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Protein

DNA polymerase delta catalytic subunit

Gene

Pold1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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

  • 3'-5'-exodeoxyribonuclease activity Source: GO_Central
  • 3'-5' exonuclease activity Source: MGI
  • 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  • chromatin binding Source: UniProtKB
  • damaged DNA binding Source: UniProtKB
  • DNA binding Source: MGI
  • DNA-directed DNA polymerase activity Source: MGI
  • enzyme binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • nucleotide binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, DNA-directed DNA polymerase, Exonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, Transferase
Biological processDNA damage, DNA excision, DNA repair, DNA replication
Ligand4Fe-4S, 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:Pold1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:97741 Pold1

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_00000464441 – 1105DNA polymerase delta catalytic subunitAdd BLAST1105

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Omega-N-methylarginineBy similarity1
Cross-linki572Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Ubl conjugation

Proteomic databases

EPDiP52431
MaxQBiP52431
PaxDbiP52431
PeptideAtlasiP52431
PRIDEiP52431

PTM databases

iPTMnetiP52431
PhosphoSitePlusiP52431

Miscellaneous databases

PMAP-CutDBiP52431

Expressioni

Gene expression databases

BgeeiENSMUSG00000038644 Expressed in 278 organ(s), highest expression level in optic fissure
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. Interacts with CIAO1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202290, 4 interactors
ComplexPortaliCPX-2098 Delta DNA polymerase complex
CORUMiP52431
DIPiDIP-45885N
IntActiP52431, 2 interactors
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

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
OMAiCLVNYTE
OrthoDBiEOG091G00TM
TreeFamiTF352785

Family and domain databases

Gene3Di3.30.420.10, 1 hit
3.90.1600.10, 1 hit
InterProiView protein in InterPro
IPR006172 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_sf
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
IPR025687 Znf-C4pol
PfamiView protein in Pfam
PF00136 DNA_pol_B, 1 hit
PF03104 DNA_pol_B_exo1, 1 hit
PF14260 zf-C4pol, 1 hit
PRINTSiPR00106 DNAPOLB
SMARTiView protein in SMART
SM00486 POLBc, 1 hit
SUPFAMiSSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS00116 DNA_POLYMERASE_B, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RFB8D6RFB8_MOUSE
DNA polymerase
Pold1
981Annotation score:
D3YVY8D3YVY8_MOUSE
DNA polymerase delta catalytic subu...
Pold1
153Annotation score:

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

Similar proteinsi

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
ComplexPortaliCPX-2098 Delta DNA polymerase complex
CORUMiP52431
DIPiDIP-45885N
IntActiP52431, 2 interactors
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
OMAiCLVNYTE
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

ChiTaRSiPold1 mouse
PMAP-CutDBiP52431
PROiPR:P52431
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038644 Expressed in 278 organ(s), highest expression level in optic fissure
ExpressionAtlasiP52431 baseline and differential
GenevisibleiP52431 MM

Family and domain databases

Gene3Di3.30.420.10, 1 hit
3.90.1600.10, 1 hit
InterProiView protein in InterPro
IPR006172 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_sf
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
IPR025687 Znf-C4pol
PfamiView protein in Pfam
PF00136 DNA_pol_B, 1 hit
PF03104 DNA_pol_B_exo1, 1 hit
PF14260 zf-C4pol, 1 hit
PRINTSiPR00106 DNAPOLB
SMARTiView protein in SMART
SM00486 POLBc, 1 hit
SUPFAMiSSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS00116 DNA_POLYMERASE_B, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDPOD1_MOUSE
AccessioniPrimary (citable) accession number: P52431
Secondary accession number(s): O54883, Q3TFX6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 156 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, Direct protein sequencing, Reference proteome

Documents

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