DPOE1_HUMAN
ID DPOE1_HUMAN Reviewed; 2286 AA.
AC Q07864; Q13533; Q86VH9;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 5.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=DNA polymerase epsilon catalytic subunit A;
DE EC=2.7.7.7 {ECO:0000250|UniProtKB:P21951};
DE AltName: Full=3'-5' exodeoxyribonuclease {ECO:0000305};
DE EC=3.1.11.- {ECO:0000250|UniProtKB:P21951};
DE AltName: Full=DNA polymerase II subunit A;
GN Name=POLE; Synonyms=POLE1;
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 PROTEIN SEQUENCE OF 48-51; 876-886 AND
RP 1338-1344.
RC TISSUE=T-cell;
RX PubMed=8486689; DOI=10.1016/s0021-9258(18)82195-0;
RA Kesti T., Frantti H., Syvaeoja J.E.;
RT "Molecular cloning of the cDNA for the catalytic subunit of human DNA
RT polymerase epsilon.";
RL J. Biol. Chem. 268:10238-10245(1993).
RN [2]
RP SEQUENCE REVISION.
RA Syvaeoja J.E.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Asahara H., Goldsmith J.S., Lee E., Linn S.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-2286.
RG NIEHS SNPs program;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND IDENTIFICATION IN EPSILON DNA POLYMERASE COMPLEX.
RC TISSUE=Cervix carcinoma;
RX PubMed=10801849; DOI=10.1074/jbc.m002548200;
RA Li Y., Pursell Z.F., Linn S.;
RT "Identification and cloning of two histone fold motif-containing subunits
RT of HeLa DNA polymerase epsilon.";
RL J. Biol. Chem. 275:23247-23252(2000).
RN [6]
RP INTERACTION WITH TOPBP1.
RX PubMed=11395493; DOI=10.1074/jbc.m102245200;
RA Maekiniemi M., Hillukkala T., Tuusa J., Reini K., Vaara M., Huang D.,
RA Pospiech H., Majuri I., Westerling T., Maekelae T.P., Syvaeoja J.E.;
RT "BRCT domain-containing protein TopBP1 functions in DNA replication and
RT damage response.";
RL J. Biol. Chem. 276:30399-30406(2001).
RN [7]
RP INTERACTION WITH RAD17.
RX PubMed=14500819; DOI=10.1093/nar/gkg765;
RA Post S.M., Tomkinson A.E., Lee E.Y.-H.P.;
RT "The human checkpoint Rad protein Rad17 is chromatin-associated throughout
RT the cell cycle, localizes to DNA replication sites, and interacts with DNA
RT polymerase epsilon.";
RL Nucleic Acids Res. 31:5568-5575(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1940, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [9]
RP FUNCTION.
RX PubMed=20227374; DOI=10.1016/j.molcel.2010.02.009;
RA Ogi T., Limsirichaikul S., Overmeer R.M., Volker M., Takenaka K.,
RA Cloney R., Nakazawa Y., Niimi A., Miki Y., Jaspers N.G., Mullenders L.H.,
RA Yamashita S., Fousteri M.I., Lehmann A.R.;
RT "Three DNA polymerases, recruited by different mechanisms, carry out NER
RT repair synthesis in human cells.";
RL Mol. Cell 37:714-727(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1184, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP INVOLVEMENT IN FILS.
RX PubMed=23230001; DOI=10.1084/jem.20121303;
RA Pachlopnik Schmid J., Lemoine R., Nehme N., Cormier-Daire V., Revy P.,
RA Debeurme F., Debre M., Nitschke P., Bole-Feysot C., Legeai-Mallet L.,
RA Lim A., de Villartay J.P., Picard C., Durandy A., Fischer A.,
RA de Saint Basile G.;
RT "Polymerase epsilon1 mutation in a human syndrome with facial dysmorphism,
RT immunodeficiency, livedo, and short stature (FILS syndrome).";
RL J. Exp. Med. 209:2323-2330(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1297 AND SER-1317, AND
RP IDENTIFICATION BY 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).
