GIY-YIG domain of uncharacterized hypothetical protein found in bacteria; The family includes a group of uncharacterized bacterial proteins with 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570726569  4 PCVYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLHRLAWFEVHETMESAISREKQLKAGNRKRKLRLIEAL 83
Cdd:cd10448   1 YYVYILANKRNGTLYIGVTSDLIRRIYEHKEGLGSGFTSKYNVTRLVYYEEFEDIEEAIAREKQLKKWRRAWKINLIEKM 80

                ....*..
gi 570726569 84 NPDWRDL 90
Cdd:cd10448  81 NPDWKDL 87

GIY-YIG domain of uncharacterized hypothetical protein found in bacteria; The family includes a group of uncharacterized bacterial proteins with 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570726569  4 PCVYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLHRLAWFEVHETMESAISREKQLKAGNRKRKLRLIEAL 83
Cdd:cd10448   1 YYVYILANKRNGTLYIGVTSDLIRRIYEHKEGLGSGFTSKYNVTRLVYYEEFEDIEEAIAREKQLKKWRRAWKINLIEKM 80

                ....*..
gi 570726569 84 NPDWRDL 90
Cdd:cd10448  81 NPDWKDL 87

GIY-YIG catalytic domain; This domain called GIY-YIG is found in the amino terminal region of excinuclease abc subunit c (uvrC), bacteriophage T4 endonucleases segA, segB, segC, segD and segE; it is also found in putative endonucleases encoded by group I introns of fungi and phage. The structure of I-TevI a GIY-YIG endonuclease, reveals a novel alpha/beta-fold with a central three-stranded antiparallel beta-sheet flanked by three helices. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 570726569   3 QPCVYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLH--RLAWFEVHETMESAISREKQLKAGNRKRKLR 78
Cdd:pfam01541  1 KGGIYIIRNKDNKLLYVGSTKNLERRLNQHNAGKGAKYTRGKGVEpfKLIYLEEFPTKSEALELEKYLIKLYRPNKYN 78

GIY-YIG nuclease superfamily protein; Validated

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570726569  1 MKQPCVYMMTNRrNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLHRLAWFEVHETMESAISREKQLKAGNRKRKLRLI 80
Cdd:PRK00329  4 MKPWFLYLLRCA-DGSLYTGITTDVERRFAQHQSGKGAKYTRGRPPLTLVFVEPVGDRSEALRAEYRFKQLTKKQKERLV 82

                ..
gi 570726569 81 EA 82
Cdd:PRK00329 83 AE 84

GIY-YIG domain of uncharacterized hypothetical protein found in bacteria; The family includes a group of uncharacterized bacterial proteins with 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 570726569  4 PCVYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLHRLAWFEVHETMESAISREKQLKAGNRKRKLRLIEAL 83
Cdd:cd10448   1 YYVYILANKRNGTLYIGVTSDLIRRIYEHKEGLGSGFTSKYNVTRLVYYEEFEDIEEAIAREKQLKKWRRAWKINLIEKM 80

                ....*..
gi 570726569 84 NPDWRDL 90
Cdd:cd10448  81 NPDWKDL 87

GIY-YIG catalytic domain; This domain called GIY-YIG is found in the amino terminal region of excinuclease abc subunit c (uvrC), bacteriophage T4 endonucleases segA, segB, segC, segD and segE; it is also found in putative endonucleases encoded by group I introns of fungi and phage. The structure of I-TevI a GIY-YIG endonuclease, reveals a novel alpha/beta-fold with a central three-stranded antiparallel beta-sheet flanked by three helices. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 570726569   3 QPCVYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLH--RLAWFEVHETMESAISREKQLKAGNRKRKLR 78
Cdd:pfam01541  1 KGGIYIIRNKDNKLLYVGSTKNLERRLNQHNAGKGAKYTRGKGVEpfKLIYLEEFPTKSEALELEKYLIKLYRPNKYN 78

Catalytic GIY-YIG domain of yeast structure-specific endonuclease subunit SLX1 and its homologs; Structure-specific endonuclease subunit SLX1 is a highly conserved protein from yeast to human, with an N-terminal GIY-YIG endonuclease domain and a C-terminal PHD-type zinc finger postulated to mediate protein-protein or protein-DNA interaction. SLX1 forms active heterodimeric complexes with its SLX4 partner, which has additional roles in the DNA damage response that are distinct from the function of the heterodimeric SLX1-SLX4 nuclease. In yeast, the SLX1-SLX4 complex functions as a 5' flap endonuclease that maintains ribosomal DNA copy number, where SLX1 and SLX4 are shown to be catalytic and regulatory subunits, respectively. This endonuclease introduces single-strand cuts in duplex DNA on the 3' side of junctions with single-strand DNA. In addition to 5' flap endonuclease activity, human SLX1-SLX4 complex has been identified as a Holliday junction resolvase that promotes symmetrical cleavage of static and migrating Holliday junctions. SLX1 also associates with MUS81, EME1, C20orf94, PLK1, and ERCC1. Some eukaryotic SLX1 homologs lack the zinc finger domain, but possess intrinsically unstructured extensions of unknown function. These unstructured segments might be involved in interactions with other proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 570726569  6 VYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVeGFTKQYSLHRLAWFEVHETMESAISREKQLKAG 71
Cdd:cd10449   2 VYILYSEKLDRYYIGYTSDLERRLEQHNSGKS-KFTSKYRPWELVYSEAFESKSEALKREKYLKSG 66

