N-terminal domain of metazoan Nei-like glycosylase 3 (NEIL3); This family contains the N-terminal domain of the Metazoan Neil3. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. In contrast, mouse NEIL3 (MmuNEIL3) forms a Schiff base intermediate via its N-terminal valine. The latter is a functional DNA glycosylase in vitro and in vivo. MmuNEIL3 prefers lesions in single-stranded DNA and in bubble structures. In duplex DNA, it recognizes the oxidized purines spiroiminodihydantoin (Sp), guanidinohydantoin (Gh), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino-5-formamidopyrimidine (FapyA), but not 8-oxo-7,8-dihydroguanine (8-oxoG). Since the expression of the MmuNeil3 glycosylase domain (MmuNeil3delta324) reduces both the high spontaneous mutation frequency and the FapyG level in a Escherichia coli mutant lacking Fpg, Nei and MutY glycosylase activites, NEIL3 may play a role in repairing FapyG in vivo. In addition to this MeNeil3_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc finger motif, plus a characteristic C-terminal extension that contains additional zinc fingers. Neil3 is one of three homologs found in eukaryotes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346   1 MVEGPGCTLNGEKIRARVQKRQKVLHIQGNETKTTSDDGSRSS----------FQSFKGGEFTGVETLGKELFMYFGVRA 70
Cdd:cd08969    1 MVEGPGCTLNGEKIRARVEKGQRVVHVRGSAPSSPSGAASRNGagskdershvLDSLTGQVYTGVETLGKELFMYFGDKA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346  71 LRLHFGMNGSMRINPL-KKDLNGKPPVLVIQLTNDAICFFDTTVEIRLSEDCEQKVRAME 129
Cdd:cd08969   81 LRIHFGMNGSMRINPLeSKDRSGASPVLEVQLTKDLICFFDSTVEIRNAAECQQKIRMME 140

GRF zinc finger; This presumed zinc binding domain is found in a variety of DNA-binding proteins. It seems likely that this domain is involved in nucleic acid binding. It is named GRF after three conserved residues in the centre of the alignment of the domain. This zinc finger may be related to pfam01396.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528500346  515 PMCHHGKRTVMKTVLKLGPNNGRNFYTCPVKMGKQCNFFQWAENG 559
Cdd:pfam06839   1 PLCPCGQRAVLLTVRKTGPNPGRQFYKCPVGREKQCGFFQWADEV 45

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....*....
gi 528500346  296 EEEWTCSLCTLINRPFNKHCDACMSPRPD 324
Cdd:pfam00641   2 EGDWDCSKCLVQNFATSTKCVACQAPKPD 30

N-terminal domain of metazoan Nei-like glycosylase 3 (NEIL3); This family contains the N-terminal domain of the Metazoan Neil3. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. In contrast, mouse NEIL3 (MmuNEIL3) forms a Schiff base intermediate via its N-terminal valine. The latter is a functional DNA glycosylase in vitro and in vivo. MmuNEIL3 prefers lesions in single-stranded DNA and in bubble structures. In duplex DNA, it recognizes the oxidized purines spiroiminodihydantoin (Sp), guanidinohydantoin (Gh), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino-5-formamidopyrimidine (FapyA), but not 8-oxo-7,8-dihydroguanine (8-oxoG). Since the expression of the MmuNeil3 glycosylase domain (MmuNeil3delta324) reduces both the high spontaneous mutation frequency and the FapyG level in a Escherichia coli mutant lacking Fpg, Nei and MutY glycosylase activites, NEIL3 may play a role in repairing FapyG in vivo. In addition to this MeNeil3_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc finger motif, plus a characteristic C-terminal extension that contains additional zinc fingers. Neil3 is one of three homologs found in eukaryotes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346   1 MVEGPGCTLNGEKIRARVQKRQKVLHIQGNETKTTSDDGSRSS----------FQSFKGGEFTGVETLGKELFMYFGVRA 70
Cdd:cd08969    1 MVEGPGCTLNGEKIRARVEKGQRVVHVRGSAPSSPSGAASRNGagskdershvLDSLTGQVYTGVETLGKELFMYFGDKA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346  71 LRLHFGMNGSMRINPL-KKDLNGKPPVLVIQLTNDAICFFDTTVEIRLSEDCEQKVRAME 129
Cdd:cd08969   81 LRIHFGMNGSMRINPLeSKDRSGASPVLEVQLTKDLICFFDSTVEIRNAAECQQKIRMME 140

