NEIL1_HUMAN
ID NEIL1_HUMAN Reviewed; 390 AA.
AC Q96FI4; D3DW75; Q6ZRA7; Q86XW7; Q9H6C3;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Endonuclease 8-like 1;
DE EC=3.2.2.-;
DE EC=4.2.99.18;
DE AltName: Full=DNA glycosylase/AP lyase Neil1;
DE AltName: Full=DNA-(apurinic or apyrimidinic site) lyase Neil1;
DE AltName: Full=Endonuclease VIII-like 1;
DE AltName: Full=FPG1;
DE AltName: Full=Nei homolog 1;
DE Short=NEH1;
DE AltName: Full=Nei-like protein 1;
GN Name=NEIL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Testis;
RX PubMed=12200441; DOI=10.1074/jbc.m206884200;
RA Takao M., Kanno S., Kobayashi K., Zhang Q.-M., Yonei S.,
RA van der Horst G.T.J., Yasui A.;
RT "A back-up glycosylase in Nth1 knock-out mice is a functional Nei
RT (endonuclease VIII) homologue.";
RL J. Biol. Chem. 277:42205-42213(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-82; ASP-83; ARG-136 AND
RP ASN-252.
RG NIEHS SNPs program;
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP MUTAGENESIS OF PRO-2 AND GLU-3, AND FUNCTION.
RX PubMed=12509226; DOI=10.1016/s1568-7864(02)00036-8;
RA Bandaru V., Sunkara S., Wallace S.S., Bond J.P.;
RT "A novel human DNA glycosylase that removes oxidative DNA damage and is
RT homologous to Escherichia coli endonuclease VIII.";
RL DNA Repair 1:517-529(2002).
RN [8]
RP MUTAGENESIS OF PRO-2, FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=11904416; DOI=10.1073/pnas.062053799;
RA Hazra T.K., Izumi T., Boldogh I., Imhoff B., Kow Y.W., Jaruga P.,
RA Dizdaroglu M., Mitra S.;
RT "Identification and characterization of a human DNA glycosylase for repair
RT of modified bases in oxidatively damaged DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:3523-3528(2002).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF LYS-54.
RX PubMed=14522990; DOI=10.1074/jbc.m308658200;
RA Dou H., Mitra S., Hazra T.K.;
RT "Repair of oxidized bases in DNA bubble structures by human DNA
RT glycosylases NEIL1 and NEIL2.";
RL J. Biol. Chem. 278:49679-49684(2003).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=17556049; DOI=10.1016/j.dnarep.2007.04.008;
RA Hildrestrand G.A., Rolseth V., Bjoras M., Luna L.;
RT "Human NEIL1 localizes with the centrosomes and condensed chromosomes
RT during mitosis.";
RL DNA Repair 6:1425-1433(2007).
RN [11]
RP RNA EDITING OF POSITION 242.
RX PubMed=21068368; DOI=10.1073/pnas.1009231107;
RA Yeo J., Goodman R.A., Schirle N.T., David S.S., Beal P.A.;
RT "RNA editing changes the lesion specificity for the DNA repair enzyme
RT NEIL1.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:20715-20719(2010).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-334, AND MUTAGENESIS OF ARG-277.
RX PubMed=15232006; DOI=10.1073/pnas.0402051101;
RA Doublie S., Bandaru V., Bond J.P., Wallace S.S.;
RT "The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a
RT zincless finger motif required for glycosylase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10284-10289(2004).
RN [13]
RP VARIANTS GLN-159 AND LYS-181.
RX PubMed=21697813; DOI=10.1038/ki.2011.148;
RA Sanna-Cherchi S., Burgess K.E., Nees S.N., Caridi G., Weng P.L.,
RA Dagnino M., Bodria M., Carrea A., Allegretta M.A., Kim H.R., Perry B.J.,
RA Gigante M., Clark L.N., Kisselev S., Cusi D., Gesualdo L., Allegri L.,
RA Scolari F., D'Agati V., Shapiro L.S., Pecoraro C., Palomero T.,
RA Ghiggeri G.M., Gharavi A.G.;
RT "Exome sequencing identified MYO1E and NEIL1 as candidate genes for human
RT autosomal recessive steroid-resistant nephrotic syndrome.";
RL Kidney Int. 80:389-396(2011).
