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 38567046 152 PIIIFSKSYCPYSKKAKSLLLGDYQidpAPYVVELDQHPLGPGIQAELGDRTGRKTVPNILVGGISIGGSDDIAKLDQEE 231
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGV---KPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....*
gi 38567046 232 TLIEK 236
Cdd:cd03419  78 KLVKL 82

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 38567046 152 PIIIFSKSYCPYSKKAKSLLLGDYQidpAPYVVELDQHPLGPGIQAELGDRTGRKTVPNILVGGISIGGSDDIAKLDQEE 231
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGV---KPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....*
gi 38567046 232 TLIEK 236
Cdd:cd03419  78 KLVKL 82

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38567046   153 IIIFSKSYCPYSKKAKSLLlgdYQIDPAPYVVELDQHplgPGIQAELGDRTGRKTVPNILVGG 215
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLL---KSLGVDFEEIDVDED---PEIREELKELSGWPTVPQVFIDG 57

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 38567046  153 IIIFSKSYCPYSKKAKSLLlgdyqidpAPYVVELDQHPL--GPGIQAELGDRTGRKTVPNILVGGISIGGSDDIAKLD 228
Cdd:PRK10638   4 VEIYTKATCPFCHRAKALL--------NSKGVSFQEIPIdgDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALD 73

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 38567046 152 PIIIFSKSYCPYSKKAKSLLLGDYQidpAPYVVELDQHPLGPGIQAELGDRTGRKTVPNILVGGISIGGSDDIAKLDQEE 231
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGV---KPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....*
gi 38567046 232 TLIEK 236
Cdd:cd03419  78 KLVKL 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 38567046 152 PIIIFSKSYCPYSKKAKSLLlGDYQIDpapyVVELDQHPlGPGIQAELGDRTGRKTVPNILVGGISIGGSDDIAKLDQ 229
Cdd:cd02066   1 KVVVFSKSTCPYCKRAKRLL-ESLGIE----FEEIDILE-DGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38567046 152 PIIIFSKSYCPYSKKAKSLLlGDYQIDPAPYVVELDqhplgPGIQAELGDRTG-RKTVPNILVGGISIGGSDDIAKLDQE 230
Cdd:cd03418   1 KVEIYTKPNCPYCVRAKALL-DKKGVDYEEIDVDGD-----PALREEMINRSGgRRTVPQIFIGDVHIGGCDDLYALERK 74

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 38567046 152 PIIIFSKSYCPYSKKAKSlLLGDYQIdpaPY-VVELDQHplgPGIQAELGDRTGRKTVPNILVGGISIGGSDDiAKLDQ 229
Cdd:COG0695   1 KVTLYTTPGCPYCARAKR-LLDEKGI---PYeEIDVDED---PEAREELRERSGRRTVPVIFIGGEHLGGFDE-GELDA 71

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 38567046 153 IIIFSKSYCPYSKKAKSLLlgdyqidpAPYVVELDQHPLGPGIQAE-LGDRTGRKTVPNILVGGISIGGSDDIAK 226
Cdd:cd03029   3 VSLFTKPGCPFCARAKAAL--------QENGISYEEIPLGKDITGRsLRAVTGAMTVPQVFIDGELIGGSDDLEK 69

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 38567046 153 IIIFSKSYCPYSKKAKsLLLGDYQIdpaPYV-VELDQHPlgpGIQAELGDRTGRKTVPNILVGGISIGGSDDIAKLD 228
Cdd:cd03027   3 VTIYSRLGCEDCTAVR-LFLREKGL---PYVeINIDIFP---ERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSLE 72

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38567046 152 PIIIFSKSYCPYSKKAKSLL--LG-DYQ-IDpapyvVELDqhplgPGIQAELGDRTGRKTVPNILVGGISIGGSDDiAKL 227
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLdeRGiPFEeVD-----VDED-----PEALEELKKLNGYRSVPVVVIGDEHLSGFRP-DKL 69

                ..
gi 38567046 228 DQ 229
Cdd:cd02976  70 RA 71

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38567046  142 EELRSILKKSPIIIFSKSYCPYSKKAKSLLlGDYQIDPAPY-VVELDQHPLGPGIQAELGDRTGRKTVPNILVGGISIGG 220
Cdd:PHA03050   4 EFVQQRLANNKVTIFVKFTCPFCRNALDIL-NKFSFKRGAYeIVDIKEFKPENELRDYFEQITGGRTVPRIFFGKTSIGG 82

                         90       100
                 ....*....|....*....|.
gi 38567046  221 SDDIAKLDQEETLIEKIMSLA 241
Cdd:PHA03050  83 YSDLLEIDNMDALGDILSSIG 103