ID NEIL3_BOVIN Reviewed; 606 AA. AC Q3MHN7; F1N383; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 16-OCT-2013, sequence version 2. DT 24-JAN-2024, entry version 104. DE RecName: Full=Endonuclease 8-like 3; DE EC=3.2.2.-; DE EC=4.2.99.18; DE AltName: Full=DNA glycosylase/AP lyase Neil3; DE AltName: Full=Endonuclease VIII-like 3; DE AltName: Full=Nei-like protein 3; GN Name=NEIL3; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Hereford; RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42; RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D., RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G., RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.; RT "A whole-genome assembly of the domestic cow, Bos taurus."; RL Genome Biol. 10:R42.01-R42.10(2009). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: DNA glycosylase which prefers single-stranded DNA (ssDNA), or CC partially ssDNA structures such as bubble and fork structures, to CC double-stranded DNA (dsDNA) (By similarity). Mediates interstrand CC cross-link repair in response to replication stress: acts by mediating CC DNA glycosylase activity, cleaving one of the two N-glycosyl bonds CC comprising the interstrand cross-link, which avoids the formation of a CC double-strand break but generates an abasic site that is bypassed by CC translesion synthesis polymerases (By similarity). In vitro, displays CC strong glycosylase activity towards the hydantoin lesions CC spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA CC and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and CC 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows CC weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, CC appears to be the primary enzyme involved in removing Sp and Gh from CC ssDNA in neonatal tissues (By similarity). CC {ECO:0000250|UniProtKB:A0A1L8HU22, ECO:0000250|UniProtKB:Q8K203}. 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: Nucleus {ECO:0000250|UniProtKB:Q8TAT5}. CC Chromosome {ECO:0000250|UniProtKB:A0A1L8HU22}. Note=Recruited to CC replication stress sites via interaction with ubiquitinated CMG CC helicase. {ECO:0000250|UniProtKB:A0A1L8HU22}. CC -!- DOMAIN: The N-terminal region (2-283) contains the glycosylase and CC lyase activities. {ECO:0000250}. CC -!- DOMAIN: The RanBP2-type zinc-finger, also named NZF zinc finger, CC recognizes and binds ubiquitinated CMG helicase complex. The GRF-type CC zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the CC lagging strand template. {ECO:0000250|UniProtKB:A0A1L8HU22}. CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000255|PROSITE- CC ProRule:PRU00392}. 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; DAAA02060028; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC105168; AAI05169.1; -; mRNA. DR RefSeq; NP_001029662.1; NM_001034490.2. DR AlphaFoldDB; Q3MHN7; -. DR SMR; Q3MHN7; -. DR STRING; 9913.ENSBTAP00000061910; -. DR PaxDb; 9913-ENSBTAP00000007661; -. DR GeneID; 515343; -. DR KEGG; bta:515343; -. DR CTD; 55247; -. DR eggNOG; ENOG502QWRN; Eukaryota. DR HOGENOM; CLU_482283_0_0_1; -. DR InParanoid; Q3MHN7; -. DR OrthoDB; 38342at2759; -. DR TreeFam; TF331502; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; ISS: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; ISS:UniProtKB. DR GO; GO:0019104; F:DNA N-glycosylase activity; ISS:UniProtKB. DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; ISS:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB. DR GO; GO:1904931; F:MCM complex binding; ISS:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006284; P:base-excision repair; ISS:UniProtKB. DR GO; GO:0036297; P:interstrand cross-link repair; ISS:UniProtKB. DR CDD; cd08969; MeNeil3_N; 1. DR Gene3D; 1.10.8.50; -; 