CC -!- FUNCTION: Involved in base excision repair of DNA damaged by oxidation
CC or by mutagenic agents. Acts as DNA glycosylase that recognizes and
CC removes damaged bases. Has a preference for oxidized pyrimidines, such
CC as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has
CC marginal activity towards 8-oxoguanine. Has AP (apurinic/apyrimidinic)
CC lyase activity and introduces nicks in the DNA strand. Cleaves the DNA
CC backbone by beta-delta elimination to generate a single-strand break at
CC the site of the removed base with both 3'- and 5'-phosphates. Has DNA
CC glycosylase/lyase activity towards mismatched uracil and thymine, in
CC particular in U:C and T:C mismatches. Specifically binds 5-
CC hydroxymethylcytosine (5hmC), suggesting that it acts as a specific
CC reader of 5hmC. {ECO:0000269|PubMed:11904416,
CC ECO:0000269|PubMed:12200441, ECO:0000269|PubMed:12509226,
CC ECO:0000269|PubMed:14522990}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'-
CC deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3-
CC dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-monophospho-
CC 2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA-
CC COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695,
CC ChEBI:CHEBI:167181; EC=4.2.99.18; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00392};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome {ECO:0000269|PubMed:17556049}. Nucleus
CC {ECO:0000269|PubMed:17556049}. Chromosome
CC {ECO:0000269|PubMed:17556049}. Note=During mitosis, associates with
CC centrosomes and condensed chromatin.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11904416}.
CC -!- INDUCTION: Up-regulated during S-phase. {ECO:0000269|PubMed:11904416}.
CC -!- RNA EDITING: Modified_positions=242 {ECO:0000269|PubMed:21068368};
CC Note=The edited form removes thymine glycol from duplex DNA 30 times
CC more slowly than the form encoded in the genome, whereas editing
CC enhances repair of the guanidinohydantoin lesion by NEIL1. The recoding
CC site is a preferred editing site for the RNA editing adenosine
CC deaminase ADAR1.;
CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000255|PROSITE-
CC ProRule:PRU00392}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK128372; Type=Miscellaneous discrepancy; Note=Erroneous CDS prediction.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NEIL1ID41519ch15q24.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/neil1/";
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DR EMBL; AB079068; BAC06476.1; -; mRNA.
DR EMBL; AK026055; BAB15337.1; -; mRNA.
DR EMBL; AK128372; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY257544; AAO74826.1; -; Genomic_DNA.
DR EMBL; AC068338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471136; EAW99255.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99260.1; -; Genomic_DNA.
DR EMBL; BC010876; AAH10876.1; -; mRNA.
DR CCDS; CCDS10278.1; -.
DR RefSeq; NP_001243481.1; NM_001256552.1.
DR RefSeq; NP_078884.2; NM_024608.3.
DR RefSeq; XP_005254716.1; XM_005254659.4.
DR RefSeq; XP_006720743.1; XM_006720680.1.
DR RefSeq; XP_006720744.1; XM_006720681.1.
DR RefSeq; XP_011520304.1; XM_011522002.1.
DR RefSeq; XP_011520305.1; XM_011522003.2.
DR RefSeq; XP_011520306.1; XM_011522004.2.
DR PDB; 1TDH; X-ray; 2.10 A; A=1-390.
DR PDB; 4NRV; X-ray; 2.60 A; A=2-290.
DR PDB; 5ITQ; X-ray; 1.48 A; A=1-290.
DR PDB; 5ITR; X-ray; 2.46 A; A/B/C=1-390.
DR PDB; 5ITT; X-ray; 2.53 A; A/B/C=1-390.
DR PDB; 5ITU; X-ray; 2.41 A; A/B/C=1-390.
