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 71998175   9 DSDFDRKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSV-FLKVDVDECRGTAATYGVNAMPTFIAFVNGQKK 87
Cdd:COG3118   7 DENFEEEVLESD-KPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVkFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90
                ....*....|....*....
gi 71998175  88 ATIQGA-DESGLRSMVAKY 105
Cdd:COG3118  86 DRFVGAlPKEQLREFLDKV 104

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 71998175   9 DSDFDRKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSV-FLKVDVDECRGTAATYGVNAMPTFIAFVNGQKK 87
Cdd:COG3118   7 DENFEEEVLESD-KPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVkFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90
                ....*....|....*....
gi 71998175  88 ATIQGA-DESGLRSMVAKY 105
Cdd:COG3118  86 DRFVGAlPKEQLREFLDKV 104

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 71998175     9 DSDFDRKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSV-FLKVDVDECRGTAATYGVNAMPTFIAFVNGQKK 87
Cdd:TIGR01068   3 DANFDETIASSD-KPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVkFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90       100
                  ....*....|....*....|
gi 71998175    88 ATIQGA-DESGLRSMVAKYA 106
Cdd:TIGR01068  82 DRSVGAlPKAALKQLINKNL 101

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175    2 PVIVVNGDSDFDRKFSaGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSVFLKVDVDECRGTAATYGVNAMPTFIAF 81
Cdd:PTZ00051   1 MVHIVTSQAEFESTLS-QN-ELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVF 78

                         90       100
                 ....*....|....*....|
gi 71998175   82 VNGQKKATIQGADESGLRSM 101
Cdd:PTZ00051  79 KNGSVVDTLLGANDEALKQL 98

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 71998175   9 DSDFDRKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSV-FLKVDVDECRGTAATYGVNAMPTFIAFVNGQKK 87
Cdd:COG3118   7 DENFEEEVLESD-KPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVkFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPV 85

                        90
                ....*....|....*....
gi 71998175  88 ATIQGA-DESGLRSMVAKY 105
Cdd:COG3118  86 DRFVGAlPKEQLREFLDKV 104

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 71998175     9 DSDFDRKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSV-FLKVDVDECRGTAATYGVNAMPTFIAFVNGQKK 87
Cdd:TIGR01068   3 DANFDETIASSD-KPVLVDFWAPWCGPCKMIAPILEELAKEYEGKVkFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90       100
                  ....*....|....*....|
gi 71998175    88 ATIQGA-DESGLRSMVAKYA 106
Cdd:TIGR01068  82 DRSVGAlPKAALKQLINKNL 101

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175    2 PVIVVNGDSDFDRKFSaGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSVFLKVDVDECRGTAATYGVNAMPTFIAF 81
Cdd:PTZ00051   1 MVHIVTSQAEFESTLS-QN-ELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVF 78

                         90       100
                 ....*....|....*....|
gi 71998175   82 VNGQKKATIQGADESGLRSM 101
Cdd:PTZ00051  79 KNGSVVDTLLGANDEALKQL 98

Thiol-disulfide isomerase or thioredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175  15 KFSAGNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSVFLKVDVDE----------------------CRGTAATYGV 72
Cdd:COG0526  22 SLADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDEnpeavkaflkelglpypvlldpDGELAKAYGV 101

                        90       100       110
                ....*....|....*....|....*....|....*
gi 71998175  73 NAMPTFIAF-VNGQKKATIQGA-DESGLRSMVAKY 105
Cdd:COG0526 102 RGIPTTVLIdKDGKIVARHVGPlSPEELEEALEKL 136

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 71998175   9 DSDFDRKFSagNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS---VFLKVDVDECRGTAATYGVNAMPTFIAFVNGQ 85
Cdd:cd02961   5 DDNFDELVK--DSKDVLVEFYAPWCGHCKALAPEYEKLAKELKGDgkvVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGS 82

                ..
gi 71998175  86 KK 87
Cdd:cd02961  83 KE 84

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 71998175  24 VFVDFTASWCGPCQYIAPIFSDLANQYKGS-VFLKVDVDECRGTAATYGVNAMPTFIAFVNGQKKATIQGA-DESGLRSM 101
Cdd:cd02956  15 VVVDFWAPRSPPSKELLPLLERLAEEYQGQfVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDGFQGAqPEEQLRQM 94

