DPOE1_MOUSE
ID DPOE1_MOUSE Reviewed; 2283 AA.
AC Q9WVF7; E9QKW1; Q9QX50;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 162.
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 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 [GENOMIC DNA / MRNA].
RX PubMed=10366722; DOI=10.1016/s0167-4781(99)00058-5;
RA Huang D., Knuuti R., Palosaari H., Pospiech H., Syvaoja J.E.;
RT "cDNA and structural organization of the gene Pole1 for the mouse DNA
RT polymerase epsilon catalytic subunit.";
RL Biochim. Biophys. Acta 1445:363-371(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalytic component of the DNA polymerase epsilon complex (By
CC similarity). Participates in chromosomal DNA replication. Required
CC during synthesis of the leading DNA strands at the replication fork and
CC binds at/or near replication origins and moves along DNA with the
CC replication fork. Has 3'-5' proofreading exonuclease activity that
CC corrects errors arising during DNA replication (By similarity). It is
CC also involved in DNA synthesis during DNA repair (By similarity).
CC {ECO:0000250|UniProtKB:P21951, ECO:0000250|UniProtKB:Q07864}.
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 -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P21951};
CC Note=Binds 1 [4Fe-4S] cluster. {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:0000250|UniProtKB:Q07864}.
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 -!- SIMILARITY: Belongs to the DNA polymerase type-B family. {ECO:0000305}.
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DR EMBL; AF123502; AAD45244.1; -; mRNA.
DR EMBL; AF126398; AAD46482.1; -; Genomic_DNA.
DR EMBL; AF126377; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126378; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126379; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126380; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126381; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126382; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126383; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126384; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126385; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126386; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126387; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126388; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126389; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126390; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126391; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126392; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126393; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126394; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126395; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126396; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AF126397; AAD46482.1; JOINED; Genomic_DNA.
DR EMBL; AC118260; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC123699; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS19525.1; -.
DR RefSeq; NP_035262.2; NM_011132.2.
DR AlphaFoldDB; Q9WVF7; -.
DR SMR; Q9WVF7; -.
DR BioGRID; 202292; 11.
DR ComplexPortal; CPX-2109; DNA polymerase epsilon complex.
DR CORUM; Q9WVF7; -.
DR STRING; 10090.ENSMUSP00000007296; -.
DR iPTMnet; Q9WVF7; -.
DR PhosphoSitePlus; Q9WVF7; -.
DR EPD; Q9WVF7; -.
DR MaxQB; Q9WVF7; -.
DR PaxDb; Q9WVF7; -.
DR PRIDE; Q9WVF7; -.
DR ProteomicsDB; 279567; -.
DR Antibodypedia; 32096; 186 antibodies from 23 providers.
DR DNASU; 18973; -.
DR Ensembl; ENSMUST00000007296; ENSMUSP00000007296; ENSMUSG00000007080.
DR GeneID; 18973; -.
DR KEGG; mmu:18973; -.
DR UCSC; uc008yqm.2; mouse.
DR CTD; 5426; -.
DR MGI; MGI:1196391; Pole.
DR VEuPathDB; HostDB:ENSMUSG00000007080; -.
DR eggNOG; KOG1798; Eukaryota.
DR GeneTree; ENSGT00390000010194; -.
DR HOGENOM; CLU_000556_0_0_1; -.
DR InParanoid; Q9WVF7; -.
DR OMA; MLDQCRY; -.
DR OrthoDB; 39650at2759; -.
DR PhylomeDB; Q9WVF7; -.
DR TreeFam; TF105017; -.
DR Reactome; R-MMU-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-MMU-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-MMU-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-MMU-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR Reactome; R-MMU-5696400; Dual Incision in GG-NER.
DR Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-MMU-68952; DNA replication initiation.
DR Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR BioGRID-ORCS; 18973; 29 hits in 108 CRISPR screens.
DR ChiTaRS; Pole; mouse.
DR PRO; PR:Q9WVF7; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9WVF7; protein.
