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Protein

DNA polymerase delta catalytic subunit

Gene

Pold1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may 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, in the presence of POLD3 and POLD4, may catalyze 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.By similarity

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster.By similarity

Enzyme regulationi

Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation. Stimulated in the presence of PCNA (By similarity). This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1010ZincBy similarity1
Metal bindingi1013ZincBy similarity1
Metal bindingi1024ZincBy similarity1
Metal bindingi1027ZincBy similarity1
Metal bindingi1056Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1059Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1069Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1074Iron-sulfur (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1010 – 1027CysA-typeAdd BLAST18

GO - Molecular functioni

GO - Biological processi

  • base-excision repair, gap-filling Source: MGI
  • cellular response to UV Source: UniProtKB
  • DNA replication Source: MGI
  • DNA replication proofreading Source: MGI
  • DNA synthesis involved in DNA repair Source: MGI
  • fatty acid homeostasis Source: UniProtKB
  • nucleotide-excision repair, DNA gap filling Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

DNA-directed DNA polymerase, Exonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, Transferase

Keywords - Biological processi

DNA damage, DNA excision, DNA repair, DNA replication

Keywords - Ligandi

4Fe-4S, DNA-binding, Iron, Iron-sulfur, Metal-binding, Zinc

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 catalytic subunit (EC:2.7.7.7, EC:3.1.11.-)
Gene namesi
Name:Pold1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:97741. Pold1.

Subcellular locationi

  • Nucleus By similarity

  • Note: Colocalizes with PCNA and POLD3 at S phase replication sites. After UV irradiation, recruited to DNA damage sites within 2 hours, independently on the cell cycle phase, nor on PCNA ubiquitination. This recruitement requires POLD3, PCNA and RFC1-replication factor C complex.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000464441 – 1105DNA polymerase delta catalytic subunitAdd BLAST1105

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Omega-N-methylarginineBy similarity1

Keywords - PTMi

Methylation

Proteomic databases

EPDiP52431.
MaxQBiP52431.
PaxDbiP52431.
PeptideAtlasiP52431.
PRIDEiP52431.

PTM databases

iPTMnetiP52431.
PhosphoSitePlusiP52431.

Miscellaneous databases

PMAP-CutDBP52431.

Expressioni

Gene expression databases

BgeeiENSMUSG00000038644.
ExpressionAtlasiP52431. baseline and differential.
GenevisibleiP52431. 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 both DNA polymerase and 3' to 5' proofreading exonuclease activities. Within Pol-delta4, directly interacts with POLD2 and POLD4. Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites. POLD1 displays different catalytic properties depending upon the complex it is found in. It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage. Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity. As POLD2 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. Also observed as a dimeric complex with POLD2 (Pol-delta2). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2.By similarity

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi202290. 4 interactors.
DIPiDIP-45885N.
IntActiP52431. 1 interactor.
STRINGi10090.ENSMUSP00000039776.

Structurei

3D structure databases

ProteinModelPortaliP52431.
SMRiP52431.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 19Nuclear localization signalSequence analysisAdd BLAST16
Motifi1056 – 1074CysB motifAdd BLAST19

Domaini

The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.By similarity

Sequence similaritiesi

Belongs to the DNA polymerase type-B family.Curated
Contains 1 CysA-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1010 – 1027CysA-typeAdd BLAST18

