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Conserved domains on  [gi|755541269|ref|XP_011242154|]
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flap endonuclease GEN homolog 1 isoform X4 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PIN_SF super family cl28905
PIN (PilT N terminus) domain: Superfamily; The PIN (PilT N terminus) domain belongs to a large ...
 16-105 8.86e-47

PIN (PilT N terminus) domain: Superfamily; The PIN (PilT N terminus) domain belongs to a large nuclease superfamily, and were originally named for their sequence similarity to the N-terminal domain of an annotated pili biogenesis protein, PilT, a domain fusion between a PIN-domain and a PilT ATPase domain. The structural properties of the PIN domain indicate its active center, consisting of three highly conserved catalytic residues which coordinate metal ions; in some members, additional metal coordinating residues can be found while some others lack several of these key catalytic residues. The PIN active site is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. The PIN domain superfamily includes: the FEN-like PIN domain family such as the PIN domains of Flap endonuclease-1 (FEN1), exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1), and Xeroderma pigmentosum complementation group G (XPG) nuclease, 5'-3' exonucleases of DNA polymerase I and bacteriophage T4- and T5-5' nucleases; the VapC-like PIN domain family which includes toxins of prokaryotic toxin/antitoxin operons FitAB and VapBC, as well as eukaryotic ribonucleases such as Smg6, ribosome assembly factor NOB1, exosome subunit Rrp44 endoribonuclease and rRNA-processing protein Fcf1; the LabA-like PIN domain family which includes the PIN domains of Synechococcus elongatus LabA (low-amplitude and bright); the PRORP-Zc3h12a-like PIN domain family which includes the PIN domains of RNase P (PRORP), ribonuclease Zc3h12a; and Bacillus subtilis YacP/Rae1-like PIN domains. It also includes the Mut7-C PIN domain family, which is not represented here as it is a shortened version of the PIN fold and lacks a core strand and helix (H3 and S3). The Mut7-C PIN domain family includes the C-terminus of Caenorhabditis elegans exonuclease Mut-7.


The actual alignment was detected with superfamily member cd09869:

Pssm-ID: 475124 [Multi-domain]  Cd Length: 227  Bit Score: 166.24  E-value: 8.86e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTISSIKSKLGL--- 92
Cdd:cd09869  117 CEELLELLGVPVVQAPGEAEALCALLNAEGLVDGCITNDGDAFLYGARTVYRNFSLNTKDGSVECYDMSDIEKRLSLrwr 196

                         90
                 ....*....|....*
gi 755541269  93 --DRDALVGLAVLLG 105
Cdd:cd09869  197 rpDLDLLQDFLLKKL 211
H3TH_StructSpec-5'-nucleases super family cl22433
H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA ...
 94-236 1.56e-40

H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA replication, repair, and recombination; The 5' nucleases of this superfamily are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. The superfamily includes the H3TH (helix-3-turn-helix) domains of Flap Endonuclease-1 (FEN1), Exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1) and Xeroderma pigmentosum complementation group G (XPG) nuclease. Also included are the H3TH domains of the 5'-3' exonucleases of DNA polymerase I and single domain protein homologs, as well as, the bacteriophage T4 RNase H, T5-5'nuclease, and other homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the C-terminal region of the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. Typically, the nucleases within this superfamily have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one or two Asp residues from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


The actual alignment was detected with superfamily member cd09905:

Pssm-ID: 473957  Cd Length: 108  Bit Score: 144.42  E-value: 1.56e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  94 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLLQIFKGQSLLQRFNQWIEDPCYSVPQSA-PKKVVHCSVCSHPGSPKDHE 172
Cdd:cd09905    1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSSDEVLDRLRNWRATSDPSSPQELkKKDKNHCSNCGHLGKKQEHI 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755541269 173 RNGCILCksdkycephdydylcpcewhqtdhnrhlseiennikKKACSCEGFPFHEVIQEFLLN 236
Cdd:cd09905   81 KSGCEDC------------------------------------DKALLDPGFPNEEIIEEFLSR 108
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 296-356 3.02e-24

Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, general protein interaction elements as well as dimerization sites. They are found in many chromatin-associated proteins that bind modified histone tails for chromatin targeting. Chromodomains often recognize modified lysines through their aromatic cage thus targeting proteins to chromatin. Family members such as GEN1 carry a chomodomain which directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. The chromodomain allows GEN1 to correctly position itself against DNA molecules, and without the chromodomain, GEN1's ability to cut DNA was severely impaired. The GEN1 chromodomain was found to be distantly related to the CDY chromodomains and chromobox proteins, particularly to the chromo-shadow domains of CBX1, CBX3 and CBX5. Furthermore, it is conserved from yeast (Yen1) to humans with the only exception being the Caenorhabditis elegans GEN1, which has a much smaller protein size of 443 amino acids compared to yeast Yen1 (759 aa) or human GEN1 (908 aa).


