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 21593494  13 VVIFSKSSCCMSYAVQVLFQDLGVHPTVHEIDKDPECREIEKALMRLGCSTPVPAIFVGGKLIGSTNEVMSLHLSGSLVP 92
Cdd:cd03419   2 VVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVK 81

                .
gi 21593494  93 L 93
Cdd:cd03419  82 L 82

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21593494  13 VVIFSKSSC--CMsyAVQVLFQDLGVHPTVHEIDKDPECREiekALM-RLGCSTpVPAIFVGGKLIG 76
Cdd:COG0695   2 VTLYTTPGCpyCA--RAKRLLDEKGIPYEEIDVDEDPEARE---ELReRSGRRT-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 21593494  13 VVIFSKSSCCMSYAVQVLFQDLGVHPTVHEIDKDPECREIEKALMRLGCSTPVPAIFVGGKLIGSTNEVMSLHLSGSLVP 92
Cdd:cd03419   2 VVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVK 81

                .
gi 21593494  93 L 93
Cdd:cd03419  82 L 82

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21593494    13 VVIFSKSSCCMSYAVQVLFQDLGVHPTVHEIDKDPecrEIEKALMRLGCSTPVPAIFVGGKLI 75
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21593494   13 VVIFSKSSCCMSYAVQVLFQDLGVhpTVHE--IDKDPECREieKALMRLGcSTPVPAIFVGGKLIGSTNEVMSLHLSGSL 90
Cdd:PRK10638   4 VEIYTKATCPFCHRAKALLNSKGV--SFQEipIDGDAAKRE--EMIKRSG-RTTVPQIFIDAQHIGGCDDLYALDARGGL 78

                 ....*
gi 21593494   91 VPLVK 95
Cdd:PRK10638  79 DPLLK 83

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 21593494  21 CCmsyAVQVLFQDLGVHPTVHEIDKDPECREIEKALMRLGCSTP-VPAIFVGGKLIGSTNEVMSLHLSGSLVPLVKPFQA 99
Cdd:cd03031  19 CN---NVRAILESFRVKFDERDVSMDSGFREELRELLGAELKAVsLPRVFVDGRYLGGAEEVLRLNESGELRKLLKGIRA 95

                ...
gi 21593494 100 NLC 102
Cdd:cd03031  96 RAG 98

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 21593494  13 VVIFSKSSCCMSYAVQVLFQDLGVHPTVHEIDKDPECREiekALMRLGCSTPVPAIFVGGKLI 75
Cdd:cd02976   2 VTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALE---ELKKLNGYRSVPVVVIGDEHL 61