GIY-YIG domain found in CAXIP1-like proteins; The family includes CAX-interacting protein-1 (CXIP1)-like proteins which contain a GIY-YIG domain that shows statistically significant similarity to the N-terminal catalytic domains of GIY-YIG family of intron-encoded homing endonuclease I-TevI and catalytic GIY-YIG domain of nucleotide excision repair endonuclease UvrC. CAXIP1 is a novel PICOT (protein kinase C-interacting cousin of thioredoxin) domain-containing Arabidopsis protein that activates H+/Ca2+ exchanger CAX1, and its homolog CAX4, but not CAX2 or CAX3.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18404699  88 GVYAVYDKSDELQFVGISRNIAASVSAHLKSVPELCGSVKVGIVEEPDKAVLTQAWKLWIEEHIKVTGKVPPGN 161
Cdd:cd10457   1 GVYAVYDKSGTLQYIGLSRKIAASLATHMEELPELCGSVKVLIVDEPSKAELTEAWKSWMEEHIAEAGAVPPGN 74

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18404699 192 PLEELIDRLVKESKVVAFIKGSRSAPQCGFSQRVVGILESQGVDYETVDVLDDEynhGLRETLKNYSNWPTFPQIFVKGE 271
Cdd:COG0278   3 DVQERIKQQIKSNPVVLFMKGTPQFPQCGFSARAVQILNACGVDFATVNVLEDP---EIRQGLKEYSNWPTIPQLYVKGE 79

                        90       100
                ....*....|....*....|..
gi 18404699 272 LVGGCDILTSMYENGELANILN 293
Cdd:COG0278  80 FIGGCDIIREMYESGELQKLLE 101

GIY-YIG domain found in CAXIP1-like proteins; The family includes CAX-interacting protein-1 (CXIP1)-like proteins which contain a GIY-YIG domain that shows statistically significant similarity to the N-terminal catalytic domains of GIY-YIG family of intron-encoded homing endonuclease I-TevI and catalytic GIY-YIG domain of nucleotide excision repair endonuclease UvrC. CAXIP1 is a novel PICOT (protein kinase C-interacting cousin of thioredoxin) domain-containing Arabidopsis protein that activates H+/Ca2+ exchanger CAX1, and its homolog CAX4, but not CAX2 or CAX3.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18404699  88 GVYAVYDKSDELQFVGISRNIAASVSAHLKSVPELCGSVKVGIVEEPDKAVLTQAWKLWIEEHIKVTGKVPPGN 161
Cdd:cd10457   1 GVYAVYDKSGTLQYIGLSRKIAASLATHMEELPELCGSVKVLIVDEPSKAELTEAWKSWMEEHIAEAGAVPPGN 74

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18404699   206 VVAFIKgsrsaPQCGFSQRVVGILESQGVDYETVDVLDDEynhGLRETLKNYSNWPTFPQIFVKGELV 273
Cdd:pfam00462   1 VVLYTK-----PTCPFCKRAKRLLKSLGVDFEEIDVDEDP---EIREELKELSGWPTVPQVFIDGEHI 60

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18404699 192 PLEELIDRLVKESKVVAFIKGSRSAPQCGFSQRVVGILESQGVDYETVDVLDDEynhGLRETLKNYSNWPTFPQIFVKGE 271
Cdd:COG0278   3 DVQERIKQQIKSNPVVLFMKGTPQFPQCGFSARAVQILNACGVDFATVNVLEDP---EIRQGLKEYSNWPTIPQLYVKGE 79

                        90       100
                ....*....|....*....|..
gi 18404699 272 LVGGCDILTSMYENGELANILN 293
Cdd:COG0278  80 FIGGCDIIREMYESGELQKLLE 101

