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Protein

DNA polymerase delta catalytic subunit

Gene

Pold1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 bindingi1008ZincBy similarity1
Metal bindingi1011ZincBy similarity1
Metal bindingi1022ZincBy similarity1
Metal bindingi1025ZincBy similarity1
Metal bindingi1054Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1057Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1067Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1072Iron-sulfur (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1008 – 1025CysA-typeAdd BLAST18

GO - Molecular functioni

GO - Biological processi

  • base-excision repair, gap-filling Source: GO_Central
  • cellular response to UV Source: UniProtKB
  • DNA biosynthetic process Source: RGD
  • DNA-dependent DNA replication Source: RGD
  • DNA replication Source: RGD
  • DNA replication proofreading Source: GO_Central
  • fatty acid homeostasis Source: UniProtKB
  • nucleotide-excision repair, DNA gap filling Source: GO_Central
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

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase delta catalytic subunit (EC:2.7.7.7, EC:3.1.11.-)
Gene namesi
Name:Pold1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621839. 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

  • delta DNA polymerase complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000464451 – 1103DNA polymerase delta catalytic subunitAdd BLAST1103

Proteomic databases

PaxDbiO54747.
PRIDEiO54747.

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026797.

Structurei

3D structure databases

ProteinModelPortaliO54747.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 17Nuclear localization signalSequence analysisAdd BLAST14
Motifi1054 – 1072CysB 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 fingeri1008 – 1025CysA-typeAdd BLAST18

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0968. Eukaryota.
COG0417. LUCA.
HOGENOMiHOG000036616.
HOVERGENiHBG051395.
InParanoidiO54747.
KOiK02327.
PhylomeDBiO54747.

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.

O54747-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDGKRRQAPS SGVPPKRACK GLWDEDEPSQ FEENLALLEE IEAENRLQEA
60 70 80 90 100
EEELQLPPEG IVGGQFSTAD IDPRWLRPTP LALDPSTEPL IFQQLEIDHY
110 120 130 140 150
VGTSPPLPEG PPASRNSVPI LRAFGVTDEG FSVCCHIHGF APYFYTPAPP
160 170 180 190 200
GFGAEHLSEL QRELNAAISR DQRGGKELSG PAVLAIELCS RESMFGYHGH
210 220 230 240 250
GPSPFLRITL ALPRLMAPAR RLLEQGIRVP GLGTPSFAPY EANVDFEIRF
260 270 280 290 300
MVDADIVGCN WLELPAGKYV RRAEKKATLC QLEVDVLWSD VISHPPEGQW
310 320 330 340 350
QRIAPLRVLS FDIECAGRKG IFPEPERDPV IQICSLGLRW GEPEPFLRLA
360 370 380 390 400
LTLRPCAPIL GAKVQSYERE EDLLQAWATF ILAMDPDVIT GYNIQNFDLP
410 420 430 440 450
YLISRAQTLK VDRFPFLGRV TGLRSNIRDS SFQSRQVGRR DSKVVSMVGR
460 470 480 490 500
VQMDMLQVLL REYKLRSYTL NAVSFHFLGE QKEDVQHSII TDLQNGNEQT
510 520 530 540 550
RRRLAVYCLK DAFLPLRLLE RLMVLVNNVE MARVTGVPLG YLLSRGQQVK
560 570 580 590 600
VVSQLLRQAM REGLLMPVVK TEGGEDYTGA TVIEPLKGYY DVPIATLDFS
610 620 630 640 650
SLYPSIMMAH NLCYTTLLRP GAAQKLGLKP DEFIKTPTGD EFVKASVRKG
660 670 680 690 700
LLPQILENLL SARKRAKAEL AQETDPLRRQ VLDGRQLALK VSPNSVYGFT
710 720 730 740 750
GAQVGKLPCL EISQSVTGFG RQMIEKTKQL VETKYTLENG YDANAKVVYG
760 770 780 790 800
DTDSVMCRFG VSSVAEAMSL GREAANWVSS HFPSPIRLEF EKVYFPYLLI
810 820 830 840 850
SKKRYAGLLF SSRSDAHDRM DCKGLEAVRR DNCPLVANLV TSSLRRILVD
860 870 880 890 900
RDPDGAVAHA KDVISDLLCN RIDISQLVIT KELTRAAADY AGKQAHVELA
910 920 930 940 950
ERMRKRDPGS APNLGDRVPY VIIGAAKGVA AYMKSEDPLF VLEHSLPIDT
960 970 980 990 1000
QYYLEQQLAK PLLRIFEPIL GEGRAESVLL RGDHTRCKTV LTSKVGGLLA
1010 1020 1030 1040 1050
FTKRRNSCIG CRSVIDHQGA VCKFCQPRES ELYQKEVSHL NALEERFSRL
1060 1070 1080 1090 1100
WTQCQRCQGS LHEDVICTSR DCPIFYMRKK VRKDLEDQER LLQRFGPPGP

EAW
Length:1,103
Mass (Da):123,601
Last modified:June 1, 1998 - v1
Checksum:i361086DDC1B50639
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222691 mRNA. Translation: CAA10946.1.
RefSeqiNP_067694.1. NM_021662.2.
UniGeneiRn.88690.

Genome annotation databases

GeneIDi59294.
KEGGirno:59294.
UCSCiRGD:621839. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ222691 mRNA. Translation: CAA10946.1.
RefSeqiNP_067694.1. NM_021662.2.
UniGeneiRn.88690.

3D structure databases

ProteinModelPortaliO54747.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000026797.

Proteomic databases

PaxDbiO54747.
PRIDEiO54747.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59294.
KEGGirno:59294.
UCSCiRGD:621839. rat.

Organism-specific databases

CTDi5424.
RGDi621839. Pold1.

Phylogenomic databases

eggNOGiKOG0968. Eukaryota.
COG0417. LUCA.
HOGENOMiHOG000036616.
HOVERGENiHBG051395.
InParanoidiO54747.
KOiK02327.
PhylomeDBiO54747.

Miscellaneous databases

PROiO54747.

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_RAT
AccessioniPrimary (citable) accession number: O54747
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.