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 19922712  33 KVVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGGTDVKRLYEQGILQ 112
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLV 80

                .
gi 19922712 113 K 113
Cdd:cd03419  81 K 81

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 19922712  33 KVVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGGTDVKRLYEQGILQ 112
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLV 80

                .
gi 19922712 113 K 113
Cdd:cd03419  81 K 81

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19922712    34 VVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRDdgnEIQAVLGEMTGSRTVPRCFIDGKFV 96
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19922712   23 QFVRDTISGNKVVIFSKSYCPYCSMAKEQFRKINVKA---TVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGG 99
Cdd:PHA03050   4 EFVQQRLANNKVTIFVKFTCPFCRNALDILNKFSFKRgayEIVDIKEFKPENELRDYFEQITGGRTVPRIFFGKTSIGGY 83

                 ...
gi 19922712  100 TDV 102
Cdd:PHA03050  84 SDL 86

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 19922712  33 KVVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGGTDVKRLYEQGILQ 112
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLV 80

                .
gi 19922712 113 K 113
Cdd:cd03419  81 K 81

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 19922712  33 KVVIFSKSYCPYCSMAKEQFRKINVKatVIELDQRDDGnEIQAVLGEMTGSRTVPRCFIDGKFVGGGTDVKRLYE 107
Cdd:cd02066   1 KVVVFSKSTCPYCKRAKRLLESLGIE--FEEIDILEDG-ELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to plants. Multiple isoforms are found in A. thaliana and O.sativa.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19922712    25 VRDTISGNKVVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGGTDVKR 104
Cdd:TIGR02189   1 VRRMVSEKAVVIFSRSSCCMCHVVKRLLLTLGVNPAVHEIDKEPAGKDIENALSRLGCSPAVPAVFVGGKLVGGLENVMA 80

                  ....*..
gi 19922712   105 LYEQGIL 111
Cdd:TIGR02189  81 LHISGSL 87

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19922712  33 KVVIFSKSYCPYCSMAKEQFRKINVKATVIELDQrdDGNEIQAVLgEMTGSRTVPRCFIDGKFVGG 98
Cdd:COG0695   1 KVTLYTTPGCPYCARAKRLLDEKGIPYEEIDVDE--DPEAREELR-ERSGRRTVPVIFIGGEHLGG 63

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 19922712    34 VVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRddgneiQAVLGEM---TGSRTVPRCFIDGKFVGGGTDVKRLYEQGI 110
Cdd:TIGR02181   1 VTIYTKPYCPYCTRAKALLSSKGVTFTEIRVDGD------PALRDEMmqrSGRRTVPQIFIGDVHVGGCDDLYALDREGK 74

                  ...
gi 19922712   111 LQK 113
Cdd:TIGR02181  75 LDP 77

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19922712   23 QFVRDTISGNKVVIFSKSYCPYCSMAKEQFRKINVKA---TVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGG 99
Cdd:PHA03050   4 EFVQQRLANNKVTIFVKFTCPFCRNALDILNKFSFKRgayEIVDIKEFKPENELRDYFEQITGGRTVPRIFFGKTSIGGY 83

                 ...
gi 19922712  100 TDV 102
Cdd:PHA03050  84 SDL 86

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 19922712  33 KVVIFSKSYCPYCSMAKEQFRKINVKATVIELDQRDdgnEIQAVLGEMTGSRTVPRCFIDGK-FVG 97
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDP---EALEELKKLNGYRSVPVVVIGDEhLSG 63

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19922712   33 KVVIFSKSYCPYCSMAKEQfrkINVKATVIELDQRDDGNEIQAVLGEMTGSRTVPRCFIDGKFVGGGTDVKRLYEQGIL 111
Cdd:PRK10638   3 NVEIYTKATCPFCHRAKAL---LNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGL 78

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19922712   34 VVIFSKSYCPYCSMAKEQFRKINVKATviELDQRDDGNEIQAVLGEMTGSRTVPrCFIDGKFV----GGGTDV 102
Cdd:NF041212   1 VVIYTKPGCPYCAAAKEDLARRGIPFE--EIDVSKDPEALEEMLRLTGGERIVP-VIVEGGEVtvgfGGGUGF 70

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19922712  25 VRDTISGNKVVIFSKSY--CPYC----------SMAKEQFRKINVkatvieLDqrDDgnEIQAVLGEMTGSRTVPRCFID 92
Cdd:cd03028   1 IKKLIKENPVVLFMKGTpeEPRCgfsrkvvqilNQLGVDFGTFDI------LE--DE--EVRQGLKEYSNWPTFPQLYVN 70

                        90       100
                ....*....|....*....|
gi 19922712  93 GKFVGGGTDVKRLYEQGILQ 112
Cdd:cd03028  71 GELVGGCDIVKEMHESGELQ 90