thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931   1 MNTVCANCQALNRIPDDRMEDGAKCGRCGHELFDGDVINATGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE 80
Cdd:PRK10996   1 MNTVCTSCQAINRLPDERIEDAAKCGRCGHDLFDGEVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 556423931  81 RSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEVIDMLNGAVPKAPFESWLNESL 139
Cdd:PRK10996  81 RSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931   1 MNTVCANCQALNRIPDDRMEDGAKCGRCGHELFDGDVINATGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE 80
Cdd:PRK10996   1 MNTVCTSCQAINRLPDERIEDAAKCGRCGHDLFDGEVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 556423931  81 RSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEVIDMLNGAVPKAPFESWLNESL 139
Cdd:PRK10996  81 RSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

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 556423931   40 ATGATLDKLLKD-DLPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEV 118
Cdd:TIGR01068   1 LTDANFDETIASsDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 556423931  119 IDMLNGAVPKAPFESWLNESL 139
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 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 556423931   37 VINATGATLDK-LLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKN 115
Cdd:pfam00085   2 VVVLTDANFDEvVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|..
gi 556423931  116 GEVIDMLNGAVPKAPFESWLNE 137
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLKA 103

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931   1 MNTVCANCQALNRIPDDRMEDGAKCGRCGHELFDGDVINATGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE 80
Cdd:PRK10996   1 MNTVCTSCQAINRLPDERIEDAAKCGRCGHDLFDGEVINATGETLDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 556423931  81 RSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEVIDMLNGAVPKAPFESWLNESL 139
Cdd:PRK10996  81 RSGKVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGAVPKAPFDSWLNEAL 139

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 556423931   40 ATGATLDKLLKD-DLPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEV 118
Cdd:TIGR01068   1 LTDANFDETIASsDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 556423931  119 IDMLNGAVPKAPFESWLNESL 139
Cdd:TIGR01068  81 VDRSVGALPKAALKQLINKNL 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 556423931   37 VINATGATLDK-LLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKN 115
Cdd:pfam00085   2 VVVLTDANFDEvVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|..
gi 556423931  116 GEVIDMLNGAVPKAPFESWLNE 137
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLKA 103

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  33 FDGDVINATGATLdkllkddlpvvIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMI 112
Cdd:PRK09381  13 FDTDVLKADGAIL-----------VDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLL 81

                         90       100
                 ....*....|....*....|....*..
gi 556423931 113 FKNGEVIDMLNGAVPKAPFESWLNESL 139
Cdd:PRK09381  82 FKNGEVAATKVGALSKGQLKEFLDANL 108

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 556423931  41 TGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE--RSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGE 117
Cdd:cd02961    4 TDDNFDELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKElkGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGS 82

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 556423931  36 DVINATGATLDKL-LKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFK 114
Cdd:cd03001    1 DVVELTDSNFDKKvLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFG 80

                 ..
gi 556423931 115 NG 116
Cdd:cd03001   81 AG 82

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  31 ELFDGDVINATGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAE---ERSGKMRFVKVNTEAEPELSARFRIRSI 107
Cdd:PTZ00102  28 HFISEHVTVLTDSTFDKFITENEIVLVKFYAPWCGHCKRLAPEYKKAAKmlkEKKSEIVLASVDATEEMELAQEFGVRGY 107

                         90       100       110
                 ....*....|....*....|....*....|
gi 556423931 108 PTIMIFKNGEVIDmLNGAVPKAPFESWLNE 137
Cdd:PTZ00102 108 PTIKFFNKGNPVN-YSGGRTADGIVSWIKK 136

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 556423931  56 VIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFK 114
Cdd:cd03004   23 LVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLYP 81

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 556423931   36 DVINATGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAE---ERSGKMRFVKVNTEAEPELSARFRIRSIPTIMI 112
Cdd:TIGR01130   2 DVLVLTKDNFDDFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADelkKKGPPIKLAKVDATEEKDLAQKYGVSGYPTLKI 81

                  ....*.
gi 556423931  113 FKNGEV 118
Cdd:TIGR01130  82 FRNGED 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 556423931  36 DVINATGATLDKLLKDD-LPVVIDFWAPWCGPCRSFAPIFEDVAE--ERSGKMRFVKVN-TEAEPELSARFRIRSIPTIM 111
Cdd:cd02998    1 NVVELTDSNFDKVVGDDkKDVLVEFYAPWCGHCKNLAPEYEKLAAvfANEDDVVIAKVDaDEANKDLAKKYGVSGFPTLK 80

                 ....*
gi 556423931 112 IFKNG 116
Cdd:cd02998   81 FFPKG 85

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  40 ATGATLDkllkddlPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEVI 119
Cdd:PTZ00443  47 STGATTG-------PWFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGYPTLLLFDKGKMY 119

                 ....*
gi 556423931 120 DMLNG 124
Cdd:PTZ00443 120 QYEGG 124

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 556423931  42 GATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE--------RSG------------KMRFVKVNtEAEPELSAR 101
Cdd:cd03011   10 GEQFDLESLSGKPVLVYFWATWCPVCRFTSPTVNQLAADypvvsvalRSGddgavarfmqkkGYGFPVIN-DPDGVISAR 88

                         90       100
                 ....*....|....*....|...
gi 556423931 102 FRIRSIPTIMIFKNGEVIDMLNG 124
Cdd:cd03011   89 WGVSVTPAIVIVDPGGIVFVTTG 111

PDIa family, TMX subfamily; composed of proteins similar to the TRX-related human transmembrane protein, TMX. TMX is a type I integral membrane protein; the N-terminal redox active TRX domain is present in the endoplasmic reticulum (ER) lumen while the C-terminus is oriented towards the cytoplasm. It is expressed in many cell types and its active site motif (CPAC) is unique. In vitro, TMX reduces interchain disulfides of insulin and renatures inactive RNase containing incorrect disulfide bonds. The C. elegans homolog, DPY-11, is expressed only in the hypodermis and resides in the cytoplasm. It is required for body and sensory organ morphogeneis. Another uncharacterized TRX-related transmembrane protein, human TMX4, is included in the alignment. The active site sequence of TMX4 is CPSC.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  35 GDVINATGATLDKLLKDDLpvVIDFWAPWCGPCRSFAPIFEDVAEE-RSGKMRFVKVNTEAEPELSARFRIRSIPTIMIF 113
Cdd:cd02994    1 SNVVELTDSNWTLVLEGEW--MIEFYAPWCPACQQLQPEWEEFADWsDDLGINVAKVDVTQEPGLSGRFFVTALPTIYHA 78

                 ....
gi 556423931 114 KNGE 117
Cdd:cd02994   79 KDGV 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 556423931  35 GDVINATGATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE------RSGKMRFVKVNTEAEPELSARFRIRSIP 108
Cdd:cd02996    1 SEIVSLTSGNIDDILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKikeefpDAGKVVWGKVDCDKESDIADRYRINKYP 80

                         90
                 ....*....|.
gi 556423931 109 TIMIFKNGEVI 119
Cdd:cd02996   81 TLKLFRNGMMM 91

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 556423931  56 VIDFWAPWCGPCRSFAPIFEDVAEERSGkMRFVKVNTEAEPEL---SARFRIRSIPTIMIFKNGEVIDM 121
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKG-VKFEAVDVDEDPALekeLKRYGVGGVPTLVVFGPGIGVKY 68

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 556423931   34 DGDVINATGATLDKL-LKDDLPVVIDFWAPWCGPCRSFAPIFEDVAEE-RSGKMRFV--KVN-TEAE-PElsarFRIRSI 107
Cdd:TIGR01130 345 EGPVKVLVGKNFDEIvLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKyKDAESDVViaKMDaTANDvPP----FEVEGF 420

                          90
                  ....*....|
gi 556423931  108 PTIMIFKNGE 117
Cdd:TIGR01130 421 PTIKFVPAGK 430

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  43 ATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIF---EDVAEERSGKMRFVKVN-TEAEPELSA---RFRIRSIPTIMIFKN 115
Cdd:cd02953    2 AALAQALAQGKPVFVDFTADWCVTCKVNEKVVfsdPEVQAALKKDVVLLRADwTKNDPEITAllkRFGVFGPPTYLFYGP 81

                 .
gi 556423931 116 G 116
Cdd:cd02953   82 G 82

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  50 KDDLPVVIDFWAPWCGPCR-----SFAPifEDVAEERSGKMRFVKVN-------------TEAEPELSARFRIRSIPTIM 111
Cdd:COG2143   38 AEGKPILLFFESDWCPYCKklhkeVFSD--PEVAAYLKENFVVVQLDaegdkevtdfdgeTLTEKELARKYGVRGTPTLV 115

                         90       100
                 ....*....|....*....|....*.
gi 556423931 112 IF-KNGEVIDMLNGAVPKAPFESWLN 136
Cdd:COG2143  116 FFdAEGKEIARIPGYLKPETFLALLK 141

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 556423931  35 GDVINATGATLDKLLK---DDLPVVIDFWAPWCGPCRSFAPIFEDVAEERSG-KMRFVKVNTEAEPELSAR--FRIRSIP 108
Cdd:cd02993    1 EAVVTLSRAEIEALAKgerRNQSTLVVLYAPWCPFCQAMEASYEELAEKLAGsNVKVAKFNADGEQREFAKeeLQLKSFP 80