:

Pssm-ID: 465841  Cd Length: 63  Bit Score: 96.18  E-value: 3.02e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755541269  296 QPIRIVKPRVRNGVHCLEIEWEKPEHYV-VEDGDPGKLSLL-TMEEASLFEAAYPDAVAVYQK 356
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPEGYFeEEDDDPGELELLtTIEPQDLVEKAYPELVEAFEK 63
 
Name Accession Description Interval E-value
PIN_GEN1 cd09869
FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, ...
 16-105 8.86e-47

FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; Gap Endonuclease 1 (GEN1) is a Holliday junction resolvase reported to symmetrically cleave Holliday junctions and allow religation without additional processing. GEN1 is a member of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.


Pssm-ID: 350217 [Multi-domain]  Cd Length: 227  Bit Score: 166.24  E-value: 8.86e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTISSIKSKLGL--- 92
Cdd:cd09869  117 CEELLELLGVPVVQAPGEAEALCALLNAEGLVDGCITNDGDAFLYGARTVYRNFSLNTKDGSVECYDMSDIEKRLSLrwr 196

                         90
                 ....*....|....*
gi 755541269  93 --DRDALVGLAVLLG 105
Cdd:cd09869  197 rpDLDLLQDFLLKKL 211
H3TH_GEN1 cd09905
H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 94-236 1.56e-40

H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; Gap Endonuclease 1 (GEN1): Holliday junction resolvase reported to symmetrically cleave Holliday junctions and allow religation without additional processing. GEN1 is a member of the structure-specific, 5' nuclease family that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of GEN1 and other similar eukaryotic 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188625  Cd Length: 108  Bit Score: 144.42  E-value: 1.56e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  94 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLLQIFKGQSLLQRFNQWIEDPCYSVPQSA-PKKVVHCSVCSHPGSPKDHE 172
Cdd:cd09905    1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSSDEVLDRLRNWRATSDPSSPQELkKKDKNHCSNCGHLGKKQEHI 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755541269 173 RNGCILCksdkycephdydylcpcewhqtdhnrhlseiennikKKACSCEGFPFHEVIQEFLLN 236
Cdd:cd09905   81 KSGCEDC------------------------------------DKALLDPGFPNEEIIEEFLSR 108
XPG_I pfam00867
XPG I-region;
24-107 6.39e-33

XPG I-region;


Pssm-ID: 459970 [Multi-domain]  Cd Length: 87  Bit Score: 121.85  E-value: 6.39e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269   24 GMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDP---HVDCYTISSIKSKLGLDRDALVGL 100
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKKskvPVEEIDLEKILKELGLTREQLIDL 80


                  ....*..
gi 755541269  101 AVLLGCD 107
Cdd:pfam00867  81 AILLGCD 87
rad2 TIGR00600
DNA excision repair protein (rad2); All proteins in this family for which functions are known ...
 16-140 6.43e-25

DNA excision repair protein (rad2); All proteins in this family for which functions are known are flap endonucleases that generate the 3' incision next to DNA damage as part of nucleotide excision repair. This family is related to many other flap endonuclease families including the fen1 family. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 273166 [Multi-domain]  Cd Length: 1034  Bit Score: 111.53  E-value: 6.43e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269    16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTmnTKDPHVDCYTISSIKSKLGLDRD 95
Cdd:TIGR00600  777 SQELLRLFGIPYIVAPMEAEAQCAILDLLDQTSGTITDDSDIWLFGARHVYKNFF--NQNKFVEYYQYVDIHNQLGLDRN 854

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 755541269    96 ALVGLAVLLGCDYlPKGVPGVGKEQALKLLQIFKGQSL--LQRFNQW 140
Cdd:TIGR00600  855 KLINLAYLLGSDY-TEGIPTVGPVSAMEILNEFPGDGLepLLKFKEW 900
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 296-356 3.02e-24

Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, general protein interaction elements as well as dimerization sites. They are found in many chromatin-associated proteins that bind modified histone tails for chromatin targeting. Chromodomains often recognize modified lysines through their aromatic cage thus targeting proteins to chromatin. Family members such as GEN1 carry a chomodomain which directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. The chromodomain allows GEN1 to correctly position itself against DNA molecules, and without the chromodomain, GEN1's ability to cut DNA was severely impaired. The GEN1 chromodomain was found to be distantly related to the CDY chromodomains and chromobox proteins, particularly to the chromo-shadow domains of CBX1, CBX3 and CBX5. Furthermore, it is conserved from yeast (Yen1) to humans with the only exception being the Caenorhabditis elegans GEN1, which has a much smaller protein size of 443 amino acids compared to yeast Yen1 (759 aa) or human GEN1 (908 aa).


Pssm-ID: 465841  Cd Length: 63  Bit Score: 96.18  E-value: 3.02e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755541269  296 QPIRIVKPRVRNGVHCLEIEWEKPEHYV-VEDGDPGKLSLL-TMEEASLFEAAYPDAVAVYQK 356
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPEGYFeEEDDDPGELELLtTIEPQDLVEKAYPELVEAFEK 63
PRK03980 PRK03980
flap endonuclease-1; Provisional
 18-124 1.70e-22

flap endonuclease-1; Provisional


Pssm-ID: 235185 [Multi-domain]  Cd Length: 292  Bit Score: 98.35  E-value: 1.70e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  18 EMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMN--TKDPHVDCY--------TISSIK 87
Cdd:PRK03980  90 KLLDLMGIPYVQAPSEGEAQAAYMAKKGDAWAVGSQDYDSLLFGAPRLVRNLTISgkRKLPGKNVYvevkpeliELEEVL 169

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 755541269  88 SKLGLDRDALVGLAVLLGCDYLPkGVPGVGKEQALKL 124
Cdd:PRK03980 170 KELGITREQLIDIAILVGTDYNP-GIKGIGPKTALKL 205
XPGI smart00484
Xeroderma pigmentosum G I-region; domain in nucleases
 23-92 1.59e-18

Xeroderma pigmentosum G I-region; domain in nucleases


Pssm-ID: 214689 [Multi-domain]  Cd Length: 73  Bit Score: 80.32  E-value: 1.59e-18
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755541269    23 LGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDpHVDCYTI--SSIKSKLGL 92
Cdd:smart00484   3 MGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLFFSGKK-KLEFRIIdlESVLKELGL 73
 
Name Accession Description Interval E-value
PIN_GEN1 cd09869
FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, ...
 16-105 8.86e-47

FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; Gap Endonuclease 1 (GEN1) is a Holliday junction resolvase reported to symmetrically cleave Holliday junctions and allow religation without additional processing. GEN1 is a member of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.


Pssm-ID: 350217 [Multi-domain]  Cd Length: 227  Bit Score: 166.24  E-value: 8.86e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTISSIKSKLGL--- 92
Cdd:cd09869  117 CEELLELLGVPVVQAPGEAEALCALLNAEGLVDGCITNDGDAFLYGARTVYRNFSLNTKDGSVECYDMSDIEKRLSLrwr 196

                         90
                 ....*....|....*
gi 755541269  93 --DRDALVGLAVLLG 105
Cdd:cd09869  197 rpDLDLLQDFLLKKL 211
H3TH_GEN1 cd09905
H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 94-236 1.56e-40

H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; Gap Endonuclease 1 (GEN1): Holliday junction resolvase reported to symmetrically cleave Holliday junctions and allow religation without additional processing. GEN1 is a member of the structure-specific, 5' nuclease family that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of GEN1 and other similar eukaryotic 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188625  Cd Length: 108  Bit Score: 144.42  E-value: 1.56e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  94 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLLQIFKGQSLLQRFNQWIEDPCYSVPQSA-PKKVVHCSVCSHPGSPKDHE 172
Cdd:cd09905    1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSSDEVLDRLRNWRATSDPSSPQELkKKDKNHCSNCGHLGKKQEHI 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755541269 173 RNGCILCksdkycephdydylcpcewhqtdhnrhlseiennikKKACSCEGFPFHEVIQEFLLN 236
Cdd:cd09905   81 KSGCEDC------------------------------------DKALLDPGFPNEEIIEEFLSR 108
PIN_FEN1-like cd09856
FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like, structure-specific, ...
 16-90 5.46e-35

FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like, structure-specific, divalent-metal-ion dependent, 5' nucleases; PIN (PilT N terminus) domain of Flap endonuclease-1 (FEN1)-like nucleases: FEN1, Gap endonuclease 1 (GEN1) and Xeroderma pigmentosum complementation group G (XPG) nuclease. Nucleases in this subfamily are members of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.