bifunctional DNA-formamidopyrimidine glycosylase/DNA-(apurinic or apyrimidinic site) lyase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346  52 FTGVETLGKELFMYFGVR-ALRLHFGMNGSMRINPLkkdlnGKPPV----LVIQLTNDAICFF-DT----TVEIRLSEDC 121
Cdd:PRK01103  50 ILAVGRRGKYLLLDLDDGgTLISHLGMSGSLRLLPE-----DTPPEkhdhVDFVLDDGTVLRYnDPrrfgAMLLTPKGDL 124

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346 122 EQKVR----AMEALDicsPKFSFSRAVEAVKTeRARMLCDVLLDQTVLPGVGNIIKNEALFDSGLNPAVKVSQLTDEQVH 197
Cdd:PRK01103 125 EAHPLlahlGPEPLS---DAFDGEYLAAKLRK-KKTAIKPALLDQTVVVGVGNIYADEALFRAGIHPERPAGSLSRAEAE 200

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346 198 HLVK-----MT----------RDFTllfykcRKNGSPLY--KHYKVYKRPN--CGQCSGTVTVCRLGdnGRMTYYCQRCQ 258
Cdd:PRK01103 201 RLVDaikavLAeaieqggttlRDYV------NADGKPGYfqQSLQVYGREGepCRRCGTPIEKIKQG--GRSTFFCPRCQ 272

GRF zinc finger; This presumed zinc binding domain is found in a variety of DNA-binding proteins. It seems likely that this domain is involved in nucleic acid binding. It is named GRF after three conserved residues in the centre of the alignment of the domain. This zinc finger may be related to pfam01396.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528500346  515 PMCHHGKRTVMKTVLKLGPNNGRNFYTCPVKMGKQCNFFQWAENG 559
Cdd:pfam06839   1 PLCPCGQRAVLLTVRKTGPNPGRQFYKCPVGREKQCGFFQWADEV 45

Formamidopyrimidine-DNA glycosylase H2TH domain; Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. This family is the central domain containing the DNA-binding helix-two turn-helix domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528500346  130 ALDICSPKFSFSRAVEAVKtERARMLCDVLLDQTVLPGVGNIIKNEALFDSGLNPAVKVSQLTDEQVHHLVKMTRD 205
Cdd:pfam06831   2 GPEPLSEDFTVDYFAERLA-KKKRPIKTALLDQTLVAGLGNIYADEVLFRAGIHPERLANSLSKEECELLHQAIKA 76

Formamidopyrimidine-DNA glycosylase N-terminal domain; This entry represents the catalytic domain of DNA glycosylase/AP lyase enzymes, which are involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Most damage to bases in DNA is repaired by the base excision repair pathway. These enzymes are primarily from bacteria, and have both DNA glycosylase activity and AP lyase activity. Examples include formamidopyrimidine-DNA glycosylases (Fpg; MutM) and endonuclease VIII (Nei). Formamidopyrimidine-DNA glycosylases (Fpg, MutM) is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidation-damaged bases (N-glycosylase activity; ) and cleaves both the 3'- and 5'-phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase activity; ). Fpg has a preference for oxidised purines, excising oxidized purine bases such as 7,8-dihydro-8-oxoguanine (8-oxoG). ITs AP (apurinic/apyrimidinic) lyase activity introduces nicks in the DNA strand, cleaving the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Fpg is a monomer composed of 2 domains connected by a flexible hinge. The two DNA-binding motifs (a zinc finger and the helix-two-turns-helix motifs) suggest that the oxidized base is flipped out from double-stranded DNA in the binding mode and excised by a catalytic mechanism similar to that of bifunctional base excision repair enzymes. Fpg binds one ion of zinc at the C-terminus, which contains four conserved and essential cysteines.. Endonuclease VIII (Nei) has the same enzyme activities as Fpg above, but with a preference for oxidized pyrimidines, such as thymine glycol, 5,6-dihydrouracil and 5,6-dihydrothymine. These protein contains three structural domains: an N-terminal catalytic core domain, a central helix-two turn-helix (H2TH) module and a C-terminal zinc finger (see PDB:1K82). The N-terminal catalytic domain and the C-terminal zinc finger straddle the DNA with the long axis of the protein oriented roughly orthogonal to the helical axis of the DNA. Residues that contact DNA are located in the catalytic domain and in a beta-hairpin loop formed by the zinc finger.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346     9 LNGEKIRARVQKRQKVLhiqgnetkTTSDDgsrssFQSF-KGGEFTGVETLGKELFMYF-GVRALRLHFGMNGSMRINPl 86
Cdd:smart00898  17 LAGRTITRVEVVRPPQL--------RFPDE-----FAAAlSGRTITSVRRRGKYLLLRLlGGLTLVVHLGMSGSLRVVP- 82

