Glutaredoxin-related protein [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493710433   1 MTTIEKIERQVKENPILLYMKGSPKLPSCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELV 80
Cdd:COG0278    2 MDVQERIKQQIKSNPVVLFMKGTPQFPQCGFSARAVQILNACGVDFATVNVLEDPEIRQGLKEYSNWPTIPQLYVKGEFI 81

                         90       100
                 ....*....|....*....|...
gi 493710433  81 GGCDIIVEMFQRGELQTLIKETA 103
Cdd:COG0278   82 GGCDIIREMYESGELQKLLEEAG 104

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 493710433   7 IERQVKENPILLYMKGSPKLPSCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELVGGCDII 86
Cdd:cd03028    1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                         90
                 ....*....|
gi 493710433  87 VEMFQRGELQ 96
Cdd:cd03028   81 KEMHESGELQ 90

Glutaredoxin-related protein [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493710433   1 MTTIEKIERQVKENPILLYMKGSPKLPSCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELV 80
Cdd:COG0278    2 MDVQERIKQQIKSNPVVLFMKGTPQFPQCGFSARAVQILNACGVDFATVNVLEDPEIRQGLKEYSNWPTIPQLYVKGEFI 81

                         90       100
                 ....*....|....*....|...
gi 493710433  81 GGCDIIVEMFQRGELQTLIKETA 103
Cdd:COG0278   82 GGCDIIREMYESGELQKLLEEAG 104

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 493710433   7 IERQVKENPILLYMKGSPKLPSCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELVGGCDII 86
Cdd:cd03028    1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                         90
                 ....*....|
gi 493710433  87 VEMFQRGELQ 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 493710433  15 PILLYMKGSpklpsCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELVGGCDIIVEMFQ 91
Cdd:cd02066    1 KVVVFSKST-----CPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 493710433  15 PILLYMKgspklPSCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELVGGCD 84
Cdd:COG0695    1 KVTLYTT-----PGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFD 65

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 493710433  27 PSCGFSAQAVQALSSCGERFAYVDILQNPD---IRAELPKYANWPTFPQLWVDGELVGGCDIIVEMFQRGELQTL 98
Cdd:cd03419    8 SYCPYCKRAKSLLKELGVKPAVVELDQHEDgseIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVKL 82

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 493710433  15 PILLYMKgspklPSCGFSAQAVQALSSCGERFAYVDILQNPDIRAELPKYANW-PTFPQLWVDGELVGGCDIIVEMFQRG 93
Cdd:cd03418    1 KVEIYTK-----PNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGGrRTVPQIFIGDVHIGGCDDLYALERKG 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 493710433  27 PSCGFSAQAVQALSSCGerFAYVDILQNPDIRAE-LPKYANWPTFPQLWVDGELVGGCDIIVEMF 90
Cdd:cd03029    9 PGCPFCARAKAALQENG--ISYEEIPLGKDITGRsLRAVTGAMTVPQVFIDGELIGGSDDLEKYF 71