Q07864 (DPOE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase epsilon catalytic subunit A
EC=2.7.7.7

Alternative name(s):
DNA polymerase II subunit A

Gene names

Name:	POLE
Synonyms:	POLE1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	2286 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	Catalytic and central component of the epsilon DNA polymerase complex consisting of four subunits: POLE, POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1. Ref.5 Ref.6 Ref.7
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. The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes By similarity.
Sequence similarities	Belongs to the DNA polymerase type-B family. Contains 1 CysA-type zinc finger.
Sequence caution	The sequence AAA15448.1 differs from that shown. Reason: Frameshift at positions 443 and 448. The sequence AAA15448.1 differs from that shown. Reason:

Ontologies

Keywords
Biological process	DNA damage DNA repair DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	4Fe-4S DNA-binding Iron Iron-sulfur Metal-binding Zinc
Molecular function	DNA-directed DNA polymerase Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication initiation Traceable author statement. Source: Reactome DNA synthesis involved in DNA repair Inferred from mutant phenotype PubMed 1730053. Source: UniProtKB G1/S transition of mitotic cell cycle Inferred from mutant phenotype PubMed 16762037. Source: UniProtKB M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome base-excision repair, gap-filling Inferred from direct assay PubMed 10559260. Source: UniProtKB nucleotide-excision repair, DNA gap filling Inferred from mutant phenotype PubMed 20227374. Source: UniProtKB telomere maintenance via recombination Traceable author statement. Source: Reactome telomere maintenance via semi-conservative replication Traceable author statement. Source: Reactome transcription-coupled nucleotide-excision repair Traceable author statement. Source: Reactome
Cellular_component	epsilon DNA polymerase complex Inferred from direct assay Ref.5. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from direct assay PubMed 16762037. Source: UniProtKB DNA-directed DNA polymerase activity Inferred from mutant phenotype PubMed 16762037. Source: UniProtKB chromatin binding Inferred from direct assay PubMed 16762037. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2286	2286	DNA polymerase epsilon catalytic subunit A		PRO_0000046455
Regions
	Zinc finger	2158 – 2190	33	CysA-type
	Motif	2221 – 2238	18	CysB motif
Sites
	Metal binding	2158	1	Zinc By similarity
	Metal binding	2161	1	Zinc By similarity
	Metal binding	2187	1	Zinc By similarity
	Metal binding	2190	1	Zinc By similarity
	Metal binding	2221	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	2224	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	2236	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	2238	1	Iron-sulfur (4Fe-4S) By similarity
Amino acid modifications
	Modified residue	1184	1	Phosphoserine Ref.9
	Modified residue	1940	1	Phosphoserine Ref.8
Natural variations