DR PDB; 5ITX; X-ray; 2.65 A; A/B/E=1-390.
DR PDB; 5ITY; X-ray; 2.48 A; A/B/C=1-390.
DR PDB; 6LWA; X-ray; 2.76 A; A/D/G=1-295.
DR PDB; 6LWB; X-ray; 2.55 A; A/D/G=1-295.
DR PDB; 6LWC; X-ray; 2.91 A; A/D=1-295.
DR PDB; 6LWD; X-ray; 2.41 A; A/D/G=1-295.
DR PDB; 6LWF; X-ray; 2.79 A; A/D=1-295.
DR PDB; 6LWG; X-ray; 2.53 A; A/D/G=1-295.
DR PDB; 6LWH; X-ray; 2.78 A; A/D/G=1-295.
DR PDB; 6LWI; X-ray; 2.72 A; A/D/G=1-295.
DR PDB; 6LWJ; X-ray; 2.83 A; A/D/G=1-295.
DR PDB; 6LWK; X-ray; 2.88 A; A/D/G=1-295.
DR PDB; 6LWL; X-ray; 2.55 A; A/D/G=1-295.
DR PDB; 6LWM; X-ray; 2.67 A; A/D/G=1-295.
DR PDB; 6LWN; X-ray; 2.74 A; A/D/G=1-295.
DR PDB; 6LWO; X-ray; 2.51 A; A/D/G=1-295.
DR PDB; 6LWP; X-ray; 2.64 A; A/D/G=1-295.
DR PDB; 6LWQ; X-ray; 2.89 A; A/D/G=1-295.
DR PDB; 6LWR; X-ray; 2.90 A; A/E=1-295.
DR PDBsum; 1TDH; -.
DR PDBsum; 4NRV; -.
DR PDBsum; 5ITQ; -.
DR PDBsum; 5ITR; -.
DR PDBsum; 5ITT; -.
DR PDBsum; 5ITU; -.
DR PDBsum; 5ITX; -.
DR PDBsum; 5ITY; -.
DR PDBsum; 6LWA; -.
DR PDBsum; 6LWB; -.
DR PDBsum; 6LWC; -.
DR PDBsum; 6LWD; -.
DR PDBsum; 6LWF; -.
DR PDBsum; 6LWG; -.
DR PDBsum; 6LWH; -.
DR PDBsum; 6LWI; -.
DR PDBsum; 6LWJ; -.
DR PDBsum; 6LWK; -.
DR PDBsum; 6LWL; -.
DR PDBsum; 6LWM; -.
DR PDBsum; 6LWN; -.
DR PDBsum; 6LWO; -.
DR PDBsum; 6LWP; -.
DR PDBsum; 6LWQ; -.
DR PDBsum; 6LWR; -.
DR AlphaFoldDB; Q96FI4; -.
DR SASBDB; Q96FI4; -.
DR SMR; Q96FI4; -.
DR BioGRID; 122787; 298.
DR CORUM; Q96FI4; -.
DR IntAct; Q96FI4; 1.
DR STRING; 9606.ENSP00000347170; -.
DR ChEMBL; CHEMBL4523426; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB14490; Ferrous ascorbate.
DR DrugBank; DB14491; Ferrous fumarate.
DR DrugBank; DB14488; Ferrous gluconate.
DR DrugBank; DB14501; Ferrous glycine sulfate.
DR DrugBank; DB14489; Ferrous succinate.
DR DrugBank; DB01592; Iron.
DR iPTMnet; Q96FI4; -.
DR PhosphoSitePlus; Q96FI4; -.
DR BioMuta; NEIL1; -.
DR DMDM; 56404654; -.
DR EPD; Q96FI4; -.
DR MassIVE; Q96FI4; -.
DR PaxDb; Q96FI4; -.
DR PeptideAtlas; Q96FI4; -.
DR PRIDE; Q96FI4; -.
DR ProteomicsDB; 76532; -.
DR Antibodypedia; 27258; 321 antibodies from 33 providers.
DR DNASU; 79661; -.
