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Conserved domains on  [gi|1810995842|ref|XP_006191445|]
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LOW QUALITY PROTEIN: flap endonuclease GEN homolog 1 [Camelus ferus]

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, ...
 2-206 7.16e-113

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: 344.97  E-value: 7.16e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   2 GVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVKKMIGTVMKPHLRNLFFRISYLTLMDVKLVFVMEGKPPKL 81
Cdd:cd09869     1 GVKGLWTILDPVKKRKPLSELRGKTLAVDLSIWICEAQTVLALFETVPKPHLRNLFFRTVNLLRLGIKPVFVLDGDAPEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  82 KADVMSKRNQIRYGPSGKTC-SQKTGRSHFKSVLKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFL 160
Cdd:cd09869    81 KLQTIKKRNAARFGGAKKKGgSKKRGRSRFSRVLKECEELLELLGVPVVQAPGEAEALCALLNAEGLVDGCITNDGDAFL 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1810995842 161 YGAQTVYRNFTMNTKDPHVDCYTMSSIKSKLGL-----DRDALVGLAVLLG 206
Cdd:cd09869   161 YGARTVYRNFSLNTKDGSVECYDMSDIEKRLSLrwrrpDLDLLQDFLLKKL 211
H3TH_StructSpec-5'-nucleases super family cl22433
H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA ...
 195-338 5.04e-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: 143.26  E-value: 5.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 195 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLIKILNGQSLLQRFNQWNEKSCYSNSQTPVVNKVAHCSVCSHPGSPKDHE 274
Cdd:cd09905     1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSSDEVLDRLRNWRATSDPSSPQELKKKDKNHCSNCGHLGKKQEHI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1810995842 275 HNGCKLCktnrycephdyeyrcpcewhlaehdrqlnavessikKKACSCEGFPFHEVVQEFLMN 338
Cdd:cd09905    81 KSGCEDC------------------------------------DKALLDPGFPNEEIIEEFLSR 108
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 398-457 1.94e-25

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: 100.03  E-value: 1.94e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1810995842 398 QPIRIIKTRIRNGVHCFEIEWEKPEHYA-MEDEHGE--LVLQTIEEESLFEAAYPEIVAIYQK 457
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, ...
 2-206 7.16e-113

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: 344.97  E-value: 7.16e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   2 GVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVKKMIGTVMKPHLRNLFFRISYLTLMDVKLVFVMEGKPPKL 81
Cdd:cd09869     1 GVKGLWTILDPVKKRKPLSELRGKTLAVDLSIWICEAQTVLALFETVPKPHLRNLFFRTVNLLRLGIKPVFVLDGDAPEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  82 KADVMSKRNQIRYGPSGKTC-SQKTGRSHFKSVLKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFL 160
Cdd:cd09869    81 KLQTIKKRNAARFGGAKKKGgSKKRGRSRFSRVLKECEELLELLGVPVVQAPGEAEALCALLNAEGLVDGCITNDGDAFL 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1810995842 161 YGAQTVYRNFTMNTKDPHVDCYTMSSIKSKLGL-----DRDALVGLAVLLG 206
Cdd:cd09869   161 YGARTVYRNFSLNTKDGSVECYDMSDIEKRLSLrwrrpDLDLLQDFLLKKL 211
H3TH_GEN1 cd09905
H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 195-338 5.04e-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: 143.26  E-value: 5.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 195 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLIKILNGQSLLQRFNQWNEKSCYSNSQTPVVNKVAHCSVCSHPGSPKDHE 274
Cdd:cd09905     1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSSDEVLDRLRNWRATSDPSSPQELKKKDKNHCSNCGHLGKKQEHI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1810995842 275 HNGCKLCktnrycephdyeyrcpcewhlaehdrqlnavessikKKACSCEGFPFHEVVQEFLMN 338
Cdd:cd09905    81 KSGCEDC------------------------------------DKALLDPGFPNEEIIEEFLSR 108
fen_arch TIGR03674
flap structure-specific endonuclease; Endonuclease that cleaves the 5'-overhanging flap ...
 1-227 1.99e-35