	Natural variant	31	1	A → S. Corresponds to variant rs34047482 [ dbSNP | Ensembl ].		VAR_061138
	Natural variant	99	1	P → L. Corresponds to variant rs5744739 [ dbSNP | Ensembl ].		VAR_028429
	Natural variant	252	1	A → V. Corresponds to variant rs5744751 [ dbSNP | Ensembl ].		VAR_020276
	Natural variant	260	1	R → Q. Corresponds to variant rs5744752 [ dbSNP | Ensembl ].		VAR_028430
	Natural variant	336	1	N → S. Corresponds to variant rs5744760 [ dbSNP | Ensembl ].		VAR_020277
	Natural variant	695	1	F → I. Corresponds to variant rs5744799 [ dbSNP | Ensembl ].		VAR_020278
	Natural variant	1382	1	R → C. Corresponds to variant rs5744904 [ dbSNP | Ensembl ].		VAR_028431
	Natural variant	1395	1	Y → C. Corresponds to variant rs5744933 [ dbSNP | Ensembl ].		VAR_020279
	Natural variant	1396	1	N → S. Corresponds to variant rs5744934 [ dbSNP | Ensembl ].		VAR_020280
	Natural variant	1399	1	E → Q. Corresponds to variant rs5744935 [ dbSNP | Ensembl ].		VAR_020281
	Natural variant	1577	1	E → A. Corresponds to variant rs5744948 [ dbSNP | Ensembl ].		VAR_028432
	Natural variant	1712	1	A → V. Corresponds to variant rs5744950 [ dbSNP | Ensembl ].		VAR_028433
	Natural variant	1857	1	K → R. Corresponds to variant rs5744971 [ dbSNP | Ensembl ].		VAR_028434
	Natural variant	1935	1	C → Y. Corresponds to variant rs5744991 [ dbSNP | Ensembl ].		VAR_028435
	Natural variant	2040	1	A → V. Corresponds to variant rs5745021 [ dbSNP | Ensembl ].		VAR_020282
	Natural variant	2140	1	E → K. Corresponds to variant rs5745066 [ dbSNP | Ensembl ].		VAR_048881
	Natural variant	2159	1	R → C. Corresponds to variant rs5745067 [ dbSNP | Ensembl ].		VAR_048882
	Natural variant	2165	1	R → H. Corresponds to variant rs5745068 [ dbSNP | Ensembl ].		VAR_020283
Experimental info
	Sequence conflict	2237	1	S → T in AAA15448. Ref.1
	Sequence conflict	2237	1	S → T in AAC19148. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q07864 [UniParc]. Last modified October 17, 2006. Version 5. Checksum: A213AE1EA8437DEC	FASTA	2,286	261,518
	10 20 30 40 50 60 MSLRSGGRRR ADPGADGEAS RDDGATSSVS ALKRLERSQW TDKMDLRFGF ERLKEPGEKT 70 80 90 100 110 120 GWLINMHPTE ILDEDKRLGS AVDYYFIQDD GSRFKVALPY KPYFYIATRK GCEREVSSFL 130 140 150 160 170 180 SKKFQGKIAK VETVPKEDLD LPNHLVGLKR NYIRLSFHTV EDLVKVRKEI SPAVKKNREQ 190 200 210 220 230 240 DHASDAYTAL LSSVLQRGGV ITDEEETSKK IADQLDNIVD MREYDVPYHI RLSIDLKIHV 250 260 270 280 290 300 AHWYNVRYRG NAFPVEITRR DDLVERPDPV VLAFDIETTK LPLKFPDAET DQIMMISYMI 310 320 330 340 350 360 DGQGYLITNR EIVSEDIEDF EFTPKPEYEG PFCVFNEPDE AHLIQRWFEH VQETKPTIMV 370 380 390 400 410 420 TYNGDFFDWP FVEARAAVHG LSMQQEIGFQ KDSQGEYKAP QCIHMDCLRW VKRDSYLPVG 430 440 450 460 470 480 SHNLKAAAKA KLGYDPVELD PEDMCRMATE QPQTLATYSV SDAVATYYLY MKYVHPFIFA 490 500 510 520 530 540 LCTIIPMEPD EVLRKGSGTL CEALLMVQAF HANIIFPNKQ EQEFNKLTDD GHVLDSETYV 550 560 570 580 590 600 GGHVEALESG VFRSDIPCRF RMNPAAFDFL LQRVEKTLRH ALEEEEKVPV EQVTNFEEVC 610 620 630 640 650 660 DEIKSKLASL KDVPSRIECP LIYHLDVGAM YPNIILTNRL QPSAMVDEAT CAACDFNKPG 670 680 690 700 710 720 ANCQRKMAWQ WRGEFMPASR SEYHRIQHQL ESEKFPPLFP