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Conserved domains on  [gi|224002667|ref|XP_002291005|]
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nuclease, Fen1 like, Rad27 family [Thalassiosira pseudonana CCMP1335]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PIN_GEN1 cd09869
FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, ...
 2-196 2.95e-63

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: 210.92  E-value: 2.95e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   2 TVSSLWTVLDEagcgrpvgiedfDTSNTSNINSRPTILAVDTSIWICEGISSTALSSFHSDPALYLVYQRTTKLLKLGLG 81
Cdd:cd09869    1 GVKGLWTILDP------------VKKRKPLSELRGKTLAVDLSIWICEAQTVLALFETVPKPHLRNLFFRTVNLLRLGIK 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  82 LVFVLEG----------KRRVRSTYQSSEHHELKQRRSGSQFWSATERCESLLRLLGVPVVRAEAEGEALCALLNAKGVC 151
Cdd:cd09869   69 PVFVLDGdapelklqtiKKRNAARFGGAKKKGGSKKRGRSRFSRVLKECEELLELLGVPVVQAPGEAEALCALLNAEGLV 148

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 224002667 152 DGVISNDGDCFLFGAKTLYTKFTMENLESrQVMCYDATALMATVD 196
Cdd:cd09869  149 DGCITNDGDAFLYGARTVYRNFSLNTKDG-SVECYDMSDIEKRLS 192
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 431-490 1.55e-13

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: 65.75  E-value: 1.55e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 224002667  431 VPEKIEKEFVKQSEPCYEVVWSID------VDPNLGDTATFTfsTIEPQSLvVNSKYSGLCKLFHQ 490
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPegyfeeEDDDPGELELLT--TIEPQDL-VEKAYPELVEAFEK 63
H3TH_StructSpec-5'-nucleases super family cl22433
H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA ...
 209-355 7.15e-09

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: 53.90  E-value: 7.15e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 209 REDLVAFALLTGSDMFGAGLSHVGHKKAVQFLHTCSSlnqrpnqRTCLEELLGWGDvAAESASKLNDNQCDDdgpstite 288
Cdd:cd09905    1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSS-------DEVLDRLRNWRA-TSDPSSPQELKKKDK-------- 64

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 224002667 289 RCCSKCLHSGSKSQHVKNGCTICgtkpgegcivvtskekflrslrEKALKmNPPFAPRGIVNEYFSP 355
Cdd:cd09905   65 NHCSNCGHLGKKQEHIKSGCEDC----------------------DKALL-DPGFPNEEIIEEFLSR 108
 
Name Accession Description Interval E-value
PIN_GEN1 cd09869
FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, ...
 2-196 2.95e-63

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: 210.92  E-value: 2.95e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   2 TVSSLWTVLDEagcgrpvgiedfDTSNTSNINSRPTILAVDTSIWICEGISSTALSSFHSDPALYLVYQRTTKLLKLGLG 81
Cdd:cd09869    1 GVKGLWTILDP------------VKKRKPLSELRGKTLAVDLSIWICEAQTVLALFETVPKPHLRNLFFRTVNLLRLGIK 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  82 LVFVLEG----------KRRVRSTYQSSEHHELKQRRSGSQFWSATERCESLLRLLGVPVVRAEAEGEALCALLNAKGVC 151
Cdd:cd09869   69 PVFVLDGdapelklqtiKKRNAARFGGAKKKGGSKKRGRSRFSRVLKECEELLELLGVPVVQAPGEAEALCALLNAEGLV 148

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 224002667 152 DGVISNDGDCFLFGAKTLYTKFTMENLESrQVMCYDATALMATVD 196
Cdd:cd09869  149 DGCITNDGDAFLYGARTVYRNFSLNTKDG-SVECYDMSDIEKRLS 192
XPG_I pfam00867
XPG I-region;
128-222 1.52e-20

XPG I-region;


Pssm-ID: 459970 [Multi-domain]  Cd Length: 87  Bit Score: 86.42  E-value: 1.52e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  128 GVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFTMENLESR--QVMCYDATALMATVDsdglngkti 205
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKKSkvPVEEIDLEKILKELG--------- 71

                          90
                  ....*....|....*..
gi 224002667  206 tLSREDLVAFALLTGSD 222
Cdd:pfam00867  72 -LTREQLIDLAILLGCD 87
PRK03980 PRK03980
flap endonuclease-1; Provisional
 118-241 1.66e-16

flap endonuclease-1; Provisional


Pssm-ID: 235185 [Multi-domain]  Cd Length: 292  Bit Score: 80.63  E-value: 1.66e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 118 ERCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLytkftMENLES---RQVMCYDATA---- 190
Cdd:PRK03980  86 EDSKKLLDLMGIPYVQAPSEGEAQAAYMAKKGDAWAVGSQDYDSLLFGAPRL-----VRNLTIsgkRKLPGKNVYVevkp 160

