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 19075805  67 PVIIFSRPGCPYSAAAKKLLTEtlrLDPPAVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGGSDSVRALYQEE 146
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKE---LGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....
gi 19075805 147 KLQS 150
Cdd:cd03419  78 KLVK 81

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19075805  67 PVIIFSRPGCPYSAAAKKLLTEtlrldpPAVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGGSDS 138
Cdd:COG0695   1 KVTLYTTPGCPYCARAKRLLDE------KGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFDE 66

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
                 ....*....|....*....|.
gi 19075805   68 VIIFSRPGCPYSAAAKKLLTE 88
Cdd:NF041212   1 VVIYTKPGCPYCAAAKEDLAR 21

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 19075805  67 PVIIFSRPGCPYSAAAKKLLTEtlrLDPPAVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGGSDSVRALYQEE 146
Cdd:cd03419   1 PVVVFSKSYCPYCKRAKSLLKE---LGVKPAVVELDQHEDGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                ....
gi 19075805 147 KLQS 150
Cdd:cd03419  78 KLVK 81

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 19075805    68 VIIFSRPGCPYSAAAKKLLTEtlrLDPPAVVVEVTDYEhtqELRDWLSSISDISTMPNIFVGGHSI 133
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKS---LGVDFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075805  67 PVIIFSRPGCPYSAAAKKLLTETlrldppAVVVEVTDYEHTQELRDWLSSISD-ISTMPNIFVGGHSIGGSDSVRALYQE 145
Cdd:cd03418   1 KVEIYTKPNCPYCVRAKALLDKK------GVDYEEIDVDGDPALREEMINRSGgRRTVPQIFIGDVHIGGCDDLYALERK 74

Glutaredoxin-like family; This family of glutaredoxin-like proteins is aparrently limited to plants. Multiple isoforms are found in A. thaliana and O.sativa.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19075805    65 ENPVIIFSRPGCPYSAAAKKLLtETLRLDPpaVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGGSDSVRALY 143
Cdd:TIGR02189   7 EKAVVIFSRSSCCMCHVVKRLL-LTLGVNP--AVHEIDKEPAGKDIENALSRLGCSPAVPAVFVGGKLVGGLENVMALH 82

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075805  65 ENPVIIF-----SRPGCPYSAAAKKLLTETlrldppAVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGGSDSV 139
Cdd:cd03028   7 ENPVVLFmkgtpEEPRCGFSRKVVQILNQL------GVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                        90
                ....*....|
gi 19075805 140 RALYQEEKLQ 149
Cdd:cd03028  81 KEMHESGELQ 90

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 19075805  67 PVIIFSRPGCPYSAAAKKLLTETlrldppAVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGGSD 137
Cdd:cd02976   1 EVTVYTKPDCPYCKATKRFLDER------GIPFEEVDVDEDPEALEELKKLNGYRSVPVVVIGDEHLSGFR 65

glutaredoxin; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19075805   66 NPVIIFSRPGCPYSAAAKKLLTETLRLDPPAVVVEVTDYEHTQELRDWLSSISDISTMPNIFVGGHSIGG 135
Cdd:PHA03050  13 NKVTIFVKFTCPFCRNALDILNKFSFKRGAYEIVDIKEFKPENELRDYFEQITGGRTVPRIFFGKTSIGG 82

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19075805  68 VIIFSRPGCPYSAAAKKLLTEtLRLdpPAVVVEVTDY-EHTQELRDwlssISDISTMPNIFVGGHSIGG 135
Cdd:cd03027   3 VTIYSRLGCEDCTAVRLFLRE-KGL--PYVEINIDIFpERKAELEE----RTGSSVVPQIFFNEKLVGG 64

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 19075805  68 VIIFSRPGCPYSAAAKKLLTEtLRLDPPAVVVEVTDYEHTQELRDWLSSiSDISTMPNIFVGGHSIG 134
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAE-LALLNKGVKFEAVDVDEDPALEKELKR-YGVGGVPTLVVFGPGIG 65