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 27-MAR-2024, entry version 188. 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). RN [14] RP VARIANTS ASP-44 AND THR-156. RX PubMed=23595123; DOI=10.1038/jhg.2013.27; RA Al-Hamed M.H., Al-Sabban E., Al-Mojalli H., Al-Harbi N., Faqeih E., RA Al Shaya H., Alhasan K., Al-Hissi S., Rajab M., Edwards N., Al-Abbad A., RA Al-Hassoun I., Sayer J.A., Meyer B.F.; RT "A molecular genetic analysis of childhood nephrotic syndrome in a cohort RT of Saudi Arabian families."; RL J. Hum. Genet. 58:480-489(2013). CC -!- FUNCTION: Involved in base excision repair of DNA damaged by oxidation CC or by mutagenic agents. Acts as a 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="https://atlasgeneticsoncology.org/gene/41519/NEIL1"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/neil1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7TMX; X-ray; 2.30 A; A/B=359-378. DR PDB; 8FTJ; X-ray; 2.30 A; A=2-290. 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 PDBsum; 7TMX; -. DR PDBsum; 8FTJ; -. DR AlphaFoldDB; Q96FI4; -. DR SASBDB; Q96FI4; -. DR SMR; Q96FI4; -. DR BioGRID; 122787; 299. 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; 9606-ENSP00000347170; -. DR PeptideAtlas; Q96FI4; -. DR ProteomicsDB; 76532; -. DR Antibodypedia; 27258; 354 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 AGR; HGNC:18448; -. DR CTD; 79661; -. DR DisGeNET; 79661; -. DR GeneCards; NEIL1; -. DR HGNC; HGNC:18448; NEIL1. DR HPA; ENSG00000140398; Low tissue specificity. DR MalaCards; NEIL1; -. 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; 3030709at2759; -. 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; 10 hits in 1146 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 170 other cell types or tissues. DR ExpressionAtlas; Q96FI4; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. 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: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: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 CDD; cd08967; MeNeil1_N; 1. DR DisProt; DP01480; -. DR Gene3D; 1.10.8.50; -; 1. DR Gene3D; 3.20.190.10; MutM-like, N-terminal; 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_uS13-like_H2TH. DR PANTHER; PTHR22993:SF9; ENDONUCLEASE 8-LIKE 1; 1. DR PANTHER; PTHR22993; FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE; 1. 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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF81624; N-terminal domain of MutM-like DNA repair proteins; 1. DR SUPFAM; SSF46946; S13-like H2TH domain; 1. DR PROSITE; PS51068; FPG_CAT; 1. DR Genevisible; Q96FI4; HS. 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 44 FT /note="A -> D (found in a patient with childhood-onset FT nephrotic syndrome, focal segmental glomerulosclerosis and FT end-stage renal disease; uncertain significance; FT dbSNP:rs1348165160)" FT /evidence="ECO:0000269|PubMed:23595123" FT /id="VAR_087607" 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 156 FT /note="A -> T (found in a patient with childhood-onset FT steroid-resistant nephrotic syndrome; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:23595123" FT /id="VAR_087608" 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 //