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 358254473   9 EFDGLLEESNshLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETV 88
Cdd:cd02947    2 EFEELIKSAK--PVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                         90
                 ....*....|....
gi 358254473  89 LGA-SIEKVEAAVK 101
Cdd:cd02947   80 VGAdPKEELEEFLE 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 358254473   9 EFDGLLEESNshLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETV 88
Cdd:cd02947    2 EFEELIKSAK--PVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                         90
                 ....*....|....
gi 358254473  89 LGA-SIEKVEAAVK 101
Cdd:cd02947   80 VGAdPKEELEEFLE 93

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 358254473   9 EFDGLLEESNsHLVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVET 87
Cdd:COG3118    9 NFEEEVLESD-KPVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPVDR 87

                         90
                 ....*....|....*...
gi 358254473  88 VLGA-SIEKVEAAVKKHI 104
Cdd:COG3118   88 FVGAlPKEQLREFLDKVL 105

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473   17 SNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETVLGA-SIE 94
Cdd:pfam00085  16 KSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGnVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVGArPKD 95

                  ....*...
gi 358254473   95 KVEAAVKK 102
Cdd:pfam00085  96 ALAAFLKA 103

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 358254473   9 EFDGLLEESNshLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETV 88
Cdd:cd02947    2 EFEELIKSAK--PVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRV 79

                         90
                 ....*....|....
gi 358254473  89 LGA-SIEKVEAAVK 101
Cdd:cd02947   80 VGAdPKEELEEFLE 93

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 358254473   9 EFDGLLEESNsHLVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVET 87
Cdd:COG3118    9 NFEEEVLESD-KPVLVDFWAPWCGPCKMLAPVLEELAAEYGGkVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPVDR 87

                         90
                 ....*....|....*...
gi 358254473  88 VLGA-SIEKVEAAVKKHI 104
Cdd:COG3118   88 FVGAlPKEQLREFLDKVL 105

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473   17 SNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETVLGA-SIE 94
Cdd:pfam00085  16 KSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGnVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDYVGArPKD 95

                  ....*...
gi 358254473   95 KVEAAVKK 102
Cdd:pfam00085  96 ALAAFLKA 103

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473  14 LEESNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKVDVDQLPE----------------------LPEEYGVT 71
Cdd:COG0526   23 LADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDENPEavkaflkelglpypvlldpdgeLAKAYGVR 102

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 358254473  72 AMPTFIFF-KNGKPVETVLGA-SIEKVEAAVKKHI 104
Cdd:COG0526  103 GIPTTVLIdKDGKIVARHVGPlSPEELEEALEKLL 137

thioredoxin TrxA;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 358254473  21 LVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETVLGA 91
Cdd:PRK09381  23 AILVDFWAEWCGPCKMIAPILDEIADEYQGkLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEVAATKVGA 94

thioredoxin 2; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473  10 FDGLLEESNShlVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETV 88
Cdd:PRK10996  45 LDKLLQDDLP--VVIDFWAPWCGPCRNFAPIFEDVAAERSGkVRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDML 122

                 ...
gi 358254473  89 LGA 91
Cdd:PRK10996 123 NGA 125

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 358254473  10 FDGLLEESNSHLVVVDFFATWCGPCKDIAPKFVALSGSY--PGVTFAKVDVDQLPELPEEYGVTA------MPTFIFFKN 81
Cdd:cd02962   38 LEEELERDKRVTWLVEFFTTWSPECVNFAPVFAELSLKYnnNNLKFGKIDIGRFPNVAEKFRVSTsplskqLPTIILFQG 117

                 ....
gi 358254473  82 GKPV 85
Cdd:cd02962  118 GKEV 121

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 358254473  10 FDGLLEESNSHlVVVDFFATWCGPCKDIAPKFVALSGSY---PGVTFAKVDVDQL-PELPEEYGVTAMPTFIFF--KNGK 83
Cdd:cd02998   10 FDKVVGDDKKD-VLVEFYAPWCGHCKNLAPEYEKLAAVFaneDDVVIAKVDADEAnKDLAKKYGVSGFPTLKFFpkGSTE 88

                 ...
gi 358254473  84 PVE 86
Cdd:cd02998   89 PVK 91

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 358254473  22 VVVDFFATWCGPCKDIAPKFVALSGSY--PGVTFAKVDVDQLP-----------------------ELPEEYGVTAMPTF 76
Cdd:cd02966   22 VLVNFWASWCPPCRAEMPELEALAKEYkdDGVEVVGVNVDDDDpaavkaflkkygitfpvlldpdgELAKAYGVRGLPTT 101

