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 79313249  69 VENDVKDNPVMIYMKGVPESPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGSDII 148
Cdd:cd03028   1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                        90
                ....*....|
gi 79313249 149 LNMHKEGELE 158
Cdd:cd03028  81 KEMHESGELQ 90

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 79313249  69 VENDVKDNPVMIYMKGVPESPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGSDII 148
Cdd:cd03028   1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                        90
                ....*....|
gi 79313249 149 LNMHKEGELE 158
Cdd:cd03028  81 KEMHESGELQ 90

monothiol glutaredoxin, Grx4 family; The gene for the member of this glutaredoxin family in E. coli, originally designated ydhD, is now designated grxD. Its protein, Grx4, is a monothiol glutaredoxin similar to Grx5 of yeast, which is involved in iron-sulfur cluster formation. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79313249    66 KDIVENDVKDNPVMIYMKGVPESPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGS 145
Cdd:TIGR00365   2 IERIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGGC 81

                          90
                  ....*....|....*.
gi 79313249   146 DIILNMHKEGELEQKL 161
Cdd:TIGR00365  82 DIIMEMYQSGELQTLL 97

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 79313249    78 VMIYMKgvpesPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFI 142
Cdd:pfam00462   1 VVLYTK-----PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

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 79313249  69 VENDVKDNPVMIYMKGVPESPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGSDII 148
Cdd:cd03028   1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                        90
                ....*....|
gi 79313249 149 LNMHKEGELE 158
Cdd:cd03028  81 KEMHESGELQ 90

monothiol glutaredoxin, Grx4 family; The gene for the member of this glutaredoxin family in E. coli, originally designated ydhD, is now designated grxD. Its protein, Grx4, is a monothiol glutaredoxin similar to Grx5 of yeast, which is involved in iron-sulfur cluster formation. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79313249    66 KDIVENDVKDNPVMIYMKGVPESPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGS 145
Cdd:TIGR00365   2 IERIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGGC 81

                          90
                  ....*....|....*.
gi 79313249   146 DIILNMHKEGELEQKL 161
Cdd:TIGR00365  82 DIIMEMYQSGELQTLL 97

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 79313249  77 PVMIYMKGVpespqCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGSDIILNMHK 153
Cdd:cd02066   1 KVVVFSKST-----CPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 79313249    78 VMIYMKgvpesPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFI 142
Cdd:pfam00462   1 VVLYTK-----PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79313249  77 PVMIYMKgvpesPQCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGSDiilnmhkEGE 156
Cdd:COG0695   1 KVTLYTT-----PGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFD-------EGE 68

                ....*.
gi 79313249 157 LEQKLK 162
Cdd:COG0695  69 LDALLA 74

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 79313249  77 PVMIYMKGVpespqCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSH-WPTFPQIFIKGEFIGGSDIILNMHKEG 155
Cdd:cd03418   1 KVEIYTKPN-----CPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGgRRTVPQIFIGDVHIGGCDDLYALERKG 75

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 79313249   78 VMIYMKGVpespqCGFSSLAVRVLQQYNVPISSRNILEDQELKNAVKSFSHWPTFPQIFIKGEFIGGSDIILNMHKEGEL 157
Cdd:PRK10638   4 VEIYTKAT-----CPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGL 78

                 ....*
gi 79313249  158 EQKLK 162
Cdd:PRK10638  79 DPLLK 83

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 79313249  89 PQCGFSSLAVRVLQQYNvpISSRNILEDQELK-NAVKSFSHWPTFPQIFIKGEFIGGSD 146
Cdd:cd03029   9 PGCPFCARAKAALQENG--ISYEEIPLGKDITgRSLRAVTGAMTVPQVFIDGELIGGSD 65