RN [14]
RP VARIANTS CRCS12 LEU-411 AND VAL-424, AND VARIANTS THR-189; HIS-231;
RP HIS-286; SER-367; ARG-436; PHE-459; TRP-762; ASN-777; ASN-1008; VAL-1255;
RP MET-1368; SER-1421; ASN-1752; ASN-2013; THR-2056 AND VAL-2213.
RX PubMed=23263490; DOI=10.1038/ng.2503;
RG CORGI Consortium;
RG WGS500 Consortium;
RA Palles C., Cazier J.B., Howarth K.M., Domingo E., Jones A.M., Broderick P.,
RA Kemp Z., Spain S.L., Guarino Almeida E., Salguero I., Sherborne A.,
RA Chubb D., Carvajal-Carmona L.G., Ma Y., Kaur K., Dobbins S., Barclay E.,
RA Gorman M., Martin L., Kovac M.B., Humphray S., Lucassen A., Holmes C.C.,
RA Bentley D., Donnelly P., Taylor J., Petridis C., Roylance R., Sawyer E.J.,
RA Kerr D.J., Clark S., Grimes J., Kearsey S.E., Thomas H.J., McVean G.,
RA Houlston R.S., Tomlinson I.;
RT "Germline mutations affecting the proofreading domains of POLE and POLD1
RT predispose to colorectal adenomas and carcinomas.";
RL Nat. Genet. 45:136-144(2013).
RN [15]
RP VARIANT CRCS12 VAL-424.
RX PubMed=24501277; DOI=10.1093/hmg/ddu058;
RA Valle L., Hernandez-Illan E., Bellido F., Aiza G., Castillejo A.,
RA Castillejo M.I., Navarro M., Segui N., Vargas G., Guarinos C., Juarez M.,
RA Sanjuan X., Iglesias S., Alenda C., Egoavil C., Segura A., Juan M.J.,
RA Rodriguez-Soler M., Brunet J., Gonzalez S., Jover R., Lazaro C.,
RA Capella G., Pineda M., Soto J.L., Blanco I.;
RT "New insights into POLE and POLD1 germline mutations in familial colorectal
RT cancer and polyposis.";
RL Hum. Mol. Genet. 23:3506-3512(2014).
RN [16]
RP VARIANT CRCS12 PHE-458.
RX PubMed=25860647; DOI=10.1007/s10689-015-9803-2;
RA Hansen M.F., Johansen J., Bjoernevoll I., Sylvander A.E., Steinsbekk K.S.,
RA Saetrom P., Sandvik A.K., Drabloes F., Sjursen W.;
RT "A novel POLE mutation associated with cancers of colon, pancreas, ovaries
RT and small intestine.";
RL Fam. Cancer 14:437-448(2015).
RN [17]
RP FUNCTION, AND VARIANT CRCS12 LEU-411.
RX PubMed=27573199; DOI=10.1007/s10689-016-9925-1;
RA Wimmer K., Beilken A., Nustede R., Ripperger T., Lamottke B., Ure B.,
RA Steinmann D., Reineke-Plaass T., Lehmann U., Zschocke J., Valle L.,
RA Fauth C., Kratz C.P.;
RT "A novel germline POLE mutation causes an early onset cancer prone syndrome
RT mimicking constitutional mismatch repair deficiency.";
RL Fam. Cancer 16:67-71(2017).
RN [18]
RP VARIANTS ARG-286; CYS-1382 AND THR-1925.
RX PubMed=27612425; DOI=10.18632/oncotarget.11862;
RA Ahn S.M., Ansari A.A., Kim J., Kim D., Chun S.M., Kim J., Kim T.W.,
RA Park I., Yu C.S., Jang S.J.;
RT "The somatic POLE P286R mutation defines a unique subclass of colorectal
RT cancer featuring hypermutation, representing a potential genomic biomarker
RT for immunotherapy.";
RL Oncotarget 7:68638-68649(2016).