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: 137.77  E-value: 1.99e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   1 MGVnDLWQILEpvKEHVLLHSLSGKTIAVDLSLWVCE-AQTVKKMIGTVMK-------PHLRNLFFRISYLTLMDVKLVF 72
Cdd:TIGR03674   1 MGV-DLRDLLA--KEEIELEDLSGKVVAVDAFNALYQfLSSIRQPDGTPLMdsrgritSHLSGLFYRTINLLENGIKPVY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  73 VMEGKPPKLKADVMSKRNQIRYGPSGK-----------TCSQKTGRSHF--KSVLKECLDMLECLGIPWVQAAGEAEAMC 139
Cdd:TIGR03674  78 VFDGKPPELKAETLEERREIREEAEEKweealekgdleEARKYAQRSSRltSEIVESSKKLLDLMGIPYVQAPSEGEAQA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 140 AYLNASGYADGCLTNDGDAFLYGAQTVYRNFT------MNTKDPHVDCY----TMSSIKSKLGLDRDALVGLAVLLGCDY 209
Cdd:TIGR03674 158 AYMAKKGDVDYVGSQDYDSLLFGAPRLVRNLTisgkrkLPGKNIYVEVKpeliELEEVLSELGITREQLIDIAILVGTDY 237

                         250
                  ....*....|....*...
gi 1810995842 210 LPkGVPGVGKEQALKLIK 227
Cdd:TIGR03674 238 NE-GVKGIGPKTALKLIK 254
XPG_I pfam00867
XPG I-region;
125-208 1.30e-33

XPG I-region;


Pssm-ID: 459970 [Multi-domain]  Cd Length: 87  Bit Score: 124.16  E-value: 1.30e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 125 GIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTMNTKDP---HVDCYTMSSIKSKLGLDRDALVGL 201
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKKskvPVEEIDLEKILKELGLTREQLIDL 80


                  ....*..
gi 1810995842 202 AVLLGCD 208
Cdd:pfam00867  81 AILLGCD 87
PRK03980 PRK03980
flap endonuclease-1; Provisional
 52-227 4.08e-32

flap endonuclease-1; Provisional


Pssm-ID: 235185 [Multi-domain]  Cd Length: 292  Bit Score: 126.86  E-value: 4.08e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  52 HLRNLFFRISYLTLMDVKLVFVMEGKPPKLKADVMSKRNQIRygpsgKTCSQK------TG----------RSHF--KSV 113
Cdd:PRK03980   10 HLSGIFYRTINLLENGIKPVYVFDGKPPELKAEEIEERREVR-----EEAEEKyeeakeEGdleearkyaqRSSRltDEI 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 114 LKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTMN--TKDPHVDCY--------T 183
Cdd:PRK03980   85 VEDSKKLLDLMGIPYVQAPSEGEAQAAYMAKKGDAWAVGSQDYDSLLFGAPRLVRNLTISgkRKLPGKNVYvevkpeliE 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1810995842 184 MSSIKSKLGLDRDALVGLAVLLGCDYLPkGVPGVGKEQALKLIK 227
Cdd:PRK03980  165 LEEVLKELGITREQLIDIAILVGTDYNP-GIKGIGPKTALKLIK 207
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 398-457 1.94e-25

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: 100.03  E-value: 1.94e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1810995842 398 QPIRIIKTRIRNGVHCFEIEWEKPEHYA-MEDEHGE--LVLQTIEEESLFEAAYPEIVAIYQK 457
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPEGYFeEEDDDPGelELLTTIEPQDLVEKAYPELVEAFEK 63
XPGN smart00485
Xeroderma pigmentosum G N-region; domain in nucleases
 1-93 4.27e-21

Xeroderma pigmentosum G N-region; domain in nucleases


Pssm-ID: 214690 [Multi-domain]  Cd Length: 99  Bit Score: 88.83  E-value: 4.27e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842    1 MGVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVK-----KMIGTVmkPHLRNLFFRISYLTLMDVKLVFVME 75
Cdd:smart00485   1 MGIKGLWPLLKPVVREVPLEALRGKTLAIDASIWLYQFLTACreklgTPLPNS--KHLMGLFYRTCRLLEFGIKPIFVFD 78

                           90
                   ....*....|....*...
gi 1810995842   76 GKPPKLKADVMSKRNQIR 93
Cdd:smart00485  79 GKPPPLKSETLAKRRERR 96
ExoIX COG0258
5'-3' exonuclease Xni/ExoIX (flap endonuclease) [Replication, recombination and repair];
117-227 9.15e-03

5'-3' exonuclease Xni/ExoIX (flap endonuclease) [Replication, recombination and repair];


