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 489495247   8 ATIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFK 87
Cdd:COG3118    1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFK 80

                         90       100
                 ....*....|....*....|....*
gi 489495247  88 DGQPVKRIVGAKGKAALLRELSDVV 112
Cdd:COG3118   81 DGQPVDRFVGALPKEQLREFLDKVL 105

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247   8 ATIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFK 87
Cdd:COG3118    1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFK 80

                         90       100
                 ....*....|....*....|....*
gi 489495247  88 DGQPVKRIVGAKGKAALLRELSDVV 112
Cdd:COG3118   81 DGQPVDRFVGALPKEQLREFLDKVL 105

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 489495247    9 TIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKD 88
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|..
gi 489495247   89 GQPVKRIVGAKGKAALLRELSD 110
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLKA 103

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247  10 IKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDG 89
Cdd:PRK09381   6 IHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNG 85

                         90
                 ....*....|....*
gi 489495247  90 QPVKRIVGAKGKAAL 104
Cdd:PRK09381  86 EVAATKVGALSKGQL 100

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 489495247   8 ATIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFK 87
Cdd:COG3118    1 AVVELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFK 80

                         90       100
                 ....*....|....*....|....*
gi 489495247  88 DGQPVKRIVGAKGKAALLRELSDVV 112
Cdd:COG3118   81 DGQPVDRFVGALPKEQLREFLDKVL 105

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 489495247    9 TIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKD 88
Cdd:pfam00085   2 VVVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKN 81

                          90       100
                  ....*....|....*....|..
gi 489495247   89 GQPVKRIVGAKGKAALLRELSD 110
Cdd:pfam00085  82 GQPVDDYVGARPKDALAAFLKA 103

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247  10 IKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDG 89
Cdd:PRK09381   6 IHLTDDSFDTDVLKADGAILVDFWAEWCGPCKMIAPILDEIADEYQGKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNG 85

                         90
                 ....*....|....*
gi 489495247  90 QPVKRIVGAKGKAAL 104
Cdd:PRK09381  86 EVAATKVGALSKGQL 100

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 489495247  15 ASFATDVLSS-NKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDGQPVK 93
Cdd:cd02956    1 QNFQQVLQEStQVPVVVDFWAPRSPPSKELLPLLERLAEEYQGQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVD 80

                         90
                 ....*....|.
gi 489495247  94 RIVGAKGKAAL 104
Cdd:cd02956   81 GFQGAQPEEQL 91

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 489495247  10 IKVTDASFaTDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATE--RATDLTVAKLDVDTNPETARNFQVVSIPTLILFK 87
Cdd:cd02961    1 VELTDDNF-DELVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKElkGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFP 79

                 ..
gi 489495247  88 DG 89
Cdd:cd02961   80 NG 81

TRX domain, PICOT (for PKC-interacting cousin of TRX) subfamily; PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT contains an N-terminal TRX-like domain, which does not contain the catalytic CXXC motif, followed by one to three glutaredoxin domains. The TRX-like domain is required for interaction with PKC theta. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 489495247  23 SSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDGQPVKRIVGA 98
Cdd:cd02984   12 DASKLLVLHFWAPWAEPCKQMNQVFEELAKEAFPSVLFLSIEAEELPEISEKFEITAVPTFVFFRNGTIVDRVSGA 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 489495247  12 VTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIAT--ERATDLTVAKLDVDT-NPETARNFQVVSIPTLILF-- 86
Cdd:cd02998    5 LTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAvfANEDDVVIAKVDADEaNKDLAKKYGVSGFPTLKFFpk 84

                 ....*..
gi 489495247  87 KDGQPVK 93
Cdd:cd02998   85 GSTEPVK 91

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 489495247  11 KVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERAT--DLTVAKLDVDTNpETARNFQVVSIPTLILFKD 88
Cdd:cd02995    4 VVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGddNVVIAKMDATAN-DVPSEFVVDGFPTILFFPA 82

                 ....*...
gi 489495247  89 G---QPVK 93
Cdd:cd02995   83 GdksNPIK 90

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 489495247    7 SATIKVTDASFAtDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIAT---ERATDLTVAKLDVDTNPETARNFQVVSIPTL 83
Cdd:TIGR01130   1 EDVLVLTKDNFD-DFIKSHEFVLVEFYAPWCGHCKSLAPEYEKAADelkKKGPPIKLAKVDATEEKDLAQKYGVSGYPTL 79

                  ....*...
gi 489495247   84 ILFKDGQP 91
Cdd:TIGR01130  80 KIFRNGED 87

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 489495247   7 SATIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILF 86
Cdd:cd03004    1 PSVITLTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALKGKVKVGSVDCQKYESLCQQANIRAYPTIRLY 80