RN [19]
RP VARIANTS IMAGEI 683-TYR--HIS-2286 DEL; PRO-1007 AND 1980-TRP--HIS-2286 DEL,
RP AND INVOLVEMENT IN IMAGEI.
RX PubMed=30503519; DOI=10.1016/j.ajhg.2018.10.024;
RG SGP Consortium;
RA Logan C.V., Murray J.E., Parry D.A., Robertson A., Bellelli R.,
RA Tarnauskaite Z., Challis R., Cleal L., Borel V., Fluteau A.,
RA Santoyo-Lopez J., Aitman T., Barroso I., Basel D., Bicknell L.S., Goel H.,
RA Hu H., Huff C., Hutchison M., Joyce C., Knox R., Lacroix A.E., Langlois S.,
RA McCandless S., McCarrier J., Metcalfe K.A., Morrissey R., Murphy N.,
RA Netchine I., O'Connell S.M., Olney A.H., Paria N., Rosenfeld J.A.,
RA Sherlock M., Syverson E., White P.C., Wise C., Yu Y., Zacharin M.,
RA Banerjee I., Reijns M., Bober M.B., Semple R.K., Boulton S.J., Rios J.J.,
RA Jackson A.P.;
RT "DNA polymerase epsilon deficiency causes IMAGe syndrome with variable
RT immunodeficiency.";
RL Am. J. Hum. Genet. 103:1038-1044(2018).
CC -!- FUNCTION: Catalytic component of the DNA polymerase epsilon complex
CC (PubMed:10801849). Participates in chromosomal DNA replication (By
CC similarity). Required during synthesis of the leading DNA strands at
CC the replication fork, binds at/or near replication origins and moves
CC along DNA with the replication fork (By similarity). Has 3'-5'
CC proofreading exonuclease activity that corrects errors arising during
CC DNA replication (By similarity). Involved in DNA synthesis during DNA
CC repair (PubMed:20227374, PubMed:27573199). Along with DNA polymerase
CC POLD1 and DNA polymerase POLK, has a role in excision repair (NER)
CC synthesis following UV irradiation (PubMed:20227374).
CC {ECO:0000250|UniProtKB:P21951, ECO:0000269|PubMed:10801849,
CC ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:27573199}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.7;
CC Evidence={ECO:0000250|UniProtKB:P21951};
CC -!- SUBUNIT: Component of the DNA polymerase epsilon complex consisting of
CC four subunits: the catalytic subunit POLE and the accessory subunits
CC POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1.
CC {ECO:0000269|PubMed:10801849, ECO:0000269|PubMed:11395493,
CC ECO:0000269|PubMed:14500819}.
CC -!- INTERACTION:
CC Q07864; O95870: ABHD16A; NbExp=3; IntAct=EBI-348526, EBI-348517;
CC Q07864; P56282: POLE2; NbExp=8; IntAct=EBI-348526, EBI-713847;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- DOMAIN: The DNA polymerase activity domain resides in the N-terminal
CC half of the protein, while the C-terminus is necessary for maintenance
CC of the complex. {ECO:0000250|UniProtKB:P21951}.
CC -!- DOMAIN: The CysA-type zinc finger is required for PCNA-binding.
CC {ECO:0000250|UniProtKB:P15436}.
CC -!- DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for the
CC formation of polymerase complexes. {ECO:0000250|UniProtKB:P15436}.