Pssm-ID: 350206 [Multi-domain]  Cd Length: 235  Bit Score: 133.05  E-value: 5.46e-35
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTISSIKSKL 90
Cdd:cd09856  128 CKHLLSLFGIPYVDAPGEAEAQCAYLEQQGIVDAVLTEDVDTFLFGSPVVYRNLTSEGKKTHVELYDASSILEGL 202
XPG_I pfam00867
XPG I-region;
24-107 6.39e-33

XPG I-region;


Pssm-ID: 459970 [Multi-domain]  Cd Length: 87  Bit Score: 121.85  E-value: 6.39e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269   24 GMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDP---HVDCYTISSIKSKLGLDRDALVGL 100
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKKskvPVEEIDLEKILKELGLTREQLIDL 80


                  ....*..
gi 755541269  101 AVLLGCD 107
Cdd:pfam00867  81 AILLGCD 87
PIN_FEN1_EXO1-like cd00128
FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like and exonuclease-1 (EXO1)-like ...
 16-88 7.60e-28

FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like and exonuclease-1 (EXO1)-like nucleases, structure-specific, divalent-metal-ion dependent, 5' nucleases; PIN (PilT N terminus) domain of Flap endonuclease-1 (FEN1) and exonuclease-1 (EXO1)-like nucleases: FEN1, EXO1, Mkt1, Gap endonuclease 1 (GEN1) and Xeroderma pigmentosum complementation group G (XPG) nuclease. These nucleases are members of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.


Pssm-ID: 350200 [Multi-domain]  Cd Length: 162  Bit Score: 110.16  E-value: 7.60e-28
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTkdPHVDCYTISSIKS 88
Cdd:cd00128   92 CKHLLSLFGIPYVVAPYEAEAQCAYLLKAGIVDAAITEDSDCLLFGAPRVIRNMTFEG--PHVEEFDASSILE 162
PIN_YEN1 cd09870
FEN-like PIN domains of Saccharomyces cerevisiae endonuclease 1 (YEN1), Chaetomium ...
 18-100 1.01e-26

FEN-like PIN domains of Saccharomyces cerevisiae endonuclease 1 (YEN1), Chaetomium thermophilum junction-resolving enzyme GEN1, and fungal homologs; Fungal Endonuclease 1 (YEN1 and GEN1, GEN1 is known as YEN1 in Saccharomyces cerevisiae) is a four-way (Holliday) junction resolvase. Members of this subgroup belong to the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.


Pssm-ID: 350218 [Multi-domain]  Cd Length: 229  Bit Score: 109.28  E-value: 1.01e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  18 EMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTISSIKSKLGLDRDAL 97
Cdd:cd09870  114 ELLDAFGFPWHEAPGEAEAELARLQRLGVVDAVLTDDSDALVFGATTVLRNFSKKLSDDDVKVYTASAIKDKADLTRTSL 193


                 ...
gi 755541269  98 VGL 100
Cdd:cd09870  194 RGP 196
rad2 TIGR00600
DNA excision repair protein (rad2); All proteins in this family for which functions are known ...
 16-140 6.43e-25

DNA excision repair protein (rad2); All proteins in this family for which functions are known are flap endonucleases that generate the 3' incision next to DNA damage as part of nucleotide excision repair. This family is related to many other flap endonuclease families including the fen1 family. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]


Pssm-ID: 273166 [Multi-domain]  Cd Length: 1034  Bit Score: 111.53  E-value: 6.43e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269    16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTmnTKDPHVDCYTISSIKSKLGLDRD 95
Cdd:TIGR00600  777 SQELLRLFGIPYIVAPMEAEAQCAILDLLDQTSGTITDDSDIWLFGARHVYKNFF--NQNKFVEYYQYVDIHNQLGLDRN 854