Pssm-ID: 440028 [Multi-domain]  Cd Length: 286  Bit Score: 39.24  E-value: 9.15e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 117 CLDMLECLGIPWVQAAG-EAEAMCAYLNASGYADGC----LTNDGDAFlygaQ------TVYRnfTMnTKDPHVDCYTMS 185
Cdd:COG0258    93 IKEVLEALGIPVLEVEGyEADDVIGTLAKQAEAEGYevliVTGDKDLL----QlvddnvTVLD--PM-KGVSELERYDPA 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1810995842 186 SIKSKLGLD----RD--ALVGLAVllgcDYLPkGVPGVGKEQALKLIK 227
Cdd:COG0258   166 EVEEKYGVPpeqiIDylALMGDSS----DNIP-GVPGIGEKTAAKLLQ 208
 
Name Accession Description Interval E-value
PIN_GEN1 cd09869
FEN-like PIN domains of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, ...
 2-206 7.16e-113

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: 344.97  E-value: 7.16e-113
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   2 GVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVKKMIGTVMKPHLRNLFFRISYLTLMDVKLVFVMEGKPPKL 81
Cdd:cd09869     1 GVKGLWTILDPVKKRKPLSELRGKTLAVDLSIWICEAQTVLALFETVPKPHLRNLFFRTVNLLRLGIKPVFVLDGDAPEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  82 KADVMSKRNQIRYGPSGKTC-SQKTGRSHFKSVLKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFL 160
Cdd:cd09869    81 KLQTIKKRNAARFGGAKKKGgSKKRGRSRFSRVLKECEELLELLGVPVVQAPGEAEALCALLNAEGLVDGCITNDGDAFL 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1810995842 161 YGAQTVYRNFTMNTKDPHVDCYTMSSIKSKLGL-----DRDALVGLAVLLG 206
Cdd:cd09869   161 YGARTVYRNFSLNTKDGSVECYDMSDIEKRLSLrwrrpDLDLLQDFLLKKL 211
PIN_FEN1-like cd09856
FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like, structure-specific, ...
 5-191 4.86e-81

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: 261.32  E-value: 4.86e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   5 DLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVKKMIG--TVMKPHLRNLFFRISYLTLMDVKLVFVMEGKPPKLK 82
Cdd:cd09856     1 GFWKIIGPSKRRISLESLRGKRVAIDASIWIYQFLTAVRGQGgnGVSNSHIRGLFYRIIRLLENGIKPVFVFDGEPPKLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  83 ADVMSKRNQIRYGPS-------------GKTCSQKTGRSHFKSVLKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYAD 149
Cdd:cd09856    81 KRTRRKRKERRQGAEesaksavedelfeEQSKDKKRSGTVTKVMTAECKHLLSLFGIPYVDAPGEAEAQCAYLEQQGIVD 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1810995842 150 GCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTMSSIKSKL 191
Cdd:cd09856   161 AVLTEDVDTFLFGSPVVYRNLTSEGKKTHVELYDASSILEGL 202
PIN_FEN1_EXO1-like cd00128
FEN-like PIN domains of Flap endonuclease-1 (FEN1)-like and exonuclease-1 (EXO1)-like ...
 6-189 6.08e-60

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: 201.06  E-value: 6.08e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   6 LWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVKKM---IGTVMKPHLRNLFFRISYLTLMDVKLVFVMEGKPPKLK 82
Cdd:cd00128     1 LWQFIGEAKEPISIESLKGKTVAIDASIWVYQFLTAKREqggDIGVTNSHLRGLFYRIIKLLSNGIKPIFVFDGGPPPLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  83 ADvmskrnqirygpsgktcsqktgrSHFKSVLKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYG 162
Cdd:cd00128    81 KE-----------------------TITKKMYQECKHLLSLFGIPYVVAPYEAEAQCAYLLKAGIVDAAITEDSDCLLFG 137

                         170       180
                  ....*....|....*....|....*..
gi 1810995842 163 AQTVYRNFTMNTkdPHVDCYTMSSIKS 189
Cdd:cd00128   138 APRVIRNMTFEG--PHVEEFDASSILE 162
PIN_YEN1 cd09870
FEN-like PIN domains of Saccharomyces cerevisiae endonuclease 1 (YEN1), Chaetomium ...
 2-201 8.61e-46