EGPARAFHEL SREEQAKYEK 730 740 750 760 770 780 RRLADYCRKA YKKIHITKVE ERLTTICQRE NSFYVDTVRA FRDRRYEFKG LHKVWKKKLS 790 800 810 820 830 840 AAVEVGDAAE VKRCKNMEVL YDSLQLAHKC ILNSFYGYVM RKGARWYSME MAGIVCFTGA 850 860 870 880 890 900 NIITQARELI EQIGRPLELD TDGIWCVLPN SFPENFVFKT TNVKKPKVTI SYPGAMLNIM 910 920 930 940 950 960 VKEGFTNDQY QELAEPSSLT YVTRSENSIF FEVDGPYLAM ILPASKEEGK KLKKRYAVFN 970 980 990 1000 1010 1020 EDGSLAELKG FEVKRRGELQ LIKIFQSSVF EAFLKGSTLE EVYGSVAKVA DYWLDVLYSK 1030 1040 1050 1060 1070 1080 AANMPDSELF ELISENRSMS RKLEDYGEQK STSISTAKRL AEFLGDQMVK DAGLSCRYII 1090 1100 1110 1120 1130 1140 SRKPEGSPVT ERAIPLAIFQ AEPTVRKHFL RKWLKSSSLQ DFDIRAILDW DYYIERLGSA 1150 1160 1170 1180 1190 1200 IQKIITIPAA LQQVKNPVPR VKHPDWLHKK LLEKNDVYKQ KKISELFTLE GRRQVTMAEA 1210 1220 1230 1240 1250 1260 SEDSPRPSAP DMEDFGLVKL PHPAAPVTVK RKRVLWESQE ESQDLTPTVP WQEILGQPPA 1270 1280 1290 1300 1310 1320 LGTSQEEWLV WLRFHKKKWQ LQARQRLARR KRQRLESAEG VLRPGAIRDG PATGLGSFLR 1330 1340 1350 1360 1370 1380 RTARSILDLP WQIVQISETS QAGLFRLWAL VGSDLHCIRL SIPRVFYVNQ RVAKAEEGAS 1390 1400 1410 1420 1430 1440 YRKVNRVLPR SNMVYNLYEY SVPEDMYQEH INEINAELSA PDIEGVYETQ VPLLFRALVH 1450 1460 1470 1480 1490 1500 LGCVCVVNKQ LVRHLSGWEA ETFALEHLEM RSLAQFSYLE PGSIRHIYLY HHAQAHKALF 1510 1520 1530 1540 1550 1560 GIFIPSQRRA SVFVLDTVRS NQMPSLGALY SAEHGLLLEK VGPELLPPPK HTFEVRAETD 1570 1580 1590 1600 1610 1620 LKTICRAIQR FLLAYKEERR GPTLIAVQSS WELKRLASEI PVLEEFPLVP ICVADKINYG 1630 1640 1650 1660 1670 1680 VLDWQRHGAR RMIRHYLNLD TCLSQAFEMS RYFHIPIGNL PEDISTFGSD LFFARHLQRH 1690 1700 1710 1720 1730 1740 NHLLWLSPTA RPDLGGKEAD DNCLVMEFDD QATVEINSSG CYSTVCVELD LQNLAVNTIL 1750 1760 1770 1780 1790 1800 QSHHVNDMEG ADSMGISFDV IQQASLEDMI TGGQAASAPA SYDETALCSN TFRILKSMVV 1810 1820 1830 1840 1850 1860 GWVKEITQYH NIYADNQVMH FYRWLRSPSS LLHDPALHRT LHNMMKKLFL QLIAEFKRLG 1870 1880 1890 1900 1910 1920 SSVIYANFNR IILCTKKRRV EDAIAYVEYI TSSIHSKETF HSLTISFSRC WEFLLWMDPS 1930 1940 1950 1960 1970 1980 NYGGIKGKVS SRIHCGLQDS QKAGGAEDEQ ENEDDEEERD GEEEEEAEES NVEDLLENNW 1990 2000 2010 2020 2030 2040 NILQFLPQAA SCQNYFLMIV SAYIVAVYHC MKDGLRRSAP GSTPVRRRGA SQLSQEAEGA 2050 2060 2070 2080 2090 2100 VGALPGMITF SQDYVANELT QSFFTITQKI QKKVTGSRNS TELSEMFPVL PGSHLLLNNP 2110 2120 2130 2140 2150 2160 ALEFIKYVCK VLSLDTNITN QVNKLNRDLL RLVDVGEFSE EAQFRDPCRS YVLPEVICRS 2170 2180 2190 2200 2210 2220 CNFCRDLDLC KDSSFSEDGA VLPQWLCSNC QAPYDSSAIE MTLVEVLQKK LMAFTLQDLV 2230 2240 2250 2260 2270 2280 CLKCRGVKET SMPVYCSCAG DFALTIHTQV FMEQIGIFRN IAQHYGMSYL LETLEWLLQK NPQLGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase epsilon." Kesti T., Frantti H., Syvaeoja J.E. J. Biol. Chem. 268:10238-10245(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 48-51; 876-886 AND 1338-1344. Tissue: T-cell.
[2]	Syvaeoja J.E. Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	Asahara H., Goldsmith J.S., Lee E., Linn S. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	NIEHS SNPs program Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-2286.