DR Bgee; ENSMUSG00000007080; Expressed in ear vesicle and 160 other tissues.
DR ExpressionAtlas; Q9WVF7; baseline and differential.
DR Genevisible; Q9WVF7; MM.
DR GO; GO:0008622; C:epsilon DNA polymerase complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0071897; P:DNA biosynthetic process; ISO:MGI.
DR GO; GO:0006260; P:DNA replication; ISO:MGI.
DR GO; GO:0045004; P:DNA replication proofreading; IBA:GO_Central.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:MGI.
DR GO; GO:0006261; P:DNA-templated DNA replication; ISO:MGI.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:MGI.
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; ISO:MGI.
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 4Fe-4S; 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..2283
FT /note="DNA polymerase epsilon catalytic subunit A"
FT /id="PRO_0000046456"
FT ZN_FING 2155..2187
FT /note="CysA-type"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1935..1968
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2014..2041
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 2218..2235
FT /note="CysB motif"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT COMPBIAS 1945..1968
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2022..2041
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 2155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2184
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 2218
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
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 2233
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P15436"
FT BINDING 2235
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:0000250|UniProtKB:Q07864"
FT MOD_RES 1296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07864"
FT MOD_RES 1316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07864"
FT CONFLICT 284
FT /note="K -> T (in Ref. 1; AAD46482)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="M -> V (in Ref. 1; AAD46482/AAD45244)"
FT /evidence="ECO:0000305"
FT CONFLICT 1309
FT /note="G -> E (in Ref. 1; AAD45244)"
FT /evidence="ECO:0000305"
FT CONFLICT 1320
FT /note="R -> K (in Ref. 1; AAD46482)"
FT /evidence="ECO:0000305"
FT CONFLICT 1386..1388
FT /note="ALP -> GLFL (in Ref. 1; AAD45244)"
FT /evidence="ECO:0000305"
FT CONFLICT 1561
FT /note="K -> E (in Ref. 1; AAD46482/AAD45244)"
FT /evidence="ECO:0000305"
FT CONFLICT 1665
FT /note="T -> I (in Ref. 1; AAD45244)"
FT /evidence="ECO:0000305"
FT CONFLICT 2086
FT /note="V -> I (in Ref. 1; AAD46482)"
FT /evidence="ECO:0000305"
FT CONFLICT 2111