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 755541269    96 ALVGLAVLLGCDYlPKGVPGVGKEQALKLLQIFKGQSL--LQRFNQW 140
Cdd:TIGR00600  855 KLINLAYLLGSDY-TEGIPTVGPVSAMEILNEFPGDGLepLLKFKEW 900
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 296-356 3.02e-24

Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, general protein interaction elements as well as dimerization sites. They are found in many chromatin-associated proteins that bind modified histone tails for chromatin targeting. Chromodomains often recognize modified lysines through their aromatic cage thus targeting proteins to chromatin. Family members such as GEN1 carry a chomodomain which directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. The chromodomain allows GEN1 to correctly position itself against DNA molecules, and without the chromodomain, GEN1's ability to cut DNA was severely impaired. The GEN1 chromodomain was found to be distantly related to the CDY chromodomains and chromobox proteins, particularly to the chromo-shadow domains of CBX1, CBX3 and CBX5. Furthermore, it is conserved from yeast (Yen1) to humans with the only exception being the Caenorhabditis elegans GEN1, which has a much smaller protein size of 443 amino acids compared to yeast Yen1 (759 aa) or human GEN1 (908 aa).


Pssm-ID: 465841  Cd Length: 63  Bit Score: 96.18  E-value: 3.02e-24
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755541269  296 QPIRIVKPRVRNGVHCLEIEWEKPEHYV-VEDGDPGKLSLL-TMEEASLFEAAYPDAVAVYQK 356
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPEGYFeEEDDDPGELELLtTIEPQDLVEKAYPELVEAFEK 63
PIN_XPG_RAD2 cd09868
FEN-like PIN domains of Xeroderma pigmentosum complementation group G (XPG) nuclease, a ...
 16-90 1.25e-22

FEN-like PIN domains of Xeroderma pigmentosum complementation group G (XPG) nuclease, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; The Xeroderma pigmentosum complementation group G (XPG) nuclease plays a central role in nucleotide excision repair (NER) in cleaving DNA bubble structures or loops. XPG is a member of the structure-specific, 5' nuclease family (FEN-like) that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons.


Pssm-ID: 350216 [Multi-domain]  Cd Length: 209  Bit Score: 96.82  E-value: 1.25e-22
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKdpHVDCYTISSIKSKL 90
Cdd:cd09868  101 IQELLRLFGIPYIVAPMEAEAQCAFLERLGLVDGVITDDSDVFLFGAKRVYKNFFNQNK--YVEYYDMEDIEREL 173
PRK03980 PRK03980
flap endonuclease-1; Provisional
 18-124 1.70e-22

flap endonuclease-1; Provisional


Pssm-ID: 235185 [Multi-domain]  Cd Length: 292  Bit Score: 98.35  E-value: 1.70e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  18 EMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMN--TKDPHVDCY--------TISSIK 87
Cdd:PRK03980  90 KLLDLMGIPYVQAPSEGEAQAAYMAKKGDAWAVGSQDYDSLLFGAPRLVRNLTISgkRKLPGKNVYvevkpeliELEEVL 169

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 755541269  88 SKLGLDRDALVGLAVLLGCDYLPkGVPGVGKEQALKL 124
Cdd:PRK03980 170 KELGITREQLIDIAILVGTDYNP-GIKGIGPKTALKL 205
XPGI smart00484
Xeroderma pigmentosum G I-region; domain in nucleases
 23-92 1.59e-18

Xeroderma pigmentosum G I-region; domain in nucleases


Pssm-ID: 214689 [Multi-domain]  Cd Length: 73  Bit Score: 80.32  E-value: 1.59e-18
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 755541269    23 LGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMNTKDpHVDCYTI--SSIKSKLGL 92
Cdd:smart00484   3 MGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLFFSGKK-KLEFRIIdlESVLKELGL 73
PTZ00217 PTZ00217
flap endonuclease-1; Provisional
 16-153 3.69e-17

flap endonuclease-1; Provisional


Pssm-ID: 240317 [Multi-domain]  Cd Length: 393  Bit Score: 84.29  E-value: 3.69e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFTMN--TKDPHVDcYTISSIKSKLGLD 93
Cdd:PTZ00217 143 AKKLLRLMGIPVIEAPCEAEAQCAELVKKGKVYAVATEDMDALTFGTPVLLRNLNFSeaKKRPIQE-INLSTVLEELGLS 221

