Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 139 LKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDII 218
Cdd:cd03028     1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                  ....*....
gi 1958649026 219 KELEASEEL 227
Cdd:cd03028    81 KEMHESGEL 89

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 139 LKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDII 218
Cdd:cd03028     1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                  ....*....
gi 1958649026 219 KELEASEEL 227
Cdd:cd03028    81 KEMHESGEL 89

Glutaredoxin-related protein [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 133 EDLNLRLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELI 212
Cdd:COG0278     2 MDVQERIKQQIKSNPVVLFMKGTPQFPQCGFSARAVQILNACGVDFATVNVLEDPEIRQGLKEYSNWPTIPQLYVKGEFI 81

                          90
                  ....*....|....*...
gi 1958649026 213 GGLDIIKELEASEELDTI 230
Cdd:COG0278    82 GGCDIIREMYESGELQKL 99

glutaredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  46 PQCVQMNDVMAELAKEHPHVSFVKleaeavpeVSEKYEISSVPTFLFFKNSQKVDRLDGAHAPELTKKVQRHVSSGSFPP 125
Cdd:PTZ00062   30 PEYEQLMDVCNALVEDFPSLEFYV--------VNLADANNEYGVFEFYQNSQLINSLEGCNTSTLVSFIRGWAQKGSSED 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 126 STNehvkedlnlRLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQL 205
Cdd:PTZ00062  102 TVE---------KIERLIRNHKILLFMKGSKTFPFCRFSNAVVNMLNSSGVKYETYNIFEDPDLREELKVYSNWPTYPQL 172

                         170       180
                  ....*....|....*....|....*..
gi 1958649026 206 YVSGELIGGLDIIKELEASEELDTICP 232
Cdd:PTZ00062  173 YVNGELIGGHDIIKELYESNSLRKVIP 199

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 1958649026  20 SARQFEELLrLKTKSLLVVHFWAPWAPQCVQMNDVMAELAKEHPH-VSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQK 98
Cdd:TIGR01068   2 TDANFDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKE 80

                          90       100
                  ....*....|....*....|.
gi 1958649026  99 VDRLDGAHAPE-LTKKVQRHV 118
Cdd:TIGR01068  81 VDRSVGALPKAaLKQLINKNL 101

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 1958649026  24 FEELLrLKTKSLLVVHFWAPWAPQCVQMNDVMAELAKEHPH-VSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRL 102
Cdd:pfam00085  10 FDEVV-QKSSKPVLVDFYAPWCGPCKMLAPEYEELAQEYKGnVVFAKVDVDENPDLASKYGVRGYPTLIFFKNGQPVDDY 88

                  ...
gi 1958649026 103 DGA 105
Cdd:pfam00085  89 VGA 91

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 139 LKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDII 218
Cdd:cd03028     1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                  ....*....
gi 1958649026 219 KELEASEEL 227
Cdd:cd03028    81 KEMHESGEL 89

Glutaredoxin-related protein [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 133 EDLNLRLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELI 212
Cdd:COG0278     2 MDVQERIKQQIKSNPVVLFMKGTPQFPQCGFSARAVQILNACGVDFATVNVLEDPEIRQGLKEYSNWPTIPQLYVKGEFI 81

                          90
                  ....*....|....*...
gi 1958649026 213 GGLDIIKELEASEELDTI 230
Cdd:COG0278    82 GGCDIIREMYESGELQKL 99

glutaredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  46 PQCVQMNDVMAELAKEHPHVSFVKleaeavpeVSEKYEISSVPTFLFFKNSQKVDRLDGAHAPELTKKVQRHVSSGSFPP 125
Cdd:PTZ00062   30 PEYEQLMDVCNALVEDFPSLEFYV--------VNLADANNEYGVFEFYQNSQLINSLEGCNTSTLVSFIRGWAQKGSSED 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026 126 STNehvkedlnlRLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQL 205
Cdd:PTZ00062  102 TVE---------KIERLIRNHKILLFMKGSKTFPFCRFSNAVVNMLNSSGVKYETYNIFEDPDLREELKVYSNWPTYPQL 172

