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 19353217   1 MVEGPGCTLNGEKIRARVLPGQAVTGVRGTALQSLLGpamspaaspadvATSAAPMNAKDSGWKLLRLFNGYVYSGVETL 80
Cdd:cd08969   1 MVEGPGCTLNGEKIRARVEKGQRVVHVRGSAPSSPSG------------AASRNGAGSKDERSHVLDSLTGQVYTGVETL 68

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19353217  81 GKELFMYFGHRALRIHFGMKGSILINPREGENRGGASPALAVQLTRDLICFYDSSVELRNSVESQQRVREME 152
Cdd:cd08969  69 GKELFMYFGDKALRIHFGMNGSMRINPLESKDRSGASPVLEVQLTKDLICFFDSTVEIRNAAECQQKIRMME 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 19353217   506 PLCKmHHRRCVLRVVRKDGENKGRQFYACSLPRGAQCGFFEWADLS 551
Cdd:pfam06839   1 PLCP-CGQRAVLLTVRKTGPNPGRQFYKCPVGREKQCGFFQWADEV 45

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 19353217   318 SEEQWSCAVCTLINRPSAKACDACLTTRPL 347
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 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 19353217   1 MVEGPGCTLNGEKIRARVLPGQAVTGVRGTALQSLLGpamspaaspadvATSAAPMNAKDSGWKLLRLFNGYVYSGVETL 80
Cdd:cd08969   1 MVEGPGCTLNGEKIRARVEKGQRVVHVRGSAPSSPSG------------AASRNGAGSKDERSHVLDSLTGQVYTGVETL 68

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19353217  81 GKELFMYFGHRALRIHFGMKGSILINPREGENRGGASPALAVQLTRDLICFYDSSVELRNSVESQQRVREME 152
Cdd:cd08969  69 GKELFMYFGDKALRIHFGMNGSMRINPLESKDRSGASPVLEVQLTKDLICFFDSTVEIRNAAECQQKIRMME 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 19353217   506 PLCKmHHRRCVLRVVRKDGENKGRQFYACSLPRGAQCGFFEWADLS 551
Cdd:pfam06839   1 PLCP-CGQRAVLLTVRKTGPNPGRQFYKCPVGREKQCGFFQWADEV 45

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353217  181 VLLDQRVLPGVGNIIKNEALFDSGLHPAVKVCQLSDKQARHLVKMTRDfsILfyrcCKA----GSAI------------- 243
Cdd:PRK01103 161 ALLDQTVVVGVGNIYADEALFRAGIHPERPAGSLSRAEAERLVDAIKA--VL----AEAieqgGTTLrdyvnadgkpgyf 234

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 19353217  244 SKHCKVYKRPN--CGQCHSKITVCRFGEnsRMTYFCPHCQK 282
Cdd:PRK01103 235 QQSLQVYGREGepCRRCGTPIEKIKQGG--RSTFFCPRCQK 273

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
                  ....*....|....*....|....*....|....*....|....*..
gi 19353217   182 LLDQRVLPGVGNIIKNEALFDSGLHPAVKVCQLSDKQARHLVKMTRD 228
Cdd:pfam06831  30 LLDQTLVAGLGNIYADEVLFRAGIHPERLANSLSKEECELLHQAIKA 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
                   ....*....|....*....|....*....|....*....|....*.
gi 19353217     65 LLRLFNGYVYSGVETLGKELFMYFGH-RALRIHFGMKGSILINPRE 109
Cdd:smart00898  39 FAAALSGRTITSVRRRGKYLLLRLLGgLTLVVHLGMSGSLRVVPAG 84

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 19353217   1 MVEGPGCTLNGEKIRARVLPGQAVTGVRGTALQSLLGpamspaaspadvATSAAPMNAKDSGWKLLRLFNGYVYSGVETL 80
Cdd:cd08969   1 MVEGPGCTLNGEKIRARVEKGQRVVHVRGSAPSSPSG------------AASRNGAGSKDERSHVLDSLTGQVYTGVETL 68

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19353217  81 GKELFMYFGHRALRIHFGMKGSILINPREGENRGGASPALAVQLTRDLICFYDSSVELRNSVESQQRVREME 152
Cdd:cd08969  69 GKELFMYFGDKALRIHFGMNGSMRINPLESKDRSGASPVLEVQLTKDLICFFDSTVEIRNAAECQQKIRMME 140

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 19353217   2 VEGPGCTLNGEKIRARvLPGQAVTGVRGTALQSLLGPAMspaaspadvatsaapmnakdsgwKLLRLFNGYVYSGVETLG 81
Cdd:cd08773   1 PELPEVELLRRKLRRA-LKGKRVTRVEVSDPRRLFTPAA-----------------------ELAAALIGRRVRGAERRG 56