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: 163.98  E-value: 8.61e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   2 GVNDLWQILEPVKEHVLLHSLSGK-----------TIAVDLSLWVCEAQTVKK--MIGTVMKPHLRNLFFRISYLTLMDV 68
Cdd:cd09870     1 GIPGLWDLLEPAAESRSLAELAVVeefnkrggrplRIGIDASIWLFHAQSSFGggHIQAGENPELRTLFYRLARLLSLPI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  69 KLVFVMEG--KPPKlkadvmsKRnqirygpsGKTcSQKTGRSHFKSVLKEcldMLECLGIPWVQAAGEAEAMCAYLNASG 146
Cdd:cd09870    81 QPVFVFDGpnRPPF-------KR--------GKK-VGKSTPHWLTKLFKE---LLDAFGFPWHEAPGEAEAELARLQRLG 141

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1810995842 147 YADGCLTNDGDAFLYGAQTVYRNFTMNTKDPHVDCYTMSSIKSKLGLDRDALVGL 201
Cdd:cd09870   142 VVDAVLTDDSDALVFGATTVLRNFSKKLSDDDVKVYTASAIKDKADLTRTSLRGP 196
PIN_XPG_RAD2 cd09868
FEN-like PIN domains of Xeroderma pigmentosum complementation group G (XPG) nuclease, a ...
 2-191 2.30e-45

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: 162.30  E-value: 2.30e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   2 GVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVceAQTVKKM----IGTVMKPHLRNLFFRISYLTLMDVKLVFVMEGK 77
Cdd:cd09868     1 GVKGLWKLLEPTGRPVSLESLEGKVLAVDASIWL--HQFVKGMrdneGNSVPNAHLLGFFRRICKLLFYGIKPVFVFDGP 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  78 PPKLKADVMSKRnqirygpsgktcsqktgRSHFKSVLKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGD 157
Cdd:cd09868    79 APALKRRTLARR-----------------RSVTDEMYEEIQELLRLFGIPYIVAPMEAEAQCAFLERLGLVDGVITDDSD 141

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1810995842 158 AFLYGAQTVYRNFTMNTKdpHVDCYTMSSIKSKL 191
Cdd:cd09868   142 VFLFGAKRVYKNFFNQNK--YVEYYDMEDIEREL 173
H3TH_GEN1 cd09905
H3TH domain of Gap Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 195-338 5.04e-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: 143.26  E-value: 5.04e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 195 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLIKILNGQSLLQRFNQWNEKSCYSNSQTPVVNKVAHCSVCSHPGSPKDHE 274
Cdd:cd09905     1 REKLIALALLCGCDYNPKGVPGVGKERALRLVNIVSSDEVLDRLRNWRATSDPSSPQELKKKDKNHCSNCGHLGKKQEHI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1810995842 275 HNGCKLCktnrycephdyeyrcpcewhlaehdrqlnavessikKKACSCEGFPFHEVVQEFLMN 338
Cdd:cd09905    81 KSGCEDC------------------------------------DKALLDPGFPNEEIIEEFLSR 108
fen_arch TIGR03674
flap structure-specific endonuclease; Endonuclease that cleaves the 5'-overhanging flap ...
 1-227 1.99e-35

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: 137.77  E-value: 1.99e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   1 MGVnDLWQILEpvKEHVLLHSLSGKTIAVDLSLWVCE-AQTVKKMIGTVMK-------PHLRNLFFRISYLTLMDVKLVF 72
Cdd:TIGR03674   1 MGV-DLRDLLA--KEEIELEDLSGKVVAVDAFNALYQfLSSIRQPDGTPLMdsrgritSHLSGLFYRTINLLENGIKPVY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  73 VMEGKPPKLKADVMSKRNQIRYGPSGK-----------TCSQKTGRSHF--KSVLKECLDMLECLGIPWVQAAGEAEAMC 139
Cdd:TIGR03674  78 VFDGKPPELKAETLEERREIREEAEEKweealekgdleEARKYAQRSSRltSEIVESSKKLLDLMGIPYVQAPSEGEAQA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 140 AYLNASGYADGCLTNDGDAFLYGAQTVYRNFT------MNTKDPHVDCY----TMSSIKSKLGLDRDALVGLAVLLGCDY 209
Cdd:TIGR03674 158 AYMAKKGDVDYVGSQDYDSLLFGAPRLVRNLTisgkrkLPGKNIYVEVKpeliELEEVLSELGITREQLIDIAILVGTDY 237

