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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313210 109 DIRMGLLYLTLCIVFLMTCKPPLYMGPEYIKYFNDKTIDEELERDKRVTWIVEFFANWSNDCQSFAPIYADLSLKYNCSG 188
Cdd:cd02962   1 DIRLGLLYLLLCIVVYLLAPQPLYMGPEHIKYFTPKTLEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNNN 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 21313210 189 LNFGKVDVGRYTDVSTRYKVSTSPLTRQLPTLILFQGGKEVIRRP-QIDKKGRAVSWTFSEENVIREFNLNE 259
Cdd:cd02962  81 LKFGKIDIGRFPNVAEKFRVSTSPLSKQLPTIILFQGGKEVARRPyYNDSKGRAVPFTFSKENVIRHFDLDR 152

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313210 109 DIRMGLLYLTLCIVFLMTCKPPLYMGPEYIKYFNDKTIDEELERDKRVTWIVEFFANWSNDCQSFAPIYADLSLKYNCSG 188
Cdd:cd02962   1 DIRLGLLYLLLCIVVYLLAPQPLYMGPEHIKYFTPKTLEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNNN 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 21313210 189 LNFGKVDVGRYTDVSTRYKVSTSPLTRQLPTLILFQGGKEVIRRP-QIDKKGRAVSWTFSEENVIREFNLNE 259
Cdd:cd02962  81 LKFGKIDIGRFPNVAEKFRVSTSPLSKQLPTIILFQGGKEVARRPyYNDSKGRAVPFTFSKENVIRHFDLDR 152

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 21313210 137 YIKYFNDKTIDEE-LERDKRVtwIVEFFANWSNDCQSFAPIYADLSLKYNcSGLNFGKVDVGRYTDVSTRYKVstspltR 215
Cdd:COG3118   1 AVVELTDENFEEEvLESDKPV--LVDFWAPWCGPCKMLAPVLEELAAEYG-GKVKFVKVDVDENPELAAQFGV------R 71

                        90
                ....*....|....*.
gi 21313210 216 QLPTLILFQGGKEVIR 231
Cdd:COG3118  72 SIPTLLLFKDGQPVDR 87

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 21313210   138 IKYFNDKTIDEEL-ERDKRVtwIVEFFANWSNDCQSFAPIYADLSLKYNcSGLNFGKVDVGRYTDVSTRYKVstspltRQ 216
Cdd:pfam00085   2 VVVLTDANFDEVVqKSSKPV--LVDFYAPWCGPCKMLAPEYEELAQEYK-GNVVFAKVDVDENPDLASKYGV------RG 72

                          90
                  ....*....|....
gi 21313210   217 LPTLILFQGGKEVI 230
Cdd:pfam00085  73 YPTLIFFKNGQPVD 86

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313210 109 DIRMGLLYLTLCIVFLMTCKPPLYMGPEYIKYFNDKTIDEELERDKRVTWIVEFFANWSNDCQSFAPIYADLSLKYNCSG 188
Cdd:cd02962   1 DIRLGLLYLLLCIVVYLLAPQPLYMGPEHIKYFTPKTLEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNNN 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 21313210 189 LNFGKVDVGRYTDVSTRYKVSTSPLTRQLPTLILFQGGKEVIRRP-QIDKKGRAVSWTFSEENVIREFNLNE 259
Cdd:cd02962  81 LKFGKIDIGRFPNVAEKFRVSTSPLSKQLPTIILFQGGKEVARRPyYNDSKGRAVPFTFSKENVIRHFDLDR 152

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 21313210 137 YIKYFNDKTIDEE-LERDKRVtwIVEFFANWSNDCQSFAPIYADLSLKYNcSGLNFGKVDVGRYTDVSTRYKVstspltR 215
Cdd:COG3118   1 AVVELTDENFEEEvLESDKPV--LVDFWAPWCGPCKMLAPVLEELAAEYG-GKVKFVKVDVDENPELAAQFGV------R 71

                        90
                ....*....|....*.
gi 21313210 216 QLPTLILFQGGKEVIR 231
Cdd:COG3118  72 SIPTLLLFKDGQPVDR 87

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 21313210 144 KTIDEELERDKRVtwIVEFFANWSNDCQSFAPIYADLSLKYNcsGLNFGKVDVGRYTDVSTRYKVstspltRQLPTLILF 223
Cdd:cd02947   1 EEFEELIKSAKPV--VVDFWAPWCGPCKAIAPVLEELAEEYP--KVKFVKVDVDENPELAEEYGV------RSIPTFLFF 70

                ....*...
gi 21313210 224 QGGKEVIR 231
Cdd:cd02947  71 KNGKEVDR 78

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313210  127 CKPPLYMGpEYIKYFNDkTIDEELERDKRVtwIVEFFANWSNDCQSFAPIYADLSLKYNcSGLNFGKVDVGRYTDVSTRY 206
Cdd:PRK10996  28 CGHDLFDG-EVINATGE-TLDKLLQDDLPV--VIDFWAPWCGPCRNFAPIFEDVAAERS-GKVRFVKVNTEAERELSARF 102

                         90       100
                 ....*....|....*....|...
gi 21313210  207 KVstspltRQLPTLILFQGGKEV 229
Cdd:PRK10996 103 RI------RSIPTIMIFKNGQVV 119