                           90       100
                   ....*....|....*....|....*.
gi 528500346    87 KKDLNGKPPVLVIQLTND-AICFFDT 111
Cdd:smart00898  83 AGTPPPKHDHVRLVLDDGtELRFNDP 108

N-terminal domain of metazoan Nei-like glycosylase 3 (NEIL3); This family contains the N-terminal domain of the Metazoan Neil3. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. In contrast, mouse NEIL3 (MmuNEIL3) forms a Schiff base intermediate via its N-terminal valine. The latter is a functional DNA glycosylase in vitro and in vivo. MmuNEIL3 prefers lesions in single-stranded DNA and in bubble structures. In duplex DNA, it recognizes the oxidized purines spiroiminodihydantoin (Sp), guanidinohydantoin (Gh), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino-5-formamidopyrimidine (FapyA), but not 8-oxo-7,8-dihydroguanine (8-oxoG). Since the expression of the MmuNeil3 glycosylase domain (MmuNeil3delta324) reduces both the high spontaneous mutation frequency and the FapyG level in a Escherichia coli mutant lacking Fpg, Nei and MutY glycosylase activites, NEIL3 may play a role in repairing FapyG in vivo. In addition to this MeNeil3_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zinc finger motif, plus a characteristic C-terminal extension that contains additional zinc fingers. Neil3 is one of three homologs found in eukaryotes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346   1 MVEGPGCTLNGEKIRARVQKRQKVLHIQGNETKTTSDDGSRSS----------FQSFKGGEFTGVETLGKELFMYFGVRA 70
Cdd:cd08969    1 MVEGPGCTLNGEKIRARVEKGQRVVHVRGSAPSSPSGAASRNGagskdershvLDSLTGQVYTGVETLGKELFMYFGDKA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346  71 LRLHFGMNGSMRINPL-KKDLNGKPPVLVIQLTNDAICFFDTTVEIRLSEDCEQKVRAME 129
Cdd:cd08969   81 LRIHFGMNGSMRINPLeSKDRSGASPVLEVQLTKDLICFFDSTVEIRNAAECQQKIRMME 140

bifunctional DNA-formamidopyrimidine glycosylase/DNA-(apurinic or apyrimidinic site) lyase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346  52 FTGVETLGKELFMYFGVR-ALRLHFGMNGSMRINPLkkdlnGKPPV----LVIQLTNDAICFF-DT----TVEIRLSEDC 121
Cdd:PRK01103  50 ILAVGRRGKYLLLDLDDGgTLISHLGMSGSLRLLPE-----DTPPEkhdhVDFVLDDGTVLRYnDPrrfgAMLLTPKGDL 124

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346 122 EQKVR----AMEALDicsPKFSFSRAVEAVKTeRARMLCDVLLDQTVLPGVGNIIKNEALFDSGLNPAVKVSQLTDEQVH 197
Cdd:PRK01103 125 EAHPLlahlGPEPLS---DAFDGEYLAAKLRK-KKTAIKPALLDQTVVVGVGNIYADEALFRAGIHPERPAGSLSRAEAE 200

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346 198 HLVK-----MT----------RDFTllfykcRKNGSPLY--KHYKVYKRPN--CGQCSGTVTVCRLGdnGRMTYYCQRCQ 258
Cdd:PRK01103 201 RLVDaikavLAeaieqggttlRDYV------NADGKPGYfqQSLQVYGREGepCRRCGTPIEKIKQG--GRSTFFCPRCQ 272

