TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  35 EFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLIGKIIG 114
Cdd:cd02947    2 EFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVG 81

                         90
                 ....*....|..
gi 763993986 115 ANPT-ALEKGIK 125
Cdd:cd02947   82 ADPKeELEEFLE 93

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  35 EFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLIGKIIG 114
Cdd:cd02947    2 EFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVG 81

                         90
                 ....*....|..
gi 763993986 115 ANPT-ALEKGIK 125
Cdd:cd02947   82 ADPKeELEEFLE 93

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 763993986   32 NLTEFRNLIKQNDKLV-IDFYATWCGPCKMMQPHLTKLIQAYP-DVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLI 109
Cdd:TIGR01068   2 TDANFDETIASSDKPVlVDFWAPWCGPCKMIAPILEELAKEYEgKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90
                  ....*....|....*....
gi 763993986  110 GKIIGANP-TALEKGIKDL 127
Cdd:TIGR01068  82 DRSVGALPkAALKQLINKN 100

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  30 LTNLTEFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLI 109
Cdd:PTZ00051   5 VTSQAEFESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVV 84

                         90
                 ....*....|..
gi 763993986 110 GKIIGANPTALE 121
Cdd:PTZ00051  85 DTLLGANDEALK 96

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  35 EFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLIGKIIG 114
Cdd:cd02947    2 EFEELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVG 81

                         90
                 ....*....|..
gi 763993986 115 ANPT-ALEKGIK 125
Cdd:cd02947   82 ADPKeELEEFLE 93

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 763993986   32 NLTEFRNLIKQNDKLV-IDFYATWCGPCKMMQPHLTKLIQAYP-DVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLI 109
Cdd:TIGR01068   2 TDANFDETIASSDKPVlVDFWAPWCGPCKMIAPILEELAKEYEgKVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEV 81

                          90
                  ....*....|....*....
gi 763993986  110 GKIIGANP-TALEKGIKDL 127
Cdd:TIGR01068  82 DRSVGALPkAALKQLINKN 100

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  30 LTNLTEFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLI 109
Cdd:PTZ00051   5 VTSQAEFESTLSQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVV 84

                         90
                 ....*....|..
gi 763993986 110 GKIIGANPTALE 121
Cdd:PTZ00051  85 DTLLGANDEALK 96

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986   8 MRMAVRPLKSIRFQSSYTSITKLTNLtefrnlikQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPD 87
Cdd:COG0526    1 MKAVGKPAPDFTLTDLDGKPLSLADL--------KGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDENPE 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 763993986  88 ----------------------IAKECEVTAMP-TFVLGKDGQLIGKIIGA-NPTALEKGIKDL 127
Cdd:COG0526   73 avkaflkelglpypvlldpdgeLAKAYGVRGIPtTVLIDKDGKIVARHVGPlSPEELEEALEKL 136

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  36 FRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPD-VRFVKCDVDESPDIAKECEVTAMPTFVLGKDGQLIGKIIG 114
Cdd:PRK10996  45 LDKLLQDDLPVVIDFWAPWCGPCRNFAPIFEDVAAERSGkVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNG 124

                 ....*
gi 763993986 115 ANPTA 119
Cdd:PRK10996 125 AVPKA 129

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 763993986  46 LVIDFYATWCGPCKMMQPHLTKLIQAYPDvRFV--KCDVDESPDIAKECEVTAMPTFVLGKDGQLIGKIIGANP 117
Cdd:cd02956   15 VVVDFWAPRSPPSKELLPLLERLAEEYQG-QFVlaKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDGFQGAQP 87

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  27 ITKLTNlTEFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTK----LIQAYPDVRFVKCDVDESPDIAKECEVTAMPTFVL 102
Cdd:PTZ00102  34 VTVLTD-STFDKFITENEIVLVKFYAPWCGHCKRLAPEYKKaakmLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKF 112

                 ....
gi 763993986 103 GKDG 106
Cdd:PTZ00102 113 FNKG 116

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 763993986  27 ITKLTNLTEFRNLIkQNDKL-VIDFYATWCGPCKMMQPHLTKLIQAYPD--VRFVKCDVDeSPDIAKE----CEvtamPT 99
Cdd:cd02948    1 QVEINNQEEWEELL-SNKGLtVVDVYQEWCGPCKAVVSLFKKIKNELGDdlLHFATAEAD-TIDTLKRyrgkCE----PT 74

                         90       100
                 ....*....|....*....|....*...
gi 763993986 100 FVLGKDGQLIGKIIGANPTALEKGIKDL 127
Cdd:cd02948   75 FLFYKNGELVAVIRGANAPLLNKTITEL 102

