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Protein

DNA polymerase delta subunit 3

Gene

POLD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA (PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200). Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4 (PubMed:19074196, PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion (PubMed:19074196, PubMed:25628356, PubMed:27185888). Also involved in TLS, as a component of the POLZ complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the minimal DNA polymerase zeta complex, consisting of only REV3L and REV7 (PubMed:24449906).12 Publications

GO - Molecular functioni

  • DNA-directed DNA polymerase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA excision, DNA repair, DNA replication

Enzyme and pathway databases

BioCyciZFISH:ENSG00000077514-MONOMER.
ReactomeiR-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-174411. Polymerase switching on the C-strand of the telomere.
R-HSA-174414. Processive synthesis on the C-strand of the telomere.
R-HSA-174417. Telomere C-strand (Lagging Strand) Synthesis.
R-HSA-174437. Removal of the Flap Intermediate from the C-strand.
R-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5696397. Gap-filling DNA repair synthesis and ligation in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-69091. Polymerase switching.
R-HSA-69166. Removal of the Flap Intermediate.
R-HSA-69183. Processive synthesis on the lagging strand.
SIGNORiQ15054.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase delta subunit 3
Alternative name(s):
DNA polymerase delta subunit C1 Publication
DNA polymerase delta subunit p66
DNA polymerase delta subunit p682 Publications
Gene namesi
Name:POLD3
Synonyms:KIAA0039
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:20932. POLD3.

Subcellular locationi

GO - Cellular componenti

  • delta DNA polymerase complex Source: UniProtKB
  • mitochondrion Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi258K → R: Partially loss of sumoylation. Complete loss of sumoylation; when associated with R-433. 1 Publication1
Mutagenesisi325K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi433K → R: Partially loss of sumoylation. Complete loss of SUMO3-sumoylation; when associated with R-285. 1 Publication1
Mutagenesisi456 – 466Missing : Complete loss of PCNA binding. 1 PublicationAdd BLAST11
Mutagenesisi458S → A: Partial loss of PCNA binding (60% of wild-type) and strong decrease of PCNA stimulation of Pol-delta4 polymerase activity. 1 Publication1
Mutagenesisi459 – 463ITGFF → ATGAA: Complete loss of PCNA binding. 1 Publication5

Organism-specific databases

DisGeNETi10714.
OpenTargetsiENSG00000077514.
PharmGKBiPA134868595.

Polymorphism and mutation databases

BioMutaiPOLD3.
DMDMi17375506.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001860472 – 466DNA polymerase delta subunit 3Add BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Cross-linki258Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Combined sources1 Publication
Modified residuei277PhosphothreonineCombined sources1
Modified residuei307PhosphoserineCombined sources1
Modified residuei407PhosphoserineCombined sources1
Modified residuei409PhosphoserineCombined sources1
Modified residuei411PhosphothreonineCombined sources1
Modified residuei413PhosphoserineCombined sources1
Cross-linki433Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei458PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Ubiquitinated, but not targeted to the proteasome (PubMed:16934752). Sumoylated (PubMed:16934752, PubMed:25218447). Sumoylation with SUMO3 may be predominant (PubMed:16934752).2 Publications
Phosphorylation at Ser-458 is catalyzed in vitro by PKA. It is thought to decrease the affinity for PCNA and Pol-delta4 processivity (PubMed:22148433). Can also be phosphorylated in vitro by CDK1-cyclin-A complex, as well as CDK2-cyclin-A and CDK2-cyclin-E complexes. PCNA interferes with CDK-cyclin phosphorylation (PubMed:11595739).2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15054.
MaxQBiQ15054.
PaxDbiQ15054.
PeptideAtlasiQ15054.
PRIDEiQ15054.

PTM databases

iPTMnetiQ15054.
PhosphoSitePlusiQ15054.

Expressioni

Developmental stagei

Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in G1.1 Publication

Gene expression databases

BgeeiENSG00000077514.
ExpressionAtlasiQ15054. baseline and differential.
GenevisibleiQ15054. HS.

Organism-specific databases

HPAiHPA039627.
HPA058846.

