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Conserved domains on  [gi|461694116|gb|AGH19908|]
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flap structure-specific endonuclease 1, partial [Xiphophorus mixei]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
H3TH_StructSpec-5'-nucleases super family cl22433
H3TH domains of structure-specific 5' nucleases (or flap endonuclease-1-like) involved in DNA ...
 1-26 1.49e-08

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 cd09907:

Pssm-ID: 473957 [Multi-domain]  Cd Length: 70  Bit Score: 44.07  E-value: 1.49e-08
                        10        20
                ....*....|....*....|....*.
gi 461694116  1 IDLIRQHGSIEEILENIDTSKHPAPE 26
Cdd:cd09907  27 LKLIKKHKSIEKILENIDKSKYPVPE 52
 
Name Accession Description Interval E-value
H3TH_FEN1-Euk cd09907
H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 1-26 1.49e-08

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: 44.07  E-value: 1.49e-08
                        10        20
                ....*....|....*....|....*.
gi 461694116  1 IDLIRQHGSIEEILENIDTSKHPAPE 26
Cdd:cd09907  27 LKLIKKHKSIEKILENIDKSKYPVPE 52
PTZ00217 PTZ00217
flap endonuclease-1; Provisional
 3-26 7.62e-07

flap endonuclease-1; Provisional


Pssm-ID: 240317 [Multi-domain]  Cd Length: 393  Bit Score: 41.53  E-value: 7.62e-07
                         10        20
                 ....*....|....*....|....
gi 461694116   3 LIRQHGSIEEILENIDTSKHPAPE 26
Cdd:PTZ00217 251 LIKKYKSIEEILEHLDKTKYPVPE 274
5_3_exonuc pfam01367
5'-3' exonuclease, C-terminal SAM fold;
1-24 1.15e-03

5'-3' exonuclease, C-terminal SAM fold;


Pssm-ID: 460176 [Multi-domain]  Cd Length: 93  Bit Score: 31.96  E-value: 1.15e-03
                         10        20
                 ....*....|....*....|....
gi 461694116   1 IDLIRQHGSIEEILENIDTSKHPA 24
Cdd:pfam01367 32 AKLLNEYGSLENILANADEIKGGK 55
ExoIX COG0258
5'-3' exonuclease Xni/ExoIX (flap endonuclease) [Replication, recombination and repair];
1-18 2.11e-03

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


Pssm-ID: 440028 [Multi-domain]  Cd Length: 286  Bit Score: 31.92  E-value: 2.11e-03
                         10
                 ....*....|....*...
gi 461694116   1 IDLIRQHGSIEEILENID 18
Cdd:COG0258  204 AKLLQEYGSLENILANAD 221
53EXOc smart00475
5'-3' exonuclease;
1-18 3.96e-03

5'-3' exonuclease;


Pssm-ID: 214682 [Multi-domain]  Cd Length: 259  Bit Score: 31.03  E-value: 3.96e-03
                           10
                   ....*....|....*...
gi 461694116     1 IDLIRQHGSIEEILENID 18
Cdd:smart00475 200 AKLLKEFGSLENILENLD 217
 
Name Accession Description Interval E-value
H3TH_FEN1-Euk cd09907
H3TH domain of Flap Endonuclease-1, a structure-specific, divalent-metal-ion dependent, 5' ...
 1-26 1.49e-08

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: 44.07  E-value: 1.49e-08
                        10        20
                ....*....|....*....|....*.
gi 461694116  1 IDLIRQHGSIEEILENIDTSKHPAPE 26
Cdd:cd09907  27 LKLIKKHKSIEKILENIDKSKYPVPE 52
PTZ00217 PTZ00217
flap endonuclease-1; Provisional
 3-26 7.62e-07

flap endonuclease-1; Provisional


Pssm-ID: 240317 [Multi-domain]  Cd Length: 393  Bit Score: 41.53  E-value: 7.62e-07
                         10        20
                 ....*....|....*....|....
gi 461694116   3 LIRQHGSIEEILENIDTSKHPAPE 26
Cdd:PTZ00217 251 LIKKYKSIEEILEHLDKTKYPVPE 274
H3TH_FEN1-like cd09901
H3TH domains of Flap endonuclease-1 (FEN1)-like structure specific 5' nucleases: FEN1 ...
 3-26 6.65e-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: 32.12  E-value: 6.65e-04
                        10        20
                ....*....|....*....|....*..
gi 461694116  3 LIRQHGSIEEILENIDTSKH---PAPE 26
Cdd:cd09901  29 LIKKHKSIEKVLKALRSNKKkkvPVPY 55
5_3_exonuc pfam01367
5'-3' exonuclease, C-terminal SAM fold;
1-24 1.15e-03

5'-3' exonuclease, C-terminal SAM fold;


Pssm-ID: 460176 [Multi-domain]  Cd Length: 93  Bit Score: 31.96  E-value: 1.15e-03
                         10        20
                 ....*....|....*....|....
gi 461694116   1 IDLIRQHGSIEEILENIDTSKHPA 24
Cdd:pfam01367 32 AKLLNEYGSLENILANADEIKGGK 55
ExoIX COG0258
5'-3' exonuclease Xni/ExoIX (flap endonuclease) [Replication, recombination and repair];
1-18 2.11e-03

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


Pssm-ID: 440028 [Multi-domain]  Cd Length: 286  Bit Score: 31.92  E-value: 2.11e-03
                         10
                 ....*....|....*...
gi 461694116   1 IDLIRQHGSIEEILENID 18
Cdd:COG0258  204 AKLLQEYGSLENILANAD 221
H3TH_53EXO cd09898
H3TH domain of the 5'-3' exonuclease of Taq DNA polymerase I and homologs; H3TH ...
 1-21 2.35e-03

H3TH domain of the 5'-3' exonuclease of Taq DNA polymerase I and homologs; H3TH (helix-3-turn-helix) domains of the 5'-3' exonuclease (53EXO) of mutli-domain DNA polymerase I and single domain protein homologs are included in this family. Taq DNA polymerase I contains a polymerase domain for synthesizing a new DNA strand and a 53EXO domain for cleaving RNA primers or damaged DNA strands. Taq's 53EXO recognizes and endonucleolytically cleaves a structure-specific DNA substrate that has a bifurcated downstream duplex and an upstream template-primer duplex that overlaps the downstream duplex by 1 bp. The 53EXO cleaves the unpaired 5'-arm of the overlap flap DNA substrate. 5'-3' exonucleases are members of the structure-specific, 5' nuclease family that catalyzes hydrolysis of DNA duplex-containing nucleic acid structures during DNA replication, repair, and recombination. 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+ or Mn2+ or Zn2+) 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 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: 188618 [Multi-domain]  Cd Length: 73  Bit Score: 30.83  E-value: 2.35e-03
                        10        20
                ....*....|....*....|.
gi 461694116  1 IDLIRQHGSIEEILENIDTSK 21
Cdd:cd09898  30 AKLLQEYGSLENILANLDELK 50
53EXOc smart00475
5'-3' exonuclease;
1-18 3.96e-03

5'-3' exonuclease;


Pssm-ID: 214682 [Multi-domain]  Cd Length: 259  Bit Score: 31.03  E-value: 3.96e-03
                           10
                   ....*....|....*...
gi 461694116     1 IDLIRQHGSIEEILENID 18
Cdd:smart00475 200 AKLLKEFGSLENILENLD 217
 
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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