MASCOT Search Results

Protein View: DPOE1_HUMAN

DNA polymerase epsilon catalytic subunit A OS=Homo sapiens GN=POLE PE=1 SV=5

Database: SwissProt
Score: 14
Nominal mass (Mr): 304276
Calculated pI: 5.98
Taxonomy: Homo sapiens

Sequence similarity is available as an NCBI BLAST search of DPOE1_HUMAN against nr.

Search parameters

Enzyme:

Trypsin/P: cuts C-term side of KR.

Fixed modifications: Methylthio (C), iTRAQ8plex (N-term), iTRAQ8plex (K)
Variable modifications: Deamidated (NQ), Oxidation (M), Oxidation (HW), Acetyl (Protein N-term), iTRAQ8plex (Y)

Protein sequence coverage: 5%

Matched peptides shown in bold red.

1 MSLRSGGRRR ADPGADGEAS RDDGATSSVS ALKRLERSQW TDKMDLRFGF
51 ERLKEPGEKT GWLINMHPTE ILDEDKRLGS AVDYYFIQDD GSRFKVALPY
101 KPYFYIATRK GCEREVSSFL SKKFQGKIAK VETVPKEDLD LPNHLVGLKR
151 NYIRLSFHTV EDLVKVRKEI SPAVKKNREQ DHASDAYTAL LSSVLQRGGV
201 ITDEEETSKK IADQLDNIVD MREYDVPYHI RLSIDLKIHV AHWYNVRYRG
251 NAFPVEITRR DDLVERPDPV VLAFDIETTK LPLKFPDAET DQIMMISYMI
301 DGQGYLITNR EIVSEDIEDF EFTPKPEYEG PFCVFNEPDE AHLIQRWFEH
351 VQETKPTIMV TYNGDFFDWP FVEARAAVHG LSMQQEIGFQ KDSQGEYKAP
401 QCIHMDCLRW VKRDSYLPVG SHNLKAAAKA KLGYDPVELD PEDMCRMATE
451 QPQTLATYSV SDAVATYYLY MKYVHPFIFA LCTIIPMEPD EVLRKGSGTL
501 CEALLMVQAF HANIIFPNKQ EQEFNKLTDD GHVLDSETYV GGHVEALESG
551 VFRSDIPCRF RMNPAAFDFL LQRVEKTLRH ALEEEEKVPV EQVTNFEEVC
601 DEIKSKLASL KDVPSRIECP LIYHLDVGAM YPNIILTNRL QPSAMVDEAT
651 CAACDFNKPG ANCQRKMAWQ WRGEFMPASR SEYHRIQHQL ESEKFPPLFP
701 EGPARAFHEL SREEQAKYEK RRLADYCRKA YKKIHITKVE ERLTTICQRE
751 NSFYVDTVRA FRDRRYEFKG LHKVWKKKLS AAVEVGDAAE VKRCKNMEVL
801 YDSLQLAHKC ILNSFYGYVM RKGARWYSME MAGIVCFTGA NIITQARELI
851 EQIGRPLELD TDGIWCVLPN SFPENFVFKT TNVKKPKVTI SYPGAMLNIM