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 763993986  47 VIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESPDI---AKECEVTAMPTFVLGKDG 106
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDPALekeLKRYGVGGVPTLVVFGPG 63

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 763993986   27 ITKLT--NLTEFrnlIKQNDKLVIDFYATWCGPCKMMQPHL----TKLIQAYPDVRFVKCDVDESPDIAKECEVTAMPT- 99
Cdd:TIGR01130   3 VLVLTkdNFDDF---IKSHEFVLVEFYAPWCGHCKSLAPEYekaaDELKKKGPPIKLAKVDATEEKDLAQKYGVSGYPTl 79

                  ....*...
gi 763993986  100 --FVLGKD 105
Cdd:TIGR01130  80 kiFRNGED 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 763993986  41 KQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYPDVRFVKCDVDESpDIAKECEVTAMPTFVLGKDGQLIGKIIG 114
Cdd:cd02957   22 SKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYKNGELIDNIVG 94

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 763993986  39 LIKQN-DKLVID--------FYATWCGPCKMMQPHLTKLIQAY---PDVRFVKCDVDES-PDIAKECEVTAMPT 99
Cdd:cd02998    5 LTDSNfDKVVGDdkkdvlveFYAPWCGHCKNLAPEYEKLAAVFaneDDVVIAKVDADEAnKDLAKKYGVSGFPT 78

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 763993986  48 IDFYATWCGPCKMMQPHLTKLIQAYPD--VRFVKCDVDESPDIAKECEVTAMPTFVLGKDG 106
Cdd:cd02994   21 IEFYAPWCPACQQLQPEWEEFADWSDDlgINVAKVDVTQEPGLSGRFFVTALPTIYHAKDG 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  30 LTNLTEFRNLIKQNDK-LVIDFYATWCGPCKMM------QPHLTKLIQAYPDVrfVKCDVDESPDI-------------A 89
Cdd:COG2143   26 LLDLEEDLALAKAEGKpILLFFESDWCPYCKKLhkevfsDPEVAAYLKENFVV--VQLDAEGDKEVtdfdgetltekelA 103

                         90       100
                 ....*....|....*....|....*....
gi 763993986  90 KECEVTAMPTFV-LGKDGQLIGKIIGANP 117
Cdd:COG2143  104 RKYGVRGTPTLVfFDAEGKEIARIPGYLK 132

PDI family, MPD1-like subfamily; composed of eukaryotic proteins similar to Saccharomyces cerevisiae MPD1 protein, which contains a single redox active TRX domain located at the N-terminus, and an ER retention signal at the C-terminus indicative of an ER-resident protein. MPD1 has been shown to suppress the maturation defect of carboxypeptidase Y caused by deletion of the yeast PDI1 gene. Other characterized members of this subfamily include the Aspergillus niger prpA protein and Giardia PDI-1. PrpA is non-essential to strain viability, however, its transcript level is induced by heterologous protein expression suggesting a possible role in oxidative protein folding during high protein production. Giardia PDI-1 has the ability to refold scrambled RNase and exhibits transglutaminase activity.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 763993986  27 ITKLTNLTEFRNLIKQNDKLVIDFYATWCGPCKMMQPHLTKLIQAYP---DVRFVKCDVDESPDIAKECEVTAMPT 99
Cdd:cd03002    2 VYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAAKELDglvQVAAVDCDEDKNKPLCGKYGVQGFPT 77

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 763993986  36 FRNLIKQNDKLV-IDFYATWCGPCKMMQP---HLTKLIQAYPDVRFVKCDVDESpDIAKECEVTAMPTFVL 102
Cdd:cd02995   10 FDEVVLDSDKDVlVEFYAPWCGHCKALAPiyeELAEKLKGDDNVVIAKMDATAN-DVPSEFVVDGFPTILF 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 763993986  36 FRNLIKQNDKLV-IDFYATWCGPCKMMQPHLTKLIQAYPD-VRFVKCDVDESPDIAKECEVTAMPT---FVLGKD 105
Cdd:cd03001   10 FDKKVLNSDDVWlVEFYAPWCGHCKNLAPEWKKAAKALKGiVKVGAVDADVHQSLAQQYGVRGFPTikvFGAGKN 84

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  27 ITKLTNLTEFRNLIKQNDK-LVIDFYATWCGPCKMMQPHLTKLIQAY--PDVRFVKCDVDESPDIAKECEVTA------M 97
Cdd:cd02962   30 IKYFTPKTLEEELERDKRVtWLVEFFTTWSPECVNFAPVFAELSLKYnnNNLKFGKIDIGRFPNVAEKFRVSTsplskqL 109