                         170       180
                  ....*....|....*....|....*..
gi 1958649026 206 YVSGELIGGLDIIKELEASEELDTICP 232
Cdd:PTZ00062  173 YVNGELIGGHDIIKELYESNSLRKVIP 199

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958649026 147 PCMLFMKGTpqeprCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDIIKELE 222
Cdd:cd02066     1 KVVVFSKST-----CPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALH 71

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 1958649026  23 QFEELLrLKTKSLLVVHFWAPWAPQCVQMNDVMAELAKEH-PHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDR 101
Cdd:COG3118     9 NFEEEV-LESDKPVLVDFWAPWCGPCKMLAPVLEELAAEYgGKVKFVKVDVDENPELAAQFGVRSIPTLLLFKDGQPVDR 87

                          90
                  ....*....|....*...
gi 1958649026 102 LDGAH-APELTKKVQRHV 118
Cdd:COG3118    88 FVGALpKEQLREFLDKVL 105

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958649026 149 MLFMKgtpqePRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELI 212
Cdd:pfam00462   2 VLYTK-----PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

thioredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  20 SARQFEELLrlKTKSLLVVHFWAPWAPQCVQMNDVMAELAKEHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKV 99
Cdd:PTZ00051    7 SQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFKNGSVV 84

                          90
                  ....*....|.
gi 1958649026 100 DRLDGAHAPEL 110
Cdd:PTZ00051   85 DTLLGANDEAL 95

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 1958649026  24 FEELLRLKTKSLLVVHFWAPWAPQCVQMNDVMAELAKEHP-HVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRL 102
Cdd:cd02956     3 FQQVLQESTQVPVVVDFWAPRSPPSKELLPLLERLAEEYQgQFVLAKVNCDAQPQIAQQFGVQALPTVYLFAAGQPVDGF 82

                  ....*..
gi 1958649026 103 DGAHaPE 109
Cdd:cd02956    83 QGAQ-PE 88

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  26 ELLRLKTKS-LLVVHFWAPWAPQCVQMNDVMAELAKEHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRLDG 104
Cdd:cd02989    14 EFFEIVKSSeRVVCHFYHPEFFRCKIMDKHLEILAKKHLETKFIKVNAEKAPFLVEKLNIKVLPTVILFKNGKTVDRIVG 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958649026  24 FEELLrlKTKSLLVVHFWAPWAPQCVQMNDVMAELAKE---HPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQK 98
Cdd:cd02961     8 FDELV--KDSKDVLVEFYAPWCGHCKALAPEYEKLAKElkgDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGSK 83

thioredoxin TrxA;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958649026  30 LKTKSLLVVHFWAPWAPQCVQMNDVMAELAKEHP-HVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQ 97
Cdd:PRK09381   18 LKADGAILVDFWAEWCGPCKMIAPILDEIADEYQgKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGE 86

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 1958649026  20 SARQFEELLRLKTKSLLVvHFWAPWAPQCVQMNDVMAELA---KEHPHVSFVKLEAEAV-PEVSEKYEISSVPTFLFF-K 94
Cdd:cd02998     6 TDSNFDKVVGDDKKDVLV-EFYAPWCGHCKNLAPEYEKLAavfANEDDVVIAKVDADEAnKDLAKKYGVSGFPTLKFFpK 84

                  ....
gi 1958649026  95 NSQK 98
Cdd:cd02998    85 GSTE 88

Phosducin (Phd)-like family, Phd subfamily; Phd is a cytosolic regulator of G protein functions. It specifically binds G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane. This impedes the formation of a functional G protein trimer (G protein alphabetagamma), thereby inhibiting G protein-mediated signal transduction. 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958649026  35 LLVVHFWAPWAPQCVQMNDVMAELAKEHPHVSFVKLEAEAVpEVSEKYEISSVPTFLFFKN 95
Cdd:cd02987    85 TVVVHIYEPGIPGCAALNSSLLCLAAEYPAVKFCKIRASAT-GASDEFDTDALPALLVYKG 144