901 VKEGFTNDQY QELAEPSSLT YVTRSENSIF FEVDGPYLAM ILPASKEEGK
951 KLKKRYAVFN EDGSLAELKG FEVKRRGELQ LIKIFQSSVF EAFLKGSTLE
1001 EVYGSVAKVA DYWLDVLYSK AANMPDSELF ELISENRSMS RKLEDYGEQK
1051 STSISTAKRL AEFLGDQMVK DAGLSCRYII SRKPEGSPVT ERAIPLAIFQ
1101 AEPTVRKHFL RKWLKSSSLQ DFDIRAILDW DYYIERLGSA IQKIITIPAA
1151 LQQVKNPVPR VKHPDWLHKK LLEKNDVYKQ KKISELFTLE GRRQVTMAEA
1201 SEDSPRPSAP DMEDFGLVKL PHPAAPVTVK RKRVLWESQE ESQDLTPTVP
1251 WQEILGQPPA LGTSQEEWLV WLRFHKKKWQ LQARQRLARR KRQRLESAEG
1301 VLRPGAIRDG PATGLGSFLR RTARSILDLP WQIVQISETS QAGLFRLWAL
1351 VGSDLHCIRL SIPRVFYVNQ RVAKAEEGAS YRKVNRVLPR SNMVYNLYEY
1401 SVPEDMYQEH INEINAELSA PDIEGVYETQ VPLLFRALVH LGCVCVVNKQ
1451 LVRHLSGWEA ETFALEHLEM RSLAQFSYLE PGSIRHIYLY HHAQAHKALF
1501 GIFIPSQRRA SVFVLDTVRS NQMPSLGALY SAEHGLLLEK VGPELLPPPK
1551 HTFEVRAETD LKTICRAIQR FLLAYKEERR GPTLIAVQSS WELKRLASEI
1601 PVLEEFPLVP ICVADKINYG VLDWQRHGAR RMIRHYLNLD TCLSQAFEMS
1651 RYFHIPIGNL PEDISTFGSD LFFARHLQRH NHLLWLSPTA RPDLGGKEAD
1701 DNCLVMEFDD QATVEINSSG CYSTVCVELD LQNLAVNTIL QSHHVNDMEG
1751 ADSMGISFDV IQQASLEDMI TGGQAASAPA SYDETALCSN TFRILKSMVV
1801 GWVKEITQYH NIYADNQVMH FYRWLRSPSS LLHDPALHRT LHNMMKKLFL
1851 QLIAEFKRLG SSVIYANFNR IILCTKKRRV EDAIAYVEYI TSSIHSKETF
1901 HSLTISFSRC WEFLLWMDPS NYGGIKGKVS SRIHCGLQDS QKAGGAEDEQ
1951 ENEDDEEERD GEEEEEAEES NVEDLLENNW NILQFLPQAA SCQNYFLMIV
2001 SAYIVAVYHC MKDGLRRSAP GSTPVRRRGA SQLSQEAEGA VGALPGMITF
2051 SQDYVANELT QSFFTITQKI QKKVTGSRNS TELSEMFPVL PGSHLLLNNP
2101 ALEFIKYVCK VLSLDTNITN QVNKLNRDLL RLVDVGEFSE EAQFRDPCRS
2151 YVLPEVICRS CNFCRDLDLC KDSSFSEDGA VLPQWLCSNC QAPYDSSAIE
2201 MTLVEVLQKK LMAFTLQDLV CLKCRGVKET SMPVYCSCAG DFALTIHTQV
2251 FMEQIGIFRN IAQHYGMSYL LETLEWLLQK NPQLGH

