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Protein

DNA polymerase delta catalytic subunit

Gene

POLD1

Organism
Bos taurus (Bovine)
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 (By similarity). 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 (PubMed:11593007).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1011ZincBy similarity1
Metal bindingi1014ZincBy similarity1
Metal bindingi1025ZincBy similarity1
Metal bindingi1028ZincBy similarity1
Metal bindingi1057Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1060Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1070Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1075Iron-sulfur (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1011 – 1028CysA-typeAdd BLAST18

GO - Molecular functioni

GO - Biological processi

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

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: GO_Central
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000464411 – 1106DNA polymerase delta catalytic subunitAdd BLAST1106

Amino acid modifications

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

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiP28339.
PRIDEiP28339.

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 (PubMed:10751307). 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 (By similarity). Interacts with POLDIP2; this interaction is indirect and most probably mediated through POLD2-binding (PubMed:12522211).By similarity2 Publications

Protein-protein interaction databases

IntActiP28339. 4 interactors.
STRINGi9913.ENSBTAP00000014714.

Structurei

3D structure databases

ProteinModelPortaliP28339.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi4 – 19Nuclear localization signalSequence analysisAdd BLAST16
Motifi1057 – 1075CysB 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 fingeri1011 – 1028CysA-typeAdd BLAST18

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0968. Eukaryota.
COG0417. LUCA.
HOVERGENiHBG051395.
InParanoidiP28339.
KOiK02327.

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.

P28339-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDGKRRPGPG PGVPPKRARG GLWDEDEAYR PSQFEEELAL MEEMEAERRL
60 70 80 90 100
QEQEEEELQS ALEAADGQFS PTAIDARWLR PAPPALDPQM EPLIFQQLEI
110 120 130 140 150
DHYVAPARPL PGAPPPSQDS VPILRAFGVT NEGVSVCCHI HGFAPYFYTP
160 170 180 190 200
APPGFGPEHL SELQRELSAA ISRDQRGGKE LTGPAVLAVE LCSRESMFGY
210 220 230 240 250
HGHGPSPFLR ITLALPRLMA PARRLLEQGI RLAGLGTPSF APYEANVDFE
260 270 280 290 300
IRFMVDTDIV GCNWLELPAG KYILRPEGKA TLCQLEADVL WSDVISHPPE
310 320 330 340 350
GEWQRIAPLR VLSFDIECAG RKGIFPEPER DPVIQICSLG LRWGEPEPFL
360 370 380 390 400
RLALTLRPCA PILGAKVQSY EREEDLLQAW STFIRIMDPD VITGYNIQNF
410 420 430 440 450
DLPYLISRAQ TLKVPGFPLL GRVIGLRSNI RESSFQSRQT GRRDSKVVSM
460 470 480 490 500
VGRVQMDMLQ VLLREYKLRS YTLNAVSFHF LGEQKEDVQH SIITDLQNGN
510 520 530 540 550
DQTRRRLAVY CLKDAFLPLR LLERLMVLVN AMEMARVTGV PLGYLLSRGQ
560 570 580 590 600
QVKVVSQLLR QAMRQGLLMP VVKTEGGEDY TGATVIEPLK GYYDVPIATL
610 620 630 640 650
DFSSLYPSIM MAHNLCYTTL LRPGAAQKLG LTEDQFIKTP TGDEFVKASV
660 670 680 690 700
RKGLLPQILE NLLSARKRAK AELAKETDPL RRQVLDGRQL ALKVSANSVY
710 720 730 740 750
GFTGAQVGRL PCLEISQSVT GFGRQMIEKT KQLVETKYTV ENGYSTSAKV
760 770 780 790 800
VYGDTDSVMC RFGVSSVAEA MALGREAADW VSGHFPSPIR LEFEKVYFPY
810 820 830 840 850
LLISKKRYAG LLFSSRPDAH DRMDCKGLEA VRRDNCPLVA NLVTASLRRL
860 870 880 890 900
LIDRDPSGAV AHAQDVISDL LCNRIDISQL VITKELTRAA ADYAGKQAHV
910 920 930 940 950
ELAERMRKRD PGSAPSLGDR VPYVIISAAK GVAAYMKSED PLFVLEHSLP
960 970 980 990 1000
IDTQYYLEQQ LAKPLLRIFE PILGEGRAEA VLLRGDHTRC KTVLTGKVGG
1010 1020 1030 1040 1050
LLAFAKRRNC CIGCRTVLSH QGAVCKFCQP RESELYQKEV SHLSALEERF
1060 1070 1080 1090 1100
SRLWTQCQRC QGSLHEDVIC TSRDCPIFYM RKKVRKDLED QERLLRRFGP

PGPEAW
Length:1,106
Mass (Da):123,709
Last modified:December 1, 1992 - v1
Checksum:iEFC2ED155B290431
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80395 mRNA. Translation: AAA30493.1.
PIRiA39299.
RefSeqiNP_776852.1. NM_174427.2.
UniGeneiBt.4749.

Genome annotation databases

GeneIDi281990.
KEGGibta:281990.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80395 mRNA. Translation: AAA30493.1.
PIRiA39299.
RefSeqiNP_776852.1. NM_174427.2.
UniGeneiBt.4749.

3D structure databases

ProteinModelPortaliP28339.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP28339. 4 interactors.
STRINGi9913.ENSBTAP00000014714.

Proteomic databases

PaxDbiP28339.
PRIDEiP28339.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281990.
KEGGibta:281990.

Organism-specific databases

CTDi5424.

Phylogenomic databases

eggNOGiKOG0968. Eukaryota.
COG0417. LUCA.
HOVERGENiHBG051395.
InParanoidiP28339.
KOiK02327.

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_BOVIN
AccessioniPrimary (citable) accession number: P28339
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
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, Direct protein sequencing, 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.