                         250
                  ....*....|....*...
gi 1810995842 210 LPkGVPGVGKEQALKLIK 227
Cdd:TIGR03674 238 NE-GVKGIGPKTALKLIK 254
XPG_I pfam00867
XPG I-region;
125-208 1.30e-33

XPG I-region;


Pssm-ID: 459970 [Multi-domain]  Cd Length: 87  Bit Score: 124.16  E-value: 1.30e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 125 GIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTMNTKDP---HVDCYTMSSIKSKLGLDRDALVGL 201
Cdd:pfam00867   1 GIPYVVAPGEAEAQCAYLQKSGLVDAVISEDSDVLLFGAPRLLRNLTGKSKKKskvPVEEIDLEKILKELGLTREQLIDL 80


                  ....*..
gi 1810995842 202 AVLLGCD 208
Cdd:pfam00867  81 AILLGCD 87
PRK03980 PRK03980
flap endonuclease-1; Provisional
 52-227 4.08e-32

flap endonuclease-1; Provisional


Pssm-ID: 235185 [Multi-domain]  Cd Length: 292  Bit Score: 126.86  E-value: 4.08e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  52 HLRNLFFRISYLTLMDVKLVFVMEGKPPKLKADVMSKRNQIRygpsgKTCSQK------TG----------RSHF--KSV 113
Cdd:PRK03980   10 HLSGIFYRTINLLENGIKPVYVFDGKPPELKAEEIEERREVR-----EEAEEKyeeakeEGdleearkyaqRSSRltDEI 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 114 LKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTMN--TKDPHVDCY--------T 183
Cdd:PRK03980   85 VEDSKKLLDLMGIPYVQAPSEGEAQAAYMAKKGDAWAVGSQDYDSLLFGAPRLVRNLTISgkRKLPGKNVYvevkpeliE 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1810995842 184 MSSIKSKLGLDRDALVGLAVLLGCDYLPkGVPGVGKEQALKLIK 227
Cdd:PRK03980  165 LEEVLKELGITREQLIDIAILVGTDYNP-GIKGIGPKTALKLIK 207
PTZ00217 PTZ00217
flap endonuclease-1; Provisional
 1-227 5.11e-27

flap endonuclease-1; Provisional


Pssm-ID: 240317 [Multi-domain]  Cd Length: 393  Bit Score: 114.33  E-value: 5.11e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   1 MGVNDLWQILE---P--VKEhVLLHSLSGKTIAVDLSLWVCEAQTVKKMIGTVMK---------PHLRNLFFRISYLTLM 66
Cdd:PTZ00217    1 MGIKGLSKFLAdkaPnaIKE-QELKNYFGRVIAIDASMALYQFLIAIRDDSQGGNltneagevtSHISGLFNRTIRLLEA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  67 DVKLVFVMEGKPPKLKADVMSKRNQIRYGP--------------SGKTCSQKTGRSHfKSVLKECLDMLECLGIPWVQAA 132
Cdd:PTZ00217   80 GIKPVYVFDGKPPELKSGELEKRRERREEAeeelekaieegddeEIKKQSKRTVRVT-KEQNEDAKKLLRLMGIPVIEAP 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 133 GEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTMN--TKDPHVDcYTMSSIKSKLGLDRDALVGLAVLLGCDYL 210
Cdd:PTZ00217  159 CEAEAQCAELVKKGKVYAVATEDMDALTFGTPVLLRNLNFSeaKKRPIQE-INLSTVLEELGLSMDQFIDLCILCGCDYC 237

                         250
                  ....*....|....*..
gi 1810995842 211 PKgVPGVGKEQALKLIK 227
Cdd:PTZ00217  238 DT-IKGIGPKTAYKLIK 253
Chromo_2 pfam18704
Chromatin organization modifier domain 2; Chromodomains serve as chromatin-targeting modules, ...
 398-457 1.94e-25

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: 100.03  E-value: 1.94e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1810995842 398 QPIRIIKTRIRNGVHCFEIEWEKPEHYA-MEDEHGE--LVLQTIEEESLFEAAYPEIVAIYQK 457
Cdd:pfam18704   1 QPIRIVKKRVRKGVPSYEIEWKKPEGYFeEEDDDPGelELLTTIEPQDLVEKAYPELVEAFEK 63
rad2 TIGR00600
DNA excision repair protein (rad2); All proteins in this family for which functions are known ...
 114-257 2.86e-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: 113.07  E-value: 2.86e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  114 LKECLDMLECLGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTmnTKDPHVDCYTMSSIKSKLGL 193
Cdd:TIGR00600  774 ILESQELLRLFGIPYIVAPMEAEAQCAILDLLDQTSGTITDDSDIWLFGARHVYKNFF--NQNKFVEYYQYVDIHNQLGL 851

