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 1335348594  14 KVVVFIKPTCPYCRKTQEILSQLPFKQGLLEfVDITAtnNTSAIQDYLQQLTGARTVPRVFIGKDCIGGCSDLISMQQTG 93
Cdd:cd03419     1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVE-LDQHE--DGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                  ..
gi 1335348594  94 EL 95
Cdd:cd03419    78 KL 79

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1335348594  15 VVVFIKPTCPYCRKTQEILSQLPFKqglLEFVDITatnNTSAIQDYLQQLTGARTVPRVFIGKDCI 80
Cdd:pfam00462   1 VVLYTKPTCPFCKRAKRLLKSLGVD---FEEIDVD---EDPEIREELKELSGWPTVPQVFIDGEHI 60

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 1335348594  15 VVVFIKPTCPYCRKTQEILSqlpfKQGlLEFVDITATNNTSAIQDyLQQLTGA-RTVP 71
Cdd:NF041212    1 VVIYTKPGCPYCAAAKEDLA----RRG-IPFEEIDVSKDPEALEE-MLRLTGGeRIVP 52

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 1335348594  14 KVVVFIKPTCPYCRKTQEILSQLPFKQGLLEfVDITAtnNTSAIQDYLQQLTGARTVPRVFIGKDCIGGCSDLISMQQTG 93
Cdd:cd03419     1 PVVVFSKSYCPYCKRAKSLLKELGVKPAVVE-LDQHE--DGSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSG 77

                  ..
gi 1335348594  94 EL 95
Cdd:cd03419    78 KL 79

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 1335348594  14 KVVVFIKPTCPYCRKTQEILSQLPFKqglLEFVDITATnntSAIQDYLQQLTGARTVPRVFIGKDCIGGCSDLISMQQ 91
Cdd:cd02066     1 KVVVFSKSTCPYCKRAKRLLESLGIE---FEEIDILED---GELREELKELSGWPTVPQIFINGEFIGGYDDLKALHE 72

Glutaredoxin, GrxC family; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This family of glutaredoxins includes the E. coli protein GrxC (Grx3) which appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulfides. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348594  15 VVVFIKPTCPYCRKTQEILSQlpfkQGLlEFVDITATNNTSAiQDYLQQLTGARTVPRVFIGKDCIGGCSDLISMQQTGE 94
Cdd:TIGR02181   1 VTIYTKPYCPYCTRAKALLSS----KGV-TFTEIRVDGDPAL-RDEMMQRSGRRTVPQIFIGDVHVGGCDDLYALDREGK 74

                  .
gi 1335348594  95 L 95
Cdd:TIGR02181  75 L 75

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348594  14 KVVVFIKPTCPYCRKTQEILSQL--PFkqgllEFVDITAtnnTSAIQDYLQQLTGARTVPRVFIGKDCIGGCSDlismqq 91
Cdd:COG0695     1 KVTLYTTPGCPYCARAKRLLDEKgiPY-----EEIDVDE---DPEAREELRERSGRRTVPVIFIGGEHLGGFDE------ 66

                  ....*....
gi 1335348594  92 tGELMTRLK 100
Cdd:COG0695    67 -GELDALLA 74

Glutaredoxin-family domain; This C-terminal domain with homology to glutaredoxin is fused to an N-terminal peroxiredoxin-like domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1335348594  15 VVVFIKPTCPYCRKTQEILsqlpfKQGLLEFVDITATNNTSAIQdyLQQLTGARTVPRVFIGKDCIGGCSDL 86
Cdd:TIGR02190  10 VVVFTKPGCPFCAKAKATL-----KEKGYDFEEIPLGNDARGRS--LRAVTGATTVPQVFIGGKLIGGSDEL 74

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 1335348594  14 KVVVFIKPTCPYCRKTQEILSqlpfKQGlLEFVDITATNNTSAIqDYLQQLTGARTVPRVFIGKD 78
Cdd:cd02976     1 EVTVYTKPDCPYCKATKRFLD----ERG-IPFEEVDVDEDPEAL-EELKKLNGYRSVPVVVIGDE 59

glutaredoxin 1; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348594  14 KVVVFIKPTCPYCRKTQEILSQL-------PFKqglleFVDITATNNTSAiqDyLQQLTG--ARTVPRVFIGKDCIGGCS 84
Cdd:PRK11200    2 FVVIFGRPGCPYCVRAKELAEKLseerddfDYR-----YVDIHAEGISKA--D-LEKTVGkpVETVPQIFVDQKHIGGCT 73

                  .
gi 1335348594  85 D 85
Cdd:PRK11200   74 D 74

Glutaredoxin-related protein [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1335348594   2 AQEFVNCKIQSGKVVVFIK-----PTCPYCRKTQEILSQL--PFkqgllEFVDITATNntsAIQDYLQQLTGARTVPRVF 74
Cdd:COG0278     4 VQERIKQQIKSNPVVLFMKgtpqfPQCGFSARAVQILNACgvDF-----ATVNVLEDP---EIRQGLKEYSNWPTIPQLY 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1335348594  75 IGKDCIGGCSDLISMQQTGELMTRLKQIGA 104
Cdd:COG0278    76 VKGEFIGGCDIIREMYESGELQKLLEEAGA 105

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 1335348594  15 VVVFIKPTCPYCRKTQEILSQLPFKQGLLEFVDITATNNtSAIQDYLQQLtGARTVPRVFIGKDCIG 81
Cdd:cd01659     1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDED-PALEKELKRY-GVGGVPTLVVFGPGIG 65

Glutaredoxin, GrxA family; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This model includes the E. coli glyutaredoxin GrxA which appears to have primary responsibility for the reduction of ribonucleotide reductase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1335348594  15 VVVFIKPTCPYCRKTQEILSQLPFKQGLLEF--VDITATNNTSAiqdYLQQLTG--ARTVPRVFIGKDCIGGCSD 85
Cdd:TIGR02183   2 VVIFGRPGCPYCVRAKQLAEKLAIERADFEFryIDIHAEGISKA---DLEKTVGkpVETVPQIFVDEKHVGGCTD 73

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 1335348594  15 VVVFIKPTCPYCRKTQEILSqlpfKQGlLEFVDITATNNTSAIQDyLQQLTGA-RTVP 71
Cdd:NF041212    1 VVIYTKPGCPYCAAAKEDLA----RRG-IPFEEIDVSKDPEALEE-MLRLTGGeRIVP 52

Protein thiol-disulfide isomerase DsbC [Posttranslational modification, protein turnover, chaperones];

                          10        20
                  ....*....|....*....|...
gi 1335348594  14 KVVVFIKPTCPYCRKTQEILSQL 36
Cdd:COG1651     3 TVVEFFDYQCPYCARFHPELPEL 25

Thiol-disulfide isomerase or thioredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1335348594  12 SGKVVV--FIKPTCPYCRKTQEILSQLPFKQGLLEFVDITATNNTSAIQDYLQQL 64
Cdd:COG0526    27 KGKPVLvnFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDENPEAVKAFLKEL 81