DPOE4_HUMAN
ID DPOE4_HUMAN Reviewed; 117 AA.
AC Q9NR33; Q53TR2;
DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=DNA polymerase epsilon subunit 4;
DE AltName: Full=DNA polymerase II subunit 4;
DE AltName: Full=DNA polymerase epsilon subunit p12;
GN Name=POLE4;
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 [GENOMIC DNA], FUNCTION, IDENTIFICATION IN EPSILON DNA
RP POLYMERASE COMPLEX, AND VARIANT VAL-17.
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-17.
RC TISSUE=Skin;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, VARIANT [LARGE SCALE
RP ANALYSIS] VAL-17, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-11, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP ANALYSIS], AND IDENTIFICATION BY 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 [7]
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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Accessory component of the DNA polymerase epsilon complex
CC (PubMed:10801849). Participates in DNA repair and in chromosomal DNA
CC replication (By similarity). {ECO:0000250|UniProtKB:P27344,
CC ECO:0000269|PubMed:10801849}.
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. Interaction with POLE3 is a prerequisite for
CC further binding with POLE and POLE2. {ECO:0000269|PubMed:10801849}.
CC -!- INTERACTION:
CC Q9NR33; P25208: NFYB; NbExp=12; IntAct=EBI-867034, EBI-389728;
CC Q9NR33; Q9NRF9: POLE3; NbExp=6; IntAct=EBI-867034, EBI-744901;
CC Q9NR33; P31321: PRKAR1B; NbExp=3; IntAct=EBI-867034, EBI-2805516;
CC Q9NR33; Q9Q2G4: ORF; Xeno; NbExp=2; IntAct=EBI-867034, EBI-6248094;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
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DR EMBL; AF261688; AAF90132.1; -; Genomic_DNA.
DR EMBL; AC007400; AAY15030.1; -; Genomic_DNA.
DR EMBL; BC031331; AAH31331.1; -; mRNA.
DR CCDS; CCDS1957.1; -.
DR RefSeq; NP_063949.2; NM_019896.3.
DR AlphaFoldDB; Q9NR33; -.
DR SMR; Q9NR33; -.
DR BioGRID; 121168; 33.
DR ComplexPortal; CPX-2108; DNA polymerase epsilon complex.
DR CORUM; Q9NR33; -.
DR IntAct; Q9NR33; 13.
DR MINT; Q9NR33; -.
DR STRING; 9606.ENSP00000420176; -.
DR DrugBank; DB00242; Cladribine.
DR GlyGen; Q9NR33; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NR33; -.
DR PhosphoSitePlus; Q9NR33; -.
DR BioMuta; POLE4; -.
DR DMDM; 116241340; -.
DR EPD; Q9NR33; -.
DR jPOST; Q9NR33; -.
DR MassIVE; Q9NR33; -.
DR MaxQB; Q9NR33; -.
DR PaxDb; Q9NR33; -.
DR PeptideAtlas; Q9NR33; -.
DR PRIDE; Q9NR33; -.
DR ProteomicsDB; 82268; -.
DR TopDownProteomics; Q9NR33; -.
DR Antibodypedia; 31631; 83 antibodies from 17 providers.
DR DNASU; 56655; -.
DR Ensembl; ENST00000483063.2; ENSP00000420176.1; ENSG00000115350.12.
DR GeneID; 56655; -.
DR KEGG; hsa:56655; -.
DR MANE-Select; ENST00000483063.2; ENSP00000420176.1; NM_019896.4; NP_063949.2.
DR UCSC; uc002snf.4; human.
DR CTD; 56655; -.
DR DisGeNET; 56655; -.
DR GeneCards; POLE4; -.
DR HGNC; HGNC:18755; POLE4.
DR HPA; ENSG00000115350; Low tissue specificity.
DR MIM; 607269; gene.
DR neXtProt; NX_Q9NR33; -.
DR OpenTargets; ENSG00000115350; -.
DR PharmGKB; PA38677; -.
DR VEuPathDB; HostDB:ENSG00000115350; -.
DR eggNOG; KOG1658; Eukaryota.
DR GeneTree; ENSGT00940000160888; -.
DR HOGENOM; CLU_045277_8_0_1; -.
DR InParanoid; Q9NR33; -.
DR OMA; HDPDRCG; -.
DR OrthoDB; 1622159at2759; -.
DR PhylomeDB; Q9NR33; -.
DR TreeFam; TF103009; -.
DR BRENDA; 2.7.7.7; 2681.
DR PathwayCommons; Q9NR33; -.
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; Q9NR33; -.
DR SIGNOR; Q9NR33; -.
DR BioGRID-ORCS; 56655; 112 hits in 1079 CRISPR screens.
DR ChiTaRS; POLE4; human.
DR GenomeRNAi; 56655; -.
DR Pharos; Q9NR33; Tdark.
DR PRO; PR:Q9NR33; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NR33; protein.
DR Bgee; ENSG00000115350; Expressed in granulocyte and 169 other tissues.
DR Genevisible; Q9NR33; HS.
DR GO; GO:0140672; C:ATAC complex; IDA:BHF-UCL.
DR GO; GO:0008622; C:epsilon DNA polymerase complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; TAS:ProtInc.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:InterPro.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:ComplexPortal.
DR Gene3D; 1.10.20.10; -; 1.
DR InterPro; IPR003958; CBFA_NFYB_domain.
DR InterPro; IPR009072; Histone-fold.
DR Pfam; PF00808; CBFD_NFYB_HMF; 1.
DR SUPFAM; SSF47113; SSF47113; 1.
PE 1: Evidence at protein level;
KW Acetylation; DNA-binding; Nucleus; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22814378"
FT CHAIN 2..117
FT /note="DNA polymerase epsilon subunit 4"
FT /id="PRO_0000191746"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22814378"
FT MOD_RES 11
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VARIANT 17
FT /note="G -> V (in dbSNP:rs12366)"
FT /evidence="ECO:0000269|PubMed:10801849,
FT ECO:0000269|PubMed:15489334, ECO:0007744|PubMed:17525332"
FT /id="VAR_028050"
SQ SEQUENCE 117 AA; 12209 MW; 1F7273FFEC9D318C CRC64;
MAAAAAAGSG TPREEEGPAG EAAASQPQAP TSVPGARLSR LPLARVKALV KADPDVTLAG
QEAIFILARA AELFVETIAK DAYCCAQQGK RKTLQRRDLD NAIEAVDEFA FLEGTLD