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19353217  82 KELFMYF-GHRALRIHFGMKGSILINPREGENrgGASPALAVQLT-RDLICFYDSSVELRNSV 142
Cdd:cd08773  57 KYLLLELsGGPWLVIHLGMTGRLRVCPEGEPP--PKHDRLVLRLAnGSQLRFTDPRKFGRVEL 117

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 19353217   553 PFCKHGKRSIMKTVLKIGPNNGKNFFVCPLEKEKQCNFFQWAENG 597
Cdd:pfam06839   1 PLCPCGQRAVLLTVRKTGPNPGRQFYKCPVGREKQCGFFQWADEV 45

DNA-formamidopyrimidine glycosylase; All proteins in the FPG family with known functions are FAPY-DNA glycosylases that function in base excision repair. Homologous to endonuclease VIII (nei). This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353217    81 GKELFMYFGHRALRIHFGMKGSILINPReGENRGGASPALAVQLTRDLICFYD----SSVEL-RNSVESQQRVREMEELD 155
Cdd:TIGR00577  58 GKYLLFELDDGALVSHLRMEGKYRLEAV-PDAPDKHDHVDFLFDDGTELRYHDprrfGTWLLlDRGQVENIPLLAKLGPE 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353217   156 ICSPKFSFsRAESEVKKQGDRMLCDVLLDQRVLPGVGNIIKNEALFDSGLHPAVKVCQLSDKQARHLVKMTRDfsILFYR 235
Cdd:TIGR00577 137 PLSEDFTA-EYLFEKLAKSKRKIKTALLDQRLVAGIGNIYADEVLFRAGIHPERLASSLSKEECELLHRAIKE--VLRKA 213

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19353217   236 CCKAGSAIS------------KHC-KVYKRPN--CGQCHSKITVCRFGenSRMTYFCPHCQ 281
Cdd:TIGR00577 214 IEMGGTTIRdfsqsdghngyfQQElQVYGRKGepCRRCGTTIEKEKVG--GRGTHFCPQCQ 272

endonuclease VIII; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353217  176 RMLCDVLLDQRVLPGVGNIIKNEALFDSGLHPAVKVCQLSDKQARHLVKMTRDFSILFYRC------CKAGSAISKHcKV 249
Cdd:PRK10445 152 RQFSGLLLDQAFLAGLGNYLRVEILWQAGLTPQHKAKDLNEAQLDALAHALLDIPRLSYATrgqvdeNKHHGALFRF-KV 230

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 19353217  250 YKRP-----NCGQCHSKITVcrfgeNSRMTYFCPHCQK 282
Cdd:PRK10445 231 FHRDgeaceRCGGIIEKTTL-----SSRPFYWCPGCQK 263

formamidopyrimidine-DNA glycosylase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353217  158 SPKFSFSRAESEVKKQgDRMLCDVLLDQRVLPGVGNIIKNEALFDSGLHPAVKVCQLSDKQARHL-------VKMT---- 226
Cdd:PRK13945 148 SPEFSVEYLKKKLKKR-TRSIKTALLDQSIVAGIGNIYADESLFKAGIHPTTPAGQLKKKQLERLreaiievLKTSigag 226

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19353217  227 ----RDFSIL------------FYRccKAGsaisKHCKVykrpnCGQCHSKITVCrfgenSRMTYFCPHCQK 282
Cdd:PRK13945 227 gttfSDFRDLegvngnyggqawVYR--RTG----KPCRK-----CGTPIERIKLA-----GRSTHWCPNCQK 282

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 19353217   318 SEEQWSCAVCTLINRPSAKACDACLTTRPL 347
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 30

Uncharacterized bacterial subgroup of the N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases; This family is an uncharacterized bacterial subgroup of the FpgNei_N 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. This N-terminal proline is conserved in this family. Escherichia coli Fpg prefers 8-oxo-7,8-dihydroguanine (8-oxoG) and oxidized purines, and Escherichia coli Nei recognizes oxidized pyrimidines. However, neither Escherichia coli Fpg or Nei belong to this family. In addition to this BaFpgNei_N_2 domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain. Most also contain a zinc-finger motif.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19353217   1 MVEGPGCTLNGEKIRArvLPGQAVTGVRGTALQsllgpAMSPAAspadvatsaapmnakdsGWKLLrlfngyvysGVETL 80
Cdd:cd08974   1 MPEGPSIVILREAAAA--FKGQTVIRASGNAKI-----DKDRLA-----------------GQKVL---------AIRSW 47

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 19353217  81 GKELFMYFGHRALRIHFGMKGSILINPREgenrgGASPALAVQLTRDLICFYDSSV 136
Cdd:cd08974  48 GKHFLLEFEDFTVRIHLLLFGSYRINERK-----DAPPRLSLGFDNGELNFYTCSV 98

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|....
gi 19353217    320 EQWSCAVCTLINRPSAKACDACLT 343
Cdd:smart00547   1 GDWECPACTFLNFASRSKCFACGA 24