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Protein

DNA polymerase delta subunit 3

Gene

POLD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Biological processDNA damage, DNA excision, DNA repair, DNA replication

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000077514.8
HGNCiHGNC:20932 POLD3
MIMi611415 gene
neXtProtiNX_Q15054

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Chemistry databases

ChEMBLiCHEMBL2363042

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); alternate1 Publication
Cross-linki258Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Cross-linki261Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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); alternate1 Publication
Cross-linki433Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
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).1 Publication
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
ProteomicsDBi60409

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 Expressed in 216 organ(s), highest expression level in testis
ExpressionAtlasiQ15054 baseline and differential
GenevisibleiQ15054 HS

Organism-specific databases

HPAiHPA058846

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

Protein-protein interaction databases

BioGridi115940, 28 interactors
ComplexPortaliCPX-2097 Delta DNA polymerase complex
CORUMiQ15054
DIPiDIP-35772N
ELMiQ15054
IntActiQ15054, 10 interactors
MINTiQ15054
STRINGi9606.ENSP00000263681

Structurei

Secondary structure

1466
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiVMSNFFG
OrthoDBiEOG091G11SX
PhylomeDBiQ15054
TreeFamiTF103006

Family and domain databases

InterProiView protein in InterPro
IPR019038 DNA_polymerase_subunit_Cdc27
PANTHERiPTHR17598 PTHR17598, 1 hit
PfamiView protein in Pfam
PF09507 CDC27, 1 hit

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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YD46H0YD46_HUMAN
DNA polymerase delta subunit 3
POLD3
149Annotation score:
H0YEX7H0YEX7_HUMAN
DNA polymerase delta subunit 3
POLD3
89Annotation score:
E9PNC0E9PNC0_HUMAN
DNA polymerase delta subunit 3
POLD3
138Annotation score:
E9PRK3E9PRK3_HUMAN
DNA polymerase delta subunit 3
POLD3
169Annotation score:
E9PM91E9PM91_HUMAN
DNA polymerase delta subunit 3
POLD3
111Annotation score:

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]
CCDS86228.1 [Q15054-2]
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

Similar proteinsi

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]
CCDS86228.1 [Q15054-2]
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
ComplexPortaliCPX-2097 Delta DNA polymerase complex
CORUMiQ15054
DIPiDIP-35772N
ELMiQ15054
IntActiQ15054, 10 interactors
MINTiQ15054
STRINGi9606.ENSP00000263681

Chemistry databases

ChEMBLiCHEMBL2363042

PTM databases

iPTMnetiQ15054
PhosphoSitePlusiQ15054

Polymorphism and mutation databases

BioMutaiPOLD3
DMDMi17375506

Proteomic databases

EPDiQ15054
MaxQBiQ15054
PaxDbiQ15054
PeptideAtlasiQ15054
PRIDEiQ15054
ProteomicsDBi60409

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
EuPathDBiHostDB:ENSG00000077514.8
GeneCardsiPOLD3
HGNCiHGNC:20932 POLD3
HPAiHPA058846
MIMi611415 gene
neXtProtiNX_Q15054
OpenTargetsiENSG00000077514
PharmGKBiPA134868595
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

ChiTaRSiPOLD3 human
EvolutionaryTraceiQ15054
GeneWikiiPOLD3
GenomeRNAii10714
PROiPR:Q15054
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077514 Expressed in 216 organ(s), highest expression level in testis
ExpressionAtlasiQ15054 baseline and differential
GenevisibleiQ15054 HS

Family and domain databases

InterProiView protein in InterPro
IPR019038 DNA_polymerase_subunit_Cdc27
PANTHERiPTHR17598 PTHR17598, 1 hit
PfamiView protein in Pfam
PF09507 CDC27, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDPOD3_HUMAN
AccessioniPrimary (citable) accession number: Q15054
Secondary accession number(s): B7ZAI6, Q32MZ9, Q32N00
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 26, 2001
Last modified: September 12, 2018
This is version 162 of the entry and version 2 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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