Interactioni

Subunit structurei

Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities (PubMed:11328591, PubMed:11595739, PubMed:17317665, PubMed:22801543). Within this complex, directly interacts with POLD2 (PubMed:11328591, PubMed:16510448, PubMed:18818516). Following stress caused by DNA damaging agents or by replication stress, POLD4 is degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3), which consists of POLD1, POLD2 and POLD3. Pol-delta3 is the major form occurring at S phase replication sites, as well as DNA damage sites (PubMed:11595739, PubMed:17317665, PubMed:22801543, PubMed:23913683). Directly interacts with PCNA, as do POLD1 and POLD4; this interaction stimulates Pol-delta polymerase activity (PubMed:11328591, PubMed:11595739, PubMed:12403614, PubMed:16510448, PubMed:22148433). POLD3 phosphorylation at Ser-458 impairs PCNA binding (PubMed:22148433). Component of the DNA polymerase zeta complex (POLZ), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (PubMed:24449906). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PCNAP120045EBI-864956,EBI-358311
POLD2P490055EBI-864956,EBI-372354

Protein-protein interaction databases

BioGridi115940. 28 interactors.
DIPiDIP-35772N.
IntActiQ15054. 8 interactors.
MINTiMINT-2789689.
STRINGi9606.ENSP00000263681.

Structurei

Secondary structure

1466
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 14Combined sources12
Turni15 – 17Combined sources3
Helixi23 – 30Combined sources8
Helixi34 – 52Combined sources19
Beta strandi58 – 81Combined sources24
Turni82 – 84Combined sources3
Helixi85 – 91Combined sources7
Beta strandi93 – 106Combined sources14
Beta strandi109 – 111Combined sources3
Helixi113 – 125Combined sources13
Helixi129 – 131Combined sources3
Beta strandi134 – 136Combined sources3
Beta strandi238 – 244Combined sources7
Helixi459 – 461Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U76X-ray2.60B/D/F452-466[»]
2N1GNMR-B231-246[»]
3E0JX-ray3.00B/D/F/H1-144[»]
ProteinModelPortaliQ15054.
SMRiQ15054.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15054.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni456 – 466Interaction with PCNA2 PublicationsAdd BLAST11

Phylogenomic databases

eggNOGiENOG410IGGV. Eukaryota.
ENOG410XSD1. LUCA.
GeneTreeiENSGT00390000015282.
HOGENOMiHOG000008055.
HOVERGENiHBG051397.
InParanoidiQ15054.
KOiK03504.
OMAiFSAIQCA.
OrthoDBiEOG091G11SX.
PhylomeDBiQ15054.
TreeFamiTF103006.

Family and domain databases

InterProiIPR019038. DNA_polymerase_subunit_Cdc27.
[Graphical view]
PfamiPF09507. CDC27. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15054-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MADQLYLENI DEFVTDQNKI VTYKWLSYTL GVHVNQAKQM LYDYVERKRK
60 70 80 90 100
ENSGAQLHVT YLVSGSLIQN GHSCHKVAVV REDKLEAVKS KLAVTASIHV
110 120 130 140 150
YSIQKAMLKD SGPLFNTDYD ILKSNLQNCS KFSAIQCAAA VPRAPAESSS
160 170 180 190 200
SSKKFEQSHL HMSSETQANN ELTTNGHGPP ASKQVSQQPK GIMGMFASKA
210 220 230 240 250
AAKTQETNKE TKTEAKEVTN ASAAGNKAPG KGNMMSNFFG KAAMNKFKVN
260 270 280 290 300
LDSEQAVKEE KIVEQPTVSV TEPKLATPAG LKKSSKKAEP VKVLQKEKKR
310 320 330 340 350
GKRVALSDDE TKETENMRKK RRRIKLPESD SSEDEVFPDS PGAYEAESPS
360 370 380 390 400
PPPPPSPPLE PVPKTEPEPP SVKSSSGENK RKRKRVLKSK TYLDGEGCIV
410 420 430 440 450
TEKVYESESC TDSEEELNMK TSSVHRPPAM TVKKEPREER KGPKKGTAAL
460
GKANRQVSIT GFFQRK
Length:466
Mass (Da):51,400
Last modified:September 26, 2001 - v2
Checksum:iE9625E0188725F45
GO
Isoform 2 (identifier: Q15054-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.

Note: No experimental confirmation available.
Show »
Length:427
Mass (Da):46,801
Checksum:i29070FF3F00F0BCB
GO
Isoform 3 (identifier: Q15054-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.