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 1958649026  23 QFEELLRLKTksLLVVHFWAPWAPQCVQM--------NDVMAELakehphVSFVKLEAEAVpEVSEKYEISSVPTFLFFK 94
Cdd:cd02948     9 EWEELLSNKG--LTVVDVYQEWCGPCKAVvslfkkikNELGDDL------LHFATAEADTI-DTLKRYRGKCEPTFLFYK 79

                          90       100
                  ....*....|....*....|...
gi 1958649026  95 NSQKVDRLDGAHAPELTKKVQRH 117
Cdd:cd02948    80 NGELVAVIRGANAPLLNKTITEL 102

Dim1 family; Dim1 is also referred to as U5 small nuclear ribonucleoprotein particle (snRNP)-specific 15kD protein. It is a component of U5 snRNP, which pre-assembles with U4/U6 snRNPs to form a [U4/U6:U5] tri-snRNP complex required for pre-mRNA splicing. Dim1 interacts with multiple splicing-associated proteins, suggesting that it functions at multiple control points in the splicing of pre-mRNA as part of a large spliceosomal complex involving many protein-protein interactions. U5 snRNP contains seven core proteins (common to all snRNPs) and nine U5-specific proteins, one of which is Dim1. Dim1 adopts a thioredoxin fold but does not contain the redox active CXXC motif. It is essential for G2/M phase transition, as a consequence to its role in pre-mRNA splicing.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  20 SARQFEELLRLKTKSLLVVHFWAPWAPQCVQMNDVMAELAkehPHVS-FVKL---EAEAVPEVSEKYEISSVPTFLFFKN 95
Cdd:cd02954     1 SGWAVDQAILSEEEKVVVIRFGRDWDPVCMQMDEVLAKIA---EDVSnFAVIylvDIDEVPDFNKMYELYDPPTVMFFFR 77

                  ....*..
gi 1958649026  96 SQ--KVD 100
Cdd:cd02954    78 NKhmKID 84

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958649026 159 PRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLD 216
Cdd:COG0695     8 PGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFD 65

TlpA-like family, suppressor for copper sensitivity D protein (ScsD) and actinobacterial DsbE homolog subfamily; composed of ScsD, the DsbE homolog of Mycobacterium tuberculosis (MtbDsbE) and similar proteins, all containing a redox-active CXXC motif. The Salmonella typhimurium ScsD is a thioredoxin-like protein which confers copper tolerance to copper-sensitive mutants of E. coli. MtbDsbE has been characterized as an oxidase in vitro, catalyzing the disulfide bond formation of substrates like hirudin. The reduced form of MtbDsbE is more stable than its oxidized form, consistent with an oxidase function. This is in contrast to the function of DsbE from gram-negative bacteria which is a specific reductase of apocytochrome c.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  37 VVHFWAPWAPQCVQMNDVMAELAKEHPHVSfVKLEAEAVPEV---------------------SEKYEISSVPTFLFFKN 95
Cdd:cd03011    24 LVYFWATWCPVCRFTSPTVNQLAADYPVVS-VALRSGDDGAVarfmqkkgygfpvindpdgviSARWGVSVTPAIVIVDP 102

                  ....*....
gi 1958649026  96 SQKVDRLDG 104
Cdd:cd03011   103 GGIVFVTTG 111

Thioredoxin domain-containing protein; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958649026  22 RQFEELLRLKTKSLL---VVHFWAPWAPQCVQMNDVMAELAKE-HPHVSFVKLEAEAVPEVSEKYEISSVPTFLFF 93
Cdd:PTZ00443   38 KNFEKLTQASTGATTgpwFVKFYAPWCSHCRKMAPAWERLAKAlKGQVNVADLDATRALNLAKRFAIKGYPTLLLF 113

