NEIL3_HUMAN
ID NEIL3_HUMAN Reviewed; 605 AA.
AC Q8TAT5; Q2PPJ3; Q8NG51; Q9NV95;
DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Endonuclease 8-like 3;
DE EC=3.2.2.-;
DE EC=4.2.99.18 {ECO:0000269|PubMed:22569481};
DE AltName: Full=DNA glycosylase FPG2;
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 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 VARIANTS LEU-443; HIS-471 AND ARG-520.
RC TISSUE=Skin;
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], AND VARIANTS LEU-443; HIS-471 AND
RP ARG-520.
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-38; ASN-58 INS; MET-76;
RP ARG-117; HIS-172; ARG-286; VAL-346; LEU-443; HIS-471; ARG-520; SER-547 AND
RP ARG-556.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ARG-117; LEU-443;
RP HIS-471 AND ARG-520.
RC TISSUE=B-cell;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12433996; DOI=10.1093/nar/gkf618;
RA Morland I., Rolseth V., Luna L., Rognes T., Bjoeraas M., Seeberg E.;
RT "Human DNA glycosylases of the bacterial Fpg/MutM superfamily: an
RT alternative pathway for the repair of 8-oxoguanine and other oxidation
RT products in DNA.";
RL Nucleic Acids Res. 30:4926-4936(2002).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=16428305; DOI=10.1093/jb/mvi168;
RA Torisu K., Tsuchimoto D., Ohnishi Y., Nakabeppu Y.;
RT "Hematopoietic tissue-specific expression of mouse Neil3 for endonuclease
RT VIII-like protein.";
RL J. Biochem. 138:763-772(2005).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=19426544; DOI=10.1186/1471-2202-10-45;
RA Hildrestrand G.A., Neurauter C.G., Diep D.B., Castellanos C.G., Krauss S.,
RA Bjoras M., Luna L.;
RT "Expression patterns of Neil3 during embryonic brain development and
RT neoplasia.";
RL BMC Neurosci. 10:45-45(2009).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF VAL-2; GLU-3; CYS-276 AND CYS-279.
RX PubMed=19170771; DOI=10.1111/j.1365-2443.2008.01271.x;
RA Takao M., Oohata Y., Kitadokoro K., Kobayashi K., Iwai S., Yasui A.,
RA Yonei S., Zhang Q.M.;
RT "Human Nei-like protein NEIL3 has AP lyase activity specific for single-
RT stranded DNA and confers oxidative stress resistance in Escherichia coli
RT mutant.";
RL Genes Cells 14:261-270(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19121397; DOI=10.1016/j.pep.2008.11.014;
RA Krokeide S.Z., Bolstad N., Laerdahl J.K., Bjoras M., Luna L.;
RT "Expression and purification of NEIL3, a human DNA glycosylase homolog.";
RL Protein Expr. Purif. 65:160-164(2009).
RN [11]
RP CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=22365498; DOI=10.1016/j.dnarep.2012.01.007;
RA Neurauter C.G., Luna L., Bjoras M.;
RT "Release from quiescence stimulates the expression of human NEIL3 under the
RT control of the Ras dependent ERK-MAP kinase pathway.";
RL DNA Repair 11:401-409(2012).
RN [12]
RP FUNCTION AS A GLYCOSYLASE, CATALYTIC ACTIVITY, AND PROBABLE CLEAVAGE OF
RP INITIATOR METHIONINE.
RX PubMed=22569481; DOI=10.1016/j.pep.2012.04.022;
RA Liu M., Bandaru V., Holmes A., Averill A.M., Cannan W., Wallace S.S.;
RT "Expression and purification of active mouse and human NEIL3 proteins.";
RL Protein Expr. Purif. 84:130-139(2012).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, PROBABLE CLEAVAGE OF INITIATOR METHIONINE,
RP AND MUTAGENESIS OF VAL-2 AND LYS-81.
RX PubMed=23755964; DOI=10.1016/j.dnarep.2013.04.026;
RA Krokeide S.Z., Laerdahl J.K., Salah M., Luna L., Cederkvist F.H.,
RA Fleming A.M., Burrows C.J., Dalhus B., Bjoras M.;
RT "Human NEIL3 is mainly a monofunctional DNA glycosylase removing
RT spiroimindiohydantoin and guanidinohydantoin.";
RL DNA Repair 12:1159-1164(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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) (PubMed:12433996, PubMed:19170771,
CC PubMed:22569481, PubMed:23755964). Mediates interstrand cross-link
CC repair in response to replication stress: acts by mediating DNA
CC 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 (PubMed:12433996, PubMed:19170771,
CC PubMed:22569481, PubMed:23755964). No activity on 8-oxoG detected
CC (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964).
CC Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity
CC (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964).
CC In vivo, appears to be the primary enzyme involved in removing Sp and
CC Gh from ssDNA in neonatal tissues (PubMed:12433996, PubMed:19170771,
CC PubMed:22569481, PubMed:23755964). {ECO:0000250|UniProtKB:A0A1L8HU22,
CC ECO:0000269|PubMed:12433996, ECO:0000269|PubMed:19170771,
CC ECO:0000269|PubMed:22569481, ECO:0000269|PubMed:23755964}.
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, ECO:0000269|PubMed:22569481};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12433996}. Chromosome
CC {ECO:0000250|UniProtKB:A0A1L8HU22}. Note=Recruited to replication
CC stress sites via interaction with ubiquitinated CMG helicase.
CC {ECO:0000250|UniProtKB:A0A1L8HU22}.
CC -!- TISSUE SPECIFICITY: Expressed in keratinocytes and embryonic
CC fibroblasts (at protein level). Also detected in thymus, testis and
CC fetal lung primary fibroblasts. {ECO:0000269|PubMed:12433996,
CC ECO:0000269|PubMed:16428305, ECO:0000269|PubMed:19426544,
CC ECO:0000269|PubMed:22365498}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during early S phase of the cell
CC cycle, and sustained through G/M phase. Low expression levels in
CC quiescent cells. {ECO:0000269|PubMed:22365498}.
CC -!- DOMAIN: The N-terminal region (2-281) 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 -!- CAUTION: Was originally thought to be inactive as a glycosylase
CC (PMID:12200441,PMID:19121397), but recent reports (PMID:22569481,
CC PMID:20185759) demonstrate that cleavage of the initiator methionine is
CC essential for catalytic activity. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/neil3/";
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; AB079071; BAC06479.1; -; mRNA.
DR EMBL; AK001720; BAA91860.1; -; mRNA.
DR EMBL; DQ310721; ABC40719.1; -; Genomic_DNA.
DR EMBL; AC027627; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025954; AAH25954.1; -; mRNA.
DR CCDS; CCDS3828.1; -.
DR RefSeq; NP_060718.2; NM_018248.2.
DR PDB; 7JL5; X-ray; 2.60 A; A/B=501-605.
DR PDBsum; 7JL5; -.
DR AlphaFoldDB; Q8TAT5; -.
DR SMR; Q8TAT5; -.
DR BioGRID; 120538; 38.
DR IntAct; Q8TAT5; 19.
DR STRING; 9606.ENSP00000264596; -.
DR iPTMnet; Q8TAT5; -.
DR PhosphoSitePlus; Q8TAT5; -.
DR BioMuta; NEIL3; -.
DR DMDM; 302393810; -.
DR EPD; Q8TAT5; -.
DR jPOST; Q8TAT5; -.
DR MassIVE; Q8TAT5; -.
DR MaxQB; Q8TAT5; -.
DR PaxDb; Q8TAT5; -.
DR PeptideAtlas; Q8TAT5; -.
DR PRIDE; Q8TAT5; -.
DR ProteomicsDB; 73916; -.
DR Antibodypedia; 17262; 188 antibodies from 29 providers.
DR DNASU; 55247; -.
DR Ensembl; ENST00000264596.4; ENSP00000264596.3; ENSG00000109674.4.
DR GeneID; 55247; -.
