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 1002225466  65 TFSSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPC 144
Cdd:TIGR01068   2 TDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90       100
                  ....*....|....*....|
gi 1002225466 145 HRFEGALPANQLIQQIESAL 164
Cdd:TIGR01068  82 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 1002225466  67 SSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPCHR 146
Cdd:pfam00085   8 ANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDD 87

                          90
                  ....*....|....*.
gi 1002225466 147 FEGALPANQLIQQIES 162
Cdd:pfam00085  88 YVGARPKDALAAFLKA 103

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 1002225466  65 TFSSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPC 144
Cdd:TIGR01068   2 TDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90       100
                  ....*....|....*....|
gi 1002225466 145 HRFEGALPANQLIQQIESAL 164
Cdd:TIGR01068  82 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 1002225466  67 SSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPCHR 146
Cdd:pfam00085   8 ANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDD 87

                          90
                  ....*....|....*.
gi 1002225466 147 FEGALPANQLIQQIES 162
Cdd:pfam00085  88 YVGARPKDALAAFLKA 103

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 1002225466  65 TFSSFDELLeKSEKPVLVDFYATWCGPCQYMVPILQEVSEKL--GDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNG- 141
Cdd:cd02961     4 TDDNFDELV-KDSKDVLVEFYAPWCGHCKALAPEYEKLAKELkgDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGs 82

                          90       100
                  ....*....|....*....|
gi 1002225466 142 -KPcHRFEGALPANQLIQQI 160
Cdd:cd02961    83 kEP-VKYEGPRTLESLVEFI 101

thioredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  69 FDELLEKSEKpVLVDFYATWCGPCQYMVPILQEVSEKLGdKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPCHRFE 148
Cdd:PTZ00051   11 FESTLSQNEL-VIVDFYAEWCGPCKRIAPFYEECSKEYT-KMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVVDTLL 88

                  ..
gi 1002225466 149 GA 150
Cdd:PTZ00051   89 GA 90

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 1002225466  67 SSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSE--KLGDKIQVVKID-TEKYTSIANRYQIEALPTFIIF-KNGK 142
Cdd:cd02998     8 SNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAvfANEDDVVIAKVDaDEANKDLAKKYGVSGFPTLKFFpKGST 87

                          90
                  ....*....|....*...
gi 1002225466 143 PCHRFEGALPANQLIQQI 160
Cdd:cd02998    88 EPVKYEGGRDLEDLVKFV 105

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 1002225466  67 SSFDELLEKS-EKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPCH 145
Cdd:cd02956     1 QNFQQVLQEStQVPVVVDFWAPRSPPSKELLPLLERLAEEYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVD 80

                          90
                  ....*....|.
gi 1002225466 146 RFEGALPANQL 156
Cdd:cd02956    81 GFQGAQPEEQL 91

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 1002225466  67 SSFDELLeKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVV--KIDTEKYT--SIANRYQIEALPTFIIFKNGK 142
Cdd:cd02997     8 EDFRKFL-KKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGVlaAVDCTKPEhdALKEEYNVKGFPTFKYFENGK 86

                  ....*..
gi 1002225466 143 PCHRFEG 149
Cdd:cd02997    87 FVEKYEG 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1002225466  81 LVDFYATWCGPCQYMVPILQEVSEKL---GDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNG 141
Cdd:cd03000    19 LVDFYAPWCGHCKKLEPVWNEVGAELkssGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGD 82

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  78 KPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQVV--KIDTEKYTSIANRYQIEALPTFIIFKN-GKPCHRFEGALPAN 154
Cdd:cd02950    21 KPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVmlNVDNPKWLPEIDRYRVDGIPHFVFLDReGNEEGQSIGLQPKQ 100

                  ....*...
gi 1002225466 155 QLIQQIES 162
Cdd:cd02950   101 VLAQNLDA 108

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are 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. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  62 KKQTFSSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKL--GDKIQVVKIDTEKyTSIANRYQIEALPTFIIFK 139
Cdd:cd02995     3 KVVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLkgDDNVVIAKMDATA-NDVPSEFVVDGFPTILFFP 81

