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 665402163 100 DFRYGLGFLLLCVLVGMVLPEPSYRGPEHITYFRNAQvFEEELARDKRTSWLICFYTVWNPSCVNFAPVFAELSAEYNTD 179
Cdd:cd02962    1 DIRLGLLYLLLCIVVYLLAPQPLYMGPEHIKYFTPKT-LEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNN 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665402163 180 HLKFGKIDIGRFPDVAQKYRISDSSFSRQLPTVILFQQGKETDRRP-CVDSKGKLQKFFFSSDNVRATFGLNQ 251
Cdd:cd02962   80 NLKFGKIDIGRFPNVAEKFRVSTSPLSKQLPTIILFQGGKEVARRPyYNDSKGRAVPFTFSKENVIRHFDLDR 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 665402163 100 DFRYGLGFLLLCVLVGMVLPEPSYRGPEHITYFRNAQvFEEELARDKRTSWLICFYTVWNPSCVNFAPVFAELSAEYNTD 179
Cdd:cd02962    1 DIRLGLLYLLLCIVVYLLAPQPLYMGPEHIKYFTPKT-LEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNN 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665402163 180 HLKFGKIDIGRFPDVAQKYRISDSSFSRQLPTVILFQQGKETDRRP-CVDSKGKLQKFFFSSDNVRATFGLNQ 251
Cdd:cd02962   80 NLKFGKIDIGRFPNVAEKFRVSTSPLSKQLPTIILFQGGKEVARRPyYNDSKGRAVPFTFSKENVIRHFDLDR 152

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 665402163  133 RNAQVFEEELARDKRTSwLICFYTVWNPSCVNFAPVFAELSAEYNTDhLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTV 212
Cdd:TIGR01068   1 LTDANFDETIASSDKPV-LVDFWAPWCGPCKMIAPILEELAKEYEGK-VKFVKLNVDENPDIAAKYGI------RSIPTL 72

                          90       100
                  ....*....|....*....|....*
gi 665402163  213 ILFQQGKETDRRPCVDSKGKLQKFF 237
Cdd:TIGR01068  73 LLFKNGKEVDRSVGALPKAALKQLI 97

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 665402163  138 FEEELARDKRTSwLICFYTVWNPSCVNFAPVFAELSAEYnTDHLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTVILFQQ 217
Cdd:pfam00085  10 FDEVVQKSSKPV-LVDFYAPWCGPCKMLAPEYEELAQEY-KGNVVFAKVDVDENPDLASKYGV------RGYPTLIFFKN 81

                  ....*
gi 665402163  218 GKETD 222
Cdd:pfam00085  82 GQPVD 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 665402163 100 DFRYGLGFLLLCVLVGMVLPEPSYRGPEHITYFRNAQvFEEELARDKRTSWLICFYTVWNPSCVNFAPVFAELSAEYNTD 179
Cdd:cd02962    1 DIRLGLLYLLLCIVVYLLAPQPLYMGPEHIKYFTPKT-LEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYNNN 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665402163 180 HLKFGKIDIGRFPDVAQKYRISDSSFSRQLPTVILFQQGKETDRRP-CVDSKGKLQKFFFSSDNVRATFGLNQ 251
Cdd:cd02962   80 NLKFGKIDIGRFPNVAEKFRVSTSPLSKQLPTIILFQGGKEVARRPyYNDSKGRAVPFTFSKENVIRHFDLDR 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 665402163 138 FEEELARDKRTSwLICFYTVWNPSCVNFAPVFAELSAEYNtDHLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTVILFQQ 217
Cdd:COG3118   10 FEEEVLESDKPV-LVDFWAPWCGPCKMLAPVLEELAAEYG-GKVKFVKVDVDENPELAAQFGV------RSIPTLLLFKD 81

                         90       100
                 ....*....|....*....|
gi 665402163 218 GKETDRRPCVDSKGKLQKFF 237
Cdd:COG3118   82 GQPVDRFVGALPKEQLREFL 101

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 665402163 134 NAQVFEEELARDKrtSWLICFYTVWNPSCVNFAPVFAELSAEYNTD-HLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTV 212
Cdd:cd02961    4 TDDNFDELVKDSK--DVLVEFYAPWCGHCKALAPEYEKLAKELKGDgKVVVAKVDCTANNDLCSEYGV------RGYPTI 75

