Q07864 · DPOE1_HUMAN
- ProteinDNA polymerase epsilon catalytic subunit A
- GenePOLE
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids2286 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalytic component of the DNA polymerase epsilon complex (PubMed:10801849).
Participates in chromosomal DNA replication (By similarity).
Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity).
Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity).
Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199).
Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374).
Participates in chromosomal DNA replication (By similarity).
Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity).
Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity).
Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199).
Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374).
Catalytic activity
- a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1)
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 2158 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2161 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2187 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2190 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2221 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2224 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2236 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2238 | [4Fe-4S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | epsilon DNA polymerase complex | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | plasma membrane | |
Molecular Function | 4 iron, 4 sulfur cluster binding | |
Molecular Function | chromatin binding | |
Molecular Function | DNA binding | |
Molecular Function | DNA-directed DNA polymerase activity | |
Molecular Function | nucleotide binding | |
Molecular Function | single-stranded DNA 3'-5' DNA exonuclease activity | |
Molecular Function | zinc ion binding | |
Biological Process | base-excision repair, gap-filling | |
Biological Process | DNA replication | |
Biological Process | DNA replication proofreading | |
Biological Process | DNA synthesis involved in DNA repair | |
Biological Process | DNA-templated DNA replication | |
Biological Process | embryonic organ development | |
Biological Process | G1/S transition of mitotic cell cycle | |
Biological Process | leading strand elongation | |
Biological Process | mitotic cell cycle | |
Biological Process | nucleotide-excision repair, DNA gap filling |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA polymerase epsilon catalytic subunit A
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ07864
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Colorectal cancer 12 (CRCS12)
- Note
- DescriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. CRCS12 is characterized by a high-penetrance predisposition to the development of colorectal adenomas and carcinomas, with a variable tendency to develop multiple and large tumors. Onset is usually before age 40 years. The histologic features of the tumors are unremarkable.
- See alsoMIM:615083
Natural variants in CRCS12
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_069343 | 411 | V>L | in CRCS12; uncertain significance; dbSNP:rs1057519945 | |
VAR_069344 | 424 | L>V | in CRCS12; dbSNP:rs483352909 | |
VAR_077350 | 458 | Y>F | in CRCS12; uncertain significance; dbSNP:rs2135996937 |
Facial dysmorphism, immunodeficiency, livedo, and short stature (FILS)
- Note
