ID:DPOE1_HUMAN DESCRIPTION: RecName: Full=DNA polymerase epsilon catalytic subunit A; EC=2.7.7.7; AltName: Full=DNA polymerase II subunit A; FUNCTION: Participates in DNA repair and in chromosomal DNA replication. CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). COFACTOR: Binds 1 4Fe-4S cluster (By similarity). SUBUNIT: Catalytic and central component of the epsilon DNA polymerase complex consisting of four subunits: POLE, POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1. SUBCELLULAR LOCATION: Nucleus. DOMAIN: The DNA polymerase activity domain resides in the N- terminal half of the protein, while the C-terminus is necessary for complexing subunits B and C. The C-terminus may also regulate the catalytic activities of the enzyme. DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes (By similarity). PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. SIMILARITY: Belongs to the DNA polymerase type-B family. SIMILARITY: Contains 1 CysA-type zinc finger. SEQUENCE CAUTION: Sequence=AAA15448.1; Type=Frameshift; Positions=443, 448; Sequence=AAA15448.1; Type=Miscellaneous discrepancy; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pole/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00136 - DNA polymerase family B PF03104 - DNA polymerase family B, exonuclease domain PF08490 - Domain of unknown function (DUF1744) PF10108 - Predicted 3'-5' exonuclease related to the exonuclease domain of PolB PF13482 - RNase_H superfamily
ModBase Predicted Comparative 3D Structure on Q07864
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0000731 DNA synthesis involved in DNA repair GO:0006260 DNA replication GO:0006272 leading strand elongation GO:0006281 DNA repair GO:0006287 base-excision repair, gap-filling GO:0006297 nucleotide-excision repair, DNA gap filling GO:0006974 cellular response to DNA damage stimulus GO:0045004 DNA replication proofreading GO:0048568 embryonic organ development GO:0071897 DNA biosynthetic process GO:0090305 nucleic acid phosphodiester bond hydrolysis
AK093003 - Homo sapiens cDNA FLJ35684 fis, clone SPLEN2019169, highly similar to DNA polymerase epsilon, catalytic subunit A (EC 2.7.7.7). AF128544 - Homo sapiens DNA polymerase epsilon catalytic subunit (POLE1) gene, 3' UTR. AK128248 - Homo sapiens cDNA FLJ46383 fis, clone THYMU2020560, moderately similar to DNA polymerase epsilon, catalytic subunit A (EC 2.7.7.7). AL080203 - Homo sapiens mRNA; cDNA DKFZp434F222 (from clone DKFZp434F222). BC011376 - Homo sapiens polymerase (DNA directed), epsilon, mRNA (cDNA clone IMAGE:3871436), containing frame-shift errors. AK025087 - Homo sapiens cDNA: FLJ21434 fis, clone COL04242. BC007599 - Homo sapiens, clone IMAGE:3347229, mRNA, partial cds. BC087613 - Homo sapiens polymerase (DNA directed), epsilon, mRNA (cDNA clone IMAGE:4591469), partial cds. BX647647 - Homo sapiens mRNA; cDNA DKFZp451G207 (from clone DKFZp451G207). BC021559 - Homo sapiens polymerase (DNA directed), epsilon, mRNA (cDNA clone IMAGE:5014786), complete cds. BC144561 - Homo sapiens cDNA clone IMAGE:9053089. S60080 - DNA polymerase epsilon catalytic subunit [human, HeLa cells, mRNA, 6794 nt]. L09561 - Homo sapiens DNA polymerase epsilon, catalytic polypeptide mRNA, complete cds. KJ901648 - Synthetic construct Homo sapiens clone ccsbBroadEn_11042 POLE gene, encodes complete protein. U49356 - Human DNA polymerase epsilon catalytic subunit mRNA, complete cds. BC172436 - Synthetic construct Homo sapiens clone IMAGE:100069130, MGC:199141 polymerase (DNA directed), epsilon (POLE) mRNA, encodes complete protein. CU676920 - Synthetic construct Homo sapiens gateway clone IMAGE:100021963 5' read POLE mRNA. LF206918 - JP 2014500723-A/14421: Polycomb-Associated Non-Coding RNAs. LF359317 - JP 2014500723-A/166820: Polycomb-Associated Non-Coding RNAs. AB209902 - Homo sapiens mRNA for DNA polymerase epsilon catalytic subunit variant protein. AF128542 - Homo sapiens DNA polymerase epsilon catalytic subunit isoform b (POLE1) mRNA, partial cds. JD251670 - Sequence 232694 from Patent EP1572962. MA442495 - JP 2018138019-A/14421: Polycomb-Associated Non-Coding RNAs. MA594894 - JP 2018138019-A/166820: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q07864 (Reactome details) participates in the following event(s):
R-HSA-68960 DNA polymerase epsilon binds at the origin R-HSA-68913 The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer at the origin R-HSA-174425 The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer on the G strand of the telomere R-HSA-68914 DNA polymerase alpha:primase binds at the origin R-HSA-5653838 POLD,POLE binds deISGylated PCNA after TLS R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA R-HSA-110364 PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1 R-HSA-5651992 PCNA-containing replication complex binds damaged dsDNA R-HSA-5651809 LIG1, APEX1 and PCNA:POLD,POLE:RPA:RFC dissociate from repaired DNA R-HSA-5653840 POLD,POLE complete replication of damaged DNA after TLS R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-110368 POLD,POLE-mediated DNA strand displacement synthesis R-HSA-110371 LIG1 binds APEX1 and PCNA at SSB R-HSA-110363 FEN1 bound to PCNA and APEX1 cleaves flap ssDNA R-HSA-5651805 LIG1 bound to APEX1 and PCNA ligates SSB R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5690997 Ligation of newly synthesized repair patch to incised DNA in GG-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-5691001 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in GG-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-68962 Activation of the pre-replicative complex R-HSA-68952 DNA replication initiation R-HSA-174430 Telomere C-strand synthesis initiation R-HSA-5656169 Termination of translesion DNA synthesis R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex R-HSA-69002 DNA Replication Pre-Initiation R-HSA-69206 G1/S Transition R-HSA-69239 Synthesis of DNA R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair R-HSA-5696400 Dual Incision in GG-NER R-HSA-6782135 Dual incision in TC-NER R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template R-HSA-73893 DNA Damage Bypass R-HSA-68874 M/G1 Transition R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69242 S Phase R-HSA-69306 DNA Replication R-HSA-180786 Extension of Telomeres R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-73894 DNA Repair R-HSA-69278 Cell Cycle (Mitotic) R-HSA-157579 Telomere Maintenance R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-73933 Resolution of Abasic Sites (AP sites) R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696398 Nucleotide Excision Repair R-HSA-1640170 Cell Cycle R-HSA-73886 Chromosome Maintenance R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-73884 Base Excision Repair R-HSA-5693538 Homology Directed Repair R-HSA-5693532 DNA Double-Strand Break Repair