NEIL1_MOUSE
ID NEIL1_MOUSE Reviewed; 389 AA.
AC Q8K4Q6; Q80V58; Q9CYT9;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 149.
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=Nei homolog 1;
DE Short=NEH1;
DE AltName: Full=Nei-like protein 1;
GN Name=Neil1; Synonyms=Nei1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP FUNCTION.
RX PubMed=23434322; DOI=10.1016/j.cell.2013.02.004;
RA Spruijt C.G., Gnerlich F., Smits A.H., Pfaffeneder T., Jansen P.W.,
RA Bauer C., Munzel M., Wagner M., Muller M., Khan F., Eberl H.C.,
RA Mensinga A., Brinkman A.B., Lephikov K., Muller U., Walter J., Boelens R.,
RA van Ingen H., Leonhardt H., Carell T., Vermeulen M.;
RT "Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized
RT derivatives.";
RL Cell 152:1146-1159(2013).
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:12200441,
CC ECO:0000269|PubMed:23434322}.
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. Nucleus. Chromosome. Note=During mitosis,
CC associates with centrosomes and condensed chromatin. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K4Q6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K4Q6-2; Sequence=VSP_012207;
CC -!- TISSUE SPECIFICITY: Detected in heart, spleen and lung.
CC {ECO:0000269|PubMed:12200441}.
CC -!- INDUCTION: Up-regulated during S-phase. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000255|PROSITE-
CC ProRule:PRU00392}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB28790.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB079069; BAC06477.1; -; mRNA.
DR EMBL; AK013322; BAB28790.1; ALT_FRAME; mRNA.
DR EMBL; BC043297; AAH43297.1; -; mRNA.
DR CCDS; CCDS23217.1; -. [Q8K4Q6-1]
DR RefSeq; NP_082623.1; NM_028347.2. [Q8K4Q6-1]
DR RefSeq; XP_006511548.1; XM_006511485.3. [Q8K4Q6-1]
DR RefSeq; XP_006511549.1; XM_006511486.2. [Q8K4Q6-1]
DR RefSeq; XP_011241120.1; XM_011242818.2.
DR AlphaFoldDB; Q8K4Q6; -.
DR SMR; Q8K4Q6; -.
DR STRING; 10090.ENSMUSP00000139917; -.
DR PhosphoSitePlus; Q8K4Q6; -.
DR EPD; Q8K4Q6; -.
DR MaxQB; Q8K4Q6; -.
DR PaxDb; Q8K4Q6; -.
DR PeptideAtlas; Q8K4Q6; -.
DR PRIDE; Q8K4Q6; -.
DR ProteomicsDB; 287357; -. [Q8K4Q6-1]
DR ProteomicsDB; 287358; -. [Q8K4Q6-2]
DR Antibodypedia; 27258; 321 antibodies from 33 providers.
DR Ensembl; ENSMUST00000034842; ENSMUSP00000034842; ENSMUSG00000032298. [Q8K4Q6-1]
DR Ensembl; ENSMUST00000186410; ENSMUSP00000141048; ENSMUSG00000032298. [Q8K4Q6-1]
DR Ensembl; ENSMUST00000190245; ENSMUSP00000139917; ENSMUSG00000032298. [Q8K4Q6-1]
DR GeneID; 72774; -.
DR KEGG; mmu:72774; -.
DR UCSC; uc009puh.1; mouse. [Q8K4Q6-1]
DR UCSC; uc009puk.1; mouse. [Q8K4Q6-2]
DR CTD; 79661; -.
DR MGI; MGI:1920024; Neil1.
DR VEuPathDB; HostDB:ENSMUSG00000032298; -.
DR eggNOG; ENOG502QSPK; Eukaryota.
DR GeneTree; ENSGT00940000153230; -.
DR HOGENOM; CLU_051284_0_0_1; -.
DR InParanoid; Q8K4Q6; -.
DR OMA; IMFEYKS; -.
DR OrthoDB; 1467835at2759; -.
DR PhylomeDB; Q8K4Q6; -.
DR TreeFam; TF333272; -.
DR Reactome; R-MMU-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine.
DR Reactome; R-MMU-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-MMU-5649702; APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway.
DR BioGRID-ORCS; 72774; 1 hit in 106 CRISPR screens.
DR ChiTaRS; Neil1; mouse.
DR PRO; PR:Q8K4Q6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8K4Q6; protein.
DR Bgee; ENSMUSG00000032298; Expressed in mesenteric lymph node and 209 other tissues.
DR Genevisible; Q8K4Q6; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
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; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0016829; F:lyase activity; IDA:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006284; P:base-excision repair; ISO:MGI.
DR GO; GO:0006281; P:DNA repair; IDA:MGI.
DR GO; GO:0032074; P:negative regulation of nuclease activity; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
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 2: Evidence at transcript level;
KW Alternative splicing; Chromosome; Cytoplasm; Cytoskeleton; DNA damage;
KW DNA repair; DNA-binding; Glycosidase; Hydrolase; Lyase;
KW Multifunctional enzyme; Nucleus; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..389
FT /note="Endonuclease 8-like 1"
FT /id="PRO_0000170906"
FT REGION 278..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 295..319
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 BINDING 176
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT VAR_SEQ 241..389
FT /note="GKGYGPERGEEDFAAFRAWLRCYGVPGMSSLRDRHGRTIWFQGDPGPLAPKG
FT GRSQKKKSQETQLGAEDRKEDLPLSSKSVSRMRRARKHPPKRIAQQSEGAGLQQNQETP
FT TAPEKGKRRGQRASTGHRRRPKTIPDTRPREAGESSAS -> EAWGGQDGRRPLP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012207"
SQ SEQUENCE 389 AA; 43586 MW; E3F1A21DDE2CB5AD CRC64;
MPEGPELHLA SHFVNETCKG LVFGGCVEKS SVSRNPEVPF ESSAYHISAL ARGKELRLTL
SPLPGSQPPQ KPLSLVFRFG MSGSFQLVPA EALPRHAHLR FYTAPPAPRL ALCFVDIRRF
GHWDPGGEWQ PGRGPCVLLE YERFRENVLR NLSDKAFDRP ICEALLDQRF FNGIGNYLRA
EILYRLKIPP FEKARTVLEA LQQCRPSPEL TLSQKIKAKL QNPDLLELCH LVPKEVVQLG
GKGYGPERGE EDFAAFRAWL RCYGVPGMSS LRDRHGRTIW FQGDPGPLAP KGGRSQKKKS
QETQLGAEDR KEDLPLSSKS VSRMRRARKH PPKRIAQQSE GAGLQQNQET PTAPEKGKRR
GQRASTGHRR RPKTIPDTRP REAGESSAS