Unformatted sequence string: 2286 residues (for pasting into other applications).

Query Start End Observed Mr(expt) Mr(calc) ppm  M Score Expect Rank U 114/113 115/113 116/113 117/113 118/113 119/113 121/113 Peptide
174436 223 237 694.1581 2772.6033 2772.5942 3.28 1 3 0.79 1Score > 28 indicates identity
Score > 14 indicates homology
U --- --- --- --- --- --- --- R.EYDVPYHIRLSIDLK.I + iTRAQ8plex (Y)
105007 392 398 717.8889 1433.7632 1433.7612 1.45 0 2 1.6 3Score > 27 indicates identity
Score > 16 indicates homology
U --- --- --- --- --- --- --- K.DSQGEYK.A
150511 560 573 677.6931 2030.0575 2030.0714 -6.87 1 0 3.1 4Score > 30 indicates identity
Score > 18 indicates homology
U --- --- --- --- --- --- --- R.FRMNPAAFDFLLQR.V + Deamidated (NQ)
170554 810 822 643.0885 2568.3249 2568.3670 -16.4 1 1 4.3 4Score > 31 indicates identity
Score > 19 indicates homology
U --- --- --- --- --- --- --- K.CILNSFYGYVMRK.G + Deamidated (NQ); Oxidation (M); iTRAQ8plex (Y)
170556 810 822 643.0892 2568.3277 2568.3670 -15.3 1 0 4.3 4Score > 31 indicates identity
Score > 19 indicates homology
U --- --- --- --- --- --- --- K.CILNSFYGYVMRK.G + Deamidated (NQ); Oxidation (M); iTRAQ8plex (Y)
170557 810 822 857.1171 2568.3295 2568.3670 -14.6 1 0 3.4 4Score > 31 indicates identity
Score > 18 indicates homology
U --- --- --- --- --- --- --- K.CILNSFYGYVMRK.G + Deamidated (NQ); Oxidation (M); iTRAQ8plex (Y)
161673 888 902 754.7507 2261.2303 2261.2625 -14.2 0 14 0.048 1Score > 31 indicates identity
Score > 14 indicates homology
U 0.984 1.135 1.488 1.278 1.119 1.128 1.078 K.VTISYPGAMLNIMVK.E + Deamidated (NQ); Oxidation (M)
102026 977 983 470.6375 1408.8907 1408.8751 11.1 0 2 10 10Score > 25 indicates identity
Score > 25 indicates homology
U --- --- --- --- --- --- --- R.GELQLIK.I + Deamidated (NQ)
109327 1116 1125 491.5810 1471.7212 1471.7461 -17.0 0 6 0.28 2Score > 24 indicates identity
Score > 13 indicates homology
U --- --- --- --- --- --- --- K.SSSLQDFDIR.A + Deamidated (NQ)
143482 1144 1155 477.0524 1904.1805 1904.1807 -0.13 0 2 11 8Score > 25 indicates identity U --- --- --- --- --- --- --- K.IITIPAALQQVK.N + 2 Deamidated (NQ)
143486 1144 1155 477.0533 1904.1841 1904.1807 1.76 0 0 15 9Score > 25 indicates identity U --- --- --- --- --- --- --- K.IITIPAALQQVK.N + 2 Deamidated (NQ)
166812 1347 1364 483.8737 2414.3321 2414.3233 3.65 1 5 0.39 1Score > 31 indicates identity
Score > 13 indicates homology
U --- --- --- --- --- --- --- R.LWALVGSDLHCIRLSIPR.V + Oxidation (HW)
166826 1347 1364 483.8767 2414.3471 2414.3233 9.86 1 3 0.59 1Score > 30 indicates identity
Score > 13 indicates homology
U --- --- --- --- --- --- --- R.LWALVGSDLHCIRLSIPR.V + Oxidation (HW)
75351 1365 1371 410.9025 1229.6857 1229.6711 11.8 0 2 0.76 1Score > 25 indicates identity
Score > 14 indicates homology
U --- --- --- --- --- --- --- R.VFYVNQR.V + Deamidated (NQ)
113820 1797 1804 510.6324 1528.8754 1528.8897 -9.38 0 4 1.2 3Score > 28 indicates identity
Score > 17 indicates homology
U --- --- --- --- --- --- --- K.SMVVGWVK.E + Oxidation (M)
113822 1797 1804 510.6327 1528.8763 1528.8897 -8.79 0 3 1.7 4Score > 28 indicates identity
Score > 18 indicates homology
U --- --- --- --- --- --- --- K.SMVVGWVK.E + Oxidation (M)
113825 1797 1804 510.6333 1528.8781 1528.8897 -7.61 0 3 1.8 4Score > 29 indicates identity
Score > 18 indicates homology
U --- --- --- --- --- --- --- K.SMVVGWVK.E + Oxidation (M)
113826 1797 1804 510.6334 1528.8784 1528.8897 -7.42 0 3 1.7 4Score > 29 indicates identity
Score > 17 indicates homology
U --- --- --- --- --- --- --- K.SMVVGWVK.E + Oxidation (M)
113829 1797 1804 510.6335 1528.8787 1528.8897 -7.22 0 4 1.8 4Score > 29 indicates identity
Score > 19 indicates homology
U --- --- --- --- --- --- --- K.SMVVGWVK.E + Oxidation (M)
113834 1797 1804 510.6339 1528.8799 1528.8897 -6.43 0 2 1.4 4Score > 28 indicates identity
Score > 16 indicates homology
U --- --- --- --- --- --- --- K.SMVVGWVK.E + Oxidation (M)

