ID NEIL2_HUMAN Reviewed; 332 AA. AC Q969S2; B4DFR7; Q7Z3Q7; Q8N842; Q8NG52; DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 11-NOV-2015, entry version 124. DE RecName: Full=Endonuclease 8-like 2; DE EC=3.2.2.-; DE EC=4.2.99.18; DE AltName: Full=DNA glycosylase/AP lyase Neil2; DE AltName: Full=DNA-(apurinic or apyrimidinic site) lyase Neil2; DE AltName: Full=Endonuclease VIII-like 2; DE AltName: Full=Nei homolog 2; DE Short=NEH2; DE AltName: Full=Nei-like protein 2; GN Name=NEIL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-103. 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] (ISOFORMS 1; 3 AND 4). RC TISSUE=Amygdala, and Testis; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Fetal kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-70; GLN-103; RP TRP-103; LEU-257 AND THR-304. RG NIEHS SNPs program; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 2-10, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=12097317; DOI=10.1074/jbc.C200355200; RA Hazra T.K., Kow Y.W., Hatahet Z., Imhoff B., Boldogh I., RA Mokkapati S.K., Mitra S., Izumi T.; RT "Identification and characterization of a novel human DNA glycosylase RT for repair of cytosine-derived lesions."; RL J. Biol. Chem. 277:30417-30420(2002). RN [8] RP FUNCTION, AND MUTAGENESIS OF LYS-50. 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 [9] RP PROTEIN SEQUENCE OF 40-57 AND 142-161, FUNCTION, MUTAGENESIS OF LYS-50 RP AND LYS-154, INTERACTION WITH EP300, AND ACETYLATION AT LYS-50 AND RP LYS-154. RX PubMed=15175427; DOI=10.1093/nar/gkh632; RA Bhakat K.K., Hazra T.K., Mitra S.; RT "Acetylation of the human DNA glycosylase NEIL2 and inhibition of its RT activity."; RL Nucleic Acids Res. 32:3033-3039(2004). RN [10] RP MUTAGENESIS OF CYS-291; HIS-295; ARG-310; CYS-315 AND CYS-318, RP FUNCTION, IDENTIFICATION OF ZINC-FINGER, ZINC-BINDING, 3D-STRUCTURE RP MODELING OF 192-319, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15339932; DOI=10.1074/jbc.M406224200; RA Das A., Rajagopalan L., Mathura V.S., Rigby S.J., Mitra S., RA Hazra T.K.; RT "Identification of a zinc finger domain in the human NEIL2 (Nei-like- RT 2) protein."; RL J. Biol. Chem. 279:47132-47138(2004). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Involved in base excision repair of DNA damaged by CC oxidation or by mutagenic agents. Has DNA glycosylase activity CC towards 5-hydroxyuracil and other oxidized derivatives of cytosine CC with a preference for mismatched double-stranded DNA (DNA CC bubbles). Has low or no DNA glycosylase activity towards thymine CC glycol, 2-hydroxyadenine, hypoxanthine and 8-oxoguanine. Has AP CC (apurinic/apyrimidinic) lyase activity and introduces nicks in the CC DNA strand. Cleaves the DNA backbone by beta-delta elimination to CC generate a single-strand break at the site of the removed base CC with both 3'- and 5'-phosphates. {ECO:0000269|PubMed:12097317, CC ECO:0000269|PubMed:14522990, ECO:0000269|PubMed:15175427, CC ECO:0000269|PubMed:15339932}. CC -!- CATALYTIC ACTIVITY: Removes damaged bases from DNA, leaving an CC abasic site. CC -!- CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or CC apyrimidinic site in DNA is broken by a beta-elimination reaction, CC leaving a 3'-terminal unsaturated sugar and a product with a CC terminal 5'-phosphate. {ECO:0000255|PROSITE-ProRule:PRU00392}. CC -!- ENZYME REGULATION: Acetylation of Lys-50 leads to loss of DNA CC nicking activity. Acetylation of Lys-154 has no effect. CC -!- SUBUNIT: Binds EP300. CC -!