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 755541269  94 RDALVGLAVLLGCDYLPKgVPGVGKEQALKLLQIFKGqslLQRFNQWIEDPCYSVPQSAP 153
Cdd:PTZ00217 222 MDQFIDLCILCGCDYCDT-IKGIGPKTAYKLIKKYKS---IEEILEHLDKTKYPVPENFD 277
PIN_FEN1 cd09867
FEN-like PIN domains of Flap endonuclease-1, a structure-specific, divalent-metal-ion ...
 16-70 1.72e-14

FEN-like PIN domains of Flap endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; Flap endonuclease-1 (FEN1) is involved in multiple DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity) and DNA repair processes (long-patch base excision repair) in eukaryotes and archaea. Interaction between FEN1 and PCNA (Proliferating cell nuclear antigen) is an essential prerequisite to FEN1's DNA replication functionality and stimulates FEN1 nuclease activity by 10-50 fold. FEN1 belongs to the FEN1-EXO1-like subfamily of structure-specific, 5' nucleases (FEN-like family). Canonical members of the FEN-like family possess a PIN domain with a two-helical structure insert (also known as the helical arch, helical clamp or I domain) of variable length (approximately 16 to 800 residues), and at the C-terminus of the PIN domain a H3TH (helix-3-turn-helix) domain, an atypical helix-hairpin-helix-2-like region. Both the H3TH domain (not included in this model) and the helical arch/clamp region are involved in DNA binding. The PIN domain belongs to a large nuclease superfamily. The structural properties of the PIN domain indicate its putative active center, consisting of invariant acidic amino acid residues (putative metal-binding residues), is geometrically similar in the active center of structure-specific 5' nucleases, PIN-domain ribonucleases of eukaryotic rRNA editing proteins, and bacterial toxins of toxin-antitoxin (TA) operons. FEN1 has a C-terminal extension containing residues forming the consensus PIP-box - Qxx(M/L/I)xxF(Y/F) which serves to anchor FEN1 to PCNA.


Pssm-ID: 350215 [Multi-domain]  Cd Length: 251  Bit Score: 73.97  E-value: 1.72e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755541269  16 CLEMLECLGMPWVQAAGEAEAMCAYLNASGHVDGCLTNDGDAFLYGAQTVYRNFT 70
Cdd:cd09867  133 AKKLLDLMGIPYVQAPSEGEAQAAYLVKKGDVYAVASQDYDSLLFGAPRLVRNLT 187
H3TH_XPG-like cd09900
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 ...
 95-139 3.55e-09

H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 (archaeal), GEN1, YEN1, and XPG; The 5' nucleases within this family are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. This family includes the H3TH (helix-3-turn-helix) domains of archaeal Flap Endonuclease-1 (FEN1), Gap Endonuclease 1 (GEN1), Yeast Endonuclease 1 (YEN1), Xeroderma pigmentosum complementation group G (XPG) nuclease, and other eukaryotic and archaeal homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. With the except of the Mkt1-like proteins, the nucleases within this family have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188620 [Multi-domain]  Cd Length: 52  Bit Score: 53.26  E-value: 3.55e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 755541269  95 DALVGLAVLLGCDYLPkGVPGVGKEQALKLLQIFKgqSLLQRFNQ 139
Cdd:cd09900    1 EQLILLALLLGTDYNP-GVPGIGPKTALELLKEFG--EDLEKFLE 42
H3TH_FEN1-XPG-like cd09897
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases; The 5' ...
 95-147 5.98e-09

H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases; The 5' nucleases within this family are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. This family includes the H3TH (helix-3-turn-helix) domains of Flap Endonuclease-1 (FEN1), Exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1), Xeroderma pigmentosum complementation group G (XPG) nuclease, and other eukaryotic and archaeal homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. With the except of the Mkt1-like proteins, the nucleases within this family have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188617 [Multi-domain]  Cd Length: 68  Bit Score: 52.98  E-value: 5.98e-09
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 755541269  95 DALVGLAVLLGCDYLPkGVPGVGKEQALKLLQIFKgqsLLQRFNQWIEDPCYS 147
Cdd:cd09897    1 EQFIDLCILSGCDYLP-GLPGIGPKTALKLIKEYG---SLEKVLKALRDDKKD 49
H3TH_XPG cd09904
H3TH domain of Xeroderma pigmentosum complementation group G (XPG) nuclease, a ...
 95-145 3.37e-08

