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 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNGE 149
Cdd:COG3118   4 ELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQ 83

                        90       100
                ....*....|....*....|..
gi 15226561 150 KRESIMGTMPKEFYISAIERVL 171
Cdd:COG3118  84 PVDRFVGALPKEQLREFLDKVL 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 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNGE 149
Cdd:COG3118   4 ELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQ 83

                        90       100
                ....*....|....*....|..
gi 15226561 150 KRESIMGTMPKEFYISAIERVL 171
Cdd:COG3118  84 PVDRFVGALPKEQLREFLDKVL 105

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 15226561  78 DSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYaGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNGEKRESIMGT 157
Cdd:cd02947   4 EELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGA 82

                        90
                ....*....|.
gi 15226561 158 MPKEFYISAIE 168
Cdd:cd02947  83 DPKEELEEFLE 93

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 15226561    69 AEVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNG 148
Cdd:pfam00085   3 VVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                          90       100
                  ....*....|....*....|.
gi 15226561   149 EKRESIMGTMPKEFYISAIER 169
Cdd:pfam00085  83 QPVDDYVGARPKDALAAFLKA 103

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 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNGE 149
Cdd:COG3118   4 ELTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYGGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQ 83

                        90       100
                ....*....|....*....|..
gi 15226561 150 KRESIMGTMPKEFYISAIERVL 171
Cdd:COG3118  84 PVDRFVGALPKEQLREFLDKVL 105

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 15226561  78 DSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYaGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNGEKRESIMGT 157
Cdd:cd02947   4 EELIKSAKPVVVDFWAPWCGPCKAIAPVLEELAEEY-PKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGA 82

                        90
                ....*....|.
gi 15226561 158 MPKEFYISAIE 168
Cdd:cd02947  83 DPKEELEEFLE 93

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 15226561    69 AEVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNG 148
Cdd:pfam00085   3 VVLTDANFDEVVQKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGNVVFAKVDVDENPDLASKYGVRGYPTLIFFKNG 82

                          90       100
                  ....*....|....*....|.
gi 15226561   149 EKRESIMGTMPKEFYISAIER 169
Cdd:pfam00085  83 QPVDDYVGARPKDALAAFLKA 103

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226561  86 PVLVEFYTSWCGPCRMVHRIIDEIAGDYAG---------------------KLNCYLLNADNDLPVAEEYEIKAVPVVLL 144
Cdd:COG0526  30 PVLVNFWATWCPPCRAEMPVLKELAEEYGGvvfvgvdvdenpeavkaflkeLGLPYPVLLDPDGELAKAYGVRGIPTTVL 109

                        90       100       110
                ....*....|....*....|....*....|
gi 15226561 145 F-KNGEKRESIMGTMPKEFYISAIERVLNS 173
Cdd:COG0526 110 IdKDGKIVARHVGPLSPEELEEALEKLLAK 139

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 15226561  70 EVTQRSWEDsVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYL--LNADNDLPVAEEYEIKAVPVVLLFKN 147
Cdd:cd02961   2 ELTDDNFDE-LVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELKGDGKVVVakVDCTANNDLCSEYGVRGYPTIKLFPN 80

                ...
gi 15226561 148 GEK 150
Cdd:cd02961  81 GSK 83

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 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYL--LNAD-NDLPvaEEYEIKAVPVVLLFK 146
Cdd:cd02995   4 VVVGKNFDEVVLDSDKDVLVEFYAPWCGHCKALAPIYEELAEKLKGDDNVVIakMDATaNDVP--SEFVVDGFPTILFFP 81

                ....*....
gi 15226561 147 NGEKRESIM 155
Cdd:cd02995  82 AGDKSNPIK 90

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 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYL--LNADND-LPVAEEYEIKAVPVVLLFK 146
Cdd:cd02998   4 ELTDSNFDKVVGDDKKDVLVEFYAPWCGHCKNLAPEYEKLAAVFANEDDVVIakVDADEAnKDLAKKYGVSGFPTLKFFP 83

                        90
                ....*....|....*..
gi 15226561 147 NGEKResimgtmPKEFY 163
Cdd:cd02998  84 KGSTE-------PVKYE 93

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226561  86 PVLVEFYTSWCGPCRMVHRII---DEIAGDYAGKLNCYLLNADNDLPV-------------AEEYEIKAVPVVLLF-KNG 148
Cdd:COG2143  42 PILLFFESDWCPYCKKLHKEVfsdPEVAAYLKENFVVVQLDAEGDKEVtdfdgetltekelARKYGVRGTPTLVFFdAEG 121

                        90       100
                ....*....|....*....|...
gi 15226561 149 EKRESIMGTMPKEFYISAIERVL 171
Cdd:COG2143 122 KEIARIPGYLKPETFLALLKYVA 144

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 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLLNADNDLPVAEEYEIKAVPVVLLFKNGE 149
Cdd:cd03001   4 ELTDSNFDKKVLNSDDVWLVEFYAPWCGHCKNLAPEWKKAAKALKGIVKVGAVDADVHQSLAQQYGVRGFPTIKVFGAGK 83