GIY-YIG domain found in CAXIP1-like proteins; The family includes CAX-interacting protein-1 (CXIP1)-like proteins which contain a GIY-YIG domain that shows statistically significant similarity to the N-terminal catalytic domains of GIY-YIG family of intron-encoded homing endonuclease I-TevI and catalytic GIY-YIG domain of nucleotide excision repair endonuclease UvrC. CAXIP1 is a novel PICOT (protein kinase C-interacting cousin of thioredoxin) domain-containing Arabidopsis protein that activates H+/Ca2+ exchanger CAX1, and its homolog CAX4, but not CAX2 or CAX3.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18404699  88 GVYAVYDKSDELQFVGISRNIAASVSAHLKSVPELCGSVKVGIVEEPDKAVLTQAWKLWIEEHIKVTGKVPPGN 161
Cdd:cd10457   1 GVYAVYDKSGTLQYIGLSRKIAASLATHMEELPELCGSVKVLIVDEPSKAELTEAWKSWMEEHIAEAGAVPPGN 74

glutaredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18404699  195 ELIDRLVKESKVVAFIKGSRSAPQCGFSQRVVGILESQGVDYETVDVLDDEynhGLRETLKNYSNWPTFPQIFVKGELVG 274
Cdd:PTZ00062 104 EKIERLIRNHKILLFMKGSKTFPFCRFSNAVVNMLNSSGVKYETYNIFEDP---DLREELKVYSNWPTYPQLYVNGELIG 180

                         90
                 ....*....|....*...
gi 18404699  275 GCDILTSMYENGELANIL 292
Cdd:PTZ00062 181 GHDIIKELYESNSLRKVI 198

Grx4 family monothiol glutaredoxin;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18404699  195 ELIDRLVKESKVVAFIKGSRSAPQCGFSQRVVGILESQGVDYETVDVLDdeyNHGLRETLKNYSNWPTFPQIFVKGELVG 274
Cdd:PRK10824   6 EKIQRQIAENPILLYMKGSPKLPSCGFSAQAVQALSACGERFAYVDILQ---NPDIRAELPKYANWPTFPQLWVDGELVG 82

                         90
                 ....*....|....*....
gi 18404699  275 GCDILTSMYENGELANILN 293
Cdd:PRK10824  83 GCDIVIEMYQRGELQQLIK 101

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 18404699 205 KVVAFIKGSrsapqCGFSQRVVGILESQGVDYETVDVldDEYNHG--LRETLKNYSNWPTFPQIFVKGELVGGCDILTSM 282
Cdd:cd03419   1 PVVVFSKSY-----CPYCKRAKSLLKELGVKPAVVEL--DQHEDGseIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMAL 73

                ....*..
gi 18404699 283 YENGELA 289
Cdd:cd03419  74 HKSGKLV 80

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18404699 215 SAPQCGFSQRVVGILESQGVDYETVDVLDDEynhGLRETLKNYSNWPTFPQIFVKGELVGGCD 277
Cdd:COG0695   6 TTPGCPYCARAKRLLDEKGIPYEEIDVDEDP---EAREELRERSGRRTVPVIFIGGEHLGGFD 65

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 18404699 224 RVVGILESQGVDYETVDV-LDDEYNHGLRETLKNYSNWPTFPQIFVKGELVGGCDILTSMYENGELANIL 292
Cdd:cd03031  21 NVRAILESFRVKFDERDVsMDSGFREELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKLL 90

GIY-YIG nuclease domain superfamily; The GIY-YIG nuclease domain superfamily includes a large and diverse group of proteins involved in many cellular processes, such as class I homing GIY-YIG family endonucleases, prokaryotic nucleotide excision repair proteins UvrC and Cho, type II restriction enzymes, the endonuclease/reverse transcriptase of eukaryotic retrotransposable elements, and a family of eukaryotic enzymes that repair stalled replication forks. All of these members contain a conserved GIY-YIG nuclease domain that may serve as a scaffold for the coordination of a divalent metal ion required for catalysis of the phosphodiester bond cleavage. By combining with different specificity, targeting, or other domains, the GIY-YIG nucleases may perform different functions.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18404699  88 GVYAVYDKSDELQFVGISRNIAASVSAHLKSVPELCG----SVKVGIVEEPDKAV--LTQAWKLWIEEH 150
Cdd:cd00719   1 GVYVLYDEDNGLIYVGQTKNLRNRIKEHLRKQRSDWTkglkPFEILYLEVAPEAEseLLDLEAALIKKL 69