CC -!- DISEASE: Colorectal cancer 12 (CRCS12) [MIM:615083]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. CRCS12 is characterized by a high-penetrance
CC predisposition to the development of colorectal adenomas and
CC carcinomas, with a variable tendency to develop multiple and large
CC tumors. Onset is usually before age 40 years. The histologic features
CC of the tumors are unremarkable. {ECO:0000269|PubMed:23263490,
CC ECO:0000269|PubMed:24501277, ECO:0000269|PubMed:25860647,
CC ECO:0000269|PubMed:27573199}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Facial dysmorphism, immunodeficiency, livedo, and short
CC stature (FILS) [MIM:615139]: A syndrome characterized by mild facial
CC dysmorphism, mainly malar hypoplasia, livedo on the skin since birth,
CC and immunodeficiency resulting in recurrent infections. Growth
CC impairment is observed during early childhood and results in variable
CC short stature in adulthood. {ECO:0000269|PubMed:23230001}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Intrauterine growth retardation, metaphyseal dysplasia,
CC adrenal hypoplasia congenita, genital anomalies, and immunodeficiency
CC (IMAGEI) [MIM:618336]: An autosomal recessive disorder characterized by
CC intrauterine growth retardation, postnatal growth failure, metaphyseal
CC dysplasia, adrenal hypoplasia congenita, growth hormone deficiency,
CC genital anomalies, and immunodeficiency resulting in increased
CC infections. {ECO:0000269|PubMed:30503519}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-B family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA15448.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA15448.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pole/";
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DR EMBL; S60080; AAA15448.1; ALT_SEQ; mRNA.
DR EMBL; L09561; AAC19148.1; -; mRNA.
DR EMBL; U49356; AAA90924.1; -; mRNA.
DR EMBL; AY273166; AAP12650.1; -; Genomic_DNA.
DR CCDS; CCDS9278.1; -.
DR PIR; G02434; G02434.
DR RefSeq; NP_006222.2; NM_006231.3.
DR PDB; 5VBN; X-ray; 2.35 A; B/F=2142-2286.
DR PDB; 7PFO; EM; 3.20 A; B=1-2286.
DR PDB; 7PLO; EM; 2.80 A; B=1-2286.
DR PDBsum; 5VBN; -.
DR PDBsum; 7PFO; -.
DR PDBsum; 7PLO; -.
DR AlphaFoldDB; Q07864; -.
DR SMR; Q07864; -.
DR BioGRID; 111422; 128.
DR ComplexPortal; CPX-2108; DNA polymerase epsilon complex.
DR CORUM; Q07864; -.
DR DIP; DIP-24243N; -.
DR IntAct; Q07864; 33.
DR MINT; Q07864; -.
DR STRING; 9606.ENSP00000322570; -.
DR ChEMBL; CHEMBL2363042; -.
DR DrugBank; DB00242; Cladribine.
DR DrugCentral; Q07864; -.
DR iPTMnet; Q07864; -.
DR MetOSite; Q07864; -.
DR PhosphoSitePlus; Q07864; -.
DR BioMuta; POLE; -.
DR DMDM; 116241339; -.
DR EPD; Q07864; -.
DR jPOST; Q07864; -.
DR MassIVE; Q07864; -.
DR MaxQB; Q07864; -.
DR PaxDb; Q07864; -.
DR PeptideAtlas; Q07864; -.
DR PRIDE; Q07864; -.
DR ProteomicsDB; 58543; -.
DR Antibodypedia; 32096; 186 antibodies from 23 providers.
DR DNASU; 5426; -.
DR Ensembl; ENST00000320574.10; ENSP00000322570.5; ENSG00000177084.18.
DR GeneID; 5426; -.
DR KEGG; hsa:5426; -.
DR MANE-Select; ENST00000320574.10; ENSP00000322570.5; NM_006231.4; NP_006222.2.
DR UCSC; uc001uks.3; human.
DR CTD; 5426; -.
DR DisGeNET; 5426; -.
DR GeneCards; POLE; -.
DR HGNC; HGNC:9177; POLE.
DR HPA; ENSG00000177084; Low tissue specificity.
DR MalaCards; POLE; -.
DR MIM; 174762; gene.
DR MIM; 615083; phenotype.
DR MIM; 615139; phenotype.
DR MIM; 618336; phenotype.
DR neXtProt; NX_Q07864; -.
DR OpenTargets; ENSG00000177084; -.
DR Orphanet; 352712; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome.
DR Orphanet; 85173; IMAGe syndrome.
DR Orphanet; 447877; Polymerase proofreading-related adenomatous polyposis.