- INTERACTION: CC P50221:MEOX1; NbExp=3; IntAct=EBI-10281234, EBI-2864512; CC Q04864:REL; NbExp=3; IntAct=EBI-10281234, EBI-307352; CC P14373:TRIM27; NbExp=3; IntAct=EBI-10281234, EBI-719493; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12097317}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q969S2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q969S2-2; Sequence=VSP_012209; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q969S2-3; Sequence=VSP_012208; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=Q969S2-4; Sequence=VSP_043343; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Detected in testis, skeletal muscle, heart, CC brain, placenta, lung, pancreas, kidney and liver. CC {ECO:0000269|PubMed:12097317}. CC -!- DOMAIN: The zinc-finger domain is important for DNA binding. CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000255|PROSITE- CC ProRule:PRU00392}. CC -!- SIMILARITY: Contains 1 FPG-type zinc finger. {ECO:0000255|PROSITE- CC ProRule:PRU00391}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/neil2/"; 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; AB079070; BAC06478.1; -; mRNA. DR EMBL; AK056206; BAB71120.1; -; mRNA. DR EMBL; AK097389; BAC05030.1; -; mRNA. DR EMBL; AK294224; BAG57528.1; -; mRNA. DR EMBL; BX537529; CAD97774.1; -; mRNA. DR EMBL; AY306127; AAP45052.1; -; Genomic_DNA. DR EMBL; AC069185; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC013952; AAH13952.1; -; mRNA. DR EMBL; BC013964; AAH13964.1; -; mRNA. DR CCDS; CCDS47802.1; -. [Q969S2-4] DR CCDS; CCDS47803.1; -. [Q969S2-3] DR CCDS; CCDS5984.1; -. [Q969S2-1] DR RefSeq; NP_001129218.1; NM_001135746.1. [Q969S2-1] DR RefSeq; NP_001129219.1; NM_001135747.1. [Q969S2-3] DR RefSeq; NP_001129220.1; NM_001135748.1. [Q969S2-4] DR RefSeq; NP_659480.1; NM_145043.2. [Q969S2-1] DR RefSeq; XP_005272438.1; XM_005272381.1. [Q969S2-1] DR RefSeq; XP_005272439.1; XM_005272382.1. [Q969S2-3] DR RefSeq; XP_005272440.1; XM_005272383.1. [Q969S2-3] DR UniGene; Hs.293818; -. DR PDB; 1VZP; Model; -; A=192-319. DR PDBsum; 1VZP; -. DR ProteinModelPortal; Q969S2; -. DR SMR; Q969S2; 129-319. DR BioGrid; 128946; 6. DR IntAct; Q969S2; 3. DR MINT; MINT-4720021; -. DR STRING; 9606.ENSP00000284503; -. DR PhosphoSite; Q969S2; -. DR BioMuta; NEIL2; -. DR DMDM; 56404653; -. DR MaxQB; Q969S2; -. DR PaxDb; Q969S2; -. DR PRIDE; Q969S2; -. DR DNASU; 252969; -. DR Ensembl; ENST00000284503; ENSP00000284503; ENSG00000154328. [Q969S2-1] DR Ensembl; ENST00000403422; ENSP00000384070; ENSG00000154328. [Q969S2-3] DR Ensembl; ENST00000436750; ENSP00000394023; ENSG00000154328. [Q969S2-1] DR Ensembl; ENST00000455213; ENSP00000397538; ENSG00000154328. [Q969S2-1] DR Ensembl; ENST00000528323; ENSP00000435657; ENSG00000154328. [Q969S2-4] DR GeneID; 252969; -. DR KEGG; hsa:252969; -. DR UCSC; uc003wue.2; human. [Q969S2-1] DR UCSC; uc011kxd.1; human. [Q969S2-4] DR CTD; 252969; -. DR GeneCards; NEIL2; -. DR HGNC; HGNC:18956; NEIL2. DR MIM; 608933; gene. DR neXtProt; NX_Q969S2; -. DR PharmGKB; PA38769; -. DR eggNOG; ENOG410IJ89; Eukaryota. DR eggNOG; ENOG4112BNS; LUCA. DR GeneTree; ENSGT00730000110955; -. DR HOGENOM; HOG000069913; -. DR HOVERGEN; HBG082014; -. DR InParanoid; Q969S2; -. DR KO; K10568; -. DR OMA; SVRKFHH; -. DR OrthoDB; EOG7Z69CR; -. DR PhylomeDB; Q969S2; -. DR TreeFam; TF331502; -. DR BRENDA; 3.2.2.23; 2681. 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 ChiTaRS; NEIL2; human. DR GeneWiki; NEIL2; -. DR GenomeRNAi; 252969; -. DR NextBio; 92030; -. DR PRO; PR:Q969S2; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; Q969S2; -. DR CleanEx; HS_NEIL2; -. DR ExpressionAtlas; Q969S2; baseline and differential. DR Genevisible; Q969S2; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005876; C:spindle microtubule; IEA:Ensembl. DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro. DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) lyase activity; IEA:UniProtKB-EC. DR GO; GO:0016799; F:hydrolase activity, hydrolyzing N-glycosyl compounds; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006284; P:base-excision repair; TAS:Reactome. DR GO; GO:0006285; P:base-excision repair, AP site formation; TAS:Reactome. DR GO; GO:0045008; P:depyrimidination; TAS:Reactome. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0006289; P:nucleotide-excision repair; IEA:InterPro. DR InterPro; IPR015886; DNA_glyclase/AP_lyase_DNA-bd. DR InterPro; IPR012319; FPG_cat. DR InterPro; IPR010979; Ribosomal_S13-like_H2TH. DR InterPro; IPR000214; Znf_DNA_glyclase/AP_lyase. DR Pfam; PF06831; H2TH; 1. DR SUPFAM; SSF46946; SSF46946; 1. DR PROSITE; PS51068; FPG_CAT; 1. DR PROSITE; PS51066; ZF_FPG_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Direct protein sequencing; DNA damage; DNA repair; DNA-binding; KW Glycosidase; Hydrolase; Lyase; Metal-binding; Multifunctional enzyme; KW Nucleus; Polymorphism; Reference proteome; Zinc; Zinc-finger. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:12097317}. FT CHAIN 2 332 Endonuclease 8-like 2. FT /FTId=PRO_0000170908. FT ZN_FING 284 320 FPG-type. {ECO:0000255|PROSITE- FT ProRule:PRU00391}. FT ACT_SITE 2 2 Schiff-base intermediate with DNA. FT {ECO:0000305}. FT ACT_SITE 3 3 Proton donor. {ECO:0000305}. FT ACT_SITE 50 50 Proton donor; for beta-elimination FT activity. {ECO:0000305}. FT ACT_SITE 310 310 Proton donor; for delta-elimination FT activity. {ECO:0000305}. FT BINDING 231 231 DNA. {ECO:0000250}. FT MOD_RES 50 50 N6-acetyllysine. FT {ECO:0000269|PubMed:15175427}. FT MOD_RES 154 154 N6-acetyllysine. FT {ECO:0000269|PubMed:15175427}. FT VAR_SEQ 1 61 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_012208. FT VAR_SEQ 48 163 Missing (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043343. FT VAR_SEQ 79 94 Missing (in isoform 2). FT {ECO:0000303|PubMed:17974005}. FT /FTId=VSP_012209. FT VARIANT 70 70 T -> S (in dbSNP:rs8191611). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020585. FT VARIANT 103 103 R -> Q (in dbSNP:rs8191613). FT {ECO:0000269|PubMed:12200441, FT ECO:0000269|Ref.4}. FT /FTId=VAR_020586. FT VARIANT 103 103 R -> W (in dbSNP:rs8191612). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020587. FT VARIANT 257 257 R -> L (in dbSNP:rs8191664). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020588. FT VARIANT 304 304 P -> T (in dbSNP:rs8191666). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_020589. FT MUTAGEN 50 50 K->R: Loss of glycosylase and AP lyase FT activity. {ECO:0000269|PubMed:14522990, FT ECO:0000269|PubMed:15175427}. FT MUTAGEN 154 154 K->R: No effect on glycosylase and AP FT lyase activity. FT {ECO:0000269|PubMed:15175427}. FT MUTAGEN 291 291 C->S: Loss of glycosylase and AP lyase FT activity. {ECO:0000269|PubMed:15339932}. FT MUTAGEN 295 295 H->A: Loss of glycosylase and AP lyase FT activity. {ECO:0000269|PubMed:15339932}. FT MUTAGEN 310 310 R->Q: Strongly reduces strand AP lyase FT activity. {ECO:0000269|PubMed:15339932}. FT MUTAGEN 315 315 C->S: Loss of glycosylase and AP lyase FT activity. {ECO:0000269|PubMed:15339932}. FT MUTAGEN 318 318 C->S: Loss of glycosylase and AP lyase FT activity. {ECO:0000269|PubMed:15339932}. SQ SEQUENCE 332 AA; 36826 MW; 8A8E76B75ABADE6D CRC64; MPEGPLVRKF HHLVSPFVGQ QVVKTGGSSK KLQPASLQSL WLQDTQVHGK KLFLRFDLDE EMGPPGSSPT PEPPQKEVQK EGAADPKQVG EPSGQKTLDG SSRSAELVPQ GEDDSEYLER DAPAGDAGRW LRVSFGLFGS VWVNDFSRAK KANKRGDWRD PSPRLVLHFG GGGFLAFYNC QLSWSSSPVV TPTCDILSEK FHRGQALEAL GQAQPVCYTL LDQRYFSGLG NIIKNEALYR AGIHPLSLGS VLSASRREVL VDHVVEFSTA WLQGKFQGRP QHTQVYQKEQ CPAGHQVMKE AFGPEDGLQR LTWWCPQCQP QLSEEPEQCQ FS //