                ..
gi 15226561 150 KR 151
Cdd:cd03001  84 NS 85

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 15226561  86 PVLVEFYTSWCGPCRMVHRIIDEIAGDYAG-----------------------KLNCYLLNA-DNDLPVAEEYEIKAVPV 141
Cdd:cd02966  21 VVLVNFWASWCPPCRAEMPELEALAKEYKDdgvevvgvnvddddpaavkaflkKYGITFPVLlDPDGELAKAYGVRGLPT 100

                        90
                ....*....|....*.
gi 15226561 142 VLLF-KNGEKRESIMG 156
Cdd:cd02966 101 TFLIdRDGRIRARHVG 116

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 15226561    77 EDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAG-KLNCYLLNAD---NDLPvaeEYEIKAVPVVLLFKNGEKRE 152
Cdd:TIGR01130 357 DEIVLDETKDVLVEFYAPWCGHCKNLAPIYEELAEKYKDaESDVVIAKMDataNDVP---PFEVEGFPTIKFVPAGKKSE 433

                  ..
gi 15226561   153 SI 154
Cdd:TIGR01130 434 PV 435

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226561   71 VTQRSWEDSVLKSETPVLVEFYTSWCGPCRMVHRIIDEIA---GDYaGKLNCYLLNAD-NDLPVaEEYEIKAVPVVLLFK 146
Cdd:PTZ00102 362 VVGNTFEEIVFKSDKDVLLEIYAPWCGHCKNLEPVYNELGekyKDN-DSIIVAKMNGTaNETPL-EEFSWSAFPTILFVK 439

                 ....
gi 15226561  147 NGEK 150
Cdd:PTZ00102 440 AGER 443

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 15226561    70 EVTQRSWEDSVLKSETpVLVEFYTSWCGPCRmvhriidEIAGDYA---------------GKLNCyllNADNDLpvAEEY 134
Cdd:TIGR01130   5 VLTKDNFDDFIKSHEF-VLVEFYAPWCGHCK-------SLAPEYEkaadelkkkgppiklAKVDA---TEEKDL--AQKY 71

                          90
                  ....*....|....*....
gi 15226561   135 EIKAVPVVLLFKNGEKRES 153
Cdd:TIGR01130  72 GVSGYPTLKIFRNGEDSVS 90

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 15226561  88 LVEFYTSWCGPCRMVHRIIDEIAGDYA--------GKLNCYLLNAdndlpVAEEYEIKAVPVVLLFKNG 148
Cdd:cd03000  19 LVDFYAPWCGHCKKLEPVWNEVGAELKssgspvrvGKLDATAYSS-----IASEFGVRGYPTIKLLKGD 82

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCRmvhriidEIAGDYA-------GKLNCYLLNADNDL--PVAEEYEIKAVP 140
Cdd:cd03002   4 ELTPKNFDKVVHNTNYTTLVEFYAPWCGHCK-------NLKPEYAkaakeldGLVQVAAVDCDEDKnkPLCGKYGVQGFP 76

                ....*.
gi 15226561 141 VVLLFK 146
Cdd:cd03002  77 TLKVFR 82

Peroxiredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15226561  86 PVLVEFYTSWCGPCRMVHRIIDEIAGDYAGK-----------------------LNcYLLNADNDLPVAEEYEIKAVPVV 142
Cdd:COG1225  23 PVVLYFYATWCPGCTAELPELRDLYEEFKDKgvevlgvssdsdeahkkfaekygLP-FPLLSDPDGEVAKAYGVRGTPTT 101

                        90       100       110
                ....*....|....*....|....*....|...
gi 15226561 143 LLF-KNGEKRESIMGTM-PKEFYISAIERVLNS 173
Cdd:COG1225 102 FLIdPDGKIRYVWVGPVdPRPHLEEVLEALLAE 134

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15226561  72 TQRSWEDSVLKSETPVLVEFYTSWCGPC-------RMVHRIIDEIAGdyAGKLNC 119
Cdd:cd03004   7 TPEDFPELVLNRKEPWLVDFYAPWCGPCqallpelRKAARALKGKVK--VGSVDC 59

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 15226561  70 EVTQRSWEDSVLKS--ETPVLVEFYTSWCGPCRMVHRIIDEIAGDYagkLNCYLLNADNDLPVAEEY-EIKAVPVVLLFK 146
Cdd:cd02957   8 EISSKEFLEEVTKAskGTRVVVHFYEPGFPRCKILDSHLEELAAKY---PETKFVKINAEKAFLVNYlDIKVLPTLLVYK 84

                        90       100
                ....*....|....*....|....*....
gi 15226561 147 NGEKRESIMGTM---PKEFYISAIERVLN 172
Cdd:cd02957  85 NGELIDNIVGFEelgGDDFTTEDLEKFLA 113

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
                ....*....|....*....|....*....|.
gi 15226561  70 EVTQRSWEDSVLKSETPVLVEFYTSWCGPCR 100
Cdd:cd02992   5 VLDAASFNSALLGSPSAWLVEFYASWCGHCR 35

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.

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gi 15226561  79 SVLKSETPVLVEFYTSWCGPCRMVHRIIDEIAGDYAGKLNCYLlNADNDLPVAEEYEIKAVPVVLLFKNGEKRESIMG 156
Cdd:cd02989  17 EIVKSSERVVCHFYHPEFFRCKIMDKHLEILAKKHLETKFIKV-NAEKAPFLVEKLNIKVLPTVILFKNGKTVDRIVG 93