DR Ensembl; ENST00000355059.9; ENSP00000347170.4; ENSG00000140398.14.
DR Ensembl; ENST00000564784.5; ENSP00000457352.1; ENSG00000140398.14.
DR Ensembl; ENST00000569035.5; ENSP00000455730.1; ENSG00000140398.14.
DR GeneID; 79661; -.
DR KEGG; hsa:79661; -.
DR MANE-Select; ENST00000355059.9; ENSP00000347170.4; NM_024608.4; NP_078884.2.
DR UCSC; uc002bad.5; human.
DR CTD; 79661; -.
DR DisGeNET; 79661; -.
DR GeneCards; NEIL1; -.
DR HGNC; HGNC:18448; NEIL1.
DR HPA; ENSG00000140398; Low tissue specificity.
DR MIM; 608844; gene.
DR neXtProt; NX_Q96FI4; -.
DR OpenTargets; ENSG00000140398; -.
DR PharmGKB; PA38334; -.
DR VEuPathDB; HostDB:ENSG00000140398; -.
DR eggNOG; ENOG502QSPK; Eukaryota.
DR GeneTree; ENSGT00940000153230; -.
DR HOGENOM; CLU_051284_0_0_1; -.
DR InParanoid; Q96FI4; -.
DR OMA; IMFEYKS; -.
DR OrthoDB; 1467835at2759; -.
DR PhylomeDB; Q96FI4; -.
DR TreeFam; TF333272; -.
DR PathwayCommons; Q96FI4; -.
DR Reactome; R-HSA-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
DR Reactome; R-HSA-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-HSA-5649702; APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway.
DR Reactome; R-HSA-9616334; Defective Base Excision Repair Associated with NEIL1.
DR SignaLink; Q96FI4; -.
DR SIGNOR; Q96FI4; -.
DR BioGRID-ORCS; 79661; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; NEIL1; human.
DR EvolutionaryTrace; Q96FI4; -.
DR GeneWiki; NEIL1; -.
DR GenomeRNAi; 79661; -.
DR Pharos; Q96FI4; Tbio.
DR PRO; PR:Q96FI4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96FI4; protein.
DR Bgee; ENSG00000140398; Expressed in right uterine tube and 168 other tissues.
DR ExpressionAtlas; Q96FI4; baseline and differential.
DR Genevisible; Q96FI4; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
DR GO; GO:0019104; F:DNA N-glycosylase activity; IBA:GO_Central.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IBA:GO_Central.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB.
DR GO; GO:0006287; P:base-excision repair, gap-filling; TAS:Reactome.
DR GO; GO:0045008; P:depyrimidination; TAS:Reactome.
DR GO; GO:0032074; P:negative regulation of nuclease activity; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR DisProt; DP01480; -.
DR Gene3D; 3.20.190.10; -; 1.
DR InterPro; IPR015886; DNA_glyclase/AP_lyase_DNA-bd.
DR InterPro; IPR015371; Endonuclease-VIII_DNA-bd.
DR InterPro; IPR012319; FPG_cat.
DR InterPro; IPR035937; MutM-like_N-ter.
DR InterPro; IPR010979; Ribosomal_S13-like_H2TH.
DR Pfam; PF01149; Fapy_DNA_glyco; 1.
DR Pfam; PF09292; Neil1-DNA_bind; 1.
DR SMART; SM00898; Fapy_DNA_glyco; 1.
DR SMART; SM01232; H2TH; 1.
DR SUPFAM; SSF46946; SSF46946; 1.
DR SUPFAM; SSF81624; SSF81624; 1.