DR PharmGKB; PA277; -.
DR VEuPathDB; HostDB:ENSG00000177084; -.
DR eggNOG; KOG1798; Eukaryota.
DR GeneTree; ENSGT00390000010194; -.
DR HOGENOM; CLU_000556_0_0_1; -.
DR InParanoid; Q07864; -.
DR OMA; MLDQCRY; -.
DR OrthoDB; 39650at2759; -.
DR PhylomeDB; Q07864; -.
DR TreeFam; TF105017; -.
DR BRENDA; 2.7.7.7; 2681.
DR PathwayCommons; Q07864; -.
DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR Reactome; R-HSA-5696400; Dual Incision in GG-NER.
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-68952; DNA replication initiation.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR SignaLink; Q07864; -.
DR SIGNOR; Q07864; -.
DR BioGRID-ORCS; 5426; 759 hits in 1091 CRISPR screens.
DR ChiTaRS; POLE; human.
DR GeneWiki; POLE_(enzyme); -.
DR GenomeRNAi; 5426; -.
DR Pharos; Q07864; Tclin.
DR PRO; PR:Q07864; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q07864; protein.
DR Bgee; ENSG00000177084; Expressed in right hemisphere of cerebellum and 147 other tissues.
DR ExpressionAtlas; Q07864; baseline and differential.
DR Genevisible; Q07864; HS.
DR GO; GO:0008622; C:epsilon DNA polymerase complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IMP:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0008310; F:single-stranded DNA 3'-5' exodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006287; P:base-excision repair, gap-filling; IDA:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB.
DR GO; GO:0045004; P:DNA replication proofreading; IBA:GO_Central.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IMP:UniProtKB.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:ComplexPortal.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0006272; P:leading strand elongation; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IMP:UniProtKB.
DR Gene3D; 1.10.132.60; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR Gene3D; 3.90.1600.10; -; 1.
DR InterPro; IPR006172; DNA-dir_DNA_pol_B.
DR InterPro; IPR006133; DNA-dir_DNA_pol_B_exonuc.
DR InterPro; IPR006134; DNA-dir_DNA_pol_B_multi_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR042087; DNA_pol_B_thumb.
DR InterPro; IPR013697; DNA_pol_e_suA_C.
DR InterPro; IPR023211; DNA_pol_palm_dom_sf.
DR InterPro; IPR029703; POL2.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR PANTHER; PTHR10670; PTHR10670; 1.
DR Pfam; PF00136; DNA_pol_B; 1.
DR Pfam; PF03104; DNA_pol_B_exo1; 1.
DR Pfam; PF08490; DUF1744; 1.
DR SMART; SM01159; DUF1744; 1.
DR SMART; SM00486; POLBc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Direct protein sequencing; Disease variant;
KW DNA damage; DNA repair; DNA replication; DNA-binding;
KW DNA-directed DNA polymerase; Hydrolase; Iron; Iron-sulfur; Metal-binding;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..2286
FT /note="DNA polymerase epsilon catalytic subunit A"
FT /id="PRO_0000046455"
FT ZN_FING 2158..2190
FT /note="CysA-type"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1939..1969
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 2221..2238
FT /note="CysB motif"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT COMPBIAS 1948..1969
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 2158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2161
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2190
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2221
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2224
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2236
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2238
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT MOD_RES 1184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1297
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1940
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VARIANT 31
FT /note="A -> S (in dbSNP:rs34047482)"
FT /id="VAR_061138"
FT VARIANT 99
FT /note="P -> L (in dbSNP:rs5744739)"
FT /id="VAR_028429"
FT VARIANT 189
FT /note="A -> T (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069339"
FT VARIANT 231
FT /note="R -> H (found in a colorectal sample; somatic
FT mutation; dbSNP:rs1060500835)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069340"
FT VARIANT 252
FT /note="A -> V (in dbSNP:rs5744751)"
FT /id="VAR_020276"
FT VARIANT 260
FT /note="R -> Q (in dbSNP:rs5744752)"
FT /id="VAR_028430"
FT VARIANT 286
FT /note="P -> H (found in a colorectal sample; somatic
FT mutation; dbSNP:rs1057519943)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069341"
FT VARIANT 286
FT /note="P -> R (found in a colorectal sample; somatic
FT mutation; dbSNP:rs1057519943)"
FT /evidence="ECO:0000269|PubMed:27612425"
FT /id="VAR_077349"
FT VARIANT 336
FT /note="N -> S (in dbSNP:rs5744760)"
FT /id="VAR_020277"
FT VARIANT 367
FT /note="F -> S (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069342"
FT VARIANT 411
FT /note="V -> L (in CRCS12; associated with disease
FT susceptibility; dbSNP:rs1057519945)"
FT /evidence="ECO:0000269|PubMed:23263490,
FT ECO:0000269|PubMed:27573199"
FT /id="VAR_069343"
FT VARIANT 424
FT /note="L -> V (in CRCS12; associated with disease
FT susceptibility; dbSNP:rs483352909)"
FT /evidence="ECO:0000269|PubMed:23263490,
FT ECO:0000269|PubMed:24501277"
FT /id="VAR_069344"
FT VARIANT 436
FT /note="P -> R (found in a colorectal sample; somatic
FT mutation; dbSNP:rs864622766)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069345"
FT VARIANT 458
FT /note="Y -> F (in CRCS12)"
FT /evidence="ECO:0000269|PubMed:25860647"
FT /id="VAR_077350"
FT VARIANT 459
FT /note="S -> F (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069346"
FT VARIANT 683..2286
FT /note="Missing (in IMAGEI)"
FT /evidence="ECO:0000269|PubMed:30503519"
FT /id="VAR_081996"
FT VARIANT 695
FT /note="F -> I (in dbSNP:rs5744799)"
FT /id="VAR_020278"
FT VARIANT 762
FT /note="R -> W (found in a colorectal sample; somatic