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1810995842  194 DRDALVGLAVLLGCDYlPKGVPGVGKEQALKLIKILNGQSL--LQRFNQW-----NEKSCYSNSQTPVVNK 257
Cdd:TIGR00600  852 DRNKLINLAYLLGSDY-TEGIPTVGPVSAMEILNEFPGDGLepLLKFKEWwheaqKDKKKRENPNDTKVKK 921
PIN_FEN1 cd09867
FEN-like PIN domains of Flap endonuclease-1, a structure-specific, divalent-metal-ion ...
 5-171 1.24e-24

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: 104.02  E-value: 1.24e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   5 DLWQILEpvKEHVLLHSLSGKTIAVDLSLWVceAQ---TVKKMIGTVMK-------PHLRNLFFRISYLTLMDVKLVFVM 74
Cdd:cd09867     2 NLSKLIA--IKEIELKDLSGKKIAIDASNAL--YQflsAIRQPDGTPLTdskgrvtSHLSGLFYRTINLLENGIKPVYVF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  75 EGKPPKLKADVMSKRNQIR---------------------YgpsgktcSQKTGR-ShfKSVLKECLDMLECLGIPWVQAA 132
Cdd:cd09867    78 DGKPPELKSGELEKRRERReeaeekleealeegdleearkY-------AKRTVRvT--KEMVEEAKKLLDLMGIPYVQAP 148

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1810995842 133 GEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFT 171
Cdd:cd09867   149 SEGEAQAAYLVKKGDVYAVASQDYDSLLFGAPRLVRNLT 187
XPGN smart00485
Xeroderma pigmentosum G N-region; domain in nucleases
 1-93 4.27e-21

Xeroderma pigmentosum G N-region; domain in nucleases


Pssm-ID: 214690 [Multi-domain]  Cd Length: 99  Bit Score: 88.83  E-value: 4.27e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842    1 MGVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEAQTVK-----KMIGTVmkPHLRNLFFRISYLTLMDVKLVFVME 75
Cdd:smart00485   1 MGIKGLWPLLKPVVREVPLEALRGKTLAIDASIWLYQFLTACreklgTPLPNS--KHLMGLFYRTCRLLEFGIKPIFVFD 78

                           90
                   ....*....|....*...
gi 1810995842   76 GKPPKLKADVMSKRNQIR 93
Cdd:smart00485  79 GKPPPLKSETLAKRRERR 96
XPGI smart00484
Xeroderma pigmentosum G I-region; domain in nucleases
 124-193 1.30e-19

Xeroderma pigmentosum G I-region; domain in nucleases


Pssm-ID: 214689 [Multi-domain]  Cd Length: 73  Bit Score: 83.40  E-value: 1.30e-19
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1810995842  124 LGIPWVQAAGEAEAMCAYLNASGYADGCLTNDGDAFLYGAQTVYRNFTMNTKDpHVDCYTM--SSIKSKLGL 193
Cdd:smart00484   3 MGIPYIVAPYEAEAQCAYLAKSGLVDAIITEDSDLLLFGAPRLYRNLFFSGKK-KLEFRIIdlESVLKELGL 73
rad2 TIGR00600
DNA excision repair protein (rad2); All proteins in this family for which functions are known ...
 1-115 1.51e-14

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: 78.40  E-value: 1.51e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842    1 MGVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLWVCEA-QTVKKMIGTVMK-PHLRNLFFRISYLTLMDVKLVFVMEGKP 78
Cdd:TIGR00600    1 MGVQGLWKLLECSGRPVSPETLEGKRLAVDISIWLNQAlKGVRDREGNAIKnSHLLTLFHRLCKLLFFRIRPIFVFDGGA 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1810995842   79 PKLKADVMSKRNQIRYGPSGKtcSQKTGRSHFKSVLK 115
Cdd:TIGR00600   81 PLLKRQTLAKRRQRRDGASED--ARKTAEKLLATFLK 115
PIN_EXO1 cd09857
FEN-like PIN domains of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 1-166 2.31e-14

