNL 109
Cdd:COG3118    82 GQPVDRFVGALPKEQLREFLDKVL 105

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 1839420794  14 KNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKNIIFTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDKII 93
Cdd:cd02947     1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                          90
                  ....*....|...
gi 1839420794  94 GSITKIQLKNFLN 106
Cdd:cd02947    81 GADPKEELEEFLE 93

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 1839420794   8 IINLNDKNFQQEINKTN-LVLVDFWAEWCNPCKIFSKVLEEVSLEYK-NIIFTKLNIENYKVITEKYNIRSVPTILLFKN 85
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSkPVLVDFYAPWCGPCKMLAPEYEELAQEYKgNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|..
gi 1839420794  86 GNIIDKIIGSITKIQLKNFLNK 107
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLKA 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 1839420794   8 IINLNDKNFQQEINKTNL-VLVDFWAEWCNPCKIFSKVLEEVSLEYKN-IIFTKLNIENYKVITEKYNIRSVPTILLFKN 85
Cdd:COG3118     2 VVELTDENFEEEVLESDKpVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKD 81

                          90       100
                  ....*....|....*....|....
gi 1839420794  86 GNIIDKIIGSITKIQLKNFLNKNL 109
Cdd:COG3118    82 GQPVDRFVGALPKEQLREFLDKVL 105

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 1839420794  14 KNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKNIIFTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDKII 93
Cdd:cd02947     1 EEFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                          90
                  ....*....|...
gi 1839420794  94 GSITKIQLKNFLN 106
Cdd:cd02947    81 GADPKEELEEFLE 93

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 1839420794   8 IINLNDKNFQQEINKTN-LVLVDFWAEWCNPCKIFSKVLEEVSLEYK-NIIFTKLNIENYKVITEKYNIRSVPTILLFKN 85
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSkPVLVDFYAPWCGPCKMLAPEYEELAQEYKgNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|..
gi 1839420794  86 GNIIDKIIGSITKIQLKNFLNK 107
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLKA 103

thioredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  16 FQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKNIIFTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDKIIGS 95
Cdd:PTZ00051   11 FESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVVDTLLGA 90

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1839420794  21 NKTNLVLVDFWAEWCNPCKIFSKVLEEVSLE-YKNIIFTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDKIIGS 95
Cdd:cd02984    12 DASKLLVLHFWAPWAEPCKQMNQVFEELAKEaFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTIVDRVSGA 87

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 1839420794  15 NFQQEIN--KTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYK-NIIFTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDK 91
Cdd:cd02956     2 NFQQVLQesTQVPVVVDFWAPRSPPSKELLPLLERLAEEYQgQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDG 81

                          90
                  ....*....|....*
gi 1839420794  92 IIGSITKIQLKNFLN 106
Cdd:cd02956    82 FQGAQPEEQLRQMLD 96

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 1839420794   8 IINLNDKnFQqEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYK----NIIFTKLNIENYKVITEKYNIRSVPTILLF 83
Cdd:cd03000     2 VLDLDDS-FK-DVRKEDIWLVDFYAPWCGHCKKLEPVWNEVGAELKssgsPVRVGKLDATAYSSIASEFGVRGYPTIKLL 79

                          90       100
                  ....*....|....*....|....
gi 1839420794  84 KNGNIIDkIIGSITKIQLKNFLNK 107
Cdd:cd03000    80 KGDLAYN-YRGPRTKDDIVEFANR 102

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  11 LNDKNFQQEINKTN---LVLVDFWAEWCNPCKIFSKVLEEVSLEYKNIIFTKLNIENyKVITEKYNIRSVPTILLFKNGN 87
Cdd:cd02957     9 ISSKEFLEEVTKASkgtRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEK-AFLVNYLDIKVLPTLLVYKNGE 87

                  ....*..
gi 1839420794  88 IIDKIIG 94
Cdd:cd02957    88 LIDNIVG 94

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794   8 IINLNDKNFQQEINKTN-LVLVDFWAEWCNPCKIFSKVLEEVSLEYKNII-FTKLNIENYKVITEKYNIRSVPTILLFKN 85
Cdd:cd03001     2 VVELTDSNFDKKVLNSDdVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVkVGAVDADVHQSLAQQYGVRGFPTIKVFGA 81

                  .
gi 1839420794  86 G 86
Cdd:cd03001    82 G 82

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 1839420794   8 IINLNDKNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKN-------IIFTKLNIENYKVITEKYNIRSVPTI 80
Cdd:cd02996     3 IVSLTSGNIDDILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKEefpdagkVVWGKVDCDKESDIADRYRINKYPTL 82

                          90
                  ....*....|.
gi 1839420794  81 LLFKNGNIIDK 91
Cdd:cd02996    83 KLFRNGMMMKR 93