                 ....*....
gi 665402163 213 ILFQQGKET 221
Cdd:cd02961   76 KLFPNGSKE 84

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665402163 151 LICFYTVWNPSCVNFAPVFAELSAEyNTDHLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTVILFQQGKETD 222
Cdd:PRK10996  56 VIDFWAPWCGPCRNFAPIFEDVAAE-RSGKVRFVKVNTEAERELSARFRI------RSIPTIMIFKNGQVVD 120

thioredoxin; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665402163 151 LICFYTVWNPSCVNFAPVFAELSAEYNTdhLKFGKIDIGRFPDVAQKYRISdssfsrQLPTVILFQQGKETD 222
Cdd:PTZ00051  22 IVDFYAEWCGPCKRIAPFYEECSKEYTK--MVFVKVDVDELSEVAEKENIT------SMPTFKVFKNGSVVD 85

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402163 151 LICFYTVWNPSCVNFAPVFAELSAEYNtDHLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTVILFQQGKETDRRPCVDSK 230
Cdd:PRK09381  25 LVDFWAEWCGPCKMIAPILDEIADEYQ-GKLTVAKLNIDQNPGTAPKYGI------RGIPTLLLFKNGEVAATKVGALSK 97

                 ....*..
gi 665402163 231 GKLQKFF 237
Cdd:PRK09381  98 GQLKEFL 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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402163 140 EELARDKRTSWLICFYTVWNPSCVNFAPVFAELSAEYNtDHLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTVILFQQGK 219
Cdd:cd03004   12 PELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALK-GKVKVGSVDCQKYESLCQQANI------RAYPTIRLYPGNA 84

                 ..
gi 665402163 220 ET 221
Cdd:cd03004   85 SK 86

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665402163 100 DFRYGLGFL---LLCVLVGMVLPEPSYRGPEHITYFrNAQVFEEELARDKRTswLICFYTVWNPSCVNFAPVFAELSAEY 176
Cdd:PTZ00102   2 GFRSILSSLfllLILLAFAVFGSAEEHFISEHVTVL-TDSTFDKFITENEIV--LVKFYAPWCGHCKRLAPEYKKAAKML 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 665402163 177 NTD--HLKFGKIDIGRFPDVAQKYRIsdssfsRQLPTVILFQQGKE 220
Cdd:PTZ00102  79 KEKksEIVLASVDATEEMELAQEFGV------RGYPTIKFFNKGNP 118

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665402163 151 LICFYTVWNPSCVNFAPVFAELSAEYNTDH-----LKFGKIDIGRFPDVAQKYRISdssfsrQLPTVILFQQG 218
Cdd:cd02996   22 LVNFYADWCRFSQMLHPIFEEAAAKIKEEFpdagkVVWGKVDCDKESDIADRYRIN------KYPTLKLFRNG 88

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665402163 151 LICFYTVWNPSCVNFAPVFAELSAEY-NTDHLKFGKIDigrfpdvAQKYRISDSSFSRQLPTVILFQQGKETD 222
Cdd:cd02995   22 LVEFYAPWCGHCKALAPIYEELAEKLkGDDNVVIAKMD-------ATANDVPSEFVVDGFPTILFFPAGDKSN 87

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 665402163 154 FYTVWNPSCVNFAPVFAELSAEYntDHLKFGKIDIGRFPDVAQKYRISDssfSRQLPTVILFQQG 218
Cdd:cd01659    4 FYAPWCPFCQALRPVLAELALLN--KGVKFEAVDVDEDPALEKELKRYG---VGGVPTLVVFGPG 63

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665402163 142 LARDKRTSWLICFYTVWNPSCVNFAPVFAELSAEYNTdhLKFGKIDIGR-FPDVAQKYRIsdssfsRQLPTVILFQQG 218
Cdd:cd02999   13 MAFNREDYTAVLFYASWCPFSASFRPHFNALSSMFPQ--IRHLAIEESSiKPSLLSRYGV------VGFPTILLFNST 82