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 1958671197  28 CVVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEYGSQFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHKEGKLL 107
Cdd:cd03419     1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLV 80

                  ..
gi 1958671197 108 PL 109
Cdd:cd03419    81 KL 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 1958671197  28 CVVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEYGSQFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHKEGKLL 107
Cdd:cd03419     1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLV 80

                  ..
gi 1958671197 108 PL 109
Cdd:cd03419    81 KL 82

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEygsQFQEALYKMTGERTVPRIFVNGIFI 91
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

glutaredoxin 3; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMveyGSQFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHKEGKLLP 108
Cdd:PRK10638    4 VEIYTKATCPFCHRAKALLNSKGVSFQEIPIDG---DAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80

                  ..
gi 1958671197 109 LV 110
Cdd:PRK10638   81 LL 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 1958671197  28 CVVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEYGSQFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHKEGKLL 107
Cdd:cd03419     1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLV 80

                  ..
gi 1958671197 108 PL 109
Cdd:cd03419    81 KL 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 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVnyKVVELDMVEYGSqFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHK 102
Cdd:cd02066     2 VVVFSKSTCPYCKRAKRLLESLGI--EFEEIDILEDGE-LREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEygsQFQEALYKMTGERTVPRIFVNGIFI 91
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

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 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKvvELDMVEYGSQFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHKEG 104
Cdd:cd03418     2 VEIYTKPNCPYCVRAKALLDKKGVDYE--EIDVDGDPALREEMINRSGGRRTVPQIFIGDVHIGGCDDLYALERKG 75

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 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEYGSqfqeALYKMTGERTVPRIFVNGIFIGGAADTHR 99
Cdd:cd03029     3 VSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGR----SLRAVTGAMTVPQVFIDGELIGGSDDLEK 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 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYkvVELDMVEYGSQFQEaLYKMTGERTVPRIFVNGIFIGGAADTHRL 100
Cdd:cd03027     3 VTIYSRLGCEDCTAVRLFLREKGLPY--VEINIDIFPERKAE-LEERTGSSVVPQIFFNEKLVGGLTDLKSL 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958671197  40 CSMAKKIFHDMNVNYKVVELDM-VEYGSQFQEALYKMTGERTVPRIFVNGIFIGGAADTHRLHKEGKLLPLVHQC 113
Cdd:cd03031    19 CNNVRAILESFRVKFDERDVSMdSGFREELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKLLKGI 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEYGsqfqEALYKMTGERTVPRIFVNGIFIGGA 94
Cdd:TIGR02190  10 VVVFTKPGCPFCAKAKATLKEKGYDFEEIPLGNDARG----RSLRAVTGATTVPQVFIGGKLIGGS 71

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKvvELDmVEYGSQFQEALYKMT-GERTVPRIFVNG 88
Cdd:NF041212    1 VVIYTKPGCPYCAAAKEDLARRGIPFE--EID-VSKDPEALEEMLRLTgGERIVPVIVEGG 58

Thioredoxin (TRX)-Glutaredoxin (GRX)-like family; composed of archaeal and bacterial proteins that show similarity to both TRX and GRX, including the C-terminal TRX-fold subdomain of Pyrococcus furiosus protein disulfide oxidoreductase (PfPDO). All members contain a redox-active CXXC motif and may function as PDOs. The archaeal proteins Mj0307 and Mt807 show structures more similar to GRX, but activities more similar to TRX. Some members of the family are similar to PfPDO in that they contain a second CXXC motif located in a second TRX-fold subdomain at the N-terminus; the superimposable N- and C-terminal TRX subdomains form a compact structure. PfPDO is postulated to be the archaeal counterpart of bacterial DsbA and eukaryotic protein disulfide isomerase (PDI). The C-terminal CXXC motif of PfPDO is required for its oxidase, reductase and isomerase activities. Also included in the family is the C-terminal TRX-fold subdomain of the N-terminal domain (NTD) of bacterial AhpF, which has a similar fold as PfPDO with two TRX-fold subdomains but without the second CXXC motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958671197  29 VVIFSKSSCSYCSMAKKIFHDMNVNYKVVELDMVEyGSQFQEaLYKMTGERTVPRIFVNG--IFIG 92
Cdd:cd02973     3 IEVFVSPTCPYCPDAVQAANRIAALNPNISAEMID-AAEFPD-LADEYGVMSVPAIVINGkvEFVG 66