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0968. Eukaryota.
COG0417. LUCA.
GeneTreeiENSGT00560000077365.
HOGENOMiHOG000036616.
HOVERGENiHBG051395.
InParanoidiP52431.
KOiK02327.
OMAiMRQGLLM.
OrthoDBiEOG091G00TM.
TreeFamiTF352785.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProiIPR006172. DNA-dir_DNA_pol_B.
IPR017964. DNA-dir_DNA_pol_B_CS.
IPR006133. DNA-dir_DNA_pol_B_exonuc.
IPR006134. DNA-dir_DNA_pol_B_multi_dom.
IPR023211. DNA_pol_palm_dom.
IPR012337. RNaseH-like_dom.
IPR025687. Znf-C4pol.
[Graphical view]
PfamiPF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
PF14260. zf-C4pol. 1 hit.
[Graphical view]
PRINTSiPR00106. DNAPOLB.
SMARTiSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P52431-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDCKRRQGPG PGVPPKRARG HLWDEDEPSP SQFEANLALL EEIEAENRLQ
60 70 80 90 100
EAEEELQLPP EGTVGGQFST ADIDPRWRRP TLRALDPSTE PLIFQQLEID
110 120 130 140 150
HYVGSAPPLP EGPLPSRNSV PILRAFGVTD EGFSVCCHIQ GFAPYFYTPA
160 170 180 190 200
PPGFGAEHLS ELQQELNAAI SRDQRGGKEL SGPAVLAIEL CSRESMFGYH
210 220 230 240 250
GHGPSPFLRI TLALPRLMAP ARRLLEQGVR VPGLGTPSFA PYEANVDFEI
260 270 280 290 300
RFMVDADIVG CNWLELPAGK YVRRAEKKAT LCQLEVDVLW SDVISHPPEG
310 320 330 340 350
QWQRIAPLRV LSFDIECAGR KGIFPEPERD PVIQICSLGL RWGEPEPFLR
360 370 380 390 400
LALTLRPCAP ILGAKVQSYE REEDLLQAWA DFILAMDPDV ITGYNIQNFD
410 420 430 440 450
LPYLISRAQA LKVDRFPFLG RVTGLRSNIR DSSFQSRQVG RRDSKVISMV
460 470 480 490 500
GRVQMDMLQV LLREHKLRSY TLNAVSFHFL GEQKEDVQHS IITDLQNGNE
510 520 530 540 550
QTRRRLAVYC LKDAFLPLRL LERLMVLVNN VEMARVTGVP LGYLLTRGQQ
560 570 580 590 600
VKVVSQLLRQ AMRQGLLMPV VKTEGSEDYT GATVIEPLKG YYDVPIATLD
610 620 630 640 650
FSSLYPSIMM AHNLCYTTLL RPGAAQKLGL KPDEFIKTPT GDEFVKSSVR
660 670 680 690 700
KGLLPQILEN LLSARKRAKA ELAQETDPLR RQVLDGRQLA LKVSANSVYG
710 720 730 740 750
FTGAQVGKLP CLEISQSVTG FGRQMIEKTK QLVESKYTVE NGYDANAKVV
760 770 780 790 800
YGDTDSVMCR FGVSSVAEAM SLGREAANWV SSHFPSPIRL EFEKVYFPYL
810 820 830 840 850
LISKKRYAGL LFSSRSDAHD KMDCKGLEAV RRDNCPLVAN LVTSSLRRIL
860 870 880 890 900
VDRDPDGAVA HAKDVISDLL CNRIDISQLV ITKELTRAAA DYAGKQAHVE
910 920 930 940 950
LAERMRKRDP GSAPSLGDRV PYVIIGAAKG VAAYMKSEDP LFVLEHSLPI
960 970 980 990 1000
DTQYYLEQQL AKPLLRIFEP ILGEGRAESV LLRGDHTRCK TVLTSKVGGL
1010 1020 1030 1040 1050
LAFTKRRNCC IGCRSVIDHQ GAVCKFCQPR ESELYQKEVS HLNALEERFS
1060 1070 1080 1090 1100
RLWTQCQRCQ GSLHEDVICT SRDCPIFYMR KKVRKDLEDQ ERLLQRFGPP