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 224002667 191 ----LMATVDSDGLNgktitlsREDLVAFALLTGSDmFGAGLSHVGHKKAVQFLH 241
Cdd:PRK03980 161 elieLEEVLKELGIT-------REQLIDIAILVGTD-YNPGIKGIGPKTALKLIK 207
fen_arch TIGR03674
flap structure-specific endonuclease; Endonuclease that cleaves the 5'-overhanging flap ...
 118-241 1.50e-15

flap structure-specific endonuclease; Endonuclease that cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Has 5'-endo-/exonuclease and 5'-pseudo-Y-endonuclease activities. Cleaves the junction between single and double-stranded regions of flap DNA


Pssm-ID: 274717 [Multi-domain]  Cd Length: 338  Bit Score: 78.45  E-value: 1.50e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  118 ERCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFTM---ENLESRQVMCYDATALMAT 194
Cdd:TIGR03674 133 ESSKKLLDLMGIPYVQAPSEGEAQAAYMAKKGDVDYVGSQDYDSLLFGAPRLVRNLTIsgkRKLPGKNIYVEVKPELIEL 212

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 224002667  195 VDS-DGLNgktitLSREDLVAFALLTGSDmFGAGLSHVGHKKAVQFLH 241
Cdd:TIGR03674 213 EEVlSELG-----ITREQLIDIAILVGTD-YNEGVKGIGPKTALKLIK 254
XPGI smart00484
Xeroderma pigmentosum G I-region; domain in nucleases
 125-174 4.79e-15

Xeroderma pigmentosum G I-region; domain in nucleases


Pssm-ID: 214689 [Multi-domain]  Cd Length: 73  Bit Score: 70.30  E-value: 4.79e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 224002667   125 RLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFT 174
Cdd:smart00484   1 RLMGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLF 50
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 431-490 1.55e-13

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: 65.75  E-value: 1.55e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 224002667  431 VPEKIEKEFVKQSEPCYEVVWSID------VDPNLGDTATFTfsTIEPQSLvVNSKYSGLCKLFHQ 490
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPegyfeeEDDDPGELELLT--TIEPQDL-VEKAYPELVEAFEK 63
H3TH_GEN1 cd09905
H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 209-355 7.15e-09

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: 53.90  E-value: 7.15e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 209 REDLVAFALLTGSDMFGAGLSHVGHKKAVQFLHTCSSlnqrpnqRTCLEELLGWGDvAAESASKLNDNQCDDdgpstite 288
Cdd:cd09905    1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSS-------DEVLDRLRNWRA-TSDPSSPQELKKKDK-------- 64

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 224002667 289 RCCSKCLHSGSKSQHVKNGCTICgtkpgegcivvtskekflrslrEKALKmNPPFAPRGIVNEYFSP 355
Cdd:cd09905   65 NHCSNCGHLGKKQEHIKSGCEDC----------------------DKALL-DPGFPNEEIIEEFLSR 108
 
Name Accession Description Interval E-value
PIN_GEN1 cd09869
FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, ...
 2-196 2.95e-63

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: 210.92  E-value: 2.95e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   2 TVSSLWTVLDEagcgrpvgiedfDTSNTSNINSRPTILAVDTSIWICEGISSTALSSFHSDPALYLVYQRTTKLLKLGLG 81
Cdd:cd09869    1 GVKGLWTILDP------------VKKRKPLSELRGKTLAVDLSIWICEAQTVLALFETVPKPHLRNLFFRTVNLLRLGIK 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  82 LVFVLEG----------KRRVRSTYQSSEHHELKQRRSGSQFWSATERCESLLRLLGVPVVRAEAEGEALCALLNAKGVC 151
Cdd:cd09869   69 PVFVLDGdapelklqtiKKRNAARFGGAKKKGGSKKRGRSRFSRVLKECEELLELLGVPVVQAPGEAEALCALLNAEGLV 148

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 224002667 152 DGVISNDGDCFLFGAKTLYTKFTMENLESrQVMCYDATALMATVD 196
Cdd:cd09869  149 DGCITNDGDAFLYGARTVYRNFSLNTKDG-SVECYDMSDIEKRLS 192
PIN_FEN1-like cd09856
FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like, structure-specific, ...
 5-200 6.72e-24

