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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 496332586   4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGKLDALL 82
Cdd:TIGR02181  1 VTIYTKPYCPYCTRAKALLSSKGVTFTEIRVDGDPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 496332586   4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGKLDALL 82
Cdd:TIGR02181  1 VTIYTKPYCPYCTRAKALLSSKGVTFTEIRVDGDPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 79

glutaredoxin 3; Provisional

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496332586  1 MATVVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGKLDA 80
Cdd:PRK10638  1 MANVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80

                ..
gi 496332586 81 LL 82
Cdd:PRK10638 81 LL 82

Glutaredoxin;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 496332586   4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHV 63
Cdd:pfam00462  1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 496332586   4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGKLDALL 82
Cdd:TIGR02181  1 VTIYTKPYCPYCTRAKALLSSKGVTFTEIRVDGDPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 79

glutaredoxin 3; Provisional

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496332586  1 MATVVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGKLDA 80
Cdd:PRK10638  1 MANVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80

                ..
gi 496332586 81 LL 82
Cdd:PRK10638 81 LL 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 496332586  4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALER 74
Cdd:cd02066   2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human 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 human GRX1 and GRX2, which are members of this subfamily. Also included in this subfamily are the N-terminal GRX domains of proteins similar to human thioredoxin reductase 1 and 3.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496332586  4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKP---QVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGKLDA 80
Cdd:cd03419   2 VVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEdgsEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVK 81

                .
gi 496332586 81 L 81
Cdd:cd03419  82 L 82

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 496332586  4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQkAGRTSVPQIWIGSTHVGGCDDL 69
Cdd:cd03029   3 VSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGRSLRAV-TGAMTVPQVFIDGELIGGSDDL 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 496332586  4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRTSVPQIWIGSTHVGGCDDLFALE 73
Cdd:cd03027   3 VTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLE 72

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 496332586  4 VVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKA-GRTSVPQI 56
Cdd:NF041212  1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLTgGERIVPVI 54

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 496332586  15 CSRAKYLLENKGVAFEEIKVDGKPQVRAEMAQKAGRT----SVPQIWIGSTHVGGCDDLFALERAGKLDALLA 83
Cdd:cd03031   19 CNNVRAILESFRVKFDERDVSMDSGFREELRELLGAElkavSLPRVFVDGRYLGGAEEVLRLNESGELRKLLK 91

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 496332586   4 VVVYSSDYCPYCSRAKYLLENKGVA-----FEEIKVDGKPQVRAEMAQKAGRT--SVPQIWIGSTHVGGCDDLFALER 74
Cdd:TIGR02183  2 VVIFGRPGCPYCVRAKQLAEKLAIEradfeFRYIDIHAEGISKADLEKTVGKPveTVPQIFVDEKHVGGCTDFEQLVK 79

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 496332586  4 VVVYSSDYCPYCSRAKYLL-----ENKGVAFEEIKVDGKPQVRAEMAQKAGRTsVPQI 56
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLaelalLNKGVKFEAVDVDEDPALEKELKRYGVGG-VPTL 57

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 496332586   4 VVVYSSDYCPYCSRAKYLLEN---KGVAFEEIKV-DGKPQVRAE--MAQKAGRTSVPQIWIGSTHVGGCDDLFALERAGK 77
Cdd:PHA03050  15 VTIFVKFTCPFCRNALDILNKfsfKRGAYEIVDIkEFKPENELRdyFEQITGGRTVPRIFFGKTSIGGYSDLLEIDNMDA 94

                 ....*..
gi 496332586  78 LDALLAA 84
Cdd:PHA03050  95 LGDILSS 101

Glutaredoxin-like protein; This family of glutaredoxin-like proteins is limited to the Actinobacteria and contains the conserved CxxC motif.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 496332586   3 TVVVYSSDYCPYCSRAKYLLENKGVAFEEIKVDGKP 38
Cdd:TIGR02200  1 TITVYGTTWCGYCAQLMRTLDKLGAAYEWVDIEEDE 36

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30
                 ....*....|....*....|....*....|
gi 496332586   6 VYSSDYCPYCSRAKYLLENKGVAFEEIKVD 35
Cdd:COG0625    4 LYGSPPSPNSRRVRIALEEKGLPYELVPVD 33

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 496332586  7 YSSDYCPYCSRAKYLLENKGVAFEEIKVD--GKPQVRAEM 44
Cdd:cd03059   4 YSGPDDVYSHRVRIVLAEKGVSVEIIDVDpdNPPEDLAEL 43

GST_N family, Glutaredoxin 2 (GRX2) subfamily; composed of bacterial proteins similar to E. coli GRX2, an atypical GRX with a molecular mass of about 24kD, compared with other GRXs which are 9-12kD in size. GRX2 adopts a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. It contains a redox active CXXC motif located in the N-terminal domain but is not able to reduce ribonucleotide reductase like other GRXs. However, it catalyzes GSH-dependent protein disulfide reduction of other substrates efficiently. GRX2 is thought to function primarily in catalyzing the reversible glutathionylation of proteins in cellular redox regulation including stress responses.

                        10        20
                ....*....|....*....|....*..
gi 496332586  6 VYSSDYCPYCSRAKYLLENKGVAFEEI 32
Cdd:cd03037   3 LYIYEHCPFCVKARMIAGLKNIPVEQI 29