                ..
gi 71998175 102 VA 103
Cdd:cd02956  95 LD 96

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 71998175   3 VIVVNgDSDFDrKFSAGNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS---VFLKVDVDEC-RGTAATYGVNAMPTF 78
Cdd:cd02998   2 VVELT-DSNFD-KVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEddvVIAKVDADEAnKDLAKKYGVSGFPTL 79

                ....*....
gi 71998175  79 IAFVNGQKK 87
Cdd:cd02998  80 KFFPKGSTE 88

PDIa family, endoplasmic reticulum protein 46 (ERp46) subfamily; ERp46 is an ER-resident protein containing three redox active TRX domains. Yeast complementation studies show that ERp46 can substitute for protein disulfide isomerase (PDI) function in vivo. It has been detected in many tissues, however, transcript and protein levels do not correlate in all tissues, suggesting regulation at a posttranscriptional level. An identical protein, named endoPDI, has been identified as an endothelial PDI that is highly expressed in the endothelium of tumors and hypoxic lesions. It has a protective effect on cells exposed to hypoxia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175  10 SDFDRKFSAGNgkaVFVDFTASWCGPCQYIAPIFSDLANQY---KGSVFL-KVDVDECRGTAATYGVNAMPTFIAFVNGQ 85
Cdd:cd03005   8 DNFDHHIAEGN---HFVKFFAPWCGHCKRLAPTWEQLAKKFnneNPSVKIaKVDCTQHRELCSEFQVRGYPTLLLFKDGE 84

                ....*...
gi 71998175  86 KKATIQGA 93
Cdd:cd03005  85 KVDKYKGT 92

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 71998175  19 GNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS-------VFLKVDVDECRGTAATYGVNAMPTFIAFVNGQ 85
Cdd:cd02996  16 QSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKEEfpdagkvVWGKVDCDKESDIADRYRINKYPTLKLFRNGM 89

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 71998175   2 PVIVVNgDSDFDRKFSAGNGkAVFVDFTASWCGPCQYIAPIFSDLANQYKGSVFL-KVDVDECRGTAATYGVNAMPTFIA 80
Cdd:cd03001   1 DVVELT-DSNFDKKVLNSDD-VWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVgAVDADVHQSLAQQYGVRGFPTIKV 78

                ....*....
gi 71998175  81 FVNGQKKAT 89
Cdd:cd03001  79 FGAGKNSPQ 87

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 71998175  26 VDFTASWCGPCQYIAPIFSDLANQYKGSV--FLKVDVDECRGTAATYGVNA------MPTFIAFVNG 84
Cdd:cd02962  52 VEFFTTWSPECVNFAPVFAELSLKYNNNNlkFGKIDIGRFPNVAEKFRVSTsplskqLPTIILFQGG 118

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175  17 SAGNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS-------------------------VFLKVDVDECRGTAATYG 71
Cdd:cd02966  15 SDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKDDgvevvgvnvddddpaavkaflkkygITFPVLLDPDGELAKAYG 94

                        90       100
                ....*....|....*....|....
gi 71998175  72 VNAMPTFiaFV---NGQKKATIQG 92
Cdd:cd02966  95 VRGLPTT--FLidrDGRIRARHVG 116

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998175  21 GKAVFVDFTASWCGPCQYI-APIFSD---LANQYKGSVFLKVDV----DECRGTAATYGVNAMPTFIAFVNGQ 85
Cdd:cd02953  11 GKPVFVDFTADWCVTCKVNeKVVFSDpevQAALKKDVVLLRADWtkndPEITALLKRFGVFGPPTYLFYGPGG 83