1. DR Gene3D; 3.20.190.10; MutM-like, N-terminal; 1. DR Gene3D; 2.30.30.380; Zn-finger domain of Sec23/24; 1. DR InterPro; IPR015886; DNA_glyclase/AP_lyase_DNA-bd. DR InterPro; IPR015887; DNA_glyclase_Znf_dom_DNA_BS. DR InterPro; IPR012319; FPG_cat. DR InterPro; IPR035937; MutM-like_N-ter. DR InterPro; IPR010979; Ribosomal_uS13-like_H2TH. DR InterPro; IPR000214; Znf_DNA_glyclase/AP_lyase. DR InterPro; IPR010666; Znf_GRF. DR InterPro; IPR001876; Znf_RanBP2. DR InterPro; IPR036443; Znf_RanBP2_sf. DR PANTHER; PTHR22993:SF10; ENDONUCLEASE 8-LIKE 3; 1. DR PANTHER; PTHR22993; FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE; 1. DR Pfam; PF06831; H2TH; 1. DR Pfam; PF06839; zf-GRF; 2. DR Pfam; PF00641; zf-RanBP; 1. DR SMART; SM01232; H2TH; 1. DR SMART; SM00547; ZnF_RBZ; 1. DR SUPFAM; SSF81624; N-terminal domain of MutM-like DNA repair proteins; 1. DR SUPFAM; SSF90209; Ran binding protein zinc finger-like; 1. DR SUPFAM; SSF46946; S13-like H2TH domain; 1. DR PROSITE; PS51068; FPG_CAT; 1. DR PROSITE; PS01242; ZF_FPG_1; 1. DR PROSITE; PS51066; ZF_FPG_2; 1. DR PROSITE; PS51999; ZF_GRF; 2. DR PROSITE; PS01358; ZF_RANBP2_1; 1. DR PROSITE; PS50199; ZF_RANBP2_2; 1. PE 2: Evidence at transcript level; KW Chromosome; DNA damage; DNA repair; DNA-binding; Glycosidase; Hydrolase; KW Lyase; Metal-binding; Multifunctional enzyme; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Zinc; Zinc-finger. FT CHAIN 1..606 FT /note="Endonuclease 8-like 3" FT /id="PRO_0000248634" FT ZN_FING 249..283 FT /note="FPG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00391" FT ZN_FING 319..348 FT /note="RanBP2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT ZN_FING 508..551 FT /note="GRF-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT ZN_FING 555..597 FT /note="GRF-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT REGION 31..51 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 2 FT /note="Schiff-base intermediate with DNA; via amino FT nitrogen" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00392" FT BINDING 194 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /evidence="ECO:0000250" FT BINDING 273 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT /evidence="ECO:0000250" FT BINDING 508 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 511 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 534 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 542 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 555 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 557 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 580 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 588 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT SITE 2 FT /note="Important for monofunctional glycosylase activity" FT /evidence="ECO:0000250" FT SITE 83 FT /note="Required for glycosylase activity" FT /evidence="ECO:0000250" FT MOD_RES 451 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8TAT5" FT CONFLICT 64 FT /note="Q -> H (in Ref. 2; AAI05169)" FT /evidence="ECO:0000305" SQ SEQUENCE 606 AA; 67384 MW; 30EE4917DC869250 CRC64; MVEGPGCTLN GEKIRARVRP GQAVTDVRGR ALQGLGGPGS PPAAPGPMGT SQAAALNNNK NSSQDFLRLF NGHGYSGVET LGKELFMYFG PKALRIHFGM KGSLVINPLE SKNKNGVSPV FEVQLTKDLI CFFDSSVEIR NSTESQQRIR VMEELDVCSP RFSFSRAESE VKKQKGRMLC DVLMDQKVLP GVGNIIKNEA LFDSGFHPSV KVCQLTDEQI HHLVKMIRNF SILFYRCCKV GSALSKHYKV YKRPNCGQCC CKITVCRLGE NNRMTYFCPH CQKENPQHVD IRMLPVRNTT VNWPSSRERH LMDCVAQKSE EQWTCEVCTL INKLSSKTCD ACLTSRPADS VLRNEGNPIV FNNLMKYPCN SFGKSKAKVK INRKTAFGTT TLVLTDFSNK HSALEREESH SHIPDGEFPS PPPNVCGSDT LNTSKERTNC RSQPSDKVNI SPVVCSQYKL FSPAHKKLKT THYSSPDLKS CNPGFSNSEL QSSMTDGPCL LNAGSPRCSK HGRPCALRVV RKSGENKGRH FYACPLAREA QCGFFEWADL SFPFCNHGKR SIMRTVLKIG PNNGKNFFVC PLGKEKQCNF FQWAQNGPGI NIIPGC //