- DescriptionA syndrome characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, and immunodeficiency resulting in recurrent infections. Growth impairment is observed during early childhood and results in variable short stature in adulthood.
- See alsoMIM:615139
Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency (IMAGEI)
- Note
- DescriptionAn autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth failure, metaphyseal dysplasia, adrenal hypoplasia congenita, growth hormone deficiency, genital anomalies, and immunodeficiency resulting in increased infections.
- See alsoMIM:618336
Natural variants in IMAGEI
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081996 | 683-2286 | missing | in IMAGEI | |
VAR_081997 | 1007 | A>P | in IMAGEI; uncertain significance; dbSNP:rs747692201 | |
VAR_081998 | 1980-2286 | missing | in IMAGEI |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_061138 | 31 | in dbSNP:rs34047482 | |||
Sequence: A → S | ||||||
Natural variant | VAR_028429 | 99 | in dbSNP:rs5744739 | |||
Sequence: P → L | ||||||
Natural variant | VAR_069339 | 189 | found in a colorectal sample; somatic mutation | |||
Sequence: A → T | ||||||
Natural variant | VAR_069340 | 231 | found in a colorectal sample; somatic mutation; dbSNP:rs1060500835 | |||
Sequence: R → H | ||||||
Natural variant | VAR_020276 | 252 | in dbSNP:rs5744751 | |||
Sequence: A → V | ||||||
Natural variant | VAR_028430 | 260 | in dbSNP:rs5744752 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_069341 | 286 | found in a colorectal sample; somatic mutation; dbSNP:rs1057519943 | |||
Sequence: P → H | ||||||
Natural variant | VAR_077349 | 286 | found in a colorectal sample; somatic mutation; dbSNP:rs1057519943 | |||
Sequence: P → R | ||||||
Natural variant | VAR_020277 | 336 | in dbSNP:rs5744760 | |||
Sequence: N → S | ||||||
Natural variant | VAR_069342 | 367 | found in a colorectal sample; somatic mutation | |||
Sequence: F → S | ||||||
Natural variant | VAR_069343 | 411 | in CRCS12; uncertain significance; dbSNP:rs1057519945 | |||
Sequence: V → L | ||||||
Natural variant | VAR_069344 | 424 | in CRCS12; dbSNP:rs483352909 | |||
Sequence: L → V | ||||||
Natural variant | VAR_069345 | 436 | found in a colorectal sample; somatic mutation; dbSNP:rs864622766 | |||
Sequence: P → R | ||||||
Natural variant | VAR_077350 | 458 | in CRCS12; uncertain significance; dbSNP:rs2135996937 | |||
Sequence: Y → F | ||||||
Natural variant | VAR_069346 | 459 | found in a colorectal sample; somatic mutation; dbSNP:rs765702675 | |||
Sequence: S → F | ||||||
Natural variant | VAR_081996 | 683-2286 | in IMAGEI | |||
Sequence: Missing | ||||||
Natural variant | VAR_020278 | 695 | in dbSNP:rs5744799 | |||
Sequence: F → I | ||||||
Natural variant | VAR_069347 | 762 | found in a colorectal sample; somatic mutation; dbSNP:rs1064794759 | |||
Sequence: R → W | ||||||
Natural variant | VAR_069348 | 777 | found in a colorectal sample; somatic mutation | |||
Sequence: K → N | ||||||
Natural variant | VAR_081997 | 1007 | in IMAGEI; uncertain significance; dbSNP:rs747692201 | |||
Sequence: A → P | ||||||
Natural variant | VAR_069349 | 1008 | found in a colorectal sample; somatic mutation; dbSNP:rs2138689242 | |||
Sequence: K → N | ||||||
Natural variant | VAR_069350 | 1255 | found in a colorectal sample; somatic mutation; dbSNP:rs745838504 | |||
Sequence: L → V | ||||||
Natural variant | VAR_069351 | 1368 | found in a colorectal sample; somatic mutation; dbSNP:rs770558983 | |||
Sequence: V → M | ||||||
Natural variant | VAR_028431 | 1382 | found in a colorectal sample; somatic mutation; dbSNP:rs5744904 | |||