Note: No experimental confirmation available.
Show »
Length:360
Mass (Da):39,320
Checksum:i70ACBAD78175C9BC
GO

Sequence cautioni

The sequence BAA05039 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064745194G → V Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_064746195M → L Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0541491 – 106Missing in isoform 3. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_0541501 – 39Missing in isoform 2. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D26018 mRNA. Translation: BAA05039.1. Different initiation.
AK316301 mRNA. Translation: BAH14672.1.
AP001104 Genomic DNA. No translation available.
AP001324 Genomic DNA. No translation available.
AP001372 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74942.1.
BC108908 mRNA. Translation: AAI08909.1.
BC108909 mRNA. Translation: AAI08910.1.
CCDSiCCDS8233.1. [Q15054-1]
RefSeqiNP_006582.1. NM_006591.2. [Q15054-1]
UniGeneiHs.82502.

Genome annotation databases

EnsembliENST00000263681; ENSP00000263681; ENSG00000077514. [Q15054-1]
ENST00000527458; ENSP00000432951; ENSG00000077514. [Q15054-2]
ENST00000532497; ENSP00000436018; ENSG00000077514. [Q15054-3]
GeneIDi10714.
KEGGihsa:10714.
UCSCiuc001ovf.3. human. [Q15054-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D26018 mRNA. Translation: BAA05039.1. Different initiation.
AK316301 mRNA. Translation: BAH14672.1.
AP001104 Genomic DNA. No translation available.
AP001324 Genomic DNA. No translation available.
AP001372 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74942.1.
BC108908 mRNA. Translation: AAI08909.1.
BC108909 mRNA. Translation: AAI08910.1.
CCDSiCCDS8233.1. [Q15054-1]
RefSeqiNP_006582.1. NM_006591.2. [Q15054-1]
UniGeneiHs.82502.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U76X-ray2.60B/D/F452-466[»]
2N1GNMR-B231-246[»]
3E0JX-ray3.00B/D/F/H1-144[»]
ProteinModelPortaliQ15054.
SMRiQ15054.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115940. 28 interactors.
DIPiDIP-35772N.
IntActiQ15054. 8 interactors.
MINTiMINT-2789689.
STRINGi9606.ENSP00000263681.

PTM databases

iPTMnetiQ15054.
PhosphoSitePlusiQ15054.

Polymorphism and mutation databases

BioMutaiPOLD3.
DMDMi17375506.

Proteomic databases

EPDiQ15054.
MaxQBiQ15054.
PaxDbiQ15054.
PeptideAtlasiQ15054.
PRIDEiQ15054.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263681; ENSP00000263681; ENSG00000077514. [Q15054-1]
ENST00000527458; ENSP00000432951; ENSG00000077514. [Q15054-2]
ENST00000532497; ENSP00000436018; ENSG00000077514. [Q15054-3]
GeneIDi10714.
KEGGihsa:10714.
UCSCiuc001ovf.3. human. [Q15054-1]

Organism-specific databases

CTDi10714.
DisGeNETi10714.
GeneCardsiPOLD3.
HGNCiHGNC:20932. POLD3.
HPAiHPA039627.
HPA058846.
MIMi611415. gene.
neXtProtiNX_Q15054.
OpenTargetsiENSG00000077514.
PharmGKBiPA134868595.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGGV. Eukaryota.
ENOG410XSD1. LUCA.
GeneTreeiENSGT00390000015282.
HOGENOMiHOG000008055.
HOVERGENiHBG051397.
InParanoidiQ15054.
KOiK03504.
OMAiFSAIQCA.
OrthoDBiEOG091G11SX.
PhylomeDBiQ15054.
TreeFamiTF103006.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000077514-MONOMER.
ReactomeiR-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-174411. Polymerase switching on the C-strand of the telomere.
R-HSA-174414. Processive synthesis on the C-strand of the telomere.
R-HSA-174417. Telomere C-strand (Lagging Strand) Synthesis.
R-HSA-174437. Removal of the Flap Intermediate from the C-strand.
R-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5696397. Gap-filling DNA repair synthesis and ligation in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-69091. Polymerase switching.
R-HSA-69166. Removal of the Flap Intermediate.
R-HSA-69183. Processive synthesis on the lagging strand.
SIGNORiQ15054.

Miscellaneous databases

EvolutionaryTraceiQ15054.
GeneWikiiPOLD3.
GenomeRNAii10714.
PROiQ15054.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077514.
ExpressionAtlasiQ15054. baseline and differential.
GenevisibleiQ15054. HS.

Family and domain databases

InterProiIPR019038. DNA_polymerase_subunit_Cdc27.
[Graphical view]
PfamiPF09507. CDC27. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDPOD3_HUMAN
AccessioniPrimary (citable) accession number: Q15054
Secondary accession number(s): B7ZAI6, Q32MZ9, Q32N00
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 26, 2001
Last modified: November 30, 2016
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.