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21313210 160 VEFFANWSNDCQSFAPIYADLSLKYNC--SGLNFGKVDVGRYTDVSTRYKVstspltRQLPTLILFQGGKEVI 230
Cdd:cd03005  21 VKFFAPWCGHCKRLAPTWEQLAKKFNNenPSVKIAKVDCTQHRELCSEFQV------RGYPTLLLFKDGEKVD 87

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 21313210 142 NDKTIDEELERDKRVTwIVEFFANWSNDCQSFAPIYADLSLKY-NCSGLNFGKVDV-GRYTDVSTRYKVSTspltrqLPT 219
Cdd:cd02998   6 TDSNFDKVVGDDKKDV-LVEFYAPWCGHCKNLAPEYEKLAAVFaNEDDVVIAKVDAdEANKDLAKKYGVSG------FPT 78

                        90       100
                ....*....|....*....|...
gi 21313210 220 LILFQGGKeviRRPQIDKKGRAV 242
Cdd:cd02998  79 LKFFPKGS---TEPVKYEGGRDL 98

PDIa family, C-terminal ERdj5 subfamily; ERdj5, also known as JPDI and macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox active TRX domains. This subfamily is composed of the three TRX domains located at the C-terminal half of the protein. ERdj5 is a ubiquitous protein localized in the endoplasmic reticulum (ER) and is abundant in secretory cells. It's transcription is induced during ER stress. It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation. Also included in the alignment is the single complete TRX domain of an uncharacterized protein from Tetraodon nigroviridis, which also contains a DnaJ domain at its N-terminus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313210 148 EELERDKRVTWIVEFFANWSNDCQSFAPIYADLSLKYNcSGLNFGKVDVGRYTDVSTRYKVstspltRQLPTLILFQGGK 227
Cdd:cd03004  12 PELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALK-GKVKVGSVDCQKYESLCQQANI------RAYPTIRLYPGNA 84

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 21313210 142 NDKTIDEELERDKRVtWIVEFFANWSNDCQSFAPIY--ADLSLKyncsglnfGKVDVG-----RYTDVSTRYKVstsplt 214
Cdd:cd03001   6 TDSNFDKKVLNSDDV-WLVEFYAPWCGHCKNLAPEWkkAAKALK--------GIVKVGavdadVHQSLAQQYGV------ 70

                        90
                ....*....|....
gi 21313210 215 RQLPTLILFQGGKE 228
Cdd:cd03001  71 RGFPTIKVFGAGKN 84

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 21313210 139 KYFNDKTIDEelerDKRVtwIVEFFANWSNDCQSFAPIYADLSLKY-NCSGLNFGKVDVgrytdvsTRYKVSTSPLTRQL 217
Cdd:cd02995   8 KNFDEVVLDS----DKDV--LVEFYAPWCGHCKALAPIYEELAEKLkGDDNVVIAKMDA-------TANDVPSEFVVDGF 74

                        90
                ....*....|
gi 21313210 218 PTLILFQGGK 227
Cdd:cd02995  75 PTILFFPAGD 84

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21313210  138 IKYFNDKTIDEELERDKRVTwIVEFFANWSNDCQSFAPIYADLSLKYNcSGLNFGKVDVGRYTDVSTRYKVstspltRQL 217
Cdd:PRK09381   5 IIHLTDDSFDTDVLKADGAI-LVDFWAEWCGPCKMIAPILDEIADEYQ-GKLTVAKLNIDQNPGTAPKYGI------RGI 76

                         90
                 ....*....|
gi 21313210  218 PTLILFQGGK 227
Cdd:PRK09381  77 PTLLLFKNGE 86

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 21313210 146 IDEELERDKRVTWIVEFFANWSNDCQSFAPIYADLSLKYNCSGLnFGKVDVGRYTDVSTRYKVstspltRQLPTLILFQG 225
Cdd:cd02956   3 FQQVLQESTQVPVVVDFWAPRSPPSKELLPLLERLAEEYQGQFV-LAKVNCDAQPQIAQQFGV------QALPTVYLFAA 75

                ....
gi 21313210 226 GKEV 229
Cdd:cd02956  76 GQPV 79

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21313210 159 IVEFFANWSNDCQSFAPIYADLSLKYNCSgLNFG--KVDVGRYTDVSTRYKVSTSP 212
Cdd:cd02950  24 LVEFYADWCTVCQEMAPDVAKLKQKYGDQ-VNFVmlNVDNPKWLPEIDRYRVDGIP 78

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 21313210 142 NDKTIDEELERDKRVTwIVEFFANWSNDCQSFAPIYAdlSLKYNCSGL-NFGKV--DVGRYTDVSTRYKVSTspltrqLP 218
Cdd:cd03002   6 TPKNFDKVVHNTNYTT-LVEFYAPWCGHCKNLKPEYA--KAAKELDGLvQVAAVdcDEDKNKPLCGKYGVQG------FP 76

                        90       100
                ....*....|....*....|.
gi 21313210 219 TLILFQGGKEVIRRPQIDKKG 239
Cdd:cd03002  77 TLKVFRPPKKASKHAVEDYNG 97