DR PROSITE; PS51068; FPG_CAT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW DNA-binding; Glycosidase; Hydrolase; Lyase; Multifunctional enzyme;
KW Nucleus; Reference proteome; RNA editing.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..390
FT /note="Endonuclease 8-like 1"
FT /id="PRO_0000170905"
FT REGION 278..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..316
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2
FT /note="Schiff-base intermediate with DNA"
FT /evidence="ECO:0000305"
FT ACT_SITE 3
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 54
FT /note="Proton donor; for beta-elimination activity"
FT /evidence="ECO:0000305"
FT ACT_SITE 339
FT /note="Proton donor; for delta-elimination activity"
FT /evidence="ECO:0000305"
FT BINDING 176
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 339
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT VARIANT 82
FT /note="S -> C (in dbSNP:rs5745905)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020580"
FT VARIANT 83
FT /note="G -> D (in dbSNP:rs5745906)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020581"
FT VARIANT 136
FT /note="C -> R (in dbSNP:rs5745907)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020582"
FT VARIANT 159
FT /note="R -> Q (in dbSNP:rs769880000)"
FT /evidence="ECO:0000269|PubMed:21697813"
FT /id="VAR_065963"
FT VARIANT 181
FT /note="E -> K (found in a patient with nephrotic syndrome
FT also carrying mutation P-159 in MYO1E; dbSNP:rs749636951)"
FT /evidence="ECO:0000269|PubMed:21697813"
FT /id="VAR_065964"
FT VARIANT 182
FT /note="I -> M (in dbSNP:rs7183491)"
FT /id="VAR_020583"
FT VARIANT 242
FT /note="K -> R (in RNA edited version)"
FT /id="VAR_065018"
FT VARIANT 252
FT /note="D -> N (in dbSNP:rs5745926)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_020584"
FT MUTAGEN 2
FT /note="P->T: Loss of glycosylase and AP lyase activity."
FT /evidence="ECO:0000269|PubMed:11904416,
FT ECO:0000269|PubMed:12509226"
FT MUTAGEN 2
FT /note="Missing: Loss of glycosylase activity."
FT /evidence="ECO:0000269|PubMed:11904416,
FT ECO:0000269|PubMed:12509226"
FT MUTAGEN 3
FT /note="E->Q: Loss of glycosylase and AP lyase activity."
FT /evidence="ECO:0000269|PubMed:12509226"
FT MUTAGEN 54
FT /note="K->L: Loss of glycosylase activity."
FT /evidence="ECO:0000269|PubMed:14522990"
FT MUTAGEN 277
FT /note="R->A: Strongly reduced glycosylase activity. Has
FT little effect on AP lyase activity."
FT /evidence="ECO:0000269|PubMed:15232006"
FT CONFLICT 147
FT /note="N -> S (in Ref. 2; BAB15337)"
FT /evidence="ECO:0000305"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 41..52
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:5ITQ"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 83..89
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:5ITQ"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 141..150
FT /evidence="ECO:0007829|PDB:5ITQ"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:5ITQ"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 194..198
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 212..218
FT /evidence="ECO:0007829|PDB:5ITQ"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 225..240
FT /evidence="ECO:0007829|PDB:5ITQ"
FT HELIX 243..245
FT /evidence="ECO:0007829|PDB:5ITU"
FT HELIX 249..259
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:5ITQ"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:5ITQ"
SQ SEQUENCE 390 AA; 43684 MW; B2B058486C4EF835 CRC64;
MPEGPELHLA SQFVNEACRA LVFGGCVEKS SVSRNPEVPF ESSAYRISAS ARGKELRLIL
SPLPGAQPQQ EPLALVFRFG MSGSFQLVPR EELPRHAHLR FYTAPPGPRL ALCFVDIRRF
GRWDLGGKWQ PGRGPCVLQE YQQFRENVLR NLADKAFDRP ICEALLDQRF FNGIGNYLRA
EILYRLKIPP FEKARSVLEA LQQHRPSPEL TLSQKIRTKL QNPDLLELCH SVPKEVVQLG
GKGYGSESGE EDFAAFRAWL RCYGMPGMSS LQDRHGRTIW FQGDPGPLAP KGRKSRKKKS
KATQLSPEDR VEDALPPSKA PSRTRRAKRD LPKRTATQRP EGTSLQQDPE APTVPKKGRR
KGRQAASGHC RPRKVKADIP SLEPEGTSAS
