Glutaredoxin (GRX) family, GRX bacterial class 1 and 3 (b_1_3)-like subfamily; composed of bacterial GRXs, 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 E. coli GRX1 and GRX3, which are members of this subfamily.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15600322  3 PVVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGST-TVPQIWIGETHVGGCDDLHALERAG 76
Cdd:cd03418  1 KVEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGGRrTVPQIFIGDVHIGGCDDLYALERKG 75

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322  3 PVVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGSTTVPQIWIGETHVGGCDDlhaleraGKLDALL 82
Cdd:COG0695  1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFDE-------GELDALL 73

Uxx-star family glutaredoxin-like (seleno)protein; A number of proteins with glutaredoxin-like folds, a length of about 75 amino acids, and a CxxC, C/UxxT, or CxxS motif near the N-terminus end with a UXX-COOH motif. That final motif typically is missed during coding region feature prediction by genome annotation pipelines. This HMM covers proteins from several distinctive families with this feature. The seed alignment illustrates the final selenocysteine or aligned Cys or Ser residues, but the HMM also hits proteins that lack an equivalent motif at the C-terminus. This C-terminal selenocysteine-containing motif has not yet been described in the literature.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 15600322   4 VVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKA-GSTTVPQI 56
Cdd:NF041212  1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLTgGERIVPVI 54

Glutaredoxin (GRX) family, GRX bacterial class 1 and 3 (b_1_3)-like subfamily; composed of bacterial GRXs, 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 E. coli GRX1 and GRX3, which are members of this subfamily.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15600322  3 PVVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGST-TVPQIWIGETHVGGCDDLHALERAG 76
Cdd:cd03418  1 KVEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGGRrTVPQIFIGDVHIGGCDDLYALERKG 75

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                       10        20        30        40        50        60        70        80
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322  3 PVVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGSTTVPQIWIGETHVGGCDDlhaleraGKLDALL 82
Cdd:COG0695  1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFDE-------GELDALL 73

Glutaredoxin;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322    4 VVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGSTTVPQIWIGETHV 63
Cdd:pfam00462  1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

Glutaredoxin; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model represents eukaryotic glutaredoxins and includes sequences from fungi, plants and metazoans as well as viruses.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322    4 VVIYTTAWCPYCIRAKQLLQRKGVDFQEI----ACDGKPELRAELARKAGSTTVPQIWIGETHVGGCDDLHALERAGKLD 79
Cdd:TIGR02180  1 VVVFSKSYCPYCKKAKEILAKLNVKPYEVveldQLSNGSEIQDYLEEITGQRTVPNIFINGKFIGGCSDLLALYKNGKLA 80

                 ...
gi 15600322   80 ALL 82
Cdd:TIGR02180 81 ELL 83

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 15600322  4 VVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAeLARKAGSTTVPQIWIGETHVGGCDDL 69
Cdd:cd03029  3 VSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGRS-LRAVTGAMTVPQVFIDGELIGGSDDL 67

Glutaredoxin (GRX) family, Dishevelled, Egl-10, and Pleckstrin (DEP) subfamily; composed of uncharacterized proteins containing a GRX domain and additional domains DEP and DUF547, both of which have unknown functions. GRX is a glutathione (GSH) dependent reductase containing a redox active CXXC motif in a TRX fold. It has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. By altering the redox state of target proteins, GRX is involved in many cellular functions.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322  4 VVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGSTTVPQIWIGETHVGGCDDLHALE 73
Cdd:cd03027  3 VTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLE 72

Glutaredoxin, GrxA family; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model includes the E. coli glyutaredoxin GrxA which appears to have primary responsibility for the reduction of ribonucleotide reductase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15600322    4 VVIYTTAWCPYCIRAKQL-----LQRKGVDFQEIACDGKPELRAELARKAGST--TVPQIWIGETHVGGCDDLHALER 74
Cdd:TIGR02183  2 VVIFGRPGCPYCVRAKQLaeklaIERADFEFRYIDIHAEGISKADLEKTVGKPveTVPQIFVDEKHVGGCTDFEQLVK 79

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322   4 VVIYTT------AWCPYCIRAKQLLQRKGVDFQE--IACDG--KPELRAELARKAGSTTVPQIWIGETHVGGCDDLHALE 73
Cdd:cd03031   2 VVLYTTslrgvrKTFEDCNNVRAILESFRVKFDErdVSMDSgfREELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLN 81

                ....*....
gi 15600322  74 RAGKLDALL 82
Cdd:cd03031  82 ESGELRKLL 90

bifunctional gluaredoxin/ribonucleoside-diphosphate reductase subunit beta; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322    1 MPPVVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPElRAELARKAGST---------TVPQIWIGETHVGGCDDLHA 71
Cdd:PRK12759   1 MVEVRIYTKTNCPFCDLAKSWFGANDIPFTQISLDDDVK-RAEFYAEVNKNillveehirTVPQIFVGDVHIGGYDNLMA 79

                 ....*....
gi 15600322   72 leRAGKLDA 80
Cdd:PRK12759  80 --RAGEVIA 86

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322    4 VVIYTTAWCPYCIRAKQLLQR----KG----VDFQEIacdgKPE--LRAELARKAGSTTVPQIWIGETHVGGCDDLHALE 73
Cdd:PHA03050  15 VTIFVKFTCPFCRNALDILNKfsfkRGayeiVDIKEF----KPEneLRDYFEQITGGRTVPRIFFGKTSIGGYSDLLEID 90

                         90
                 ....*....|.
gi 15600322   74 RAGKLDALLSA 84
Cdd:PHA03050  91 NMDALGDILSS 101

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15600322  4 VVIYTTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGSTTVPQIWIGETHV 63
Cdd:cd00570  1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLEDGGLVL 60

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 15600322  3 PVVIY-----TTAWCPYCIRAKQLLQRKGVDFQEIACDGKPELRAELARKAGSTTVPQIWI-GEThVGGCDDLHALERAG 76
Cdd:cd03028  9 PVVLFmkgtpEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVnGEL-VGGCDIVKEMHESG 87

               ..
gi 15600322 77 KL 78
Cdd:cd03028 88 EL 89

Thioredoxin-like domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15600322     4 VVIYTTAWCPYCIR-AKQLLQRKGV--------DFQEIACDGKPELRA---------ELARKAGSTTVPQIWI 58
Cdd:pfam13098   8 LVVFTDPDCPYCKKlKKELLEDPDVtvylgpnfVFIAVNIWCAKEVAKaftdilenkELGRKYGVRGTPTIVF 80

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega GSTs. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Class Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|..
gi 15600322  5 VIYTTAWCPYCIRAKQLLQRKG--VDFQEIACDGKPelrAELARKAGSTTVP 54
Cdd:cd03060  2 ILYSFRRCPYAMRARMALLLAGitVELREVELKNKP---AEMLAASPKGTVP 50