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 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM-GYSSAPVTVDEatGEHWHGYLPDRY 92
Cdd:cd02976     1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIG--DEHLSGFRPDKL 69

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 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM-GYSSAPVTVDEatGEHWHGYLPDRY 92
Cdd:cd02976     1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIG--DEHLSGFRPDKL 69

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKL-RKMGYSSAPVTV 76
Cdd:TIGR02196   1 KVKVYTTPWCPPCVKAKEYLTSKGVAFEEIDVEKDAAAREELlKVYGQRGVPVIV 55

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 1546271758  25 TIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM--GYSSAPVTVDE 78
Cdd:NF041212    2 VIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLtgGERIVPVIVEG 57

FtsK/SpoIIIE family; FtsK has extensive sequence similarity to wide variety of proteins from prokaryotes and plasmids, termed the FtsK/SpoIIIE family. This domain contains a putative ATP binding P-loop motif. It is found in the FtsK cell division protein from E. coli and the stage III sporulation protein E SpoIIIE, which has roles in regulation of prespore specific gene expression in B. subtilis. A mutation in FtsK causes a temperature sensitive block in cell division and it is involved in peptidoglycan synthesis or modification. The SpoIIIE protein is implicated in intercellular chromosomal DNA transfer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1546271758 104 DMQATIDLGPVEAGEHVLWD--PHQGHLLIIGDRDSGKSVIQRGIMETAVSVGW----QAWGLGLP-GELDKVED--HRY 174
Cdd:pfam01580  14 YSRLPIALGKDISGNPEVFDlkKMPVHLLIAGATGSGKSVALNTLILSLAYMHTpeevQLYCIDPKmGELSAYEDipHLL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1546271758 175 AQVVTADVSDQLERIRAASELMRERYHL---------------------------------VEVASLAQECPEPFQPIVL 221
Cdd:pfam01580  94 SVPVATDPKRALRALEWLVDEMERRYALfralgvrsiagyngeiaedpldgfgdvflviygVHVMCTAGRWLEILPYLVV 173

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1546271758 222 VLDDYAHLRQrwadlaPAGEHEADVAENLLLGIHRLGRSVGIHL 265
Cdd:pfam01580 174 IVDERAELRL------AAPKDSEMRVEDAIVRLAQKGRAAGIHL 211

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 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM-GYSSAPVTVDEatGEHWHGYLPDRY 92
Cdd:cd02976     1 EVTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLnGYRSVPVVVIG--DEHLSGFRPDKL 69

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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKL-RKMGYSSAPVTV 76
Cdd:TIGR02196   1 KVKVYTTPWCPPCVKAKEYLTSKGVAFEEIDVEKDAAAREELlKVYGQRGVPVIV 55

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 1546271758  25 TIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM--GYSSAPVTVDE 78
Cdd:NF041212    2 VIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLtgGERIVPVIVEG 57

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        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1546271758  25 TIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKMgYSSAPVTVDE 78
Cdd:cd02977     2 TIYGNPNCSTSRKALAWLEEHGIEYEFIDYLKEPPTKEELKEL-LAKLGLGVED 54

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM 67
Cdd:COG1393     1 MITIYGNPNCSTSRKALAWLEEAGIEYEFIDYLKTPPTAEELKEL 45

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 1546271758  25 TIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM 67
Cdd:cd02066     3 VVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKEL 45

transcriptional regulator Spx; Reviewed

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1546271758  23 MYTIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKLRKM 67
Cdd:PRK01655    1 MVTLFTSPSCTSCRKAKAWLEEHDIPFTERNIFSSPLTIDEIKQI 45

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
                  ....*....|....*....|....*....|....*....|
gi 1546271758  25 TIYTSPGCGPCMTVKAHLRAHKIPHTLVDVSQDPAAVEKL 64
Cdd:cd03418     3 EIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEM 42

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 1546271758  25 TIYTSPGCGPCMTVKAHLRA-----HKIPHTLVDVSQDPAAVEKLRKMGYSSAPVTVD 77
Cdd:cd01659     2 VLFYAPWCPFCQALRPVLAElallnKGVKFEAVDVDEDPALEKELKRYGVGGVPTLVV 59