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: 101.08  E-value: 6.72e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   5 SLWTVLDEAGcgRPVGIEDFdtsntsninsRPTILAVDTSIWICEGISSTALSSFHSD--PALYLVYQRTTKLLKLGLGL 82
Cdd:cd09856    1 GFWKIIGPSK--RRISLESL----------RGKRVAIDASIWIYQFLTAVRGQGGNGVsnSHIRGLFYRIIRLLENGIKP 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  83 VFVLEGK--------RRVRSTYQSSEHHELKQ--------------RRSGSQFWSATERCESLLRLLGVPVVRAEAEGEA 140
Cdd:cd09856   69 VFVFDGEppklkkrtRRKRKERRQGAEESAKSavedelfeeqskdkKRSGTVTKVMTAECKHLLSLFGIPYVDAPGEAEA 148

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 224002667 141 LCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFTMENLESrQVMCYDATALM-------ATVDSDGL 200
Cdd:cd09856  149 QCAYLEQQGIVDAVLTEDVDTFLFGSPVVYRNLTSEGKKT-HVELYDASSILeglflpwSTPDLEGL 214
PIN_XPG_RAD2 cd09868
FEN-like PIN domains of Xeroderma pigmentosum complementation group G (XPG) nuclease, a ...
 3-188 9.58e-24

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: 99.90  E-value: 9.58e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   3 VSSLWTVLDEagCGRPVGIEDfdtsntsninSRPTILAVDTSIWICEGI--SSTALSSFHSDPALYLVYQRTTKLLKLGL 80
Cdd:cd09868    2 VKGLWKLLEP--TGRPVSLES----------LEGKVLAVDASIWLHQFVkgMRDNEGNSVPNAHLLGFFRRICKLLFYGI 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  81 GLVFVLEG-----KRRVrstyqssehheLKQRRSGSQfWSATErCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVI 155
Cdd:cd09868   70 KPVFVFDGpapalKRRT-----------LARRRSVTD-EMYEE-IQELLRLFGIPYIVAPMEAEAQCAFLERLGLVDGVI 136

                        170       180       190
                 ....*....|....*....|....*....|...
gi 224002667 156 SNDGDCFLFGAKTLYTKFTMENlesRQVMCYDA 188
Cdd:cd09868  137 TDDSDVFLFGAKRVYKNFFNQN---KYVEYYDM 166
PIN_FEN1_EXO1-like cd00128
FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like and exonuclease-1 (EXO1)-like ...
 6-188 1.03e-21

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: 92.44  E-value: 1.03e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   6 LWTVLDEAGcgRPVGIEDFdtsntsninsRPTILAVDTSIWICEGISSTA---LSSFHSDPALYLVYQRTTKLLKLGLGL 82
Cdd:cd00128    1 LWQFIGEAK--EPISIESL----------KGKTVAIDASIWVYQFLTAKReqgGDIGVTNSHLRGLFYRIIKLLSNGIKP 68

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  83 VFVLEGkrrvrstyqssehhELKQRRSGSQFWSATERCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCF 162
Cdd:cd00128   69 IFVFDG--------------GPPPLKKETITKKMYQECKHLLSLFGIPYVVAPYEAEAQCAYLLKAGIVDAAITEDSDCL 134

                        170       180
                 ....*....|....*....|....*.
gi 224002667 163 LFGAKTLYTKFTMENLesrQVMCYDA 188
Cdd:cd00128  135 LFGAPRVIRNMTFEGP---HVEEFDA 157
XPG_I pfam00867
XPG I-region;
128-222 1.52e-20

XPG I-region;


Pssm-ID: 459970 [Multi-domain]  Cd Length: 87  Bit Score: 86.42  E-value: 1.52e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  128 GVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFTMENLESR--QVMCYDATALMATVDsdglngkti 205
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKKSkvPVEEIDLEKILKELG--------- 71

                          90
                  ....*....|....*..
gi 224002667  206 tLSREDLVAFALLTGSD 222
Cdd:pfam00867  72 -LTREQLIDLAILLGCD 87
PIN_YEN1 cd09870
FEN-like PIN domains of Saccharomyces cerevisiae endonuclease 1 (YEN1), Chaetomium ...
 3-234 3.40e-20

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: 90.02  E-value: 3.40e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   3 VSSLWTVLDEAGCGRPVGIEDFDTSNTSNiNSRPTILAVDTSIWICEGISST--ALSSFHSDPALYLVYQRTTKLLKLGL 80
Cdd:cd09870    2 IPGLWDLLEPAAESRSLAELAVVEEFNKR-GGRPLRIGIDASIWLFHAQSSFggGHIQAGENPELRTLFYRLARLLSLPI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  81 GLVFVLEGKRR--------VRSTYQSSEHHELKQrrsgsqfwsatercesLLRLLGVPVVRAEAEGEALCALLNAKGVCD 152
Cdd:cd09870   81 QPVFVFDGPNRppfkrgkkVGKSTPHWLTKLFKE----------------LLDAFGFPWHEAPGEAEAELARLQRLGVVD 144