FT /note="L -> Q (in Ref. 1; AAD45244)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2283 AA; 262100 MW; 746B2A94D2E8A151 CRC64;
MVLRNSGRRH PEPGADGEGS RDDGPSSSVS ALKRLERSQW TDKMDLRFGF ERLKEPGERT
GWLINMHPTE ILDEDKRLVS AVDYYFIQDD GSRFKVALPY MPYFYIAARK GCDREVSSFL
SKKFQGKIAK LENVPKEDLD LPNHLVGLKR SYIKLSFHTV EDLVKVRKEI SPAVKKNREQ
DHASDEYTTM LSSILQGGSV ITDEDETSKK IADQLDNIVD MREYDVPYHI RLSIDLRIHV
AHWYNVRFRG NAFPVEITRR DDLVERPDPV VLAFDIETTK LPLKFPDAET DQIMMISYMI
DGQGYLITNR EIVSEDIEDF EFTPKPEYEG PFCVFNEPDE VHLIQRWFEH IQETKPTIMV
TYNGDFFDWP FVEARAAIHG LSMYQEIGFQ KDSQGEYKAP QCIHMDCLRW VKRDSYLPVG
SHNLKAAAKA KLGYDPVELD PEDMCRMATE QPQTLATYSV SDAVATYYLY MKYVHPFIFA
LCTIIPMEPD EVLRKGSGTL CEALLMVQAF HANIIFPNKQ EQEFNKLTDD GHMLDAETYV
GGHVEALESG VFRSDIPCRF RMNPAAFDFL LQRVEKTMRH AIEEEEKVPV EQATNFQEVC
EQIKTKLTSL KDVPNRIECP LIYHLDVGAM YPNIILTNRL QPSAIVDEAT CAACDFNKPG
ASCQRKMAWQ WRGEFMPASR SEYHRIQHQL ESEKFPPLFP EGPARAFHEL SREEQAKYEK
RRLADYCRKA YKKIHVTKVE ERLTTICQRE NSFYVDTVRA FRDRRYEFKG LHKVWKKKLS
AAVEVGDASE VKRCKNMEIL YDSLQLAHKC ILNSFYGYVM RKGARWYSME MAGIVCFTGA
NIITQARELI EQIGRPLELD TDGIWCVLPN SFPENFVIKT TNAKKPKLTI SYPGAMLNIM
VKEGFTNHQY QELTEPSSLT YVTHSENSIF FEVDGPYLAM ILPASKEEGK KLKKRYAVFN
EDGSLAELKG FEVKRRGELQ LIKIFQSSVF EAFLKGSTLE EVYGSVAKVA DYWLDVLYSK
AANMPDSELF ELISENRSMS RKLEDYGEQK STSISTAKRL AEFLGDQMVK DAGLSCRYII
SRKPEGSPVT ERAIPLAIFQ AEPTVRKHFL RKWLKSSSLQ DFDIRTILDW DYYIERLGSA
IQKIITIPAA LQQVKNPVPR VKHPDWLHKK LLEKNDIYKQ KKISELFVLE GKRQIVMAQA
SENSLSLCTP DMEDIGLTKP HHSTVPVATK RKRVWETQKE SQDIALTVPW QEVLGQPPSL
GTTQEEWLVW LQFHKKKWQL QAQQRLALRK KQRLESAEDM PRLGPIREGP STGLGSFLRR
TARSIMDLPW QIIQISETRQ AGLFRLWAII GNDLHCIKLS IPRVFYVNQR VAKAEDGPAY
RKVNRALPRS NIVYNLYEYS VPEDMYQEHI NEINTELSVP DIEGVYETQV PLLFRALVQL
GCVCVVNKQL TRHLSGWEAE TFALEHLEMR SLAQFSYLEP GSIRHIYLYH HTQGHKALFG
VFIPSQRRAS VFVLDTVRSN QMPGLSALYS SEHSLLLDKV DPKLLPPPKH TFEVRAETNL
KTICRAIQRF LLAYKEERRG PTLIAVQSSW ELCRLTSEIP VLEEFPLVPI RVADKISYAV
LDWQRHGARR MIRHYLNLDL CLSQAFEMSR YFHIPVGNLP EDISTFGSDL FFARHLQHHN
HLLWLSPTSR PDLGGKEADD NRLVMEFDDR ATVEINSSGC YSTVCVELDI QNLAVNTILQ
SHHVNDMEGA GSMGISFDVI QQASLEDMVT GNQAASALAN YDETALCSST FRILKSMVVG
WVKEITQYHN IYADNQVMHF YRWLQSPCSL LHDPALHRTL HNMMKKLFLQ LIAEFKRLGS
SVVYANFNRI ILCTKKRRIE DALAYVEYIT NSIHSKEIFH SLTISFSRCW EFLLWMDPSN
YGGIKGKVPS SIHCGQVKEQ DSQAREETDE EEEDKEKDEE EEGMGESEVE DLLENNWNIL
QFLPQAASCQ SYFLMIVSAY IVAVYQSMKE ELRHSAPGST PVKRKGASQF SQESEGATGS
LPGMITFSQD YVANELTQSF FTITQKIQKK VTGSRNTTEP SEMFPVLPGS HLLLNNPALE
FIKYVCKVLS LDTNITNQVN KLNRDLLRLV DVGEFSEEAQ FRDPCHSYVL PEVICHSCNF
CRDLDLCKDS SFSQDGAILP QWLCSNCQAP YDSSAIESAL VEALQRKLMA FTLQDLVCLK
CRGMKETHMP VYCSCAGDFT LTIRTEVFME QIRIFQNIAK YYSMSYLQET IEWLLQTSPV
SNC
