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 6320720   53 VFVAAKTYCPYCKATLStLFQELNVpksKALVLELDEMSNGSEIQDALEEISGQKTVPNVYINGKHIGGNSDLETLKKNG 132
Cdd:cd03419   2 VVVFSKSYCPYCKRAKS-LLKELGV---KPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....*
gi 6320720  133 KLAEI 137
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 6320720   53 VFVAAKTYCPYCKATLStLFQELNVpksKALVLELDEMSNGSEIQDALEEISGQKTVPNVYINGKHIGGNSDLETLKKNG 132
Cdd:cd03419   2 VVVFSKSYCPYCKRAKS-LLKELGV---KPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....*
gi 6320720  133 KLAEI 137
Cdd:cd03419  78 KLVKL 82

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 6320720     53 VFVAAKTYCPYCKATLSTLfQELNVpksKALVLELDEMSngsEIQDALEEISGQKTVPNVYINGKHI 119
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLL-KSLGV---DFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320720    58 KTYCPYC---KATLST---LFQELNVPKSKALvleLDEMsngseIQDaleeiSGQKTVPNVYINGKHIGGNSDLETLKKN 131
Cdd:PRK10638   9 KATCPFChraKALLNSkgvSFQEIPIDGDAAK---REEM-----IKR-----SGRTTVPQIFIDAQHIGGCDDLYALDAR 75

                 ....*...
gi 6320720   132 GKLAEILK 139
Cdd:PRK10638  76 GGLDPLLK 83

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 6320720   53 VFVAAKTYCPYCKATLStLFQELNVpksKALVLELDEMSNGSEIQDALEEISGQKTVPNVYINGKHIGGNSDLETLKKNG 132
Cdd:cd03419   2 VVVFSKSYCPYCKRAKS-LLKELGV---KPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....*
gi 6320720  133 KLAEI 137
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 6320720   53 VFVAAKTYCPYCKATLStLFQELNVPkskalVLELDEMSNGsEIQDALEEISGQKTVPNVYINGKHIGGNSDLETLKK 130
Cdd:cd02066   2 VVVFSKSTCPYCKRAKR-LLESLGIE-----FEEIDILEDG-ELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

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 6320720     58 KTYCPYCKATLSTL------FQELNVPKSKALvleLDEMSngseiqdaleEISGQKTVPNVYINGKHIGGNSDLETLKKN 131
Cdd:TIGR02181   6 KPYCPYCTRAKALLsskgvtFTEIRVDGDPAL---RDEMM----------QRSGRRTVPQIFIGDVHVGGCDDLYALDRE 72

                  ....*..
gi 6320720    132 GKLAEIL 138
Cdd:TIGR02181  73 GKLDPLL 79

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 6320720   58 KTYCPYCKATLSTL------FQELNVPKSKALvleLDEMSNGSEiqdaleeisGQKTVPNVYINGKHIGGNSDLETLKKN 131
Cdd:cd03418   7 KPNCPYCVRAKALLdkkgvdYEEIDVDGDPAL---REEMINRSG---------GRRTVPQIFIGDVHIGGCDDLYALERK 74

                .
gi 6320720  132 G 132
Cdd:cd03418  75 G 75

Glutaredoxin-family domain; This C-terminal domain with homology to glutaredoxin is fused to an N-terminal peroxiredoxin-like domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320720     50 QKEVFVAAKTYCPYC---KATLstlfqelnvpksKALVLELDEMSNGSEIQD-ALEEISGQKTVPNVYINGKHIGGNSDL 125
Cdd:TIGR02190   7 PESVVVFTKPGCPFCakaKATL------------KEKGYDFEEIPLGNDARGrSLRAVTGATTVPQVFIGGKLIGGSDEL 74

                  ..
gi 6320720    126 ET 127
Cdd:TIGR02190  75 EA 76

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6320720    44 VKDLIGQKEVFVAAKTYCPYCKATLSTLfQELNVPKSKALVLELDEMSNGSEIQDALEEISGQKTVPNVYINGKHIGGNS 123
Cdd:PHA03050   6 VQQRLANNKVTIFVKFTCPFCRNALDIL-NKFSFKRGAYEIVDIKEFKPENELRDYFEQITGGRTVPRIFFGKTSIGGYS 84

                         90
                 ....*....|....*...
gi 6320720   124 DLETLKKNGKLAEILKPV 141
Cdd:PHA03050  85 DLLEIDNMDALGDILSSI 102

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
                ....*....|....*....|....*....|....*....|....*....|...
gi 6320720   90 MSNG--SEIQDALEEISGQKTVPNVYINGKHIGGNSDLETLKKNGKLAEILKP 140
Cdd:cd03031  40 MDSGfrEELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKLLKG 92

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 6320720   52 EVFVAAKTYCPYCKATLSTL------FQELNVPKSKALVleldemsngseiqDALEEISGQKTVPNVYINGKHIGGnSDL 125
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLdergipFEEVDVDEDPEAL-------------EELKKLNGYRSVPVVVIGDEHLSG-FRP 66

                ....*
gi 6320720  126 ETLKK 130
Cdd:cd02976  67 DKLRA 71

DSBA-like thioredoxin domain; This family contains a diverse set of proteins with a thioredoxin-like structure pfam00085. This family also includes 2-hydroxychromene-2-carboxylate (HCCA) isomerase enzymes catalyze one step in prokaryotic polyaromatic hydrocarbon (PAH) catabolic pathways. This family also contains members with functions other than HCCA isomerization, such as Kappa family GSTs, whose similarity to HCCA isomerases was not previously recognized. The sequence Swiss:O07298 has been annotated as a dioxygenase but is almost certainly an HCCA isomerase enzyme. Similarly, the sequence Swiss:Q9ZI67 has been annotated as a dehydrogenase, but is most probably also an HCCA isomerase enzyme. In addition, the Rhizobium leguminosarum Swiss:Q52782 protein has been annotated as a putative glycerol-3-phosphate transfer protein, but is also most likely to be an HCCA isomerase enzyme.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 6320720     86 ELDEMSNGSEIQDALEE---------ISGqktVPNVYINGKHIGGNSDLETLKK 130
Cdd:pfam01323 138 EFDEFLDSPAVKEAVREntaaaislgVFG---VPTFVVGGKMVFGADRLDTLAD 188