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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513 306 KVVLYTTSMGIIRETYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRMQSG--QVRVPQLYVEGQHIGDAETVERM 383
Cdd:cd03031   1 RVVLYTTSLRGVRKTFEDCNNVRAILESFRVKFDERDVSMDSGFREELRELLGAElkAVSLPRVFVDGRYLGGAEEVLRL 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24644513 384 NESGELRQLLKPYKSMASTYTCQTCGGYRLLPCPSCNGSKKSVHRNHFtAEFVALKCMNCDEVGLVKC 451
Cdd:cd03031  81 NESGELRKLLKGIRARAGGGVCEGCGGARFVPCSECNGSCKVFAENAT-AAGGFLRCPECNENGLVRC 147

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513 306 KVVLYTTSMGIIRETYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRMQSG--QVRVPQLYVEGQHIGDAETVERM 383
Cdd:cd03031   1 RVVLYTTSLRGVRKTFEDCNNVRAILESFRVKFDERDVSMDSGFREELRELLGAElkAVSLPRVFVDGRYLGGAEEVLRL 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24644513 384 NESGELRQLLKPYKSMASTYTCQTCGGYRLLPCPSCNGSKKSVHRNHFtAEFVALKCMNCDEVGLVKC 451
Cdd:cd03031  81 NESGELRKLLKGIRARAGGGVCEGCGGARFVPCSECNGSCKVFAENAT-AAGGFLRCPECNENGLVRC 147

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513 306 KVVLYTTSmgiireTYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRmqSGQVRVPQLYVEGQHIGDAetvermnE 385
Cdd:COG0695   1 KVTLYTTP------GCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRER--SGRRTVPVIFIGGEHLGGF-------D 65

                ....*....
gi 24644513 386 SGELRQLLK 394
Cdd:COG0695  66 EGELDALLA 74

glutaredoxin 3; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513  319 ETYTK-----CANVKQILRTLLVKFEERDVFMSVEYQAEMRQRmqSGQVRVPQLYVEGQHIGDAETVERMNESGELRQLL 393
Cdd:PRK10638   5 EIYTKatcpfCHRAKALLNSKGVSFQEIPIDGDAAKREEMIKR--SGRTTVPQIFIDAQHIGGCDDLYALDARGGLDPLL 82

                 .
gi 24644513  394 K 394
Cdd:PRK10638  83 K 83

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513 306 KVVLYTTSMGIIRETYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRMQSG--QVRVPQLYVEGQHIGDAETVERM 383
Cdd:cd03031   1 RVVLYTTSLRGVRKTFEDCNNVRAILESFRVKFDERDVSMDSGFREELRELLGAElkAVSLPRVFVDGRYLGGAEEVLRL 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24644513 384 NESGELRQLLKPYKSMASTYTCQTCGGYRLLPCPSCNGSKKSVHRNHFtAEFVALKCMNCDEVGLVKC 451
Cdd:cd03031  81 NESGELRKLLKGIRARAGGGVCEGCGGARFVPCSECNGSCKVFAENAT-AAGGFLRCPECNENGLVRC 147

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24644513   307 VVLYTTSmgiireTYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRmqSGQVRVPQLYVEGQHI 374
Cdd:pfam00462   1 VVLYTKP------TCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKEL--SGWPTVPQVFIDGEHI 60

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 24644513   319 ETYTK-----CANVKQILRTLLVKFEERDVFMSVEYQAEMRQRmqSGQVRVPQLYVEGQHIGDAETVERMNESGELRQLL 393
Cdd:TIGR02181   2 TIYTKpycpyCTRAKALLSSKGVTFTEIRVDGDPALRDEMMQR--SGRRTVPQIFIGDVHVGGCDDLYALDREGKLDPLL 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24644513 324 CANVKQILRTLLVKF--EERDVF--MSvEYQAEMRQRmqSGQVRVPQLYVEGQHIGDAETVERMNESGELRQL 392
Cdd:cd03419  13 CKRAKSLLKELGVKPavVELDQHedGS-EIQDYLQEL--TGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVKL 82

SH3-binding, glutamic acid-rich protein;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513   310 YTTSMGIIRETYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRMQSGQVRVPQLYVEGQHIGDAETVERMNESGEL 389
Cdd:pfam04908   6 YVASSSGSPEIKKKQQRVLMILDANKIPFDEVDITKDEEQRRWMRENPPNGAPLPPQIFNEDQYCGDYDAFFEAVEANTL 85

                  ....*
gi 24644513   390 RQLLK 394
Cdd:pfam04908  86 YEFLG 90

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 24644513 306 KVVLYTTSMGiireTYtkCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRmqSGQVR-VPQLYVEGQHIG 375
Cdd:cd03418   1 KVEIYTKPNC----PY--CVRAKALLDKKGVDYEEIDVDGDPALREEMINR--SGGRRtVPQIFIGDVHIG 63

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 24644513 306 KVVLYTTSMGIiretytKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQrmQSGQVRVPQLYVEGQHI 374
Cdd:cd02976   1 EVTVYTKPDCP------YCKATKRFLDERGIPFEEVDVDEDPEALEELKK--LNGYRSVPVVVIGDEHL 61

Glutaredoxin (GRX) family, SH3BGR (SH3 domain binding glutamic acid-rich protein) subfamily; a recently-identified subfamily composed of SH3BGR and similar proteins possessing significant sequence similarity to GRX, but without a redox active CXXC motif. The SH3BGR gene was cloned in an effort to identify genes mapping to chromosome 21, which could be involved in the pathogenesis of congenital heart disease affecting Down syndrome newborns. Several human SH3BGR-like (SH3BGRL) genes have been identified since, mapping to different locations in the chromosome. Of these, SH3BGRL3 was identified as a tumor necrosis factor (TNF) alpha inhibitory protein and was also named TIP-B1. Upregulation of expression of SH3BGRL3 is associated with differentiation. It has been suggested that it functions as a regulator of differentiation-related signal transduction pathways.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24644513 308 VLYTTSMGIiRETYTKCANVKQILRTLLVKFEERDVFMSVEYQAEMRQRM--QSGQVRVPQLYVEGQHIGDAETVERMNE 385
Cdd:cd03030   4 VYIASSSGS-TEIKKRQQEVLGFLEAKKIEFEEVDISMNEENRQWMRENVpnENGKPLPPQIFNGDEYCGDYEAFFEAKE 82

                        90
                ....*....|
gi 24644513 386 SGELRQLLKP 395
Cdd:cd03030  83 NNTLEEFLKL 92