                 ....*
gi 556423931 109 TIMIF 113
Cdd:cd02993   81 TILFF 85

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  54 PVVIDFWAPWCGPCRSFAPIFEDVAEERSGK-MRFVKVNTE---------------------AEPELSARFRIRSIPTIM 111
Cdd:COG1225   23 PVVLYFYATWCPGCTAELPELRDLYEEFKDKgVEVLGVSSDsdeahkkfaekyglpfpllsdPDGEVAKAYGVRGTPTTF 102

                         90       100       110
                 ....*....|....*....|....*....|
gi 556423931 112 IF-KNGEVIDMLNGAVPKAP-FESWLNESL 139
Cdd:COG1225  103 LIdPDGKIRYVWVGPVDPRPhLEEVLEALL 132

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  55 VVIDFWAPWCGPCRSFAPIFEDVAEeRSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNGEVIDMLNG 124
Cdd:cd02989   25 VVCHFYHPEFFRCKIMDKHLEILAK-KHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTVDRIVG 93

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 556423931   43 ATLDKLLKDDLPVVIDFWAPWCGPCRSFAPIF---EDVAEERSGKMRFVKVN-TEAEPELSARFRIRSIPTIMIF 113
Cdd:pfam13899   8 EALAAAAERGKPVLVDFGADWCFTCQVLERDFlshEEVKAALAKNFVLLRLDwTSRDANITRAFDGQGVPHIAFL 82

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  57 IDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPELSARFRIRSIPTIMIFKNG 116
Cdd:cd03003   23 VNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSG 82

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 556423931  56 VIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNT-----EAEPELSARFRIRSIPTIMIFK 114
Cdd:cd02992   23 LVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAvdcadEENVALCRDFGVTGYPTLRYFP 86

Tryparedoxin (TryX)-like family; composed of TryX and related proteins including nucleoredoxin (NRX), rod-derived cone viability factor (RdCVF) and the nematode homolog described as a 16-kD class of TRX. Most members of this family, except RdCVF, are protein disulfide oxidoreductases containing an active site CXXC motif, similar to TRX.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 556423931  55 VVIDFWAPWCGPCRSFAPI----FEDVAEERSG--------------------KMR---FVKVNTEA-EPELSARFRIRS 106
Cdd:cd02964   20 VGLYFSASWCPPCRAFTPKlvefYEKLKEEGKNfeivfvsrdrseesfneyfsEMPpwlAVPFEDEElRELLEKQFKVEG 99

                         90
                 ....*....|....
gi 556423931 107 IPTIMIFK-NGEVI 119
Cdd:cd02964  100 IPTLVVLKpDGDVV 113

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        40
                 ....*....|....*....|....*....|....*....|....*....
gi 556423931  54 PVVIDFWAPWCGPCRSFAPIFEDVAEErsGKMRFVKVNTEAEPELSARF 102
Cdd:cd03010   27 PYLLNVWASWCAPCREEHPVLMALARQ--GRVPIYGINYKDNPENALAW 73

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 556423931   37 VINATGATLDKLLKDDLP--VVIDFWAPW----CGPCRSFAPIFEDVA-------EERSGKMRFVKVNTEAEPELSARFR 103
Cdd:pfam04756  13 VIKLNDSNYKRLLSGPRDysVVVLLTALDprfgCQLCREFQPEFELVAkswfkdhKAGSSKLFFATLDFDDGKDVFQSLG 92

                          90
                  ....*....|
gi 556423931  104 IRSIPTIMIF 113
Cdd:pfam04756  93 LQTAPHLLLF 102

Intermembrane transporter PqiABC subunit PqiA [Cell wall/membrane/envelope biogenesis];

                         10        20        30
                 ....*....|....*....|....*....|.
gi 556423931   3 TVCANCQALNRIPDDRMEDGAKCGRCGHELF 33
Cdd:COG2995   14 IACPHCDLLLRRPPLPPGERARCPRCGAVLH 44

Endoplasmic reticulum protein 19 (ERp19) family; ERp19 is also known as ERp18, a protein located in the ER containing one redox active TRX domain. Denaturation studies indicate that the reduced form is more stable than the oxidized form, suggesting that the protein is involved in disulfide bond formation. In vitro, ERp19 has been shown to possess thiol-disulfide oxidase activity which is dependent on the presence of both active site cysteines. Although described as protein disulfide isomerase (PDI)-like, the protein does not complement for PDI activity. ERp19 shows a wide tissue distribution but is most abundant in liver, testis, heart and kidney.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 556423931  43 ATLDKLLKD----DLPVVIDFWAPWCGPCRSFAPIFEDVAEERSGKMRFVKVNTEAEPE 97
Cdd:cd02959    6 VTLEDGIKEakdsGKPLMLLIHKTWCGACKALKPKFAESKEISELSHNFVMVNLEDDEE 64