Sequence: R → C | ||||||
Natural variant | VAR_020279 | 1395 | in dbSNP:rs5744933 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_020280 | 1396 | in dbSNP:rs5744934 | |||
Sequence: N → S | ||||||
Natural variant | VAR_020281 | 1399 | in dbSNP:rs5744935 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_069352 | 1421 | in dbSNP:rs2138558999 | |||
Sequence: P → S | ||||||
Natural variant | VAR_028432 | 1577 | in dbSNP:rs5744948 | |||
Sequence: E → A | ||||||
Natural variant | VAR_028433 | 1712 | in dbSNP:rs5744950 | |||
Sequence: A → V | ||||||
Natural variant | VAR_069353 | 1752 | found in a colorectal sample; somatic mutation; dbSNP:rs1335665224 | |||
Sequence: D → N | ||||||
Natural variant | VAR_028434 | 1857 | in dbSNP:rs5744971 | |||
Sequence: K → R | ||||||
Natural variant | VAR_077351 | 1925 | found in a colorectal sample; somatic mutation; dbSNP:rs2138485353 | |||
Sequence: I → T | ||||||
Natural variant | VAR_028435 | 1935 | in dbSNP:rs5744991 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_081998 | 1980-2286 | in IMAGEI | |||
Sequence: Missing | ||||||
Natural variant | VAR_069354 | 2013 | ||||
Sequence: D → N | ||||||
Natural variant | VAR_020282 | 2040 | in dbSNP:rs5745021 | |||
Sequence: A → V | ||||||
Natural variant | VAR_069355 | 2056 | found in a colorectal sample; somatic mutation; dbSNP:rs58916399 | |||
Sequence: A → T | ||||||
Natural variant | VAR_048881 | 2140 | in dbSNP:rs5745066 | |||
Sequence: E → K | ||||||
Natural variant | VAR_048882 | 2159 | in dbSNP:rs5745067 | |||
Sequence: R → C | ||||||
Natural variant | VAR_020283 | 2165 | in dbSNP:rs5745068 | |||
Sequence: R → H | ||||||
Natural variant | VAR_069356 | 2213 | found in a colorectal sample; somatic mutation | |||
Sequence: A → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 7,663 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000046455 | 1-2286 | UniProt | DNA polymerase epsilon catalytic subunit A | |||
Sequence: MSLRSGGRRRADPGADGEASRDDGATSSVSALKRLERSQWTDKMDLRFGFERLKEPGEKTGWLINMHPTEILDEDKRLGSAVDYYFIQDDGSRFKVALPYKPYFYIATRKGCEREVSSFLSKKFQGKIAKVETVPKEDLDLPNHLVGLKRNYIRLSFHTVEDLVKVRKEISPAVKKNREQDHASDAYTALLSSVLQRGGVITDEEETSKKIADQLDNIVDMREYDVPYHIRLSIDLKIHVAHWYNVRYRGNAFPVEITRRDDLVERPDPVVLAFDIETTKLPLKFPDAETDQIMMISYMIDGQGYLITNREIVSEDIEDFEFTPKPEYEGPFCVFNEPDEAHLIQRWFEHVQETKPTIMVTYNGDFFDWPFVEARAAVHGLSMQQEIGFQKDSQGEYKAPQCIHMDCLRWVKRDSYLPVGSHNLKAAAKAKLGYDPVELDPEDMCRMATEQPQTLATYSVSDAVATYYLYMKYVHPFIFALCTIIPMEPDEVLRKGSGTLCEALLMVQAFHANIIFPNKQEQEFNKLTDDGHVLDSETYVGGHVEALESGVFRSDIPCRFRMNPAAFDFLLQRVEKTLRHALEEEEKVPVEQVTNFEEVCDEIKSKLASLKDVPSRIECPLIYHLDVGAMYPNIILTNRLQPSAMVDEATCAACDFNKPGANCQRKMAWQWRGEFMPASRSEYHRIQHQLESEKFPPLFPEGPARAFHELSREEQAKYEKRRLADYCRKAYKKIHITKVEERLTTICQRENSFYVDTVRAFRDRRYEFKGLHKVWKKKLSAAVEVGDAAEVKRCKNMEVLYDSLQLAHKCILNSFYGYVMRKGARWYSMEMAGIVCFTGANIITQARELIEQIGRPLELDTDGIWCVLPNSFPENFVFKTTNVKKPKVTISYPGAMLNIMVKEGFTNDQYQELAEPSSLTYVTRSENSIFFEVDGPYLAMILPASKEEGKKLKKRYAVFNEDGSLAELKGFEVKRRGELQLIKIFQSSVFEAFLKGSTLEEVYGSVAKVADYWLDVLYSKAANMPDSELFELISENRSMSRKLEDYGEQKSTSISTAKRLAEFLGDQMVKDAGLSCRYIISRKPEGSPVTERAIPLAIFQAEPTVRKHFLRKWLKSSSLQDFDIRAILDWDYYIERLGSAIQKIITIPAALQQVKNPVPRVKHPDWLHKKLLEKNDVYKQKKISELFTLEGRRQVTMAEASEDSPRPSAPDMEDFGLVKLPHPAAPVTVKRKRVLWESQEESQDLTPTVPWQEILGQPPALGTSQEEWLVWLRFHKKKWQLQARQRLARRKRQRLESAEGVLRPGAIRDGPATGLGSFLRRTARSILDLPWQIVQISETSQAGLFRLWALVGSDLHCIRLSIPRVFYVNQRVAKAEEGASYRKVNRVLPRSNMVYNLYEYSVPEDMYQEHINEINAELSAPDIEGVYETQVPLLFRALVHLGCVCVVNKQLVRHLSGWEAETFALEHLEMRSLAQFSYLEPGSIRHIYLYHHAQAHKALFGIFIPSQRRASVFVLDTVRSNQMPSLGALYSAEHGLLLEKVGPELLPPPKHTFEVRAETDLKTICRAIQRFLLAYKEERRGPTLIAVQSSWELKRLASEIPVLEEFPLVPICVADKINYGVLDWQRHGARRMIRHYLNLDTCLSQAFEMSRYFHIPIGNLPEDISTFGSDLFFARHLQRHNHLLWLSPTARPDLGGKEADDNCLVMEFDDQATVEINSSGCYSTVCVELDLQNLAVNTILQSHHVNDMEGADSMGISFDVIQQASLEDMITGGQAASAPASYDETALCSNTFRILKSMVVGWVKEITQYHNIYADNQVMHFYRWLRSPSSLLHDPALHRTLHNMMKKLFLQLIAEFKRLGSSVIYANFNRIILCTKKRRVEDAIAYVEYITSSIHSKETFHSLTISFSRCWEFLLWMDPSNYGGIKGKVSSRIHCGLQDSQKAGGAEDEQENEDDEEERDGEEEEEAEESNVEDLLENNWNILQFLPQAASCQNYFLMIVSAYIVAVYHCMKDGLRRSAPGSTPVRRRGASQLSQEAEGAVGALPGMITFSQDYVANELTQSFFTITQKIQKKVTGSRNSTELSEMFPVLPGSHLLLNNPALEFIKYVCKVLSLDTNITNQVNKLNRDLLRLVDVGEFSEEAQFRDPCRSYVLPEVICRSCNFCRDLDLCKDSSFSEDGAVLPQWLCSNCQAPYDSSAIEMTLVEVLQKKLMAFTLQDLVCLKCRGVKETSMPVYCSCAGDFALTIHTQVFMEQIGIFRNIAQHYGMSYLLETLEWLLQKNPQLGH | |||||||
Modified residue | 1184 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1184 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1204 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1297 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1297 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1317 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1317 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1940 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1940 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2023 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 2080 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q07864 | ABHD16A O95870 | 3 | EBI-348526, EBI-348517 | |
BINARY | Q07864 | POLE2 P56282 | 11 | EBI-348526, EBI-713847 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, zinc finger, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-30 | Disordered | ||||
Sequence: MSLRSGGRRRADPGADGEASRDDGATSSVS | ||||||
Region | 1939-1969 | Disordered | ||||
Sequence: DSQKAGGAEDEQENEDDEEERDGEEEEEAEE | ||||||
Compositional bias | 1948-1969 | Acidic residues | ||||
Sequence: DEQENEDDEEERDGEEEEEAEE | ||||||
Zinc finger | 2158-2190 | CysA-type | ||||
Sequence: CRSCNFCRDLDLCKDSSFSEDGAVLPQWLCSNC | ||||||
Motif | 2221-2238 | CysB motif | ||||
Sequence: CLKCRGVKETSMPVYCSC |
Domain
The DNA polymerase activity domain resides in the N-terminal half of the protein, while the C-terminus is necessary for maintenance of the complex.
The CysA-type zinc finger is required for PCNA-binding.
The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.
Sequence similarities
Belongs to the DNA polymerase type-B family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length2,286
- Mass (Da)261,518
- Last updated2006-10-17 v5
- ChecksumA213AE1EA8437DEC
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A5F9ZI42 | A0A5F9ZI42_HUMAN | POLE | 121 | ||
A0A5F9ZHD6 | A0A5F9ZHD6_HUMAN | POLE | 207 | ||
A0A8V8TQH1 | A0A8V8TQH1_HUMAN | POLE | 147 | ||
A0A8V8TQW1 | A0A8V8TQW1_HUMAN | POLE | 294 | ||
F5H7E4 | F5H7E4_HUMAN | POLE | 310 | ||
A0A087WW42 | A0A087WW42_HUMAN | POLE | 308 | ||
A0A087WX51 | A0A087WX51_HUMAN | POLE | 154 | ||
F5H1D6 | F5H1D6_HUMAN | POLE | 2259 |
Sequence caution
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1948-1969 | Acidic residues | ||||
Sequence: DEQENEDDEEERDGEEEEEAEE | ||||||
Sequence conflict | 2237 | in Ref. 1; AAA15448/AAC19148 | ||||
Sequence: S → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S60080 EMBL· GenBank· DDBJ | AAA15448.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
L09561 EMBL· GenBank· DDBJ | AAC19148.1 EMBL· GenBank· DDBJ | mRNA | ||
U49356 EMBL· GenBank· DDBJ | AAA90924.1 EMBL· GenBank· DDBJ | mRNA | ||
AY273166 EMBL· GenBank· DDBJ | AAP12650.1 EMBL· GenBank· DDBJ | Genomic DNA |