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Protein

DNA polymerase delta subunit 3

Gene

Pold3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 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 (PubMed:10219083, PubMed:27524497). Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA. 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. 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. 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. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR). 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. 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 (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA excision, DNA repair, DNA replication

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase delta subunit 3
Alternative name(s):
DNA polymerase delta subunit p66
Gene namesi
Name:Pold3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1915217. Pold3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

In a conditional knockdown, embryonic lethal when homozygous. Induction of the knockdown in adult animals results in a generalized accumulation of DNA damage and ultimately death of all mice within 15 weeks after the beginning of the treatment. Heterozygous animals are born at sub-Mendelian ratios, and, of those born, some are dwarfs, present hydrocephaly and have a reduced lifespan. In cells, Pold3 deficiency leads to replication stress and cell death.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001860482 – 462DNA polymerase delta subunit 3Add BLAST461

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Cross-linki256Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei306PhosphoserineCombined sources1
Modified residuei403PhosphoserineBy similarity1
Modified residuei405PhosphoserineBy similarity1
Modified residuei407PhosphothreonineBy similarity1
Modified residuei409PhosphoserineBy similarity1
Cross-linki429Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei454PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated, but not targeted to the proteasome. Sumoylated. Sumoylation by SUMO3 may be predominant.By similarity
Phosphorylation at Ser-454 is thought to decrease the affinity for PCNA and Pol-delta4 processivity. May be phosphorylated by CDK1-cyclin-A complex, as well as CDK2-cyclin-A and CDK2-cyclin-E complexes. PCNA interferes with CDK-cyclin phosphorylation.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9EQ28.
MaxQBiQ9EQ28.
PaxDbiQ9EQ28.
PRIDEiQ9EQ28.

PTM databases

iPTMnetiQ9EQ28.
PhosphoSitePlusiQ9EQ28.

Expressioni

Gene expression databases

BgeeiENSMUSG00000030726.

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:27524497). Within this complex, directly interacts with POLD2. 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. Directly interacts with PCNA, as do POLD1 and POLD4; this interaction stimulates Pol-delta polymerase activity. POLD3 phosphorylation at Ser-454 impairs PCNA binding. Component of the DNA polymerase zeta complex (POLZ), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (By similarity).By similarity1 Publication

Protein-protein interaction databases

IntActiQ9EQ28. 1 interactor.
STRINGi10090.ENSMUSP00000032969.

Structurei

3D structure databases

ProteinModelPortaliQ9EQ28.
SMRiQ9EQ28.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni452 – 462Interaction with PCNABy similarityAdd BLAST11

Phylogenomic databases

eggNOGiENOG410IGGV. Eukaryota.
ENOG410XSD1. LUCA.
HOGENOMiHOG000008055.
HOVERGENiHBG051397.
InParanoidiQ9EQ28.
PhylomeDBiQ9EQ28.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

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

Q9EQ28-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEQLYLENI DEFVTDQNKI VTYKWLSYTL GVHVNQAKQM LYEYVERKRK
60 70 80 90 100
ENSGAQLHVT YLVSGSLIQN GHSCHKVAVV REDKLEAVKS KLAVTASIHV
110 120 130 140 150
YSIQKAMLKD SGPLFNTDYD ILKSNLQNCS KFSAIQCAAA VPRAPAESPS
160 170 180 190 200
SRKYEQSNLQ AASEAQASEL TTNGHGPPAS KQASQQPKGI MGMLISKAAT
210 220 230 240 250
KTQDTNKETK PEAREVTSAS SAGGKAPGKG SVMSNFFGKA AMNKLKVNLD
260 270 280 290 300
SEQAVKEEKT VEQPPVSVTE PKLAAPPAQK KSSRKSEPGK VQQKEKSSRG
310 320 330 340 350
KRVDLSDEEA KETEHLKKKR RRIKLPQSDS SEDEVFEDSP EMYEADSPSP
360 370 380 390 400
PPVSPPPDPM PKTEPPPVKR SSGETKRRRK RVLKSKTFVD EEGCIVTEKV
410 420 430 440 450
YESESCTDSE EELKMKPASA HKPPAAAVKR EPREERKGPK KGAAALGKAN
460
RQVSITGFFQ KK
Length:462
Mass (Da):50,836
Last modified:September 26, 2001 - v2
Checksum:iFF3F67E065A08B36
GO

Sequence cautioni

The sequence AAG45967 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF294329 mRNA. Translation: AAG45967.1. Different initiation.
RefSeqiXP_006508212.2. XM_006508149.2.
UniGeneiMm.37562.

Genome annotation databases

GeneIDi67967.
UCSCiuc009imk.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF294329 mRNA. Translation: AAG45967.1. Different initiation.
RefSeqiXP_006508212.2. XM_006508149.2.
UniGeneiMm.37562.

3D structure databases

ProteinModelPortaliQ9EQ28.
SMRiQ9EQ28.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9EQ28. 1 interactor.
STRINGi10090.ENSMUSP00000032969.

PTM databases

iPTMnetiQ9EQ28.
PhosphoSitePlusiQ9EQ28.

Proteomic databases

EPDiQ9EQ28.
MaxQBiQ9EQ28.
PaxDbiQ9EQ28.
PRIDEiQ9EQ28.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi67967.
UCSCiuc009imk.1. mouse.

Organism-specific databases

CTDi10714.
MGIiMGI:1915217. Pold3.

Phylogenomic databases

eggNOGiENOG410IGGV. Eukaryota.
ENOG410XSD1. LUCA.
HOGENOMiHOG000008055.
HOVERGENiHBG051397.
InParanoidiQ9EQ28.
PhylomeDBiQ9EQ28.

Miscellaneous databases

PROiQ9EQ28.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030726.

Family and domain databases

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

Entry informationi

Entry nameiDPOD3_MOUSE
AccessioniPrimary (citable) accession number: Q9EQ28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: November 30, 2016
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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.