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 1056835902  3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKAL-GYLQAPVVITDDDHWSGFRPDKIATL 72
Cdd:cd02976    2 VTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIGDEHLSGFRPDKLRAL 72

glutaredoxin-like protein NrdH;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1056835902  1 MAVTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKALGYLQAPVVITDDDHWSGFRPDKIATL 72
Cdd:PRK10329   1 MRITIYTRNDCVQCHATKRAMESRGFDFEMINVDRVPEAAETLRAQGFRQLPVVIAGDLSWSGFRPDMINRL 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 1056835902  3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKAL--GYLQAPVVITDDD 59
Cdd:NF041212   1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLtgGERIVPVIVEGGE 59

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 1056835902  3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKAL-GYLQAPVVITDDDHWSGFRPDKIATL 72
Cdd:cd02976    2 VTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIGDEHLSGFRPDKLRAL 72

glutaredoxin-like protein NrdH;

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1056835902  1 MAVTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKALGYLQAPVVITDDDHWSGFRPDKIATL 72
Cdd:PRK10329   1 MRITIYTRNDCVQCHATKRAMESRGFDFEMINVDRVPEAAETLRAQGFRQLPVVIAGDLSWSGFRPDMINRL 72

Glutaredoxin-like protein, YruB-family; This glutaredoxin-like protein family contains the conserved CxxC motif and includes the Clostridium pasteurianum protein YruB which has been cloned from a rubredoxin operon. Somewhat related to NrdH, it is unknown whether this protein actually interacts with glutathione/glutathione reducatase, or, like NrdH, some other reductant system.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1056835902  3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAV-KALGYLQAPVVITDDDHWSGFRPDKI 69
Cdd:TIGR02196  2 VKVYTTPWCPPCVKAKEYLTSKGVAFEEIDVEKDAAAREELlKVYGQRGVPVIVIGHKIVVGFDPEKL 69

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
                 ....*....|....*....|....*....|....*....|....
gi 1056835902  3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKAL 46
Cdd:cd02066    2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKEL 45

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1056835902   3 VTVYTKPSCVQCTATYRALDSKGIDYEVFD-----------------------------------LSVDEKALEAVKALG 47
Cdd:COG1393     2 ITIYGNPNCSTSRKALAWLEEAGIEYEFIDylktpptaeelkellaklglgveellntrgttyreLGLKDKALSEEEALA 81

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1056835902  48 YLQA-------PVVITDDDHWSGFRPDKIATL 72
Cdd:COG1393    82 LMLEhpslikrPIVVTGDKALVGFPPEEVLAL 113

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 1056835902   3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVD 36
Cdd:cd02977     1 ITIYGNPNCSTSRKALAWLEEHGIEYEFIDYLKE 34

Glutathione S-transferase, N-terminal domain;

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 1056835902  6 YTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKALGYLQAPVVITDDD 59
Cdd:pfam13417  2 YGFPGSPYARRVRIALNEKGLPYEFVPIPPGDHPPELLAKNPLGKVPVLEDDGG 55

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 1056835902  3 VTVYTKPSCVQCTATYRALDSKGIDYEVFDLSVDEKALEAVKALGYL-QAPVVITDD 58
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLgKVPVLEDGG 57