                  ...
gi 1002225466 140 NGK 142
Cdd:cd02995    82 AGD 84

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 1002225466  65 TFSSFDEllEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKL---GDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNG 141
Cdd:cd03005     6 TEDNFDH--HIAEGNHFVKFFAPWCGHCKRLAPTWEQLAKKFnneNPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDG 83

                  ....*....
gi 1002225466 142 KPCHRFEGA 150
Cdd:cd03005    84 EKVDKYKGT 92

disulphide isomerase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  65 TFSSFDELLEKSEKpVLVDFYATWCGPCQYMVPILQEVSEKLGDK---IQVVKIDTEKYTSIANRYQIEALPTFIIFKNG 141
Cdd:PTZ00102   38 TDSTFDKFITENEI-VLVKFYAPWCGHCKRLAPEYKKAAKMLKEKkseIVLASVDATEEMELAQEFGVRGYPTIKFFNKG 116

                          90       100
                  ....*....|....*....|
gi 1002225466 142 KPChRFEGALPANQLIQQIE 161
Cdd:PTZ00102  117 NPV-NYSGGRTADGIVSWIK 135

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  34 SAAPVVVAAGLRRAAAPSRRGATLRVQAKKQTFSSFDE----LLEKSEKPVLVDFYATWCGPCQYM---VPILQEVSEKL 106
Cdd:COG4232   273 GLALLLGALSGADPLQPLAAGAAAAAAAAGLAWQADLEaalaEARAEGKPVFVDFTADWCVTCKENertVFSDPEVQAAL 352

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1002225466 107 GDKIQVVKID----TEKYTSIANRYQIEALPTFIIF-KNGKPCHRFEGALPANQLIQQIESALE 165
Cdd:COG4232   353 ADDVVLLKADvtdnDPEITALLKRFGRFGVPTYVFYdPDGEELPRLGFMLTADEFLAALEKAKG 416

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1002225466  67 SSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQV--VKIDTEKYTSIANRYQIEALPTFIIFKNGKP 143
Cdd:cd03002     8 KNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVQVaaVDCDEDKNKPLCGKYGVQGFPTLKVFRPPKK 86

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 1002225466  67 SSFDELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGD---KIQVVKIDtekytSIAN---RYQIEALPTFIIFKN 140
Cdd:TIGR01130 354 KNFDEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDaesDVVIAKMD-----ATANdvpPFEVEGFPTIKFVPA 428

                  ..
gi 1002225466 141 GK 142
Cdd:TIGR01130 429 GK 430

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  74 EKSEKPVLVDFYATWCGPCQYMVPIL---QEVSEKLGDKIQVVKI-------------DTEKYTSIANRYQIEALPTFII 137
Cdd:pfam13098   1 KGNGKPVLVVFTDPDCPYCKKLKKELledPDVTVYLGPNFVFIAVniwcakevakaftDILENKELGRKYGVRGTPTIVF 80

                          90       100
                  ....*....|....*....|...
gi 1002225466 138 FKNGKPCHRFEGALPANQLIQQI 160
Cdd:pfam13098  81 FDGKGELLRLPGYVPAEEFLALL 103

TlpA-like family, suppressor for copper sensitivity D protein (ScsD) and actinobacterial DsbE homolog subfamily; composed of ScsD, the DsbE homolog of Mycobacterium tuberculosis (MtbDsbE) and similar proteins, all containing a redox-active CXXC motif. The Salmonella typhimurium ScsD is a thioredoxin-like protein which confers copper tolerance to copper-sensitive mutants of E. coli. MtbDsbE has been characterized as an oxidase in vitro, catalyzing the disulfide bond formation of substrates like hirudin. The reduced form of MtbDsbE is more stable than its oxidized form, consistent with an oxidase function. This is in contrast to the function of DsbE from gram-negative bacteria which is a specific reductase of apocytochrome c.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  68 SFDeLLEKSEKPVLVDFYATWCGPCQYMVPILQEVSeklgDKIQVVKI--------------DTEKYT---------SIA 124
Cdd:cd03011    12 QFD-LESLSGKPVLVYFWATWCPVCRFTSPTVNQLA----ADYPVVSValrsgddgavarfmQKKGYGfpvindpdgVIS 86