                         90
                 ....*....|....*
gi 358254473  77 IFF-KNGKPVETVLG 90
Cdd:cd02966  102 FLIdRDGRIRARHVG 116

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 358254473  14 LEESNSHLVV-----VDFFATWCGPCKDIAPKFVALS--GSYPGVTFAKVDVDQLPELPEEYGVTAMPTFIFFKNG 82
Cdd:cd02994    6 LTDSNWTLVLegewmIEFYAPWCPACQQLQPEWEEFAdwSDDLGINVAKVDVTQEPGLSGRFFVTALPTIYHAKDG 81

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 358254473  17 SNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQ---LPELpEEYGVTAMPTFIFFKN-GKPVETVLG 90
Cdd:cd02950   18 SNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGDqVNFVMLNVDNpkwLPEI-DRYRVDGIPHFVFLDReGNEEGQSIG 95

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 358254473   2 KEIAAKCEFDGLLeeSNSHLVVVDFFATWCGPCKDIAPKFVALS---GSYPgVTFAKVDVDQLPELpEEYGVTAMPTFIF 78
Cdd:cd02948    2 VEINNQEEWEELL--SNKGLTVVDVYQEWCGPCKAVVSLFKKIKnelGDDL-LHFATAEADTIDTL-KRYRGKCEPTFLF 77

                         90       100
                 ....*....|....*....|....*
gi 358254473  79 FKNGKPVETVLGASIEKVEAAVKKH 103
Cdd:cd02948   78 YKNGELVAVIRGANAPLLNKTITEL 102

TRX family, chloroplastic drought-induced stress protein of 32 kD (CDSP32); CDSP32 is composed of two TRX domains, a C-terminal TRX domain which contains a redox active CXXC motif and an N-terminal TRX-like domain which contains an SXXS sequence instead of the redox active motif. CDSP32 is a stress-inducible TRX, i.e., it acts as a TRX by reducing protein disulfides and is induced by environmental and oxidative stress conditions. It plays a critical role in plastid defense against oxidative damage, a role related to its function as a physiological electron donor to BAS1, a plastidic 2-cys peroxiredoxin. Plants lacking CDSP32 exhibit decreased photosystem II photochemical efficiencies and chlorophyll retention compared to WT controls, as well as an increased proportion of BAS1 in its overoxidized monomeric form.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473   9 EFDGLLEESNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKV---DVDQLPELPEEYGVTAMPTFIFFKNGKPV 85
Cdd:cd02985    5 ELDEALKKAKGRLVVLEFALKHSGPSVKIYPTMVKLSRTCNDVVFLLVngdENDSTMELCRREKIIEVPHFLFYKDGEKI 84

TRX domain, novel NADPH thioredoxin reductase (NTR) family; composed of fusion proteins found only in oxygenic photosynthetic organisms containing both TRX and NTR domains. The TRX domain functions as a protein disulfide reductase via the reversible oxidation of an active center dithiol present in a CXXC motif, while the NTR domain functions as a reductant to oxidized TRX. The fusion protein is bifunctional, showing both TRX and NTR activities, but it is not an independent NTR/TRX system. In plants, the protein is found exclusively in shoots and mature leaves and is localized in the chloroplast. It is involved in plant protection against oxidative stress.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473  13 LLEESNsHLVVVDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGKPVETVLGA 91
Cdd:cd02949    8 LYHESD-RLILVLYTSPTCGPCRTLKPILNKVIDEFDGaVHFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGV 86

                 ....
gi 358254473  92 SIEK 95
Cdd:cd02949   87 KMKS 90

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 358254473  10 FDGLLEESNsHLVVVDFFATWCGPCKDIAPKFVALSGSYPGVT-FAKVDVDQLP--ELPEEYGVTAMPTFIFFKNGKPV 85
Cdd:cd03002   10 FDKVVHNTN-YTTLVEFYAPWCGHCKNLKPEYAKAAKELDGLVqVAAVDCDEDKnkPLCGKYGVQGFPTLKVFRPPKKA 87

PDIa family, endoplasmic reticulum protein 44 (ERp44)-like subfamily; composed of uncharacterized PDI-like eukaryotic proteins containing only one redox active TRX (a) domain with a CXXS motif, similar to ERp44. CXXS is still a redox active motif; however, the mixed disulfide formed with the substrate is more stable than those formed by CXXC motif proteins. PDI-related proteins are usually involved in the oxidative protein folding in the ER by acting as catalysts and folding assistants. ERp44 is involved in thiol-mediated retention in the ER.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 358254473  13 LLEESNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKVDV-DQLPELPEEYGVTAMPTFIFF 79
Cdd:cd02999   12 LMAFNREDYTAVLFYASWCPFSASFRPHFNALSSMFPQIRHLAIEEsSIKPSLLSRYGVVGFPTILLF 79