DR KEGG; hsa:55247; -.
DR MANE-Select; ENST00000264596.4; ENSP00000264596.3; NM_018248.3; NP_060718.3.
DR UCSC; uc003iut.3; human.
DR CTD; 55247; -.
DR DisGeNET; 55247; -.
DR GeneCards; NEIL3; -.
DR HGNC; HGNC:24573; NEIL3.
DR HPA; ENSG00000109674; Group enriched (bone marrow, lymphoid tissue).
DR MIM; 608934; gene.
DR neXtProt; NX_Q8TAT5; -.
DR OpenTargets; ENSG00000109674; -.
DR PharmGKB; PA134889634; -.
DR VEuPathDB; HostDB:ENSG00000109674; -.
DR eggNOG; ENOG502QWRN; Eukaryota.
DR GeneTree; ENSGT00940000153230; -.
DR HOGENOM; CLU_482283_0_0_1; -.
DR InParanoid; Q8TAT5; -.
DR OMA; CSPEFSF; -.
DR OrthoDB; 1467835at2759; -.
DR PhylomeDB; Q8TAT5; -.
DR TreeFam; TF331502; -.
DR PathwayCommons; Q8TAT5; -.
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-110330; Recognition and association of DNA glycosylase with site containing an affected purine.
DR Reactome; R-HSA-110331; Cleavage of the damaged purine.
DR Reactome; R-HSA-9629232; Defective Base Excision Repair Associated with NEIL3.
DR Reactome; R-HSA-9636003; NEIL3-mediated resolution of ICLs.
DR SignaLink; Q8TAT5; -.
DR BioGRID-ORCS; 55247; 7 hits in 1084 CRISPR screens.
DR ChiTaRS; NEIL3; human.
DR GeneWiki; NEIL3_(gene); -.
DR GenomeRNAi; 55247; -.
DR Pharos; Q8TAT5; Tbio.
DR PRO; PR:Q8TAT5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8TAT5; protein.
DR Bgee; ENSG00000109674; Expressed in ventricular zone and 90 other tissues.
DR ExpressionAtlas; Q8TAT5; baseline and differential.
DR Genevisible; Q8TAT5; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA: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; IDA:HGNC.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006284; P:base-excision repair; IDA:HGNC.
DR GO; GO:0006285; P:base-excision repair, AP site formation; TAS:Reactome.
DR GO; GO:0045007; P:depurination; TAS:Reactome.
DR GO; GO:0036297; P:interstrand cross-link repair; ISS:UniProtKB.
DR Gene3D; 3.20.190.10; -; 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_S13-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 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; SSF46946; SSF46946; 1.
DR SUPFAM; SSF81624; SSF81624; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS51068; FPG_CAT; 1.
DR PROSITE; PS01242; ZF_FPG_1; 1.
DR PROSITE; PS51066; ZF_FPG_2; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; DNA damage; DNA repair; DNA-binding; Glycosidase;
KW Hydrolase; Lyase; Metal-binding; Multifunctional enzyme; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT CHAIN 2..605
FT /note="Endonuclease 8-like 3"
FT /id="PRO_0000170910"
FT ZN_FING 247..281
FT /note="FPG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00391"
FT ZN_FING 317..346
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 506..549
FT /note="GRF-type 1"
FT ZN_FING 552..595
FT /note="GRF-type 2"
FT REGION 456..477
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 192
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 271
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT SITE 2
FT /note="Important for monofunctional glycosylase activity"
FT SITE 81
FT /note="Required for glycosylase and lyase activities"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 38
FT /note="R -> C (in dbSNP:rs34007209)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025806"
FT VARIANT 58
FT /note="N -> NN"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025807"
FT VARIANT 76
FT /note="V -> M (in dbSNP:rs34112288)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025808"
FT VARIANT 117
FT /note="P -> R (in dbSNP:rs7689099)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_020590"
FT VARIANT 172
FT /note="Q -> H (in dbSNP:rs17064658)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025809"
FT VARIANT 286
FT /note="H -> R (in dbSNP:rs34193982)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025810"
FT VARIANT 346
FT /note="I -> V (in dbSNP:rs17064676)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025811"
FT VARIANT 443
FT /note="P -> L (in dbSNP:rs13112358)"
FT /evidence="ECO:0000269|PubMed:12200441,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.3"
FT /id="VAR_020591"
FT VARIANT 471
FT /note="Q -> H (in dbSNP:rs13112390)"
FT /evidence="ECO:0000269|PubMed:12200441,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.3"
FT /id="VAR_025812"
FT VARIANT 520
FT /note="G -> R (in dbSNP:rs1876268)"
FT /evidence="ECO:0000269|PubMed:12200441,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|Ref.3"
FT /id="VAR_020592"
FT VARIANT 547
FT /note="A -> S (in dbSNP:rs36005630)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025813"
FT VARIANT 556
FT /note="H -> R (in dbSNP:rs35418725)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025814"
FT MUTAGEN 2
FT /note="V->P: No effect on AP lyase activity. Impairs
FT monofunctional glycosylase activity."
