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 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALA-KRTSVPQIFVGDVHVGGYDDMMAMHRAG 88
Cdd:cd03418     2 VEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSgGRRTVPQIFIGDVHIGGCDDLYALERKG 75

glutaredoxin 3; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAKRTSVPQIFVGDVHVGGYDDMMAMHRAGKLEPLL 94
Cdd:PRK10638    4 VEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDPLL 82

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 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAK-RTSVPQIFVGD-VHVG 76
Cdd:NF041212    1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLTGgERIVPVIVEGGeVTVG 63

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 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALA-KRTSVPQIFVGDVHVGGYDDMMAMHRAG 88
Cdd:cd03418     2 VEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSgGRRTVPQIFIGDVHIGGCDDLYALERKG 75

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 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAKRTSVPQIFVGDVHVGGYDDMMAMHR 86
Cdd:cd02066     2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAKRTSVPQIFVGDVHV 75
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

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 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAKRTSVPQIFVGDVHVGGYDD 80
Cdd:cd02976     2 VTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLNGYRSVPVVVIGDEHLSGFRP 66

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 1702513773  15 QITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAKRTSVPQIFVGDVHVGGYDDMMAM 84
Cdd:cd03027     2 RVTIYSRLGCEDCTAVRLFLREKGLPYVEINIDIFPERKAELEERTGSSVVPQIFFNEKLVGGLTDLKSL 71

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 1702513773  15 QITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDrMIALAKRTSVPQIFVGDVHVGGYDDM 81
Cdd:cd03029     2 SVSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGRS-LRAVTGAMTVPQVFIDGELIGGSDDL 67

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 1702513773  16 ITLYSSAICPYCVAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAK-RTSVPQIFVGD-VHVG 76
Cdd:NF041212    1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLTGgERIVPVIVEGGeVTVG 63

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1702513773  27 CVAAKNFLKSKGktwteVRIDldpaERD-------------RMIALAKRTSVPQIFVGDVHVGGYDDMMAMHRAGKLEPL 93
Cdd:cd03031    19 CNNVRAILESFR-----VKFD----ERDvsmdsgfreelreLLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKL 89

                  ....*....
gi 1702513773  94 LAGSAGGQA 102
Cdd:cd03031    90 LKGIRARAG 98

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1702513773  16 ITLYSSAICPYC-----VAAKNFLKSKGKTWTEVRIDLDPAERDRMIALAKRTsVPQIFVGD 72
Cdd:cd01659     1 LVLFYAPWCPFCqalrpVLAELALLNKGVKFEAVDVDEDPALEKELKRYGVGG-VPTLVVFG 61

glutaredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1702513773   1 MSQDHTEQDAASGpQITLYSSAICPYCVAAKNFLKS---KGKTWTEVRI-DLDPAER--DRMIALAKRTSVPQIFVGDVH 74
Cdd:PHA03050    1 MAEEFVQQRLANN-KVTIFVKFTCPFCRNALDILNKfsfKRGAYEIVDIkEFKPENElrDYFEQITGGRTVPRIFFGKTS 79

                          90       100
                  ....*....|....*....|.
gi 1702513773  75 VGGYDDMMAMHRAGKLEPLLA 95
Cdd:PHA03050   80 IGGYSDLLEIDNMDALGDILS 100

SH3-binding, glutamic acid-rich protein;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1702513773  33 FLKSKGKTWTEVRIDLDPAERDRMIALAKRTSV--PQIFVGDVHVGGYDD 80
Cdd:pfam04908  26 ILDANKIPFDEVDITKDEEQRRWMRENPPNGAPlpPQIFNEDQYCGDYDA 75