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: 72.82  E-value: 2.31e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   1 MGVNDLWQILEPVKEHVLLHSLSGKTIAVDLSLW-----------VCEAQTVKKMIGTVMKphlrnlffRISYLTLMDVK 69
Cdd:cd09857     1 MGIQGLLPFLKPIQRPVHISEYAGKTVAVDAYCWlhrgayscaeeLALGKPTDKYIDYCMK--------RVNMLLHHGIT 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  70 LVFVMEGKPPKLKADVMSKRNQIR---------YGPSGKTcsqKTGRSHF-KSV------LKECLDMLECLGIPWVQAAG 133
Cdd:cd09857    73 PILVFDGAPLPSKAGTEEERRERReealekaleLLREGKK---SEARECFqRAVditpemAHELIKALRKENVEYIVAPY 149

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1810995842 134 EAEAMCAYLNASGYADGCLTNDGDAFLYGAQTV 166
Cdd:cd09857   150 EADAQLAYLAKTGYVDAVITEDSDLLAFGCPKV 182
XPG_N pfam00752
XPG N-terminal domain;
2-93 1.64e-12

XPG N-terminal domain;


Pssm-ID: 395609 [Multi-domain]  Cd Length: 100  Bit Score: 64.30  E-value: 1.64e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842   2 GVNDLWQILEPVKE--HVLLHSLSGKTIAVDLSLWVCEA-QTVKKMIGTVMK--PHLRNLFFRISYLTLMDVKLVFVMEG 76
Cdd:pfam00752   1 GIKGLLPILKPVALirPVDIEALEGKTLAIDASIWLYQFlKAVRDQLGNALQntSHLMGFFSRLCRLKDFGIKPIFVFDG 80

                          90
                  ....*....|....*..
gi 1810995842  77 KPPKLKADVMSKRNQIR 93
Cdd:pfam00752  81 GPPPLKAETLQKRSARR 97
H3TH_XPG-like cd09900
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 ...
 196-240 1.80e-08

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: 51.33  E-value: 1.80e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1810995842 196 DALVGLAVLLGCDYLPkGVPGVGKEQALKLIKIlnGQSLLQRFNQ 240
Cdd:cd09900     1 EQLILLALLLGTDYNP-GVPGIGPKTALELLKE--FGEDLEKFLE 42
H3TH_FEN1-XPG-like cd09897
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases; The 5' ...
 196-253 8.56e-08

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: 49.90  E-value: 8.56e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1810995842 196 DALVGLAVLLGCDYLPkGVPGVGKEQALKLIKILNgqsLLQRFNQWNEKSCYSNSQTP 253
Cdd:cd09897     1 EQFIDLCILSGCDYLP-GLPGIGPKTALKLIKEYG---SLEKVLKALRDDKKDKVPVP 54
H3TH_XPG cd09904
H3TH domain of Xeroderma pigmentosum complementation group G (XPG) nuclease, a ...
 196-257 1.27e-06

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: 47.63  E-value: 1.27e-06
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1810995842 196 DALVGLAVLLGCDYLPkGVPGVGKEQALKLIKILNGQSLLQRFNQWNEKSCYSNSQTPVVNK 257
Cdd:cd09904     1 DKLIRLALLLGSDYTE-GVSGIGPVNAMEILSEFPGEEDLEKFKDWWENAQPEKSEDSDNDK 61
H3TH_FEN1-Arc cd09903
H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 196-227 6.10e-06

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: 44.51  E-value: 6.10e-06
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1810995842 196 DALVGLAVLLGCDYLPKGVPGVGKEQALKLIK 227
Cdd:cd09903     1 EQLIDIAILVGTDYNPGGVKGIGPKTALKLVK 32
PIN_FEN-like cd09853
FEN-like PIN domains of structure-specific 5' nucleases (or Flap endonuclease-1-like) involved ...
 53-168 3.27e-05

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: 45.17  E-value: 3.27e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  53 LRNLFF----RISYLTLMDVKLVFVMEGKPPKLKADVMSKRNQIRYGPSGKTCSQKTGRSHFKSVLKE--------CLDM 120
Cdd:cd09853    25 DFQGYFsavdDLVKKLKPGIKPILLFDGGKPKAKKGNRDKRRERRAREEDRKKGQLKEHKEFDKRLIElgpeylirLFEL 104

