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 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEGREMEKALLRLGCTAPVPAVFIGGKLMGSTNEIMSLHLSGSLTQ 92
Cdd:cd03419     2 VVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVK 81

                  .
gi 1012360431  93 M 93
Cdd:cd03419    82 L 82

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEGR-EMEKallRLGCTApVPAVFIGGKLMG 76
Cdd:COG0695     2 VTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDEDPEAReELRE---RSGRRT-VPVIFIGGEHLG 62

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 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEGREMEKALLRLGCTAPVPAVFIGGKLMGSTNEIMSLHLSGSLTQ 92
Cdd:cd03419     2 VVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVK 81

                  .
gi 1012360431  93 M 93
Cdd:cd03419    82 L 82

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEGREmekALLRLGCTAPVPAVFIGGKL 74
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIRE---ELKELSGWPTVPQVFIDGEH 59

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 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEgREMEkaLLRLGCTAPVPAVFIGGKLMGSTNEIMSL 84
Cdd:cd03027     3 VTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPE-RKAE--LEERTGSSVVPQIFFNEKLVGGLTDLKSL 71

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 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEGRE--MEKAllrlGCTAPVPAVFIGGKLMGSTNEIMSLHLSG 88
Cdd:cd03418     2 VEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREemINRS----GGRRTVPQIFIGDVHIGGCDDLYALERKG 75

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1012360431  13 VVIFTKSSCCLCYAVNILFHELGVRPVVHEIDHDPEGR-EMEKALLRLGctapVPAVFIGGK 73
Cdd:cd02976     2 VTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALeELKKLNGYRS----VPVVVIGDE 59