PDIa family, endoplasmic reticulum protein 44 (ERp44) subfamily; ERp44 is an ER-resident protein, induced during stress, involved in thiol-mediated ER retention. It contains an N-terminal TRX domain, similar to that of PDIa, with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. The CXFS motif in the N-terminal domain allows ERp44 to form stable reversible mixed disulfides with its substrates. Through this activity, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. It also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473  10 FDGLLEesNSHLVVVDFFATWCGPCKDIAPKFVALSG----SYPG---VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNG 82
Cdd:cd02996   11 IDDILQ--SAELVLVNFYADWCRFSQMLHPIFEEAAAkikeEFPDagkVVWGKVDCDKESDIADRYRINKYPTLKLFRNG 88

Thioredoxin domain-containing protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 358254473  24 VDFFATWCGPCKDIAPKFVALSGSYPG-VTFAKVDVDQLPELPEEYGVTAMPTFIFFKNGK 83
Cdd:PTZ00443  57 VKFYAPWCSHCRKMAPAWERLAKALKGqVNVADLDATRALNLAKRFAIKGYPTLLLFDKGK 117

TlpA-like family, DsbE (also known as CcmG and CycY) subfamily; DsbE is a membrane-anchored, periplasmic TRX-like reductase containing a CXXC motif that specifically donates reducing equivalents to apocytochrome c via CcmH, another cytochrome c maturation (Ccm) factor with a redox active CXXC motif. Assembly of cytochrome c requires the ligation of heme to reduced thiols of the apocytochrome. In bacteria, this assembly occurs in the periplasm. The reductase activity of DsbE in the oxidizing environment of the periplasm is crucial in the maturation of cytochrome c.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473  20 HLVVVDFFATWCGPCKDIAPKFVALS--GSYP--GVT------------------FAKVDVDQLPELPEEYGVTAMP-TF 76
Cdd:cd03010   26 KPYLLNVWASWCAPCREEHPVLMALArqGRVPiyGINykdnpenalawlarhgnpYAAVGFDPDGRVGIDLGVYGVPeTF 105

                 ....*..
gi 358254473  77 IFFKNGK 83
Cdd:cd03010  106 LIDGDGI 112

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 358254473  22 VVVDFFATWCGPCKDI------APKFVALSGSypGVTFAKVDV----DQLPELPEEYGVTAMPTFIFFKNGKPVE 86
Cdd:cd02953   14 VFVDFTADWCVTCKVNekvvfsDPEVQAALKK--DVVLLRADWtkndPEITALLKRFGVFGPPTYLFYGPGGEPE 86

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 358254473  15 EESNSHLVVVDFFATWCGPCKDIAPKFVALSGSYPGVTFAKVDVDQLpELPEEYGVTAMPTFIFFKNGKPVETVLG 90
Cdd:cd02957   20 KASKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYKNGELIDNIVG 94

Thioredoxin-like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 358254473   16 ESNSHLVVVDFFATWCGPCK------------------DIAPKFVALSGSyPGVTFAKVDVDQLPELPEEYGVTAMPTFI 77
Cdd:pfam13098   1 KGNGKPVLVVFTDPDCPYCKklkkelledpdvtvylgpNFVFIAVNIWCA-KEVAKAFTDILENKELGRKYGVRGTPTIV 79

                          90
                  ....*....|...
gi 358254473   78 FFkNGKPVETVLG 90
Cdd:pfam13098  80 FF-DGKGELLRLP 91

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 358254473   31 CGPCKDIAPKFVALSGSY--------PGVTFAKVDVDQLPELPEEYGVTAMPTFIFF 79
Cdd:pfam04756  46 CQLCREFQPEFELVAKSWfkdhkagsSKLFFATLDFDDGKDVFQSLGLQTAPHLLLF 102

disulphide isomerase; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 358254473  22 VVVDFFATWCGPCKDIAPKFVALS---GSYPGVTFAKVDVDQLPELPEEYGVTAMPTFIFFKNG 82
Cdd:PTZ00102 378 VLLEIYAPWCGHCKNLEPVYNELGekyKDNDSIIVAKMNGTANETPLEEFSWSAFPTILFVKAG 441