Error distribution


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   10-OCT-2018, entry version 188.
DE   RecName: Full=DNA polymerase epsilon catalytic subunit A;
DE            EC=2.7.7.7;
DE   AltName: Full=DNA polymerase II subunit A;
GN   Name=POLE; Synonyms=POLE1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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;
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   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
RT   subunits 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
RT   and 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
RT   throughout the cell cycle, localizes to DNA replication sites, and
RT   interacts with DNA polymerase epsilon.";
RL   Nucleic Acids Res. 31:5568-5575(2003).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1940, AND IDENTIFICATION
RP   BY 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,
RA   Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA   Lerenthal Y., Shiloh Y., 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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1184, AND IDENTIFICATION
RP   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.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [10]
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.,
RA   Buerckstuemmer T., 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   [11]
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
RT   dysmorphism, immunodeficiency, livedo, and short stature (FILS
RT   syndrome).";
RL   J. Exp. Med. 209:2323-2330(2012).
RN   [12]
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   [13]
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;
RP   VAL-1255; MET-1368; SER-1421; ASN-1752; ASN-2013; THR-2056 AND
RP   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.,
RA   Broderick P., Kemp Z., Spain S.L., Guarino Almeida E., Salguero I.,
RA   Sherborne A., Chubb D., Carvajal-Carmona L.G., Ma Y., Kaur K.,
RA   Dobbins S., Barclay E., Gorman M., Martin L., Kovac M.B., Humphray S.,
RA   Lucassen A., Holmes C.C., Bentley D., Donnelly P., Taylor J.,
RA   Petridis C., Roylance R., Sawyer E.J., Kerr D.J., Clark S., Grimes J.,
RA   Kearsey S.E., Thomas H.J., McVean G., Houlston R.S., Tomlinson I.;
RT   "Germline mutations affecting the proofreading domains of POLE and
RT   POLD1 predispose to colorectal adenomas and carcinomas.";
RL   Nat. Genet. 45:136-144(2013).
RN   [14]
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.,
RA   Juarez M., Sanjuan X., Iglesias S., Alenda C., Egoavil C., Segura A.,
RA   Juan M.J., Rodriguez-Soler M., Brunet J., Gonzalez S., Jover R.,
RA   Lazaro C., Capella G., Pineda M., Soto J.L., Blanco I.;
RT   "New insights into POLE and POLD1 germline mutations in familial
RT   colorectal cancer and polyposis.";
RL   Hum. Mol. Genet. 23:3506-3512(2014).
RN   [15]
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.,
RA   Steinsbekk K.S., Saetrom P., Sandvik A.K., Drabloes F., Sjursen W.;
RT   "A novel POLE mutation associated with cancers of colon, pancreas,
RT   ovaries and small intestine.";
RL   Fam. Cancer 14:437-448(2015).
RN   [16]
RP   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
RT   syndrome mimicking constitutional mismatch repair deficiency.";
RL   Fam. Cancer 16:67-71(2017).
RN   [17]
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
RT   colorectal cancer featuring hypermutation, representing a potential
RT   genomic biomarker for immunotherapy.";
RL   Oncotarget 7:68638-68649(2016).
CC   -!- FUNCTION: Participates in DNA repair and in chromosomal DNA
CC       replication.
CC   -!- CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) =
CC       diphosphate + DNA(n+1).
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000250};
CC       Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250};
CC   -!- SUBUNIT: Catalytic and central component of the epsilon DNA
CC       polymerase complex consisting of four subunits: POLE, POLE2, POLE3
CC       and POLE4. Interacts with RAD17 and TOPBP1.
CC       {ECO:0000269|PubMed:10801849, ECO:0000269|PubMed:11395493,
CC       ECO:0000269|PubMed:14500819}.
CC   -!- INTERACTION:
CC       P56282:POLE2; NbExp=5; IntAct=EBI-348526, EBI-713847;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- DOMAIN: The DNA polymerase activity domain resides in the N-
CC       terminal half of the protein, while the C-terminus is necessary
CC       for complexing subunits B and C. The C-terminus may also regulate
CC       the catalytic activities of the enzyme.
CC   -!- DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for
CC       the formation of polymerase complexes. {ECO:0000250}.
CC   -!- DISEASE: Colorectal cancer 12 (CRCS12) [MIM:615083]: A complex
CC       disease characterized by malignant lesions arising from the inner
CC       wall of the large intestine (the colon) and the rectum. Genetic
CC       alterations are often associated with progression from
CC       premalignant lesion (adenoma) to invasive adenocarcinoma. Risk
CC       factors for cancer of the colon and rectum include colon polyps,
CC       long-standing ulcerative colitis, and genetic family history.
CC       CRCS12 is characterized by a high-penetrance predisposition to the
CC       development of colorectal adenomas and carcinomas, with a variable
CC       tendency to develop multiple and large tumors. Onset is usually
CC       before age 40 years. The histologic features of the tumors are
CC       unremarkable. {ECO:0000269|PubMed:23263490,
CC       ECO:0000269|PubMed:24501277, ECO:0000269|PubMed:25860647,
CC       ECO:0000269|PubMed:27573199}. Note=Disease susceptibility is
CC       associated with variations affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Facial dysmorphism, immunodeficiency, livedo, and short
CC       stature (FILS) [MIM:615139]: A syndrome characterized by mild
CC       facial dysmorphism, mainly malar hypoplasia, livedo on the skin
CC       since birth, and immunodeficiency resulting in recurrent
CC       infections. Growth impairment is observed during early childhood
CC       and results in variable short stature in adulthood.
CC       {ECO:0000269|PubMed:23230001}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the DNA polymerase type-B family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA15448.1; Type=Frameshift; Positions=443, 448; 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/";
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   UniGene; Hs.524871; -.
DR   PDB; 5VBN; X-ray; 2.35 A; B/F=2142-2286.
DR   PDBsum; 5VBN; -.
DR   ProteinModelPortal; Q07864; -.
DR   SMR; Q07864; -.
DR   BioGrid; 111422; 50.
DR   ComplexPortal; CPX-2108; epsilon DNA polymerase complex.
DR   CORUM; Q07864; -.
DR   DIP; DIP-24243N; -.
DR   IntAct; Q07864; 19.
DR   MINT; Q07864; -.
DR   STRING; 9606.ENSP00000322570; -.
DR   ChEMBL; CHEMBL2363042; -.
DR   DrugBank; DB00242; Cladribine.
DR   iPTMnet; Q07864; -.
DR   PhosphoSitePlus; Q07864; -.
DR   BioMuta; POLE; -.
DR   DMDM; 116241339; -.
DR   EPD; Q07864; -.
DR   MaxQB; Q07864; -.
DR   PaxDb; Q07864; -.
DR   PeptideAtlas; Q07864; -.
DR   PRIDE; Q07864; -.
DR   ProteomicsDB; 58543; -.
DR   DNASU; 5426; -.
DR   Ensembl; ENST00000320574; ENSP00000322570; ENSG00000177084.
DR   GeneID; 5426; -.
DR   KEGG; hsa:5426; -.
DR   UCSC; uc001uks.3; human.
DR   CTD; 5426; -.
DR   DisGeNET; 5426; -.
DR   EuPathDB; HostDB:ENSG00000177084.16; -.
DR   GeneCards; POLE; -.
DR   H-InvDB; HIX0022184; -.
DR   HGNC; HGNC:9177; POLE.
DR   HPA; HPA058210; -.
DR   HPA; HPA067385; -.
DR   MalaCards; POLE; -.
DR   MIM; 174762; gene.
DR   MIM; 615083; phenotype.
DR   MIM; 615139; phenotype.
DR   neXtProt; NX_Q07864; -.
DR   OpenTargets; ENSG00000177084; -.
DR   Orphanet; 352712; Facial dysmorphism - immunodeficiency - livedo - short stature.
DR   PharmGKB; PA277; -.
DR   eggNOG; KOG1798; Eukaryota.
DR   eggNOG; COG0417; LUCA.
DR   GeneTree; ENSGT00390000010194; -.
DR   HOVERGEN; HBG051398; -.
DR   InParanoid; Q07864; -.
DR   KO; K02324; -.
DR   OMA; IHSKEIF; -.
DR   OrthoDB; EOG091G006J; -.
DR   PhylomeDB; Q07864; -.
DR   TreeFam; TF105017; -.
DR   Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR   Reactome; R-HSA-174430; Telomere C-strand synthesis initiation.
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   ChiTaRS; POLE; human.
DR   GeneWiki; POLE_(enzyme); -.
DR   GenomeRNAi; 5426; -.
