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 519054651    3 VMETIKQQLSENPVILYMKGSPNAPQCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYANWPTYPQLWVNGELVGG 82
Cdd:TIGR00365   1 TIERIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGG 80

                          90
                  ....*....|....*..
gi 519054651   83 CDIVTEMYENGELKTLI 99
Cdd:TIGR00365  81 CDIIMEMYQSGELQTLL 97

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 519054651   7 IKQQLSENPVILYMKGSPNAPQCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYANWPTYPQLWVNGELVGGCDIV 86
Cdd:cd03028    1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                         90
                 ....*....|
gi 519054651  87 TEMYENGELK 96
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 519054651    3 VMETIKQQLSENPVILYMKGSPNAPQCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYANWPTYPQLWVNGELVGG 82
Cdd:TIGR00365   1 TIERIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGG 80

                          90
                  ....*....|....*..
gi 519054651   83 CDIVTEMYENGELKTLI 99
Cdd:TIGR00365  81 CDIIMEMYQSGELQTLL 97

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 519054651   7 IKQQLSENPVILYMKGSPNAPQCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYANWPTYPQLWVNGELVGGCDIV 86
Cdd:cd03028    1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                         90
                 ....*....|
gi 519054651  87 TEMYENGELK 96
Cdd:cd03028   81 KEMHESGELQ 90

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 519054651  15 PVILYMKGSpnapqCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYANWPTYPQLWVNGELVGGCDIVTEMYE 91
Cdd:cd02066    1 KVVVFSKST-----CPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 519054651  15 PVILYMKgspnaPQCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYANWPTYPQLWVNGELVGGCDivtemyeNGE 94
Cdd:COG0695    1 KVTLYTT-----PGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFD-------EGE 68

                 ....*.
gi 519054651  95 LKTLIE 100
Cdd:COG0695   69 LDALLA 74

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 519054651  55 PELREGLKQYANWPTYPQLWVNGELVGGCDIVTEMYENGELKTLIESAAS 104
Cdd:cd03031   46 EELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKLLKGIRA 95

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 519054651  15 PVILYMKgspnaPQCGFSQRTSQAVMACGQRFAYVDILSNPELREGLKQYAN-WPTYPQLWVNGELVGGCDIVTEMYENG 93
Cdd:cd03418    1 KVEIYTK-----PNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGgRRTVPQIFIGDVHIGGCDDLYALERKG 75