glutaredoxin 3; Provisional

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896  1 MAHIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80
Cdd:PRK10638  1 MANVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80

                ..
gi 695712896 81 LL 82
Cdd:PRK10638 81 LL 82

glutaredoxin 3; Provisional

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896  1 MAHIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80
Cdd:PRK10638  1 MANVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80

                ..
gi 695712896 81 LL 82
Cdd:PRK10638 81 LL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 695712896  3 HIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSG-RTTVPQIFIDAQHIGGCDDLYALDARG 76
Cdd:cd03418   1 KVEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGgRRTVPQIFIGDVHIGGCDDLYALERKG 75

Glutaredoxin;

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896   4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHI 63
Cdd:pfam00462  1 VVLYTKPTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

glutaredoxin 3; Provisional

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896  1 MAHIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80
Cdd:PRK10638  1 MANVEIYTKATCPFCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDP 80

                ..
gi 695712896 81 LL 82
Cdd:PRK10638 81 LL 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 695712896  3 HIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSG-RTTVPQIFIDAQHIGGCDDLYALDARG 76
Cdd:cd03418   1 KVEIYTKPNCPYCVRAKALLDKKGVDYEEIDVDGDPALREEMINRSGgRRTVPQIFIGDVHIGGCDDLYALERKG 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 695712896  4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGGCDDLYALD 73
Cdd:cd02066   2 VVVFSKSTCPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALH 71

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896  6 IYTKATCPFCHRAKALLNSKGVTFQ--ELPI--DGDAIkREEMIQRSGRTTVPQIFIDAQHIGGCDDLYALDARGGLDPL 81
Cdd:cd03419   4 VFSKSYCPYCKRAKSLLKELGVKPAvvELDQheDGSEI-QDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVKL 82

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 695712896  4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKReEMIQRSGRTTVPQIFIDAQHIGGCDDL 69
Cdd:cd03029   3 VSLFTKPGCPFCARAKAALQENGISYEEIPLGKDITGR-SLRAVTGAMTVPQVFIDGELIGGSDDL 67

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 695712896  4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGG 65
Cdd:cd02976   2 VTVYTKPDCPYCKATKRFLDERGIPFEEVDVDEDPEALEELKKLNGYRSVPVVVIGDEHLSG 63

glutaredoxin 1; Provisional

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 695712896  4 IEIYTKATCPFCHRAKALLNS-----KGVTFQELPIDGDAIKREEMIQRSGRT--TVPQIFIDAQHIGGCDDLYAL 72
Cdd:PRK11200  3 VVIFGRPGCPYCVRAKELAEKlseerDDFDYRYVDIHAEGISKADLEKTVGKPveTVPQIFVDQKHIGGCTDFEAY 78

bifunctional gluaredoxin/ribonucleoside-diphosphate reductase subunit beta; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896   1 MAHIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDaIKREEMIQRSGRT---------TVPQIFIDAQHIGGCDDLYA 71
Cdd:PRK12759   1 MVEVRIYTKTNCPFCDLAKSWFGANDIPFTQISLDDD-VKRAEFYAEVNKNillveehirTVPQIFVGDVHIGGYDNLMA 79

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 695712896  4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRS-GRTTVPQI 56
Cdd:NF041212  1 VVIYTKPGCPYCAAAKEDLARRGIPFEEIDVSKDPEALEEMLRLTgGERIVPVI 54

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 695712896  15 CHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRT----TVPQIFIDAQHIGGCDDLYALDARGGLDPLLG 83
Cdd:cd03031   19 CNNVRAILESFRVKFDERDVSMDSGFREELRELLGAElkavSLPRVFVDGRYLGGAEEVLRLNESGELRKLLK 91

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 695712896  4 IEIYTKATCPFCHRAKALLN-----SKGVTFQELPIDGDAIKREEMiQRSGRTTVPQIFID 59
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAelallNKGVKFEAVDVDEDPALEKEL-KRYGVGGVPTLVVF 60

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 695712896 12 CPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGGCDDLYALDARGGL 78
Cdd:cd03028  23 CGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIVKEMHESGEL 89

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 695712896  11 TCPFCHRAKALLNSKGVTFQELPIDGDAI-KREEMIQRSGRTTVPQIFID 59
Cdd:pfam13409  1 FSPFSHRVRLALEEKGLPYEIELVDLDPKdKPPELLALNPLGTVPVLVLP 50

glutaredoxin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 695712896  11 TCPFCHRAKA---LLNSKGVTFQELPIDGDAIKREEMIQRSGRTTVPQIFIDAQHIGGCD 67
Cdd:PTZ00062 124 TFPFCRFSNAvvnMLNSSGVKYETYNIFEDPDLREELKVYSNWPTYPQLYVNGELIGGHD 183

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 695712896  7 YTKATCPFCHRAKALLNSKGVTFQELPIDGDAiKREEMIQRSGRTTVP 54
Cdd:cd03059   4 YSGPDDVYSHRVRIVLAEKGVSVEIIDVDPDN-PPEDLAELNPYGTVP 50

Glutaredoxin-like protein; This family of glutaredoxin-like proteins is limited to the Actinobacteria and contains the conserved CxxC motif.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 695712896   3 HIEIYTKATCPFCHRAKALLNSKGVTFQELPIDGD 37
Cdd:TIGR02200  1 TITVYGTTWCGYCAQLMRTLDKLGAAYEWVDIEED 35

GST_N family; microsomal Prostaglandin E synthase Type 2 (mPGES2) subfamily; mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH or other thiol compounds. PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature and mediation of inflammation. mPGES2 contains an N-terminal hydrophobic domain which is membrane associated, and a C-terminal soluble domain with a GST-like structure.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 695712896  4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIdgDAIKREEmIQRSGRTTVPQIFIDAQ 61
Cdd:cd03040   2 ITLYQYKTCPFCCKVRAFLDYHGIPYEVVEV--NPVSRKE-IKWSSYKKVPILRVESG 56

Arsenate Reductase (ArsC) family, Spx subfamily; Spx is a unique RNA polymerase (RNAP)-binding protein present in bacilli and some mollicutes. It inhibits transcription by binding to the C-terminal domain of the alpha subunit of RNAP, disrupting complex formation between RNAP and certain transcriptional activator proteins like ResD and ComA. In response to oxidative stress, Spx can also activate transcription, making it a general regulator that exerts both positive and negative control over transcription initiation. Spx has been shown to exert redox-sensitive transcriptional control over genes like trxA (TRX) and trxB (TRX reductase), genes that function in thiol homeostasis. This redox-sensitive activity is dependent on the presence of a CXXC motif, present in some members of the Spx subfamily, that acts as a thiol/disulfide switch. Spx has also been shown to repress genes in a sulfate-dependent manner independent of the presence of the CXXC motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 695712896   4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREEMIQ 46
Cdd:cd03032    2 IKLYTSPSCSSCRKAKQWLEEHQIPFEERNLFKQPLTKEELKE 44

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
                 ....*....|....*....|....*....|....*....|....*....
gi 695712896   4 IEIYTKATCPFCHRAKALLNSKGVTFQELPIDGDAIKREE---MIQRSG 49
Cdd:cd02977    1 ITIYGNPNCSTSRKALAWLEEHGIEYEFIDYLKEPPTKEElkeLLAKLG 49