DR   PRO; PR:Q07864; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000177084; Expressed in 186 organ(s), highest expression level in right testis.
DR   CleanEx; HS_POLE; -.
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: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:0006297; P:nucleotide-excision repair, DNA gap filling; IMP:UniProtKB.
DR   Gene3D; 3.30.420.10; -; 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; IPR013697; DNA_pol_e_suA_C.
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; 2.
PE   1: Evidence at protein level;
KW   3D-structure; 4Fe-4S; Complete proteome; Direct protein sequencing;
KW   Disease mutation; DNA damage; DNA repair; DNA replication;
KW   DNA-binding; DNA-directed DNA polymerase; Iron; Iron-sulfur;
KW   Metal-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein;
KW   Polymorphism; Reference proteome; Transferase; Zinc; Zinc-finger.
FT   CHAIN         1   2286       DNA polymerase epsilon catalytic subunit
FT                                A.
FT                                /FTId=PRO_0000046455.
FT   ZN_FING    2158   2190       CysA-type.
FT   MOTIF      2221   2238       CysB motif.
FT   METAL      2158   2158       Zinc. {ECO:0000250}.
FT   METAL      2161   2161       Zinc. {ECO:0000250}.
FT   METAL      2187   2187       Zinc. {ECO:0000250}.
FT   METAL      2190   2190       Zinc. {ECO:0000250}.
FT   METAL      2221   2221       Iron-sulfur (4Fe-4S). {ECO:0000250}.
FT   METAL      2224   2224       Iron-sulfur (4Fe-4S). {ECO:0000250}.
FT   METAL      2236   2236       Iron-sulfur (4Fe-4S). {ECO:0000250}.
FT   METAL      2238   2238       Iron-sulfur (4Fe-4S). {ECO:0000250}.
FT   MOD_RES    1184   1184       Phosphoserine.
FT                                {ECO:0000244|PubMed:20068231}.
FT   MOD_RES    1297   1297       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1317   1317       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1940   1940       Phosphoserine.
FT                                {ECO:0000244|PubMed:17525332}.
FT   VARIANT      31     31       A -> S (in dbSNP:rs34047482).
FT                                /FTId=VAR_061138.
FT   VARIANT      99     99       P -> L (in dbSNP:rs5744739).
FT                                /FTId=VAR_028429.
FT   VARIANT     189    189       A -> T (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069339.
FT   VARIANT     231    231       R -> H (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs1060500835).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069340.
FT   VARIANT     252    252       A -> V (in dbSNP:rs5744751).
FT                                /FTId=VAR_020276.
FT   VARIANT     260    260       R -> Q (in dbSNP:rs5744752).
FT                                /FTId=VAR_028430.
FT   VARIANT     286    286       P -> H (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs1057519943).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069341.
FT   VARIANT     286    286       P -> R (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:27612425}.
FT                                /FTId=VAR_077349.
FT   VARIANT     336    336       N -> S (in dbSNP:rs5744760).
FT                                /FTId=VAR_020277.
FT   VARIANT     367    367       F -> S (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069342.
FT   VARIANT     411    411       V -> L (in CRCS12; associated with
FT                                disease susceptibility;
FT                                dbSNP:rs1057519945).
FT                                {ECO:0000269|PubMed:23263490,
FT                                ECO:0000269|PubMed:27573199}.
FT                                /FTId=VAR_069343.
FT   VARIANT     424    424       L -> V (in CRCS12; associated with
FT                                disease susceptibility;
FT                                dbSNP:rs483352909).
FT                                {ECO:0000269|PubMed:23263490,
FT                                ECO:0000269|PubMed:24501277}.
FT                                /FTId=VAR_069344.
FT   VARIANT     436    436       P -> R (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs864622766).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069345.
FT   VARIANT     458    458       Y -> F (in CRCS12).
FT                                {ECO:0000269|PubMed:25860647}.