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1810995842 121 LE-CLGIPWVQAAGEAEAMCAYL----NASGYADGCLTNDGDAFLYGAQTVYR 168
Cdd:cd09853   105 LKhFMGIPVMDAPGEAEDEIAYLvkkhKHLGTVHLIISTDGDFLLLGTDHPYI 157
H3TH_YEN1 cd09906
H3TH domain of Yeast Endonuclease 1, a structure-specific, divalent-metal-ion dependent, 5' ...
 195-243 1.66e-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: 1.66e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1810995842 195 RDALVGLAVLLGCDYLPKGVPGVGKEQALKLIKILNGQSLLQRFNQWNE 243
Cdd:cd09906     1 RGGMVLFALLSGGDYDTVGLPGCGKKTALELAKLGFGDSLLEAAEDLSE 49
H3TH_FEN1-like cd09901
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 ...
 196-227 1.67e-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: 40.59  E-value: 1.67e-04
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1810995842 196 DALVGLAVLLGCDYLPkGVPGVGKEQALKLIK 227
Cdd:cd09901     1 EQFIDLCILSGCDYLP-SIPGIGPKTAYKLIK 31
H3TH_StructSpec-5'-nucleases cd00080
H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA ...
 196-227 3.41e-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: 39.67  E-value: 3.41e-04
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1810995842 196 DALVGLAVLLGCDYLP-KGVPGVGKEQALKLIK 227
Cdd:cd00080     1 EQFIDLCALVGCDYSDnPGVPGIGPKTAAKLAL 33
H3TH_FEN1-Euk cd09907
H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 196-227 7.90e-04

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: 38.68  E-value: 7.90e-04
                          10        20        30
                  ....*....|....*....|....*....|..
gi 1810995842 196 DALVGLAVLLGCDYLPKgVPGVGKEQALKLIK 227
Cdd:cd09907     1 EQFIDLCILLGCDYCES-IKGIGPKTALKLIK 31
H3TH_EXO1 cd09908
H3TH domain of Exonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' nuclease; ...
 202-227 5.45e-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: 36.40  E-value: 5.45e-03
                          10        20
                  ....*....|....*....|....*.
gi 1810995842 202 AVLLGCDYLPkGVPGVGKEQALKLIK 227
Cdd:cd09908     7 CILSGCDYLP-SLPGIGLKKAYKLVR 31
53EXOc smart00475
5'-3' exonuclease;
119-227 7.62e-03

5'-3' exonuclease;


Pssm-ID: 214682 [Multi-domain]  Cd Length: 259  Bit Score: 39.12  E-value: 7.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842  119 DMLECLGIPWVQAAG-EAEAMCAYLNASGYADGC----LTNDGDAF-LYGAQTVYRNFTMNTKDphVDCYTMSSIKSKLG 192
Cdd:smart00475  91 ELLDALGIPVLEVEGyEADDVIATLAKKAEAEGYevriVSGDKDLLqLVSDKVSVLDPTKGIKE--FELYTPENVIEKYG 168

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1810995842  193 LDRDALVGLAVLLG--CDYLPkGVPGVGKEQALKLIK 227
Cdd:smart00475 169 LTPEQIIDYKALMGdsSDNIP-GVPGIGEKTAAKLLK 204
ExoIX COG0258
5'-3' exonuclease Xni/ExoIX (flap endonuclease) [Replication, recombination and repair];
117-227 9.15e-03

5'-3' exonuclease Xni/ExoIX (flap endonuclease) [Replication, recombination and repair];


Pssm-ID: 440028 [Multi-domain]  Cd Length: 286  Bit Score: 39.24  E-value: 9.15e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1810995842 117 CLDMLECLGIPWVQAAG-EAEAMCAYLNASGYADGC----LTNDGDAFlygaQ------TVYRnfTMnTKDPHVDCYTMS 185
Cdd:COG0258    93 IKEVLEALGIPVLEVEGyEADDVIGTLAKQAEAEGYevliVTGDKDLL----QlvddnvTVLD--PM-KGVSELERYDPA 165

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1810995842 186 SIKSKLGLD----RD--ALVGLAVllgcDYLPkGVPGVGKEQALKLIK 227
Cdd:COG0258   166 EVEEKYGVPpeqiIDylALMGDSS----DNIP-GVPGIGEKTAAKLLQ 208
 
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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