FT /evidence="ECO:0000269|PubMed:19170771,
FT ECO:0000269|PubMed:23755964"
FT MUTAGEN 3
FT /note="E->A: No effect on AP lyase activity."
FT /evidence="ECO:0000269|PubMed:19170771"
FT MUTAGEN 81
FT /note="K->A: Loss of glycosylase and lyase activities."
FT /evidence="ECO:0000269|PubMed:23755964"
FT MUTAGEN 276
FT /note="C->S: Abolishes AP lyase activity."
FT /evidence="ECO:0000269|PubMed:19170771"
FT MUTAGEN 279
FT /note="C->S: Abolishes AP lyase activity."
FT /evidence="ECO:0000269|PubMed:19170771"
FT CONFLICT 35
FT /note="L -> P (in Ref. 2; BAA91860)"
FT /evidence="ECO:0000305"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 515..518
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:7JL5"
FT TURN 524..527
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 529..532
FT /evidence="ECO:0007829|PDB:7JL5"
FT TURN 537..539
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 544..547
FT /evidence="ECO:0007829|PDB:7JL5"
FT HELIX 548..550
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 561..564
FT /evidence="ECO:0007829|PDB:7JL5"
FT TURN 570..573
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 575..578
FT /evidence="ECO:0007829|PDB:7JL5"
FT HELIX 583..585
FT /evidence="ECO:0007829|PDB:7JL5"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:7JL5"
SQ SEQUENCE 605 AA; 67769 MW; 528B17873ABC9D89 CRC64;
MVEGPGCTLN GEKIRARVLP GQAVTGVRGS ALRSLQGRAL RLAASTVVVS PQAAALNNDS
SQNVLSLFNG YVYSGVETLG KELFMYFGPK ALRIHFGMKG FIMINPLEYK YKNGASPVLE
VQLTKDLICF FDSSVELRNS MESQQRIRMM KELDVCSPEF SFLRAESEVK KQKGRMLGDV
LMDQNVLPGV GNIIKNEALF DSGLHPAVKV CQLTDEQIHH LMKMIRDFSI LFYRCRKAGL
ALSKHYKVYK RPNCGQCHCR ITVCRFGDNN RMTYFCPHCQ KENPQHVDIC KLPTRNTIIS
WTSSRVDHVM DSVARKSEEH WTCVVCTLIN KPSSKACDAC LTSRPIDSVL KSEENSTVFS
HLMKYPCNTF GKPHTEVKIN RKTAFGTTTL VLTDFSNKSS TLERKTKQNQ ILDEEFQNSP
PASVCLNDIQ HPSKKTTNDI TQPSSKVNIS PTISSESKLF SPAHKKPKTA QYSSPELKSC
NPGYSNSELQ INMTDGPRTL NPDSPRCSKH NRLCILRVVG KDGENKGRQF YACPLPREAQ
CGFFEWADLS FPFCNHGKRS TMKTVLKIGP NNGKNFFVCP LGKEKQCNFF QWAENGPGIK
IIPGC