GRF zinc finger; This presumed zinc binding domain is found in a variety of DNA-binding proteins. It seems likely that this domain is involved in nucleic acid binding. It is named GRF after three conserved residues in the centre of the alignment of the domain. This zinc finger may be related to pfam01396.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 528500346  515 PMCHHGKRTVMKTVLKLGPNNGRNFYTCPVKMGKQCNFFQWAENG 559
Cdd:pfam06839   1 PLCPCGQRAVLLTVRKTGPNPGRQFYKCPVGREKQCGFFQWADEV 45

N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases; DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. These enzymes initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycolsylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. The FpgNei DNA glycosylases represent one of the two structural superfamilies of DNA glycosylases that recognize oxidized bases (the other is the HTH-GPD superfamily exemplified by Escherichia coli Nth). Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. One exception is mouse Nei-like glycosylase 3 (Neil3) which forms a Schiff base intermediate via its N-terminal valine. In addition to this FpgNei_N domain, FpgNei proteins have a helix-two-turn-helix (H2TH) domain and a zinc (or zincless)-finger motif which also contribute residues to the active site. FpgNei DNA glycosylases have a broad substrate specificity. They are bifunctional, in addition to the glycosylase (recognition) activity, they have a lyase (cleaving) activity on the phosphodiester backbone of the DNA at the AP site. This superfamily includes eukaryotic, bacterial, and viral proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346   2 VEGPGCTLNGEKIRARVqKRQKVLHIQGNETKTTSDDGSRSSFQsFKGGEFTGVETLGKELFMYF-GVRALRLHFGMNGS 80
Cdd:cd08773    1 PELPEVELLRRKLRRAL-KGKRVTRVEVSDPRRLFTPAAELAAA-LIGRRVRGAERRGKYLLLELsGGPWLVIHLGMTGR 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 528500346  81 MRINPLKKDlNGKPPVLVIQLTND-AICFFDT 111
Cdd:cd08773   79 LRVCPEGEP-PPKHDRLVLRLANGsQLRFTDP 109

Formamidopyrimidine-DNA glycosylase H2TH domain; Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines from damaged DNA. This family is the central domain containing the DNA-binding helix-two turn-helix domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 528500346  130 ALDICSPKFSFSRAVEAVKtERARMLCDVLLDQTVLPGVGNIIKNEALFDSGLNPAVKVSQLTDEQVHHLVKMTRD 205
Cdd:pfam06831   2 GPEPLSEDFTVDYFAERLA-KKKRPIKTALLDQTLVAGLGNIYADEVLFRAGIHPERLANSLSKEECELLHQAIKA 76

formamidopyrimidine-DNA glycosylase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346 135 SPKFSFSRAVEAVKTeRARMLCDVLLDQTVLPGVGNIIKNEALFDSGLNPAVKVSQLTDEQVHHL-------VKMT---- 203
Cdd:PRK13945 148 SPEFSVEYLKKKLKK-RTRSIKTALLDQSIVAGIGNIYADESLFKAGIHPTTPAGQLKKKQLERLreaiievLKTSigag 226

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 528500346 204 -------RDFTLLfykcrkNGSplykhYK----VYKRPN--CGQCSGTVTVCRLGdnGRMTYYCQRCQT 259
Cdd:PRK13945 227 gttfsdfRDLEGV------NGN-----YGgqawVYRRTGkpCRKCGTPIERIKLA--GRSTHWCPNCQK 282

formamidopyrimidine-DNA glycosylase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 528500346 159 LLDQTVLPGVGNIIKNEALFDSGLNPAVKVSQLTDEQVHHLVKMTRDftLLFYKCRKNGSPLYKH-------------YK 225
Cdd:PRK14810 161 LLNQTLLRGVGNIYADEALFRAGIRPQRLASSLSRERLRKLHDAIGE--VLREAIELGGSSVSDYvdaegrsgffqlsHR 238

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 528500346 226 VYKRPN--CGQCSGTVTvcRLGDNGRMTYYCQRCQ 258
Cdd:PRK14810 239 VYQRTGepCLNCKTPIR--RVVVAGRSSHYCPHCQ 271