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 570726569  6 VYMMTNRRNGTLYVGVTSNLVQRVWQHKSGVVEGFTKQYSLHRLAWFEVHETMESAI-SREKQLK 69
Cdd:cd00719   2 VYVLYDEDNGLIYVGQTKNLRNRIKEHLRKQRSDWTKGLKPFEILYLEVAPEAESELlDLEAALI 66

N-terminal catalytic domain of GIY-YIG intron endonuclease I-TevI, I-BmoI, I-BanI, I-BthII and similar proteins; I-TevI is a site-specific GIY-YIG homing endonuclease encoded within the group I intron of the thymidylate synthase gene (td) from Escherichia coli phage T4. It functions as an endonuclease that catalyzes the first step in intron homing by generating a double-strand break in the intronless td allele within a sequence designated the homing site. I-TevI recognizes its extensive 37 base pair DNA target in a site-specific, but sequence-tolerant manner. The cleavage site is located at 23 (upper strand) and 25 (lower strand) nucleotides upstream of the intron insertion site. A divalent cation, such as Mg2+, is required for the catalysis. I-TevI also acts as a repressor of its own transcription. It binds an operator that is located upstream of the I-TevI coding sequence and overlaps the T4 late promoter, which drives I-TevI expression from within the td intron. I-TevI binds the homing sites and the operator with the same affinity, but cleaves the homing site more efficiently than the operator. I-TevI consists of an N-terminal catalytic domain, containing the GIY-YIG motif, and a C-terminal DNA-binding domain that binds DNA as a monomer, joined by a flexible linker. The C-terminal domain includes three subdomains: a zinc finger, a minor-groove binding alpha-helix (NUMOD3, nuclease-associated modular domain 3), and a helix-turn-helix domain (HTH). The last two are responsible for DNA-binding. The zinc finger is part of the linker and not required for DNA-binding. It is implicated as a distance sensor to constrain the catalytic domain to cleave the homing site at a fixed position. None of other GIY-YIG endonucleases have been found to have the zinc finger motif. This family also includes a reduced activity isoschizomer of I-TevI, I-BmoI, which is encoded within the group I intron of the thymidylate synthase (TS) gene (thyA) from Bacillus mojavensis. I-BmoI catalyzes the first step in intron homing by generating a double-strand break in the intronless td allele within a sequence designated the homing site in the presence of a divalent cation cofactor, such as Mg2+. In the absence of Mg2+, I-Bmol only nicks one of the strands. Both I-BmoI and I-TevI bind a homologous stretch of TS-encoding DNA as monomers, but use different strategies to distinguish intronless from intron-containing substrates. I-TevI recognizes substrates at the level of DNA-binding. However, I-BmoI binds both intron-containing and intronless TS-encoding substrates, but efficiently cleaves only intronless substrate. Afterwards they cleave their respective intronless substrates in the same positions, and both require a critical G-C base pair adjacent to the top strand site for efficient cleavage. The C-terminal domain of I-BmoI has nuclease-associated modular DNA-binding domains (NUMODs), but lacks the zinc finger, which is different from that of I-TevI. Although the zinc finger implicated as a distance determination in I-TevI is absent, I-BmoI still possesses some cleavage distance discrimination. Besides I-TevI and I-BmoI, this family contains a putative GIY-YIG homing endonuclease, I-BanI, encoded within the self-splicing group I intron of nrdE gene from Bacillus anthracis. It contains two major domains, the N-terminal GIY-YIG domain and the C-terminal DNA-binding domain that consists of a minor-groove DNA binding alpha-helix motif and a helix-turn-helix (HTH) motif. I-BanI generates a double-strand break (DSB) in the intronless nrdE gene. The cleavage site is located at 5 and 7 nucleotides upstream of the intron insertion site, with 2-nucleotide 3' extensions. The recognition site is 35 to 40 base pairs and covers the cleavage site with a bias toward the downstream region including the (intervening sequence) IVS insertion site. Moreover, this family contains another putative GIY-YIG homing endonuclease, I-BthII, encoded within the self-splicing group I intron of nrdF gene from Bacillus thuringiensis ssp. pakistani. It contains a GIY-YIG motif that generates a double-strand break (DSB) in the intronless nrdF gene. The cleavage site is located at 7 and 9 nucleotides upstream of the intron insertion site, leaving 2-nucleotide 3' extensions. The recognition site is 27 to 29 base pairs with the DSB cleavage site at the 5'-end of the top strand, and with the intervening sequence (IVS) insertion site approximately in the middle of the recognition site.

                        10        20
                ....*....|....*....|....*....
gi 570726569  6 VYMMTNRRNGTLYVGVTSNLVQRVWQHKS 34
Cdd:cd10437   3 IYKITNLENGKIYIGSSKNILKRLSQHKR 31