                          90
                  ....*....|....*...
gi 1002225466 125 NRYQIEALPTFIIFKNGK 142
Cdd:cd03011    87 ARWGVSVTPAIVIVDPGG 104

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  64 QTFSSFDELLE--KSEKPVLVDFYATWCGPCQYMVPILQEVSEK-LGDKiqVVKIDTEKYTSIANRYQIEALPTFIIFKN 140
Cdd:cd02989     7 REVSDEKEFFEivKSSERVVCHFYHPEFFRCKIMDKHLEILAKKhLETK--FIKVNAEKAPFLVEKLNIKVLPTVILFKN 84

                  ....*....
gi 1002225466 141 GKPCHRFEG 149
Cdd:cd02989    85 GKTVDRIVG 93

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1002225466  81 LVDFYATWCGPCQYMVPILQEVSeKLGDKIQVVKIDTEKYTSIAN---RYQIEALPTFIIFKNGKP 143
Cdd:cd01659     1 LVLFYAPWCPFCQALRPVLAELA-LLNKGVKFEAVDVDEDPALEKelkRYGVGGVPTLVVFGPGIG 65

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  68 SFDELLEKS-EKPVLVDFYATWCGPCQYMVPILQEVSEKLGDKI--QVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPC 144
Cdd:cd02985     5 ELDEALKKAkGRLVVLEFALKHSGPSVKIYPTMVKLSRTCNDVVflLVNGDENDSTMELCRREKIIEVPHFLFYKDGEKI 84

                          90
                  ....*....|....*.
gi 1002225466 145 HRFEGALPaNQLIQQI 160
Cdd:cd02985    85 HEEEGIGP-DELIGDV 99

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1002225466  74 EKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDkIQVVKIDTEKyTSIANRYQIEALPTFIIFKNGKPCHRF 147
Cdd:cd02957    21 ASKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPE-TKFVKINAEK-AFLVNYLDIKVLPTLLVYKNGELIDNI 92

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 1002225466  73 LEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKL-GDKIQVVKIDTEKYTSIANR--YQIEALPTFIIF-KNGKPCHRFE 148
Cdd:cd02993    17 GERRNQSTLVVLYAPWCPFCQAMEASYEELAEKLaGSNVKVAKFNADGEQREFAKeeLQLKSFPTILFFpKNSRQPIKYP 96

                  .
gi 1002225466 149 G 149
Cdd:cd02993    97 S 97

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 1002225466  65 TFSSF-DELLEKS-EKPVLVDFYATWCGPCQYMVP----ILQEVsEKLGDKIQVVKIDTEKytSIANRYQIEALPTFIIF 138
Cdd:cd02963    10 TFSQYeNEIVPKSfKKPYLIKITSDWCFSCIHIEPvwkeVIQEL-EPLGVGIATVNAGHER--RLARKLGAHSVPAIVGI 86

                  ....
gi 1002225466 139 KNGK 142
Cdd:cd02963    87 INGQ 90

5'-adenylylsulfate reductase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1002225466  73 LEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKL-GDKIQVVKI--DTEKYTSIANRYQIEALPTFIIFKNGKP 143
Cdd:PLN02309  361 LENRKEPWLVVLYAPWCPFCQAMEASYEELAEKLaGSGVKVAKFraDGDQKEFAKQELQLGSFPTILLFPKNSS 434

thiol-disulfide oxidoreductase ResA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  71 ELLEKSEKPVLVDFYATWCGPCQYMVPILQEVSEKLGDK-IQVVKIDT----------------------EKYTSIANRY 127
Cdd:PRK03147   55 ELKDLKGKGVFLNFWGTWCKPCEKEMPYMNELYPKYKEKgVEIIAVNVdetelavknfvnrygltfpvaiDKGRQVIDAY 134