                 ....
gi 489495247  87 KDGQ 90
Cdd:cd03004   81 PGNA 84

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247   5 EKSATIKVTDASFATDVLSSNK----PVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSI 80
Cdd:PTZ00443  28 DANALVLLNDKNFEKLTQASTGattgPWFVKFYAPWCSHCRKMAPAWERLAKALKGQVNVADLDATRALNLAKRFAIKGY 107

                         90
                 ....*....|
gi 489495247  81 PTLILFKDGQ 90
Cdd:PTZ00443 108 PTLLLFDKGK 117

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 489495247  22 LSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTN---PETaRNFQVVSIPTLILF-KDGQPVKRIVG 97
Cdd:cd02950   17 LSNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDQVNFVMLNVDNPkwlPEI-DRYRVDGIPHFVFLdREGNEEGQSIG 95

                         90       100
                 ....*....|....*....|....
gi 489495247  98 AKGK---AALLRELSD--VVPNLN 116
Cdd:cd02950   96 LQPKqvlAQNLDALVAgePLPYAN 119

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247  22 LSSNKPVLVDFWATWCGPCK-MVAPVL--EEIATERATDLTVAKLDV-DTNPETAR---NFQVVSIPTLILF-KDGQPVK 93
Cdd:COG4232  317 RAEGKPVFVDFTADWCVTCKeNERTVFsdPEVQAALADDVVLLKADVtDNDPEITAllkRFGRFGVPTYVFYdPDGEELP 396

                         90       100
                 ....*....|....*....|
gi 489495247  94 RIVGAKGKAALLRELSDVVP 113
Cdd:COG4232  397 RLGFMLTADEFLAALEKAKG 416

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 489495247  20 DVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATE------RATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDGQPVK 93
Cdd:cd02996   13 DILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKikeefpDAGKVVWGKVDCDKESDIADRYRINKYPTLKLFRNGMMMK 92

                 .
gi 489495247  94 R 94
Cdd:cd02996   93 R 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 489495247  29 LVDFWATWCGPCKMVAPVLEEIAtERATDLTVAKLDVDTNP---ETARNFQVVSIPTLILFKDGQPVK 93
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELA-LLNKGVKFEAVDVDEDPaleKELKRYGVGGVPTLVVFGPGIGVK 67

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 489495247  12 VTDASFaTDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPE----TARNFQVVSIPTLILFK 87
Cdd:cd02997    5 LTDEDF-RKFLKKEKHVLVMFYAPWCGHCKKMKPEFTKAATELKEDGKGVLAAVDCTKPehdaLKEEYNVKGFPTFKYFE 83

                         90
                 ....*....|....*...
gi 489495247  88 DGQPVKRIVGAKGKAALL 105
Cdd:cd02997   84 NGKFVEKYEGERTAEDII 101

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247  25 NKPVLVDFWATWCGPC-KMVAPVL--EEIATERATDLTVAKLDVD-------------TNPETARNFQVVSIPTLILF-K 87
Cdd:COG2143   40 GKPILLFFESDWCPYCkKLHKEVFsdPEVAAYLKENFVVVQLDAEgdkevtdfdgetlTEKELARKYGVRGTPTLVFFdA 119

                         90       100
                 ....*....|....*....|....*
gi 489495247  88 DGQPVKRIVGAKGKAALLRELSDVV 112
Cdd:COG2143  120 EGKEIARIPGYLKPETFLALLKYVA 144

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247   23 SSNKPVLVDFWATWCGPCKMVAPVLEEIA--TER--------------ATDLTVAKLDVDTNPETARNFQVVSIPTLILF 86
Cdd:pfam13098   2 GNGKPVLVVFTDPDCPYCKKLKKELLEDPdvTVYlgpnfvfiavniwcAKEVAKAFTDILENKELGRKYGVRGTPTIVFF 81

                          90       100
                  ....*....|....*....|...
gi 489495247   87 kDGQ-PVKRIVGAKGKAALLREL 108
Cdd:pfam13098  82 -DGKgELLRLPGYVPAEEFLALL 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 489495247   6 KSATIKVTDASFATDVLSSnKPVLVDFWATWCGPCKMVAPVLEEIATERATdLTVAKLD--------------------V 65
Cdd:cd03011    2 LFTATTLDGEQFDLESLSG-KPVLVYFWATWCPVCRFTSPTVNQLAADYPV-VSVALRSgddgavarfmqkkgygfpviN 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 489495247  66 DTNPETARNFQVVSIPTLILFKDGQPVKRIVG 97
Cdd:cd03011   80 DPDGVISARWGVSVTPAIVIVDPGGIVFVTTG 111