PDIa family, PDIR subfamily; composed of proteins similar to human PDIR (for Protein Disulfide Isomerase Related). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress. Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794   8 IINLNDKNFQQEINKTNLVLVDFWAEWCNPCK----IFSKVLEEVSLEYKnIIFTKLNI--ENYKVITEKYNIRSVPTIL 81
Cdd:cd02997     2 VVHLTDEDFRKFLKKEKHVLVMFYAPWCGHCKkmkpEFTKAATELKEDGK-GVLAAVDCtkPEHDALKEEYNVKGFPTFK 80

                          90       100
                  ....*....|....*....|....
gi 1839420794  82 LFKNGNIIDKIIGSITKIQLKNFL 105
Cdd:cd02997    81 YFENGKFVEKYEGERTAEDIIEFM 104

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 1839420794  10 NLNDKNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKN----II--------------FTKLNIENYKV---- 67
Cdd:cd02966     6 DLDGKPVSLSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKDdgveVVgvnvddddpaavkaFLKKYGITFPVlldp 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1839420794  68 ---ITEKYNIRSVPTILLF-KNGNIIDKIIG 94
Cdd:cd02966    86 dgeLAKAYGVRGLPTTFLIdRDGRIRARHVG 116

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1839420794  26 VLVDFWAEWCNPCKIFSKVL---EEVSLEYK-NIIFTKLNI-ENYKVITE---KYNIRSVPTILLFKNGNIIDKII 93
Cdd:cd02953    14 VFVDFTADWCVTCKVNEKVVfsdPEVQAALKkDVVLLRADWtKNDPEITAllkRFGVFGPPTYLFYGPGGEPEPLR 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  26 VLVDFWAEWCNPCKIFSKVL---EEVSLEYK-NIIFTKLNIENYKVIT-------------EKYNIRSVPTILLF-KNGN 87
Cdd:COG2143    43 ILLFFESDWCPYCKKLHKEVfsdPEVAAYLKeNFVVVQLDAEGDKEVTdfdgetltekelaRKYGVRGTPTLVFFdAEGK 122

                          90       100
                  ....*....|....*....|
gi 1839420794  88 IIDKIIGSITKIQLKNFLNK 107
Cdd:COG2143   123 EIARIPGYLKPETFLALLKY 142

thiol-disulfide oxidoreductase ResA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  11 LNDKNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYK---------NIIFTKLNIENY---------------K 66
Cdd:PRK03147   49 LEGKKIELKDLKGKGVFLNFWGTWCKPCEKEMPYMNELYPKYKekgveiiavNVDETELAVKNFvnrygltfpvaidkgR 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1839420794  67 VITEKYNIRSVP-TILLFKNGNIIDKIIGSITKIQLKNFLNK 107
Cdd:PRK03147  129 QVIDAYGVGPLPtTFLIDKDGKVVKVITGEMTEEQLEEYLEK 170

Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  26 VLVDFWAEWCNPCKIF-------SKVLEEVSleyKNIIFTKLNI-ENYKVIT---EKYNIRSVPTILLF-KNGNIIDKII 93
Cdd:COG4232   323 VFVDFTADWCVTCKENertvfsdPEVQAALA---DDVVLLKADVtDNDPEITallKRFGRFGVPTYVFYdPDGEELPRLG 399

                          90
                  ....*....|....*..
gi 1839420794  94 GSITKIQLKNFLNKNLK 110
Cdd:COG4232   400 FMLTADEFLAALEKAKG 416

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1839420794  14 KNFQQEINK-TNLVLVDFWAEWCNPCKIFSKVLEEVSLEYK----NIIFTKLNIENYKVitEKYNIRSVPTILLFKNGN 87
Cdd:TIGR01130 354 KNFDEIVLDeTKDVLVEFYAPWCGHCKNLAPIYEELAEKYKdaesDVVIAKMDATANDV--PPFEVEGFPTIKFVPAGK 430

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794   6 NIIINLNDKNFQQEIN-----KTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKNII-FTKLNIENYKVITEKYNIRSVPT 79
Cdd:PTZ00443   30 NALVLLNDKNFEKLTQastgaTTGPWFVKFYAPWCSHCRKMAPAWERLAKALKGQVnVADLDATRALNLAKRFAIKGYPT 109

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1839420794  80 ILLFKNGNIIDKIIGSITKIQLKNFLNKNLK 110
Cdd:PTZ00443  110 LLLFDKGKMYQYEGGDRSTEKLAAFALGDFK 140

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  25 LVLVDFWAEWCNPCKIFSKVLEEVSLEYKNII-FTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDKIIGSITKIQLKN 103
Cdd:cd02949    15 LILVLYTSPTCGPCRTLKPILNKVIDEFDGAVhFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKSEYRE 94

                  ..
gi 1839420794 104 FL 105
Cdd:cd02949    95 FI 96

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  12 NDKNFQQEINKTNLVLVDFWAEWCNPCK----IFSKVLEEVSLEykNIIFTKLNIENYKVItEKYNIRSVPTILLFKNGN 87
Cdd:cd02948     6 NQEEWEELLSNKGLTVVDVYQEWCGPCKavvsLFKKIKNELGDD--LLHFATAEADTIDTL-KRYRGKCEPTFLFYKNGE 82