GPEAW
Length:1,105
Mass (Da):123,790
Last modified:July 27, 2011 - v2
Checksum:i2AE377D42E3A6A86
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti112G → R in CAA79895 (PubMed:8262377).Curated1
Sequence conflicti114L → P in AAB99910 (PubMed:9434960).Curated1
Sequence conflicti576S → G in CAA79895 (PubMed:8262377).Curated1
Sequence conflicti576S → G in AAB99910 (PubMed:9434960).Curated1
Sequence conflicti793E → K in AAB99910 (PubMed:9434960).Curated1
Sequence conflicti1000L → F in AAB99910 (PubMed:9434960).Curated1
Sequence conflicti1035Y → S in CAA79895 (PubMed:8262377).Curated1
Sequence conflicti1045 – 1052LEERFSRL → WKNGSLRF in AAB99910 (PubMed:9434960).Curated8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21848 mRNA. Translation: CAA79895.1.
AF024570 Genomic DNA. Translation: AAB99910.1.
AK167569 mRNA. Translation: BAE39632.1.
AK168967 mRNA. Translation: BAE40772.1.
AK169040 mRNA. Translation: BAE40829.1.
CCDSiCCDS21210.1.
PIRiS40243.
RefSeqiNP_035261.3. NM_011131.3.
UniGeneiMm.16549.

Genome annotation databases

EnsembliENSMUST00000049343; ENSMUSP00000039776; ENSMUSG00000038644.
GeneIDi18971.
KEGGimmu:18971.
UCSCiuc009gpx.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z21848 mRNA. Translation: CAA79895.1.
AF024570 Genomic DNA. Translation: AAB99910.1.
AK167569 mRNA. Translation: BAE39632.1.
AK168967 mRNA. Translation: BAE40772.1.
AK169040 mRNA. Translation: BAE40829.1.
CCDSiCCDS21210.1.
PIRiS40243.
RefSeqiNP_035261.3. NM_011131.3.
UniGeneiMm.16549.

3D structure databases

ProteinModelPortaliP52431.
SMRiP52431.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202290. 4 interactors.
DIPiDIP-45885N.
IntActiP52431. 1 interactor.
STRINGi10090.ENSMUSP00000039776.

PTM databases

iPTMnetiP52431.
PhosphoSitePlusiP52431.

Proteomic databases

EPDiP52431.
MaxQBiP52431.
PaxDbiP52431.
PeptideAtlasiP52431.
PRIDEiP52431.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000049343; ENSMUSP00000039776; ENSMUSG00000038644.
GeneIDi18971.
KEGGimmu:18971.
UCSCiuc009gpx.2. mouse.

Organism-specific databases

CTDi5424.
MGIiMGI:97741. Pold1.

Phylogenomic databases

eggNOGiKOG0968. Eukaryota.
COG0417. LUCA.
GeneTreeiENSGT00560000077365.
HOGENOMiHOG000036616.
HOVERGENiHBG051395.
InParanoidiP52431.
KOiK02327.
OMAiMRQGLLM.
OrthoDBiEOG091G00TM.
TreeFamiTF352785.

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.

Miscellaneous databases

PMAP-CutDBP52431.
PROiP52431.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038644.
ExpressionAtlasiP52431. baseline and differential.
GenevisibleiP52431. MM.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProiIPR006172. DNA-dir_DNA_pol_B.
IPR017964. DNA-dir_DNA_pol_B_CS.
IPR006133. DNA-dir_DNA_pol_B_exonuc.
IPR006134. DNA-dir_DNA_pol_B_multi_dom.
IPR023211. DNA_pol_palm_dom.
IPR012337. RNaseH-like_dom.
IPR025687. Znf-C4pol.
[Graphical view]
PfamiPF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
PF14260. zf-C4pol. 1 hit.
[Graphical view]
PRINTSiPR00106. DNAPOLB.
SMARTiSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDPOD1_MOUSE
AccessioniPrimary (citable) accession number: P52431
Secondary accession number(s): O54883, Q3TFX6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 143 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
  2. SIMILARITY comments
    Index of protein domains and families

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.