FT mutation; dbSNP:rs1064794759)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069347"
FT VARIANT 777
FT /note="K -> N (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069348"
FT VARIANT 1007
FT /note="A -> P (in IMAGEI; unknown pathological
FT significance; dbSNP:rs747692201)"
FT /evidence="ECO:0000269|PubMed:30503519"
FT /id="VAR_081997"
FT VARIANT 1008
FT /note="K -> N (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069349"
FT VARIANT 1255
FT /note="L -> V (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069350"
FT VARIANT 1368
FT /note="V -> M (found in a colorectal sample; somatic
FT mutation; dbSNP:rs770558983)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069351"
FT VARIANT 1382
FT /note="R -> C (found in a colorectal sample; somatic
FT mutation; dbSNP:rs5744904)"
FT /evidence="ECO:0000269|PubMed:27612425"
FT /id="VAR_028431"
FT VARIANT 1395
FT /note="Y -> C (in dbSNP:rs5744933)"
FT /id="VAR_020279"
FT VARIANT 1396
FT /note="N -> S (in dbSNP:rs5744934)"
FT /id="VAR_020280"
FT VARIANT 1399
FT /note="E -> Q (in dbSNP:rs5744935)"
FT /id="VAR_020281"
FT VARIANT 1421
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069352"
FT VARIANT 1577
FT /note="E -> A (in dbSNP:rs5744948)"
FT /id="VAR_028432"
FT VARIANT 1712
FT /note="A -> V (in dbSNP:rs5744950)"
FT /id="VAR_028433"
FT VARIANT 1752
FT /note="D -> N (found in a colorectal sample; somatic
FT mutation; dbSNP:rs1335665224)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069353"
FT VARIANT 1857
FT /note="K -> R (in dbSNP:rs5744971)"
FT /id="VAR_028434"
FT VARIANT 1925
FT /note="I -> T (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:27612425"
FT /id="VAR_077351"
FT VARIANT 1935
FT /note="C -> Y (in dbSNP:rs5744991)"
FT /id="VAR_028435"
FT VARIANT 1980..2286
FT /note="Missing (in IMAGEI)"
FT /evidence="ECO:0000269|PubMed:30503519"
FT /id="VAR_081998"
FT VARIANT 2013
FT /note="D -> N"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069354"
FT VARIANT 2040
FT /note="A -> V (in dbSNP:rs5745021)"
FT /id="VAR_020282"
FT VARIANT 2056
FT /note="A -> T (found in a colorectal sample; somatic
FT mutation; dbSNP:rs58916399)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069355"
FT VARIANT 2140
FT /note="E -> K (in dbSNP:rs5745066)"
FT /id="VAR_048881"
FT VARIANT 2159
FT /note="R -> C (in dbSNP:rs5745067)"
FT /id="VAR_048882"
FT VARIANT 2165
FT /note="R -> H (in dbSNP:rs5745068)"
FT /id="VAR_020283"
FT VARIANT 2213
FT /note="A -> V (found in a colorectal sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:23263490"
FT /id="VAR_069356"
FT CONFLICT 2237
FT /note="S -> T (in Ref. 1; AAA15448/AAC19148)"
FT /evidence="ECO:0000305"
FT STRAND 2152..2157
FT /evidence="ECO:0007829|PDB:5VBN"
FT TURN 2159..2161
FT /evidence="ECO:0007829|PDB:5VBN"
FT STRAND 2164..2168
FT /evidence="ECO:0007829|PDB:5VBN"
FT TURN 2169..2171
FT /evidence="ECO:0007829|PDB:5VBN"
FT STRAND 2188..2190
FT /evidence="ECO:0007829|PDB:5VBN"
FT HELIX 2196..2216