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 153 GVISNDGDCFLFGAKTLYTKFTmENLESRQVMCYDATALMATVDSDglNGKTITLSREDLVAFALLTgSDMFGAGLSHVG 232
Cdd:cd09870  145 AVLTDDSDALVFGATTVLRNFS-KKLSDDDVKVYTASAIKDKADLT--RTSLRGPREPDLPRLAALC-EKYFSWGTKEIL 220


                 ..
gi 224002667 233 HK 234
Cdd:cd09870  221 KR 222
PRK03980 PRK03980
flap endonuclease-1; Provisional
 118-241 1.66e-16

flap endonuclease-1; Provisional


Pssm-ID: 235185 [Multi-domain]  Cd Length: 292  Bit Score: 80.63  E-value: 1.66e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 118 ERCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLytkftMENLES---RQVMCYDATA---- 190
Cdd:PRK03980  86 EDSKKLLDLMGIPYVQAPSEGEAQAAYMAKKGDAWAVGSQDYDSLLFGAPRL-----VRNLTIsgkRKLPGKNVYVevkp 160

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 224002667 191 ----LMATVDSDGLNgktitlsREDLVAFALLTGSDmFGAGLSHVGHKKAVQFLH 241
Cdd:PRK03980 161 elieLEEVLKELGIT-------REQLIDIAILVGTD-YNPGIKGIGPKTALKLIK 207
fen_arch TIGR03674
flap structure-specific endonuclease; Endonuclease that cleaves the 5'-overhanging flap ...
 118-241 1.50e-15

flap structure-specific endonuclease; Endonuclease that cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Has 5'-endo-/exonuclease and 5'-pseudo-Y-endonuclease activities. Cleaves the junction between single and double-stranded regions of flap DNA


Pssm-ID: 274717 [Multi-domain]  Cd Length: 338  Bit Score: 78.45  E-value: 1.50e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  118 ERCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFTM---ENLESRQVMCYDATALMAT 194
Cdd:TIGR03674 133 ESSKKLLDLMGIPYVQAPSEGEAQAAYMAKKGDVDYVGSQDYDSLLFGAPRLVRNLTIsgkRKLPGKNIYVEVKPELIEL 212

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 224002667  195 VDS-DGLNgktitLSREDLVAFALLTGSDmFGAGLSHVGHKKAVQFLH 241
Cdd:TIGR03674 213 EEVlSELG-----ITREQLIDIAILVGTD-YNEGVKGIGPKTALKLIK 254
XPGI smart00484
Xeroderma pigmentosum G I-region; domain in nucleases
 125-174 4.79e-15

Xeroderma pigmentosum G I-region; domain in nucleases


Pssm-ID: 214689 [Multi-domain]  Cd Length: 73  Bit Score: 70.30  E-value: 4.79e-15
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 224002667   125 RLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFT 174
Cdd:smart00484   1 RLMGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLF 50
PIN_FEN1 cd09867
FEN-like PIN domains of Flap endonuclease-1, a structure-specific, divalent-metal-ion ...
 118-169 2.43e-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: 73.59  E-value: 2.43e-14
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 224002667 118 ERCESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTL 169
Cdd:cd09867  131 EEAKKLLDLMGIPYVQAPSEGEAQAAYLVKKGDVYAVASQDYDSLLFGAPRL 182
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 431-490 1.55e-13

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: 65.75  E-value: 1.55e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 224002667  431 VPEKIEKEFVKQSEPCYEVVWSID------VDPNLGDTATFTfsTIEPQSLvVNSKYSGLCKLFHQ 490
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPegyfeeEDDDPGELELLT--TIEPQDL-VEKAYPELVEAFEK 63
rad2 TIGR00600
DNA excision repair protein (rad2); All proteins in this family for which functions are known ...
 120-241 2.81e-13

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: 73.78  E-value: 2.81e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667   120 CESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKFTMENlesRQVMCYDATALMatvdsdg 199
Cdd:TIGR00600  777 SQELLRLFGIPYIVAPMEAEAQCAILDLLDQTSGTITDDSDIWLFGARHVYKNFFNQN---KFVEYYQYVDIH------- 846

