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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 499992978  3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDALKAK-GFQAVPVVQFSEEKAVaGFRPDLLKKLA 75
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIGDEHLS-GFRPDKLRALL 73

glutaredoxin-like protein NrdH;

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 499992978  3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDALKAKGFQAVPVVqFSEEKAVAGFRPDLLKKL 74
Cdd:PRK10329  2 RITIYTRNDCVQCHATKRAMESRGFDFEMINVDRVPEAAETLRAQGFRQLPVV-IAGDLSWSGFRPDMINRL 72

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 499992978  4 IIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYID-ALK-AKGFQAVPVV 55
Cdd:NF041212  1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEeMLRlTGGERIVPVI 54

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 499992978  3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDALKAK-GFQAVPVVQFSEEKAVaGFRPDLLKKLA 75
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIGDEHLS-GFRPDKLRALL 73

glutaredoxin-like protein NrdH;

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 499992978  3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDALKAKGFQAVPVVqFSEEKAVAGFRPDLLKKL 74
Cdd:PRK10329  2 RITIYTRNDCVQCHATKRAMESRGFDFEMINVDRVPEAAETLRAQGFRQLPVV-IAGDLSWSGFRPDMINRL 72

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 499992978  3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDALKAK-GFQAVPVVqFSEEKAVAGFrpDLLKKL 74
Cdd:cd02066   1 KVVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKELsGWPTVPQI-FINGEFIGGY--DDLKAL 70

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 499992978  3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDAL--KAKGFQAVPVVqFSEEKAVAGFrpDLLKKLA 75
Cdd:cd03418   1 KVEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMinRSGGRRTVPQI-FIGDVHIGGC--DDLYALE 72

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 499992978  4 IIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYID-ALK-AKGFQAVPVV 55
Cdd:NF041212  1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEeMLRlTGGERIVPVI 54

Arsenate Reductase (ArsC) family; composed of TRX-fold arsenic reductases and similar proteins including the transcriptional regulator, Spx. ArsC catalyzes the reduction of arsenate [As(V)] to arsenite [As(III)], using reducing equivalents derived from glutathione (GSH) via glutaredoxin (GRX), through a single catalytic cysteine. This family of predominantly bacterial enzymes is unrelated to two other families of arsenate reductases which show similarity to low-molecular-weight acid phosphatases and phosphotyrosyl phosphatases. Spx is a general regulator that exerts negative and positive control over transcription initiation by binding to the C-terminal domain of the alpha subunit of RNA polymerase.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 499992978   4 IIVYTKNNCIQCKMTKRFLSENGVTFEERNINANP 38
Cdd:cd02977    1 ITIYGNPNCSTSRKALAWLEEHGIEYEFIDYLKEP 35

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 499992978  4 IIVYTKNNCIQCKMTKRFLSEN-----GVTFEERNINANPEYIDALKAKGFQAVPVVQF 57
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAELallnkGVKFEAVDVDEDPALEKELKRYGVGGVPTLVV 59

Arsenate reductase or related protein, glutaredoxin family [Inorganic ion transport and metabolism];

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 499992978   3 KIIVYTKNNCIQCKMTKRFLSENGVTFEERNINANP 38
Cdd:COG1393    1 MITIYGNPNCSTSRKALAWLEEAGIEYEFIDYLKTP 36

transcriptional regulator Spx; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 499992978   4 IIVYTKNNCIQCKMTKRFLSENGVTFEERNINANPEYIDALKAkgfqavpVVQFSEEKA 62
Cdd:PRK12559   2 VVLYTTASCASCRKAKAWLEENQIDYTEKNIVSNSMTVDELKS-------ILRLTEEGA 53