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 489495247  12 VTDASFAtdvlssNKPVLVDFWATWCGPCKMVAPVLEEIAteRATDLTVAKLDVDTNPETARNF 75
Cdd:cd03010   18 LTSADLK------GKPYLLNVWASWCAPCREEHPVLMALA--RQGRVPIYGINYKDNPENALAW 73

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247  10 IKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIAT-----ERAtdLTVAKLDV--DTNPETARNFQVVSIPT 82
Cdd:cd02992    4 IVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARdlrkwRPV--VRVAAVDCadEENVALCRDFGVTGYPT 81

                 ....*
gi 489495247  83 LILFK 87
Cdd:cd02992   82 LRYFP 86

bifunctional peptide-methionine (S)-S-oxide reductase MsrA/peptide-methionine (R)-S-oxide reductase MsrB;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247   9 TIKVTDASFATDVLSSNKPVLVDFWATWCGPCKMVAPVLEEIATERATD----LTVA----------------------- 61
Cdd:PRK14018  40 TLKTADNRPASVYLKKDKPTLIKFWASWCPLCLSELGETEKWAQDAKFSsanlITVAspgflhekkdgdfqkwyagldyp 119

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 489495247  62 KLDV--DTNPETARNFQVVSIPT-LILFKDGQPVKRIVG--AKGKAALLRE 107
Cdd:PRK14018 120 KLPVltDNGGTLAQSLNISVYPSwAIIGKDGDVQRIVKGsiSEAQALALIR 170

thiol:disulfide interchange protein precursor; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489495247  26 KPVLVDFWATWCGPCK----------MVAPVLEEIATERAtDLTvakldvDTNPETA---RNFQVVSIPTLILF-KDGQP 91
Cdd:PRK00293 475 KPVMLDLYADWCVACKefekytfsdpQVQQALADTVLLQA-DVT------ANNAEDVallKHYNVLGLPTILFFdAQGQE 547

                         90       100
                 ....*....|....*....|....
gi 489495247  92 VK--RIVGAKGKAALLRELSDVVP 113
Cdd:PRK00293 548 IPdaRVTGFMDAAAFAAHLRQLQP 571

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 489495247  39 PCKMVAPVLEEIAtERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDGQPVKRIVG 97
Cdd:cd02989   36 RCKIMDKHLEILA-KKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTVDRIVG 93

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 489495247  24 SNKPVLVDFWATWCGPCKMVAPVLEEIATERA-TDLTVAKLDVD-TNPETAR-NFQVVSIPTLILFKDG--QPVK 93
Cdd:cd02993   20 RNQSTLVVLYAPWCPFCQAMEASYEELAEKLAgSNVKVAKFNADgEQREFAKeELQLKSFPTILFFPKNsrQPIK 94

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 489495247  25 NKPVLVDFWATWCGPCKMVAPVLEEIAteRATDLTVAKL----DVDTNPETARNFQVVSIPTLILFKDGQPVKRIVGAkG 100
Cdd:cd02985   15 GRLVVLEFALKHSGPSVKIYPTMVKLS--RTCNDVVFLLvngdENDSTMELCRREKIIEVPHFLFYKDGEKIHEEEGI-G 91

                 ....*...
gi 489495247 101 KAALLREL 108
Cdd:cd02985   92 PDELIGDV 99

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 489495247  12 VTDASFATDVL--SSNKPVLVDFWATWCGPCKMVAPVLEEIATE-RATDLTVAKLDVDTNPETARNFQVVSIPTLILFKD 88
Cdd:cd02963    9 LTFSQYENEIVpkSFKKPYLIKITSDWCFSCIHIEPVWKEVIQElEPLGVGIATVNAGHERRLARKLGAHSVPAIVGIIN 88

                 ..
gi 489495247  89 GQ 90
Cdd:cd02963   89 GQ 90

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 489495247  25 NKPVLVDFWATWCGPCKMVAPVL----EEIATERA--------TD----------------LTVAKLDVDTNPETARNFQ 76
Cdd:cd02964   17 GKTVGLYFSASWCPPCRAFTPKLvefyEKLKEEGKnfeivfvsRDrseesfneyfsemppwLAVPFEDEELRELLEKQFK 96

                         90
                 ....*....|....*....
gi 489495247  77 VVSIPTLILFK-DGQPVKR 94
Cdd:cd02964   97 VEGIPTLVVLKpDGDVVTT 115

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 489495247  29 LVDFWATWCGPCKMVAPVLEEIATERATDLTVAKLDVDTNPETARNFQVVSIPTLILFKDG-QPVK 93
Cdd:cd03003   22 FVNFYSPRCSHCHDLAPTWREFAKEMDGVIRIGAVNCGDDRMLCRSQGVNSYPSLYVFPSGmNPEK 87