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Protein

DNA polymerase delta subunit 2

Gene

Pold2

Organism
Mus musculus (Mouse)
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. 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. 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 POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the minimal DNA polymerase zeta complex, consisting of only REV3L and REV7.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase delta subunit 2
Alternative name(s):
DNA polymerase delta subunit p50
Gene namesi
Name:Pold2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1097163 Pold2

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

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000961671 – 469DNA polymerase delta subunit 2Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei257PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO35654
MaxQBiO35654
PaxDbiO35654
PeptideAtlasiO35654
PRIDEiO35654

PTM databases

PhosphoSitePlusiO35654

Expressioni

Gene expression databases

BgeeiENSMUSG00000020471
ExpressionAtlasiO35654 baseline and differential
GenevisibleiO35654 MM

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. Within Pol-delta4, directly interacts with POLD1, POLD3 and POLD4. 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. Also observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. Contrary to the other components of Pol-delta4, does not directly interact with PCNA. As POLD1 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity. Directly interacts with POLDIP2 and POLDIP3. Directly interacts with KCTD13/PDIP1; in the presence of PCNA, this interaction may stimulate DNA polymerase activity. Component of the DNA polymerase zeta complex (POLZ), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (By similarity). Interacts with KCTD10 (By similarity).By similarity

Protein-protein interaction databases

BioGridi202291, 1 interactor
ComplexPortaliCPX-2098 Delta DNA polymerase complex
CORUMiO35654
IntActiO35654, 2 interactors
STRINGi10090.ENSMUSP00000099986

Structurei

3D structure databases

ProteinModelPortaliO35654
SMRiO35654
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2732 Eukaryota
COG1311 LUCA
GeneTreeiENSGT00390000006780
HOGENOMiHOG000189057
HOVERGENiHBG051396
InParanoidiO35654
KOiK02328
OMAiTRLIQMR
OrthoDBiEOG091G094I
TreeFamiTF101073

Family and domain databases

InterProiView protein in InterPro
IPR007185 DNA_pol_alpha/epsilon_bsu
IPR024826 DNA_pol_delta/II_ssu
PANTHERiPTHR10416 PTHR10416, 1 hit
PfamiView protein in Pfam
PF04042 DNA_pol_E_B, 1 hit

Sequencei

Sequence statusi: Complete.

O35654-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFSEQAAQRA HTLLAPPSAS NATFARVPVA TYTNSSQPFR LGERSFNRQY
60 70 80 90 100
AHIYATRLIQ MRPFLVSRAQ QHWGSRVEVK KLCELQPGEQ CCVVGTLFKA
110 120 130 140 150
MSLQPSILRE ISEEHNLVPQ PPRSKYIHPD DELVLEDELQ RIKLKGTIDV
160 170 180 190 200
SKLVTGTVLA VLGSAKDDGR FQVEDHCFAD LAPQKPVPPL DTDRFVLLVS
210 220 230 240 250
GLGLGGGGGE SLLGTQLLVD VVTGQLGDEG EQCSAAHVSR VILAGNLLSH
260 270 280 290 300
NTQSRDSINK AKYLTKKTQA ASVEAVKMLD EILLQLSASV PVDVMPGEFD
310 320 330 340 350
PTNYTLPQQP LHPCMFPLAT AYSTLQLVTN PYQATIDGVR FLGTSGQNVS
360 370 380 390 400
DIFRYSSMED HLEILEWTLR VRHISPTAPD TLGCYPFYKT DPFIFPECPH
410 420 430 440 450
VYFCGNTPSF GSKIIRGPED QVVLLVAVPD FSSTQTACLV NLRSLACQPI
460
SFAGFGAEQE DLEGLGLGP
Length:469
Mass (Da):51,355
Last modified:July 27, 2011 - v2
Checksum:i1203465743C80900
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti67S → T in CAA96567 (PubMed:9286699).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z72486 mRNA Translation: CAA96567.1
AL627069 Genomic DNA Translation: CAI25442.1
CH466574 Genomic DNA Translation: EDL40563.1
BC003342 mRNA Translation: AAH03342.1
CCDSiCCDS24407.1
RefSeqiNP_032920.2, NM_008894.2
XP_006514650.1, XM_006514587.3
UniGeneiMm.35788

Genome annotation databases

EnsembliENSMUST00000102922; ENSMUSP00000099986; ENSMUSG00000020471
GeneIDi18972
KEGGimmu:18972
UCSCiuc007hxk.2 mouse

Similar proteinsi

Entry informationi

Entry nameiDPOD2_MOUSE
AccessioniPrimary (citable) accession number: O35654
Secondary accession number(s): Q99J61
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 129 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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