H3TH domain of Xeroderma pigmentosum complementation group G (XPG) nuclease, a structure-specific, divalent-metal-ion dependent, 5' nuclease; The Xeroderma pigmentosum complementation group G (XPG) nuclease plays a central role in nucleotide excision repair (NER) in cleaving DNA bubble structures or loops. XPG is a member of the structure-specific, 5' nuclease family that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of XPG and other similar eukaryotic 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188624 [Multi-domain]  Cd Length: 97  Bit Score: 51.87  E-value: 3.37e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 755541269  95 DALVGLAVLLGCDYLPkGVPGVGKEQALKLLQIFKGQSLLQRFNQWIEDPC 145
Cdd:cd09904    1 DKLIRLALLLGSDYTE-GVSGIGPVNAMEILSEFPGEEDLEKFKDWWENAQ 50
H3TH_YEN1 cd09906
H3TH domain of Yeast Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 94-139 1.46e-04

H3TH domain of Yeast Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; Yeast Endonuclease 1 (YEN1): Holliday junction resolvase which promotes reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast. YEN1 is a member of the structure-specific, 5' nuclease family that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of YEN1 and other similar fungal 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188626  Cd Length: 105  Bit Score: 41.52  E-value: 1.46e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 755541269  94 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLLQIFKGQSLLQRFNQ 139
Cdd:cd09906    1 RGGMVLFALLSGGDYDTVGLPGCGKKTALELAKLGFGDSLLEAAED 46
H3TH_StructSpec-5'-nucleases cd00080
H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA ...
 95-126 1.47e-04

H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA replication, repair, and recombination; The 5' nucleases of this superfamily are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. The superfamily includes the H3TH (helix-3-turn-helix) domains of Flap Endonuclease-1 (FEN1), Exonuclease-1 (EXO1), Mkt1, Gap Endonuclease 1 (GEN1) and Xeroderma pigmentosum complementation group G (XPG) nuclease. Also included are the H3TH domains of the 5'-3' exonucleases of DNA polymerase I and single domain protein homologs, as well as, the bacteriophage T4 RNase H, T5-5'nuclease, and other homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the C-terminal region of the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. Typically, the nucleases within this superfamily have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one or two Asp residues from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188616 [Multi-domain]  Cd Length: 71  Bit Score: 40.82  E-value: 1.47e-04
                         10        20        30
                 ....*....|....*....|....*....|...
gi 755541269  95 DALVGLAVLLGCDYLP-KGVPGVGKEQALKLLQ 126
Cdd:cd00080    1 EQFIDLCALVGCDYSDnPGVPGIGPKTAAKLAL 33
H3TH_FEN1-Arc cd09903
H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 95-124 1.94e-04

H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease: Archaeal homologs; Members of this subgroup include the H3TH (helix-3-turn-helix) domains of archaeal Flap endonuclease-1 (FEN1), 5' nucleases. FEN1 is involved in multiple DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity) and DNA repair processes (long-patch base excision repair) in eukaryotes and archaea. Interaction between FEN1 and PCNA (Proliferating cell nuclear antigen) is an essential prerequisite to FEN1's DNA replication functionality and stimulates FEN1 nuclease activity by 10-50 fold. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. The nucleases within this subfamily have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases. Also, FEN1 has a C-terminal extension containing residues forming the consensus PIP-box - Qxx(M/L/I)xxF(Y/F) which serves to anchor FEN1 to PCNA.


Pssm-ID: 188623 [Multi-domain]  Cd Length: 65  Bit Score: 40.27  E-value: 1.94e-04
                         10        20        30
                 ....*....|....*....|....*....|
gi 755541269  95 DALVGLAVLLGCDYLPKGVPGVGKEQALKL 124
Cdd:cd09903    1 EQLIDIAILVGTDYNPGGVKGIGPKTALKL 30
H3TH_FEN1-like cd09901
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 ...
 95-126 7.28e-04

H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 (eukaryotic) and EXO1; The 5' nucleases within this family are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner, and are involved in DNA replication, repair, and recombination. This family includes the H3TH (helix-3-turn-helix) domains of eukaryotic Flap Endonuclease-1 (FEN1), Exonuclease-1 (EXO1), and other eukaryotic homologs. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. The nucleases within this family have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (i. e., Mg2+, Mn2+, Zn2+, or Co2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases.


