Glutaredoxin, GrxC 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 family of glutaredoxins includes the E. coli protein GrxC (Grx3) which appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulfides. [Energy metabolism, Electron transport]

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDRTGKLLPLL 87
Cdd:TIGR02181  1 VTIYTKPYCPYCTRAKALLSSKGV-TFTEIRVDGDPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 79

Glutaredoxin, GrxC 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 family of glutaredoxins includes the E. coli protein GrxC (Grx3) which appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulfides. [Energy metabolism, Electron transport]

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDRTGKLLPLL 87
Cdd:TIGR02181  1 VTIYTKPYCPYCTRAKALLSSKGV-TFTEIRVDGDPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 79

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDRTGKLLPLL 87
Cdd:PRK10638   4 VEIYTKATCPFCHRAKALLNSKGV-SFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDPLL 82

Glutaredoxin;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHV 68
Cdd:pfam00462  1 VVLYTKPTCPFCKRAKRLLKSLGV-DFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

Glutaredoxin, GrxC 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 family of glutaredoxins includes the E. coli protein GrxC (Grx3) which appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulfides. [Energy metabolism, Electron transport]

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDRTGKLLPLL 87
Cdd:TIGR02181  1 VTIYTKPYCPYCTRAKALLSSKGV-TFTEIRVDGDPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 79

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDRTGKLLPLL 87
Cdd:PRK10638   4 VEIYTKATCPFCHRAKALLNSKGV-SFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDPLL 82

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 2562027150  7 PVRMYTSAVCPFCVRAERLLGERGVQnIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDR 79
Cdd:cd02066    1 KVVVFSKSTCPYCKRAKRLLESLGIE-FEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHV 68
Cdd:pfam00462  1 VVLYTKPTCPFCKRAKRLLKSLGV-DFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

NrdH-redoxin (NrdH) family; NrdH is a small monomeric protein with a conserved redox active CXXC motif within a TRX fold, characterized by a glutaredoxin (GRX)-like sequence and TRX-like activity profile. In vitro, it displays protein disulfide reductase activity that is dependent on TRX reductase, not glutathione (GSH). It is part of the NrdHIEF operon, where NrdEF codes for class Ib ribonucleotide reductase (RNR-Ib), an efficient enzyme at low oxygen levels. Under these conditions when GSH is mostly conjugated to spermidine, NrdH can still function and act as a hydrogen donor for RNR-Ib. It has been suggested that the NrdHEF system may be the oldest RNR reducing system, capable of functioning in a microaerophilic environment, where GSH was not yet available. NrdH from Corynebacterium ammoniagenes can form domain-swapped dimers, although it is unknown if this happens in vivo. Domain-swapped dimerization, which results in the blocking of the TRX reductase binding site, could be a mechanism for regulating the oxidation state of the protein.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2562027150  7 PVRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGcddlFDLDRTGKLL 84
Cdd:cd02976    1 EVTVYTKPDCPYCKATKRFLDERGI-PFEEVDVDEDPEALEELKKLNGYRSVPVVVIGDEHLSG----FRPDKLRALL 73

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 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVqNIEKIRVDLDpAQKEKMMAETGRRTVPQIYIGSTHVGGCDDL 74
Cdd:cd03029    3 VSLFTKPGCPFCARAKAALQENGI-SYEEIPLGKD-ITGRSLRAVTGAMTVPQVFIDGELIGGSDDL 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 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVQNIEkIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLD 78
Cdd:cd03027    3 VTIYSRLGCEDCTAVRLFLREKGLPYVE-INIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLE 72

glutaredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2562027150   5 HSPVRMYTSAVCPFCVRAERLLGE----RGVQNIEKIRvDLDPAQKEKMMAE--TGRRTVPQIYIGSTHVGGCDDLFDLD 78
Cdd:PHA03050   12 NNKVTIFVKFTCPFCRNALDILNKfsfkRGAYEIVDIK-EFKPENELRDYFEqiTGGRTVPRIFFGKTSIGGYSDLLEID 90

                  ....*....
gi 2562027150  79 RTGKLLPLL 87
Cdd:PHA03050   91 NMDALGDIL 99

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 2562027150  8 VRMYTSAVCPFCVRAERLLGERGVQnIEKIRVDLDPAQKEKMMAET-GRRTVPQI 61
Cdd:NF041212   1 VVIYTKPGCPYCAAAKEDLARRGIP-FEEIDVSKDPEALEEMLRLTgGERIVPVI 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2562027150 16 CPFCVRAERLLGERGVQnIEKIRVDLDPAQKEKMMAETGRRTVPQIYIGSTHVGGCDDLFDLDRTGKL 83
Cdd:cd03028   23 CGFSRKVVQILNQLGVD-FGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIVKEMHESGEL 89