                 ....*....
gi 763993986  98 PTFVLGKDG 106
Cdd:cd02962  110 PTIILFQGG 118

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 763993986   36 FRNLIKQNDKLV-IDFYATWCGPCKMMQPHLTKLIQAY----PDVRFVKCD--VDESPDIakecEVTAMPTFVLGKDG 106
Cdd:TIGR01130 356 FDEIVLDETKDVlVEFYAPWCGHCKNLAPIYEELAEKYkdaeSDVVIAKMDatANDVPPF----EVEGFPTIKFVPAG 429

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 763993986  26 SITKLTNLTEFRNLIKQNDKLVIDFYATWCGPCKMMQPH---LTKLIQAYP---DVRFVKCDVDESPDIAKECEVTAMPT 99
Cdd:cd02992    2 PVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTwkkLARDLRKWRpvvRVAAVDCADEENVALCRDFGVTGYPT 81

                 ....*
gi 763993986 100 FVLGK 104
Cdd:cd02992   82 LRYFP 86

thiol-disulfide oxidoreductase ResA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  48 IDFYATWCGPCKMMQPHLTKLIQAYPD--VRFVKCDVDESP----------------DIAKECEVT------AMP-TFVL 102
Cdd:PRK03147  66 LNFWGTWCKPCEKEMPYMNELYPKYKEkgVEIIAVNVDETElavknfvnrygltfpvAIDKGRQVIdaygvgPLPtTFLI 145

                         90
                 ....*....|...
gi 763993986 103 GKDGQLIGKIIGA 115
Cdd:PRK03147 146 DKDGKVVKVITGE 158

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 763993986  41 KQNDKLV-IDFYATWCGPCKMM------QPHLTKLIQAypDVRFVKCDVDE-SPDIA---KECEVTAMPTFVL-GKDGQL 108
Cdd:COG4232  317 RAEGKPVfVDFTADWCVTCKENertvfsDPEVQAALAD--DVVLLKADVTDnDPEITallKRFGRFGVPTYVFyDPDGEE 394

                 ....
gi 763993986 109 IGKI 112
Cdd:COG4232  395 LPRL 398

Phosducin (Phd)-like family, Viral inhibitor of apoptosis (IAP)-associated factor (VIAF) subfamily; VIAF is a Phd-like protein that functions in caspase activation during apoptosis. It was identified as an IAP binding protein through a screen of a human B-cell library using a prototype IAP. VIAF lacks a consensus IAP binding motif and while it does not function as an IAP antagonist, it still plays a regulatory role in the complete activation of caspases. VIAF itself is a substrate for IAP-mediated ubiquitination, suggesting that it may be a target of IAPs in the prevention of cell death. The similarity of VIAF to Phd points to a potential role distinct from apoptosis regulation. Phd functions as a cytosolic regulator of G protein by specifically binding to G protein betagamma (Gbg)-subunits. 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 763993986  58 CKMMQPHLTKLIQAYPDVRFVKCDVDES----PDiakecevTAMPTFVLGKDGQLIGKIIG 114
Cdd:cd02988  117 CRLLNQHLSELARKFPDTKFVKIISTQCipnyPD-------KNLPTILVYRNGDIVKQFIG 170

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 763993986  36 FRNLIKQNDKLV-IDFYATWCGPCKMMQPHLTKLIQAYPD-----VRFVKCDVDESPdiAKECEVTAMPTFVLGKDG 106
Cdd:PTZ00102 367 FEEIVFKSDKDVlLEIYAPWCGHCKNLEPVYNELGEKYKDndsiiVAKMNGTANETP--LEEFSWSAFPTILFVKAG 441

periplasmic protein thiol:disulfide oxidoreductases, DsbE subfamily; Involved in the biogenesis of c-type cytochromes as well as in disulfide bond formation in some periplasmic proteins. [Protein fate, Protein folding and stabilization]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 763993986   39 LIKQNDKLViDFYATWCGPCKMMQPHLTKLiqAYPDVRFVKCDV-DESPDIAKECEVTAMPTFVLGKDG 106
Cdd:TIGR00385  60 LTQGKPVLL-NVWASWCPPCRAEHPYLNEL--AKQGLPIVGVDYkDDRQNAIKFLKELGNPYQLSLFDP 125

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 763993986  45 KLVIdFYATWCGPCKMMQPHLTKLiqaypDVRFVKCDVDESPDIAKE 91
Cdd:COG0695    1 KVTL-YTTPGCPYCARAKRLLDEK-----GIPYEEIDVDEDPEAREE 41