Pssm-ID: 188621 [Multi-domain]  Cd Length: 73  Bit Score: 38.67  E-value: 7.28e-04
                         10        20        30
                 ....*....|....*....|....*....|..
gi 755541269  95 DALVGLAVLLGCDYLPkGVPGVGKEQALKLLQ 126
Cdd:cd09901    1 EQFIDLCILSGCDYLP-SIPGIGPKTAYKLIK 31
H3TH_FEN1-Euk cd09907
H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 95-149 2.81e-03

H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease: Eukaryotic homologs; Members of this subgroup include the H3TH (helix-3-turn-helix) domains of eukaryotic Flap endonuclease-1 (FEN1), 5' nucleases. FEN1 is involved in multiple DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity) and DNA repair processes (long-patch base excision repair) in eukaryotes and archaea. Interaction between FEN1 and PCNA (Proliferating cell nuclear antigen) is an essential prerequisite to FEN1's DNA replication functionality and stimulates FEN1 nuclease activity by 10-50 fold. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. The nucleases within this subfamily have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases. Also, FEN1 has a C-terminal extension containing residues forming the consensus PIP-box - Qxx(M/L/I)xxF(Y/F) which serves to anchor FEN1 to PCNA.


Pssm-ID: 188627 [Multi-domain]  Cd Length: 70  Bit Score: 37.14  E-value: 2.81e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755541269  95 DALVGLAVLLGCDYLPKgVPGVGKEQALKLLQIFKGqslLQRFNQWIEDPCYSVP 149
Cdd:cd09907    1 EQFIDLCILLGCDYCES-IKGIGPKTALKLIKKHKS---IEKILENIDKSKYPVP 51
H3TH_EXO1 cd09908
H3TH domain of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; ...
 101-130 8.25e-03

H3TH domain of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; Exonuclease-1 (EXO1) is involved in multiple, eukaryotic DNA metabolic pathways, including DNA replication processes (5' flap DNA endonuclease activity and double stranded DNA 5'-exonuclease activity), DNA repair processes (DNA mismatch repair (MMR) and post-replication repair (PRR), recombination, and telomere integrity. EXO1 functions in the MMS2 error-free branch of the PRR pathway in the maintenance and repair of stalled replication forks. Studies also suggest that EXO1 plays both structural and catalytic roles during MMR-mediated mutation avoidance. Members of this subgroup include the H3TH (helix-3-turn-helix) domains of EXO1 and other similar eukaryotic 5' nucleases. These nucleases contain a PIN (PilT N terminus) domain with a helical arch/clamp region/I domain (not included here) and inserted within the PIN domain is an atypical helix-hairpin-helix-2 (HhH2)-like region. This atypical HhH2 region, the H3TH domain, has an extended loop with at least three turns between the first two helices, and only three of the four helices appear to be conserved. Both the H3TH domain and the helical arch/clamp region are involved in DNA binding. Studies suggest that a glycine-rich loop in the H3TH domain contacts the phosphate backbone of the template strand in the downstream DNA duplex. These nucleases have a carboxylate rich active site that is involved in binding essential divalent metal ion cofactors (Mg2+ or Mn2+) required for nuclease activity. The first metal binding site is composed entirely of Asp/Glu residues from the PIN domain, whereas, the second metal binding site is composed generally of two Asp residues from the PIN domain and one Asp residue from the H3TH domain. Together with the helical arch and network of amino acids interacting with metal binding ions, the H3TH region defines a positively charged active-site DNA-binding groove in structure-specific 5' nucleases. EXO1 nucleases also have C-terminal Mlh1- and Msh2-binding domains which allow interaction with MMR and PRR proteins, respectively.


Pssm-ID: 188628 [Multi-domain]  Cd Length: 73  Bit Score: 35.63  E-value: 8.25e-03
                         10        20        30
                 ....*....|....*....|....*....|
gi 755541269 101 AVLLGCDYLPkGVPGVGKEQALKLLQIFKG 130
Cdd:cd09908    7 CILSGCDYLP-SLPGIGLKKAYKLVRRHRT 35
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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