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18404699 223 QRVVGILESQGVDYETVDVLDDEYNHG-LRETLKNYSNWPTFPQIFVKGELVGGCDILTSMYENGEL 288
Cdd:cd03030  20 QEVLGFLEAKKIEFEEVDISMNEENRQwMRENVPNENGKPLPPQIFNGDEYCGDYEAFFEAKENNTL 86

Catalytic GIY-YIG domain of nucleotide excision repair endonucleases UvrC, Cho, and similar proteins; UvrC is essential for nucleotide excision repair (NER). The N-terminal catalytic GIY-YIG domain of UvrC (also known as Uri domain) is responsible for the 3' incision reaction and the C-terminal half of UvrC, consisting of an UvrB-binding domain (UvrBb), EndoV-like nuclease domain and a helix-hairpin-helix (HhH) DNA-binding domain, contains the residues involved in 5' incision. The N- and C-terminal regions are joined by a common Cys-rich domain containing four conserved Cys residues. Besides UvrC, protein Cho (UvrC homolog) serves as a second endonuclease in E. coli NER. Cho contains GIY-YIG motif followed by a Cys-rich region and shares sequence homology with the N-terminal half of UvrC. It is capable of incising the DNA at the 3' side of a lesion in the presence of the UvrA and UvrB proteins during NER. The C-terminal half of Cho is a unique uncharacterized domain, which is distinct from that of UvrC. Moreover, unlike UvrC, Cho does not require the UvrC-binding domain of UvrB for the 3' incision reaction, which might cause the shift in incision position and the difference in incision efficiencies between Cho and UvrC on different damaged substrates. Due to this, the range of NER in E. coli can be broadened by combining action of Cho and UvrC. This family also includes many uncharacterized epsilon proofreading subunits of DNA polymerase III, which have an additional N-terminal ExoIII domain and a 3'-5' exonuclease domain homolog, fused to an UvrC-like region or a Cho-like region. The UvrC-like region includes a GIY-YIG motif, followed by a Cys-rich region, and an UvrB-binding domain (UvrBb), but lacks the EndoV-like nuclease domain and the helix-hairpin-helix (HhH) DNA-binding domain. The Cho-like region consists of a GIY-YIG motif, followed by the Cys-rich region, and the unique uncharacterized domain presenting in the C-terminal half of Cho. Some family members may not carry the Cys-rich region. This family also includes a specific Cho-like protein from G. violaceus, which possesses only UvrBb domain at the C-terminus, but lacks the additional N-terminal ExoIII domain. The oother two remote homologs of UvrC, Bacillus-I and -II, are included in this family as well. Both of them contain a GIY-YIG domain, but no Cys-rich region. Moreover, the whole C-terminal region of Bacillus-I is replaces by an unknown domain, and Bacillus-II possesses another unknown N-terminal extension.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 18404699  83 IPSASGVYAVYDKSDELQFVGISRNIAASVSAHLKS 118
Cdd:cd10434   1 LPDSPGVYLFKDADGEVLYVGKAKNLRKRVSSYFTG 36

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18404699 204 SKVVAFIKgsrsaPQCGFSQRVVGILESQGVDYETVDVLDDEYNHGLRETlknySNWPTFPQIFVKGELVGGCDILT 280
Cdd:cd03029   1 ESVSLFTK-----PGCPFCARAKAALQENGISYEEIPLGKDITGRSLRAV----TGAMTVPQVFIDGELIGGSDDLE 68