FT /evidence="ECO:0007829|PDB:5VBN"
FT STRAND 2219..2224
FT /evidence="ECO:0007829|PDB:5VBN"
FT STRAND 2230..2232
FT /evidence="ECO:0007829|PDB:5VBN"
FT STRAND 2237..2239
FT /evidence="ECO:0007829|PDB:5VBN"
FT STRAND 2241..2246
FT /evidence="ECO:0007829|PDB:5VBN"
FT HELIX 2248..2265
FT /evidence="ECO:0007829|PDB:5VBN"
FT HELIX 2268..2279
FT /evidence="ECO:0007829|PDB:5VBN"
SQ SEQUENCE 2286 AA; 261518 MW; A213AE1EA8437DEC CRC64;
MSLRSGGRRR ADPGADGEAS RDDGATSSVS ALKRLERSQW TDKMDLRFGF ERLKEPGEKT
GWLINMHPTE ILDEDKRLGS AVDYYFIQDD GSRFKVALPY KPYFYIATRK GCEREVSSFL
SKKFQGKIAK VETVPKEDLD LPNHLVGLKR NYIRLSFHTV EDLVKVRKEI SPAVKKNREQ
DHASDAYTAL LSSVLQRGGV ITDEEETSKK IADQLDNIVD MREYDVPYHI RLSIDLKIHV
AHWYNVRYRG NAFPVEITRR DDLVERPDPV VLAFDIETTK LPLKFPDAET DQIMMISYMI
DGQGYLITNR EIVSEDIEDF EFTPKPEYEG PFCVFNEPDE AHLIQRWFEH VQETKPTIMV
TYNGDFFDWP FVEARAAVHG LSMQQEIGFQ KDSQGEYKAP QCIHMDCLRW VKRDSYLPVG
SHNLKAAAKA KLGYDPVELD PEDMCRMATE QPQTLATYSV SDAVATYYLY MKYVHPFIFA
LCTIIPMEPD EVLRKGSGTL CEALLMVQAF HANIIFPNKQ EQEFNKLTDD GHVLDSETYV
GGHVEALESG VFRSDIPCRF RMNPAAFDFL LQRVEKTLRH ALEEEEKVPV EQVTNFEEVC
DEIKSKLASL KDVPSRIECP LIYHLDVGAM YPNIILTNRL QPSAMVDEAT CAACDFNKPG
ANCQRKMAWQ WRGEFMPASR SEYHRIQHQL ESEKFPPLFP EGPARAFHEL SREEQAKYEK
RRLADYCRKA YKKIHITKVE ERLTTICQRE NSFYVDTVRA FRDRRYEFKG LHKVWKKKLS
AAVEVGDAAE VKRCKNMEVL YDSLQLAHKC ILNSFYGYVM RKGARWYSME MAGIVCFTGA
NIITQARELI EQIGRPLELD TDGIWCVLPN SFPENFVFKT TNVKKPKVTI SYPGAMLNIM
VKEGFTNDQY QELAEPSSLT YVTRSENSIF FEVDGPYLAM ILPASKEEGK KLKKRYAVFN
EDGSLAELKG FEVKRRGELQ LIKIFQSSVF EAFLKGSTLE EVYGSVAKVA DYWLDVLYSK
AANMPDSELF ELISENRSMS RKLEDYGEQK STSISTAKRL AEFLGDQMVK DAGLSCRYII
SRKPEGSPVT ERAIPLAIFQ AEPTVRKHFL RKWLKSSSLQ DFDIRAILDW DYYIERLGSA
IQKIITIPAA LQQVKNPVPR VKHPDWLHKK LLEKNDVYKQ KKISELFTLE GRRQVTMAEA
SEDSPRPSAP DMEDFGLVKL PHPAAPVTVK RKRVLWESQE ESQDLTPTVP WQEILGQPPA
LGTSQEEWLV WLRFHKKKWQ LQARQRLARR KRQRLESAEG VLRPGAIRDG PATGLGSFLR
RTARSILDLP WQIVQISETS QAGLFRLWAL VGSDLHCIRL SIPRVFYVNQ RVAKAEEGAS
YRKVNRVLPR SNMVYNLYEY SVPEDMYQEH INEINAELSA PDIEGVYETQ VPLLFRALVH
LGCVCVVNKQ LVRHLSGWEA ETFALEHLEM RSLAQFSYLE PGSIRHIYLY HHAQAHKALF
GIFIPSQRRA SVFVLDTVRS NQMPSLGALY SAEHGLLLEK VGPELLPPPK HTFEVRAETD
LKTICRAIQR FLLAYKEERR GPTLIAVQSS WELKRLASEI PVLEEFPLVP ICVADKINYG
VLDWQRHGAR RMIRHYLNLD TCLSQAFEMS RYFHIPIGNL PEDISTFGSD LFFARHLQRH
NHLLWLSPTA RPDLGGKEAD DNCLVMEFDD QATVEINSSG CYSTVCVELD LQNLAVNTIL
QSHHVNDMEG ADSMGISFDV IQQASLEDMI TGGQAASAPA SYDETALCSN TFRILKSMVV
GWVKEITQYH NIYADNQVMH FYRWLRSPSS LLHDPALHRT LHNMMKKLFL QLIAEFKRLG
SSVIYANFNR IILCTKKRRV EDAIAYVEYI TSSIHSKETF HSLTISFSRC WEFLLWMDPS
NYGGIKGKVS SRIHCGLQDS QKAGGAEDEQ ENEDDEEERD GEEEEEAEES NVEDLLENNW
NILQFLPQAA SCQNYFLMIV SAYIVAVYHC MKDGLRRSAP GSTPVRRRGA SQLSQEAEGA
VGALPGMITF SQDYVANELT QSFFTITQKI QKKVTGSRNS TELSEMFPVL PGSHLLLNNP
ALEFIKYVCK VLSLDTNITN QVNKLNRDLL RLVDVGEFSE EAQFRDPCRS YVLPEVICRS
CNFCRDLDLC KDSSFSEDGA VLPQWLCSNC QAPYDSSAIE MTLVEVLQKK LMAFTLQDLV
CLKCRGVKET SMPVYCSCAG DFALTIHTQV FMEQIGIFRN IAQHYGMSYL LETLEWLLQK
NPQLGH