                  ....*...
gi 1839420794  88 IIDKIIGS 95
Cdd:cd02948    83 LVAVIRGA 90

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 1839420794   8 IINLNDKNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKNII-FTKLNIENYKVITEKYNIRSVPTILLFKNG 86
Cdd:cd03003     3 IVTLDRGDFDAAVNSGEIWFVNFYSPRCSHCHDLAPTWREFAKEMDGVIrIGAVNCGDDRMLCRSQGVNSYPSLYVFPSG 82

                          90
                  ....*....|....*...
gi 1839420794  87 NIIDKIIGSITKIQLKNF 104
Cdd:cd03003    83 MNPEKYYGDRSKESLVKF 100

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1839420794  18 QEINKTNLVLVDFWAEWCNPCKIFSKVLEEVSLEYKNII 56
Cdd:TIGR00385  58 DVLTQGKPVLLNVWASWCPPCRAEHPYLNELAKQGLPIV 96

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1839420794  26 VLVDFWAEWCNPCKIFSKVL---EEVSLEY-KNIIFTKLNIEN-YKVITEKYNIRSVPTILLF 83
Cdd:pfam13899  20 VLVDFGADWCFTCQVLERDFlshEEVKAALaKNFVLLRLDWTSrDANITRAFDGQGVPHIAFL 82

Phosducin (Phd)-like family, Viral inhibitor of apoptosis (IAP)-associated factor (VIAF) subfamily; VIAF is a Phd-like protein that functions in caspase activation during apoptosis. It was identified as an IAP binding protein through a screen of a human B-cell library using a prototype IAP. VIAF lacks a consensus IAP binding motif and while it does not function as an IAP antagonist, it still plays a regulatory role in the complete activation of caspases. VIAF itself is a substrate for IAP-mediated ubiquitination, suggesting that it may be a target of IAPs in the prevention of cell death. The similarity of VIAF to Phd points to a potential role distinct from apoptosis regulation. Phd functions as a cytosolic regulator of G protein by specifically binding to G protein betagamma (Gbg)-subunits. 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  38 CKIFSKVLEEVSLEYKNIIFTKLNienYKVITEKYNIRSVPTILLFKNGNIIDKIIGSIT 97
Cdd:cd02988   117 CRLLNQHLSELARKFPDTKFVKII---STQCIPNYPDKNLPTILVYRNGDIVKQFIGLLE 173

TRX domain, DnaJ domain containing protein family; composed of uncharacterized proteins of about 500-800 amino acids, containing an N-terminal DnaJ domain followed by one redox active TRX domain. DnaJ is a member of the 40 kDa heat-shock protein (Hsp40) family of molecular chaperones, which regulate the activity of Hsp70s. TRX is involved in the redox regulation of many protein substrates through the reduction of disulfide bonds. TRX has been implicated to catalyse the reduction of Hsp33, a chaperone holdase that binds to unfolded protein intermediates. The presence of DnaJ and TRX domains in members of this family suggests that they could be involved in a redox-regulated chaperone network.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794  27 LVDFWAEWCNPC----KIFSKVLEEvsLEYKNIIFTKLNIENYKVITEKYNIRSVPTILLFKNGNIIDKIIGSITKIQLK 102
Cdd:cd02963    28 LIKITSDWCFSCihiePVWKEVIQE--LEPLGVGIATVNAGHERRLARKLGAHSVPAIVGIINGQVTFYHDSSFTKQHVV 105

                  ....*
gi 1839420794 103 NFLNK 107
Cdd:cd02963   106 DFVRK 110

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 1839420794   8 IINLNDKNFQQEI-NKTNLVLVDFWAEWCNPCKIFSKVLEEVS---LEYKNII-FTKLNI---ENYKVITEkYNIRSVPT 79
Cdd:cd02992     3 VIVLDAASFNSALlGSPSAWLVEFYASWCGHCRAFAPTWKKLArdlRKWRPVVrVAAVDCadeENVALCRD-FGVTGYPT 81

                  ....*
gi 1839420794  80 ILLFK 84
Cdd:cd02992    82 LRYFP 86

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1839420794   4 KTNIIINLNDKNFQQEINK----TNLVLvdFWAEW----CNPCKIFSKVLEEVSLEY--------KNIIFTKLNIENYKV 67
Cdd:pfam04756   9 KSNGVIKLNDSNYKRLLSGprdySVVVL--LTALDprfgCQLCREFQPEFELVAKSWfkdhkagsSKLFFATLDFDDGKD 86

                          90
                  ....*....|....*.
gi 1839420794  68 ITEKYNIRSVPTILLF 83
Cdd:pfam04756  87 VFQSLGLQTAPHLLLF 102

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        30
                  ....*....|....*....|....*....|....*..
gi 1839420794  13 DKNFQQEINKTNLVLVDFWAEWCNPCKIFSKVLEEVS 49
Cdd:cd03010    15 DKTLTSADLKGKPYLLNVWASWCAPCREEHPVLMALA 51