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 224002667   200 lngKTITLSREDLVAFALLTGSDmFGAGLSHVGHKKAVQFLH 241
Cdd:TIGR00600  847 ---NQLGLDRNKLINLAYLLGSD-YTEGIPTVGPVSAMEILN 884
H3TH_GEN1 cd09905
H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 209-355 7.15e-09

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: 53.90  E-value: 7.15e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 209 REDLVAFALLTGSDMFGAGLSHVGHKKAVQFLHTCSSlnqrpnqRTCLEELLGWGDvAAESASKLNDNQCDDdgpstite 288
Cdd:cd09905    1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSS-------DEVLDRLRNWRA-TSDPSSPQELKKKDK-------- 64

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 224002667 289 RCCSKCLHSGSKSQHVKNGCTICgtkpgegcivvtskekflrslrEKALKmNPPFAPRGIVNEYFSP 355
Cdd:cd09905   65 NHCSNCGHLGKKQEHIKSGCEDC----------------------DKALL-DPGFPNEEIIEEFLSR 108
PTZ00217 PTZ00217
flap endonuclease-1; Provisional
 38-174 4.79e-06

flap endonuclease-1; Provisional


Pssm-ID: 240317 [Multi-domain]  Cd Length: 393  Bit Score: 49.62  E-value: 4.79e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  38 ILAVDTSIWICEGISSTALSSFHSDPA---------LYLVYQRTTKLLKLGLGLVFVLEGKrrvRSTYQSSEHHELKQRR 108
Cdd:PTZ00217  30 VIAIDASMALYQFLIAIRDDSQGGNLTneagevtshISGLFNRTIRLLEAGIKPVYVFDGK---PPELKSGELEKRRERR 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667 109 SGSQ--FWSATER-----------------------CESLLRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFL 163
Cdd:PTZ00217 107 EEAEeeLEKAIEEgddeeikkqskrtvrvtkeqnedAKKLLRLMGIPVIEAPCEAEAQCAELVKKGKVYAVATEDMDALT 186

                        170
                 ....*....|.
gi 224002667 164 FGAKTLYTKFT 174
Cdd:PTZ00217 187 FGTPVLLRNLN 197
PIN_FEN-like cd09853
FEN-like PIN domains of structure-specific 5' nucleases (or Flap endonuclease-1-like) involved ...
 88-185 1.06e-04

FEN-like PIN domains of structure-specific 5' nucleases (or Flap endonuclease-1-like) involved in DNA replication, repair, and recombination; Structure-specific 5' nucleases are capable of both 5'-3' exonucleolytic activity and cleaving bifurcated or branched DNA, in an endonucleolytic, structure-specific manner. The family includes the PIN (PilT N terminus) 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 PIN domains of the 5'-3' exonucleases of DNA polymerase I and single domain protein homologs, as well as, the bacteriophage T4- and T5-5' nucleases, and other homologs. Canonical members of this 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: 350204 [Multi-domain]  Cd Length: 174  Bit Score: 43.63  E-value: 1.06e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224002667  88 GKRRVRSTYQSSE------HHELKQRRSGSQFWSATERCESLLRL-LGVPVVRAEAEGEALCALL----NAKGVCDGVIS 156
Cdd:cd09853   63 DKRRERRAREEDRkkgqlkEHKEFDKRLIELGPEYLIRLFELLKHfMGIPVMDAPGEAEDEIAYLvkkhKHLGTVHLIIS 142

                         90       100
                 ....*....|....*....|....*....
gi 224002667 157 NDGDCFLFGakTLYTKFTMENLESRQVMC 185
Cdd:cd09853  143 TDGDFLLLG--TDHPYIPRNLLTVKEETF 169
PIN_EXO1 cd09857
FEN-like PIN domains of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 124-173 1.06e-03

FEN-like PIN domains of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease and homologs; 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. 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. EXO1 nucleases also have C-terminal Mlh1- and Msh2-binding domains which allow interaction with MMR and PRR proteins, respectively.


Pssm-ID: 350207 [Multi-domain]  Cd Length: 202  Bit Score: 40.85  E-value: 1.06e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 224002667 124 LRLLGVPVVRAEAEGEALCALLNAKGVCDGVISNDGDCFLFGAKTLYTKF 173
Cdd:cd09857  137 LRKENVEYIVAPYEADAQLAYLAKTGYVDAVITEDSDLLAFGCPKVLFKL 186
H3TH_XPG-like cd09900
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 ...
 210-249 1.18e-03

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: 37.46  E-value: 1.18e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 224002667 210 EDLVAFALLTGSDmFGAGLSHVGHKKAVQFLHTCSSLNQR 249
Cdd:cd09900    1 EQLILLALLLGTD-YNPGVPGIGPKTALELLKEFGEDLEK 39
 
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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