[5]	"Identification and cloning of two histone fold motif-containing subunits of HeLa DNA polymerase epsilon." Li Y., Pursell Z.F., Linn S. J. Biol. Chem. 275:23247-23252(2000) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN EPSILON DNA POLYMERASE COMPLEX. Tissue: Cervix carcinoma.
[6]	"BRCT domain-containing protein TopBP1 functions in DNA replication and damage response." Maekiniemi M., Hillukkala T., Tuusa J., Reini K., Vaara M., Huang D., Pospiech H., Majuri I., Westerling T., Maekelae T.P., Syvaeoja J.E. J. Biol. Chem. 276:30399-30406(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TOPBP1.
[7]	"The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, and interacts with DNA polymerase epsilon." Post S.M., Tomkinson A.E., Lee E.Y.-H.P. Nucleic Acids Res. 31:5568-5575(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAD17.
[8]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1940, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1184, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	S60080 mRNA. Translation: AAA15448.1. Sequence problems. L09561 mRNA. Translation: AAC19148.1. U49356 mRNA. Translation: AAA90924.1. AY273166 Genomic DNA. Translation: AAP12650.1.
IPI	IPI00939602.
PIR	G02434.
RefSeq	NP_006222.2. NM_006231.2.
UniGene	Hs.524871.
3D structure databases
ProteinModelPortal	Q07864.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-24243N.
IntAct	Q07864. 6 interactions.
STRING	9606.ENSP00000322570.
PTM databases
PhosphoSite	Q07864.
Polymorphism databases
DMDM	116241339.
Proteomic databases
PaxDb	Q07864.
PRIDE	Q07864.
Protocols and materials databases
DNASU	5426.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000320574; ENSP00000322570; ENSG00000177084.
GeneID	5426.
KEGG	hsa:5426.
UCSC	uc001uks.1. human.
Organism-specific databases
CTD	5426.
GeneCards	GC12M133200.
H-InvDB	HIX0022184.
HGNC	HGNC:9177. POLE.
MIM	174762. gene.
neXtProt	NX_Q07864.
PharmGKB	PA277.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0417.
HOVERGEN	HBG051398.
InParanoid	Q07864.
KO	K02324.
PhylomeDB	Q07864.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_21300. Mitotic M-M/G1 phases. REACT_216. DNA Repair. REACT_383. DNA Replication.
Gene expression databases
ArrayExpress	Q07864.
Bgee	Q07864.
CleanEx	HS_POLE.
Genevestigator	Q07864.
GermOnline	ENSG00000177084. Homo sapiens.
Family and domain databases
InterPro	IPR006172. DNA-dir_DNA_pol_B. IPR006133. DNA-dir_DNA_pol_B_exonuc. IPR006134. DNA-dir_DNA_pol_B_multi_dom. IPR013697. DNA_pol_e_suA_C. IPR012337. RNaseH-like_dom. [Graphical view]
Pfam	PF00136. DNA_pol_B. 1 hit. PF03104. DNA_pol_B_exo1. 1 hit. PF08490. DUF1744. 1 hit. [Graphical view]
SMART	SM00486. POLBc. 1 hit. [Graphical view]
SUPFAM	SSF53098. RNaseH_fold. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	POLE. human.
GenomeRNAi	5426.
NextBio	20993.
SOURCE	Search...

Entry information

Entry name

DPOE1_HUMAN

Accession

Primary (citable) accession number: Q07864
Secondary accession number(s): Q13533, Q86VH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 17, 2006
Last modified:	April 3, 2013
This is version 131 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.