TRX domain, TRX and NDP-kinase (NDPK) fusion protein family; most members of this group are fusion proteins which contain one redox active TRX domain containing a CXXC motif and three NDPK domains, and are characterized as intermediate chains (ICs) of axonemal outer arm dynein. Dyneins are molecular motors that generate force against microtubules to produce cellular movement, and are divided into two classes: axonemal and cytoplasmic. They are supramolecular complexes consisting of three protein groups classified according to size: dynein heavy, intermediate and light chains. Axonemal dyneins form two structures, the inner and outer arms, which are attached to doublet microtubules throughout the cilia and flagella. The human homolog is the sperm-specific Sptrx-2, presumed to be a component of the human sperm axoneme architecture. Included in this group is another human protein, TRX-like protein 2, a smaller fusion protein containing one TRX and one NDPK domain, which is also associated with microtubular structures. The other members of this group are hypothetical insect proteins containing a TRX domain and outer arm dynein light chains (14 and 16kDa) of Chlamydomonas reinhardtii. Using standard assays, the fusion proteins have shown no TRX enzymatic activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175   4 IVVNGDSDFDRKFSagNGKAVFVDFTASWCGPCQYIAPIFSDLANQyKGSVFLKVDVDECR--GTAATYGVNAMPTFIAF 81
Cdd:cd02948   2 VEINNQEEWEELLS--NKGLTVVDVYQEWCGPCKAVVSLFKKIKNE-LGDDLLHFATAEADtiDTLKRYRGKCEPTFLFY 78

                        90       100
                ....*....|....*....|.
gi 71998175  82 VNGQKKATIQGADESGLRSMV 102
Cdd:cd02948  79 KNGELVAVIRGANAPLLNKTI 99

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 71998175     2 PVIVVNGDsDFDrKFSAGNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS----VFLKVDvdecrGTA---ATYGVNA 74
Cdd:TIGR01130 347 PVKVLVGK-NFD-EIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDAesdvVIAKMD-----ATAndvPPFEVEG 419

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 71998175    75 MPTfIAFVNGQKKATIqgADESGLRSM------VAKYASTSA 110
Cdd:TIGR01130 420 FPT-IKFVPAGKKSEP--VPYDGDRTLedfskfIAKHATFPL 458

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 71998175     4 IVVNGDSDFDrKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYK---GSVFL-KVDVDECRGTAATYGVNAMPTFI 79
Cdd:TIGR01130   3 VLVLTKDNFD-DFIKSH-EFVLVEFYAPWCGHCKSLAPEYEKAADELKkkgPPIKLaKVDATEEKDLAQKYGVSGYPTLK 80

                  ....*
gi 71998175    80 AFVNG 84
Cdd:TIGR01130  81 IFRNG 85

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 71998175   9 DSDFdRKFSAGNgKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS---VFLKVDV--DECRGTAATYGVNAMPTFIAFVN 83
Cdd:cd02997   7 DEDF-RKFLKKE-KHVLVMFYAPWCGHCKKMKPEFTKAATELKEDgkgVLAAVDCtkPEHDALKEEYNVKGFPTFKYFEN 84

                ....
gi 71998175  84 GQKK 87
Cdd:cd02997  85 GKFV 88

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175    4 IVVNGDSDFDRKFSAGNGKAV---FVDFTASWCGPCQYIAPIFSDLANQYKGSVFLkVDVDECRG--TAATYGVNAMPTF 78
Cdd:PTZ00443  32 LVLLNDKNFEKLTQASTGATTgpwFVKFYAPWCSHCRKMAPAWERLAKALKGQVNV-ADLDATRAlnLAKRFAIKGYPTL 110

                 ....*..
gi 71998175   79 IAFVNGQ 85
Cdd:PTZ00443 111 LLFDKGK 117

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175  20 NGKAVFVDFTASWCGPCQYI-APIFSD------LANQYkgsVFLKVDVDecRGTAAT------YGVNAMPtFIAFVNGQK 86
Cdd:COG4232 319 EGKPVFVDFTADWCVTCKENeRTVFSDpevqaaLADDV---VLLKADVT--DNDPEItallkrFGRFGVP-TYVFYDPDG 392

                .
gi 71998175  87 K 87
Cdd:COG4232 393 E 393

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998175  26 VDFTASWCGPCQYIAPIFSDLANQYK--GSVFLKVDVDECRGTAATYGVNAMPTFIAFVNG 84
Cdd:cd02994  21 IEFYAPWCPACQQLQPEWEEFADWSDdlGINVAKVDVTQEPGLSGRFFVTALPTIYHAKDG 81