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958649026  38 VHFWAPWAPQCVQMNDVMAELAK----EHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRLDGA 105
Cdd:cd03005    21 VKFFAPWCGHCKRLAPTWEQLAKkfnnENPSVKIAKVDCTQHRELCSEFQVRGYPTLLLFKDGEKVDKYKGT 92

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  25 EELLRLKTKSLLVVHFWAPWAPQCVQM----NDVMAELAKEHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVD 100
Cdd:cd03000     7 DSFKDVRKEDIWLVDFYAPWCGHCKKLepvwNEVGAELKSSGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGDLAYN 86

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 1958649026  36 LVVHFWAPWAPQCVQMNDVMAELAKEHPH-------VSFVKLEAEAV------------------PEVSEKYEISSVPTF 90
Cdd:cd02966    22 VLVNFWASWCPPCRAEMPELEALAKEYKDdgvevvgVNVDDDDPAAVkaflkkygitfpvlldpdGELAKAYGVRGLPTT 101

                  ...
gi 1958649026  91 LFF 93
Cdd:cd02966   102 FLI 104

Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of uncharacterized eukaryotic proteins containing a GRX-like domain having only one conserved cysteine, aligning to the C-terminal cysteine of the CXXC motif of GRXs. This subfamily is predominantly composed of plant proteins. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins via a redox active CXXC motif using a similar dithiol mechanism employed by TRXs. GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. Proteins containing only the C-terminal cysteine are generally redox inactive.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958649026 170 ILHKHNIQFSSFDIFSD----EEVRQGLKTYSNWPTYPQLYVSGELIGGLDIIKELEASEELDTICPKAPKLE 238
Cdd:cd03031    25 ILESFRVKFDERDVSMDsgfrEELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKLLKGIRARA 97

5'-adenylylsulfate reductase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  25 EELLRLKT--KSLLVVhFWAPWAPQCVQMNDVMAELAK--EHPHVSFVKLEAEAV--PEVSEKYEISSVPTFLFF-KNSQ 97
Cdd:PLN02309  356 ENLLKLENrkEPWLVV-LYAPWCPFCQAMEASYEELAEklAGSGVKVAKFRADGDqkEFAKQELQLGSFPTILLFpKNSS 434

                  ..
gi 1958649026  98 KV 99
Cdd:PLN02309  435 RP 436

Glutaredoxin (GRX) family, PRX5 hybrid subfamily; composed of hybrid proteins containing peroxiredoxin (PRX) and GRX domains, which is found in some pathogenic bacteria and cyanobacteria. PRXs are thiol-specific antioxidant (TSA) proteins that confer a protective antioxidant role in cells through their peroxidase activity in which hydrogen peroxide, peroxynitrate, and organic hydroperoxides are reduced and detoxified using reducing equivalents derived from either thioredoxin, glutathione, trypanothione and AhpF. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins. PRX-GRX hybrid proteins from Haemophilus influenza and Neisseria meningitis exhibit GSH-dependent peroxidase activity. The flow of reducing equivalents in the catalytic cycle of the hybrid protein goes from NADPH -> GSH reductase -> GSH -> GRX domain of hybrid -> PRX domain of hybrid -> peroxide substrate.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958649026 150 LFMKgtpqePRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQgLKTYSNWPTYPQLYVSGELIGGLD 216
Cdd:cd03029     5 LFTK-----PGCPFCARAKAALQENGISYEEIPLGKDITGRS-LRAVTGAMTVPQVFIDGELIGGSD 65

U5 snRNP protein, DIM1 family; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649026  35 LLVVHFWAPWAPQCVQMNDVMAELAKEHPHVS-FVKLEAEAVPEVSEKYEISSVPTFLFF 93
Cdd:PLN00410   25 LVVIRFGHDWDETCMQMDEVLASVAETIKNFAvIYLVDITEVPDFNTMYELYDPCTVMFF 84