Conserved Protein Domain Family
MeNeil3_N

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cd08969: MeNeil3_N 
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.
Statistics
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PSSM-Id: 176803
View PSSM: cd08969
Aligned: 10 rows
Threshold Bit Score: 154.494
Threshold Setting Gi: 224000619
Author:
Barrantes-Reynolds
Author Information
Name: Ramiro Barrantes-Reynolds
Address: Department of Microbiology and Molecular Genetics
University of Vermont
89 Beaumont Avenue
Burlington, VT 05405
USA
Created: 3-Jul-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
Feature 1:catalytic residue [active site]
Evidence:
  • Comment:This catalytic proline is almost perfectly conserved in FpgNei DNA glycolsylases. It acts as a nucleophile in catalysis.
  • Citation:PMID 9030608
  • Comment:Site-directed mutagenesis of this residue renders Fpg proteins defective in catalysis but still able to make the Schiff-base intermediate.
  • Citation:PMID 9654091
  • Comment:Site-directed mutagensis of this residue renders Escherichia coli Nei inactive but still able to make the Schiff-base intermediate.
  • Comment:1KFV_A , is a structure of a mutant Lactococcus Lactis Fpg which has a Gly in place of a Pro at this position.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         #                                                                              
NP_060718      1 MVEGPGCTLNGEKIRAr------vLPGQAVt---GVRGSALRSLQGralrlaastvvvspq------------------- 52  human
NP_001007336   1 MVEGPGCTLNGEKIRAr------vQKRQKVl---HIQGNETKTTSDdgsrs----------------------------- 42  zebrafish
XP_426306      1 MVEGPCCALFAERLRAr------vHRGQVVr---SARGSALSTEARaavrnragsrilgaryvvqprsprvafirhelai 71  chicken
NP_001017201   1 MVEGPGCTLNGEKIRAr------vEKGQSVv---ELRGSAVSGTPPsscyn----------------------------- 42  western clawed ...
XP_002188348   1 MVEGPGCALCAERLRAr------lRRGQRVr---AARGGGAVRAQGrgraqgrggtaaalaarppgqgaaaasgsaaqrc 71  zebra finch
CAG04636       1 MVEGPGCALNGEKIRSk------vQKGQEVi---DVRGTLTKSKHGavtcyfgsnltg---------------------- 49  spotted green p...
XP_002289982   1 MVEGPGCTRNGRKVQIa------vGKAATAa--vHVADSNDASPSSstsplp---------------------------- 44  Thalassiosira p...
XP_001371089   1 MVEGPGCKLNGEKIRTq------vRPGQVVt---GIRGGAPQPPRGdcldlestspiispsthal--------------- 56  gray short-tail...
XP_001926185   6 TNVGMGCRTNPQKPVNqflialvlEYLQNAnlgrHPWTREPLEESRcqrrns---------------------------- 57  pig
XP_002598139   1 MVEGPGCKLKGERLVR--------LKGQRVv--qTQWGRNRTRPEGaakgsgaeqk------------------------ 46  Florida lancelet
Feature 1                                                                                        
NP_060718     53 ------------------------------------aaalnndssqnvlslFNGYVYSGVETLGKELFMYFG------PK 90  human
NP_001007336  43 -----------------------------------------------sfqsFTGGEFTGVETLGKELFMYFG------VR 69  zebrafish
XP_426306     72 t---------------grsrvsalglqtvaevlaaaettvaseertsshdfLTGQVFRGVETLGKELFMYFD------QK 130 chicken
NP_001017201  43 -----------------------------------------------alssLTGCSYTGVQTLGKELFMYFG------LK 69  western clawed ...
XP_002188348  72 cswvpavvkgarfhrlltmakacpllitvfmrvstmmttaaskerisghdfLVGHVYRGVETLGKELFMYFD------QK 145 zebra finch
CAG04636      50 ----------------------------------------lclqksdvyrtFCGYQYTGVDTLGKELFMYFG------SR 83  spotted green p...
XP_002289982  45 ---------------------------------------------hhvaqeLSEQTLTEAFTVGKELFLVFSdtn-ekDN 78  Thalassiosira p...
XP_001371089  57 ---------------------------------hstlarnnkdscwnfpglLNGCVYSGVETLGKELFMYFG------LK 97  gray short-tail...
XP_001926185  58 ---------------------------------------------gvllekKCKFGCTGERTRGTLPALPLPhggtalCC 92  pig
XP_002598139  47 ------------------------------------------dttseksdhLVGLPLSNVETLGKELFVYFG------DF 78  Florida lancelet
Feature 1                                                                             
NP_060718     91 ALRIHFGMKGFIMINPLe-----YKYKNGASPVLEVQLTKDLICFFDSS---VELRNSMESQQRIRMMK 151 human
NP_001007336  70 ALRLHFGMNGSMRINPL------KKDLHGKPPVLVIQLTNDAICFFDTT---VEIRLSEDCEQKVRAME 129 zebrafish
XP_426306    131 ALRIHFGMNGSMRINPDg-----RQDRSGALPVLEIRLTEDTICFFEVT---AEYRNVTECEQRVRMME 191 chicken
NP_001017201  70 AIRVHFGMNGSIRLNQAvkk-gqENSRPMPVAVLEVQLEKDLICFYEST---VDVRNVSECQEKIRFLE 134 western clawed frog
XP_002188348 146 ALRIHFGMNGSMHINPDg-----SKDRNGAQPILEIQLMEDTVCFWDVT---VEYRNAAECEQKVRMME 206 zebra finch
CAG04636      84 ALRVHFGMNGSMRINPAe-----RKDRSSSMPVLEIHLTNDIVCFFDST---VEARSTEDCVQKVRAME 144 spotted green pufferfish
XP_002289982  79 VLRLHFGMNGSLNARRAytnksnQKKASGAAPWKQNKTPCLRLYFTEVNyktVSADAARDKLFRLNSRD 147 Thalassiosira pseudonana C...
XP_001371089  98 ALRIHFGMNGFVLINPLk-----SKNQTKTPPVFEVQLTKDLICFYDSS---VEFRNAMESKQKIRMME 158 gray short-tailed opossum
XP_001926185  93 GGLIHFGMKGSLAINPLe-----SKSKNGVSPVFEVQLTKDLICFFDSS---VEIRNTAESQQRIRMME 153 pig
XP_002598139  79 CLRVHFGMNGSVQIKGHr----nKAFQKTSEPVLTLTLTVDSVSFHDCT---VQIRSSSDCHDKYLQFQ 140 Florida lancelet

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