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175  20 NGKAVFVDFTASWCGPCQYI-APIFSD--LANQYKGS-VFLKVDVDECR------GT-------AATYGVNAMPTFIaFV 82
Cdd:COG2143  39 EGKPILLFFESDWCPYCKKLhKEVFSDpeVAAYLKENfVVVQLDAEGDKevtdfdGEtltekelARKYGVRGTPTLV-FF 117

                        90
                ....*....|...
gi 71998175  83 NGQKK--ATIQGA 93
Cdd:COG2143 118 DAEGKeiARIPGY 130

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71998175  35 PCQYIAPIFSDLANQYKGSVFLKVDVDECRGTAATYGVNAMPTFIAFVNGQKKATIQGADESG 97
Cdd:cd02989  36 RCKIMDKHLEILAKKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTVDRIVGFEELG 98

Phosducin (Phd)-like family; composed of Phd and Phd-like proteins (PhLP), characterized as cytosolic regulators of G protein functions. Phd and PhLPs specifically bind G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane and impeding G protein-mediated signal transduction by inhibiting the formation of a functional G protein trimer (G protein alphabetagamma). Phd also inhibits the GTPase activity of G protein alpha. Phd can be phosphorylated by protein kinase A and G protein-coupled receptor kinase 2, leading to its inactivation. Phd was originally isolated from the retina, where it is highly expressed and has been implicated to play an important role in light adaptation. It is also found in the pineal gland, liver, spleen, striated muscle and the brain. The C-terminal domain of Phd adopts a thioredoxin fold, but it does not contain a CXXC motif. Phd interacts with G protein beta mostly through the N-terminal helical domain. Also included in this family is a PhLP characterized as a viral inhibitor of apoptosis (IAP)-associated factor, named VIAF, that functions in caspase activation during apoptosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998175  17 SAGNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGSVFLKVDVDECrGTAATYGVNAMPTFIAFVNGQKKATIQGADES 96
Cdd:cd02957  20 KASKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYKNGELIDNIVGFEEL 98

                .
gi 71998175  97 G 97
Cdd:cd02957  99 G 99

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
                  ....*....|....*....|....*....|....*....|....*..
gi 71998175    21 GKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS-----VFLKVDVDE 62
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKLKKKknveiVFVSLDRDL 47

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 71998175  17 SAGNGKAVFVDFTASWCGPCQYIAPIFSDLANQYKGS------VFLKVDVDE 62
Cdd:cd03009  14 SSLEGKTVGLYFSASWCPPCRAFTPKLVEFYEKLKESgknfeiVFISWDRDE 65

PDIa family, TMX3 subfamily; composed of eukaryotic proteins similar to human TMX3, a TRX related transmembrane protein containing one redox active TRX domain at the N-terminus and a classical ER retrieval sequence for type I transmembrane proteins at the C-terminus. The TMX3 transcript is found in a variety of tissues with the highest levels detected in skeletal muscle and the heart. In vitro, TMX3 showed oxidase activity albeit slightly lower than that of protein disulfide isomerase.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998175  25 FVDFTASWCGPCQYIAPIFSDLANQYKGSV----FLKVDVDECRGTAATYGVNAMPTFIAFVNG 84
Cdd:cd03000  19 LVDFYAPWCGHCKKLEPVWNEVGAELKSSGspvrVGKLDATAYSSIASEFGVRGYPTIKLLKGD 82

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 71998175     3 VIVVNgDSDFDRkFSAGNGK-AVFVDFTASW----CGPCQYIAPIFSDLANQYKGS--------VFLKVDVDECRGTAAT 69
Cdd:pfam04756  13 VIKLN-DSNYKR-LLSGPRDySVVVLLTALDprfgCQLCREFQPEFELVAKSWFKDhkagssklFFATLDFDDGKDVFQS 90

                          90
                  ....*....|..
gi 71998175    70 YGVNAMPTFIAF 81
Cdd:pfam04756  91 LGLQTAPHLLLF 102