                          90
                  ....*....|....*.
gi 1002225466 128 QIEALP-TFIIFKNGK 142
Cdd:PRK03147  135 GVGPLPtTFLIDKDGK 150

Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO)-like family, N-terminal TRX-fold subdomain; composed of proteins with similarity to PfPDO, a redox active thermostable protein believed to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI), which are both involved in oxidative protein folding. PfPDO contains two redox active CXXC motifs in two contiguous TRX-fold subdomains. The active site in the N-terminal TRX-fold subdomain is required for isomerase but not for reductase activity of PfPDO. The exclusive presence of PfPDO-like proteins in extremophiles may suggest that they have a special role in adaptation to extreme conditions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002225466  70 DELLEKSEKPVLVDFY--ATWCGPCQYMVPILQEVSEkLGDKIQVVKIDTEKYTSIANRYQIEALPTFIIFKNGKPCH-- 145
Cdd:cd02975    13 EEFFKEMKNPVDLVVFssKEGCQYCEVTKQLLEELSE-LSDKLKLEIYDFDEDKEKAEKYGVERVPTTIFLQDGGKDGgi 91

                          90       100
                  ....*....|....*....|
gi 1002225466 146 RFEGaLPANQ----LIQQIE 161
Cdd:cd02975    92 RYYG-LPAGYefasLIEDIV 110

thioredoxin-like protein

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1002225466  84 FYATWCGPCQYMVPILQEVSEKLgdkiqvVKIDTEKYTSIANRYQIEALPTFIifkNGKPCHRFEGaLPAN 154
Cdd:PHA02125    5 FGAEWCANCKMVKPMLANVEYTY------VDVDTDEGVELTAKHHIRSLPTLV---NTSTLDRFTG-VPRN 65

Thioredoxin;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1002225466  69 FDELLEKSEKP--VLVdFYATWCGPCQYMVPILQEVSEkLGDKIQVVKIDTEKYTSIANRYQIE---ALPTFIIF 138
Cdd:pfam14595  32 LIEKIKSIEKPlrILV-ITEDWCGDAAQNVPVLAKIAE-LNPNIELRILLRDENLELMDQYLTGggrAIPTFIFL 104

Tryparedoxin (TryX)-like family, TryX and nucleoredoxin (NRX) subfamily; TryX and NRX are thioredoxin (TRX)-like protein disulfide oxidoreductases that alter the redox state of target proteins via the reversible oxidation of an active center CXXC motif. TryX is involved in the regulation of oxidative stress in parasitic trypanosomatids by reducing TryX peroxidase, which in turn catalyzes the reduction of hydrogen peroxide and organic hydroperoxides. TryX derives reducing equivalents from reduced trypanothione, a polyamine peptide conjugate unique to trypanosomatids, which is regenerated by the NADPH-dependent flavoprotein trypanothione reductase. Vertebrate NRX is a 400-amino acid nuclear protein with one redox active TRX domain containing a CPPC active site motif followed by one redox inactive TRX-like domain. Mouse NRX transcripts are expressed in all adult tissues but is restricted to the nervous system and limb buds in embryos. Plant NRX, longer than the vertebrate NRX by about 100-200 amino acids, is a nuclear protein containing a redox inactive TRX-like domain between two redox active TRX domains. Both vertebrate and plant NRXs show thiol oxidoreductase activity in vitro. Their localization in the nucleus suggests a role in the redox regulation of nuclear proteins such as transcription factors.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 1002225466  78 KPVLVDFYATWCGPCQYMVPILQEVSEKLGDKIQ 111
Cdd:cd03009    19 KTVGLYFSASWCPPCRAFTPKLVEFYEKLKESGK 52