FT                                /FTId=VAR_077350.
FT   VARIANT     459    459       S -> F (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069346.
FT   VARIANT     695    695       F -> I (in dbSNP:rs5744799).
FT                                /FTId=VAR_020278.
FT   VARIANT     762    762       R -> W (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs1064794759).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069347.
FT   VARIANT     777    777       K -> N (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069348.
FT   VARIANT    1008   1008       K -> N (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069349.
FT   VARIANT    1255   1255       L -> V (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069350.
FT   VARIANT    1368   1368       V -> M (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs770558983).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069351.
FT   VARIANT    1382   1382       R -> C (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs5744904).
FT                                {ECO:0000269|PubMed:27612425}.
FT                                /FTId=VAR_028431.
FT   VARIANT    1395   1395       Y -> C (in dbSNP:rs5744933).
FT                                /FTId=VAR_020279.
FT   VARIANT    1396   1396       N -> S (in dbSNP:rs5744934).
FT                                /FTId=VAR_020280.
FT   VARIANT    1399   1399       E -> Q (in dbSNP:rs5744935).
FT                                /FTId=VAR_020281.
FT   VARIANT    1421   1421       P -> S. {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069352.
FT   VARIANT    1577   1577       E -> A (in dbSNP:rs5744948).
FT                                /FTId=VAR_028432.
FT   VARIANT    1712   1712       A -> V (in dbSNP:rs5744950).
FT                                /FTId=VAR_028433.
FT   VARIANT    1752   1752       D -> N (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs1335665224).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069353.
FT   VARIANT    1857   1857       K -> R (in dbSNP:rs5744971).
FT                                /FTId=VAR_028434.
FT   VARIANT    1925   1925       I -> T (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:27612425}.
FT                                /FTId=VAR_077351.
FT   VARIANT    1935   1935       C -> Y (in dbSNP:rs5744991).
FT                                /FTId=VAR_028435.
FT   VARIANT    2013   2013       D -> N. {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069354.
FT   VARIANT    2040   2040       A -> V (in dbSNP:rs5745021).
FT                                /FTId=VAR_020282.
FT   VARIANT    2056   2056       A -> T (found in a colorectal sample;
FT                                somatic mutation; dbSNP:rs58916399).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069355.
FT   VARIANT    2140   2140       E -> K (in dbSNP:rs5745066).
FT                                /FTId=VAR_048881.
FT   VARIANT    2159   2159       R -> C (in dbSNP:rs5745067).
FT                                /FTId=VAR_048882.
FT   VARIANT    2165   2165       R -> H (in dbSNP:rs5745068).
FT                                /FTId=VAR_020283.
FT   VARIANT    2213   2213       A -> V (found in a colorectal sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:23263490}.
FT                                /FTId=VAR_069356.
FT   CONFLICT   2237   2237       S -> T (in Ref. 1; AAA15448/AAC19148).
FT                                {ECO:0000305}.
FT   STRAND     2152   2157       {ECO:0000244|PDB:5VBN}.
FT   TURN       2159   2161       {ECO:0000244|PDB:5VBN}.
FT   STRAND     2164   2168       {ECO:0000244|PDB:5VBN}.
FT   TURN       2169   2171       {ECO:0000244|PDB:5VBN}.
FT   STRAND     2188   2190       {ECO:0000244|PDB:5VBN}.
FT   HELIX      2196   2216       {ECO:0000244|PDB:5VBN}.
FT   STRAND     2219   2224       {ECO:0000244|PDB:5VBN}.
FT   STRAND     2230   2232       {ECO:0000244|PDB:5VBN}.
FT   STRAND     2237   2239       {ECO:0000244|PDB:5VBN}.
FT   STRAND     2241   2246       {ECO:0000244|PDB:5VBN}.
FT   HELIX      2248   2265       {ECO:0000244|PDB:5VBN}.
FT   HELIX      2268   2279       {ECO:0000244|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
Mascot: http://www.matrixscience.com/