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Protein

DNA polymerase delta subunit 2

Gene

POLD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (PubMed:12403614, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200). 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 (PubMed:19074196, PubMed:20334433). 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 (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation (PubMed:20227374). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR) (PubMed:24310611). 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 (PubMed:24449906).8 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA excision, DNA repair, DNA replication

Enzyme and pathway databases

BioCyciZFISH:HS02933-MONOMER.
ReactomeiR-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-174411. Polymerase switching on the C-strand of the telomere.
R-HSA-174414. Processive synthesis on the C-strand of the telomere.
R-HSA-174417. Telomere C-strand (Lagging Strand) Synthesis.
R-HSA-174437. Removal of the Flap Intermediate from the C-strand.
R-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5696397. Gap-filling DNA repair synthesis and ligation in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-69091. Polymerase switching.
R-HSA-69166. Removal of the Flap Intermediate.
R-HSA-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:9176. POLD2.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi217L → W: Loss of POLD3-binding in a yeast two-hybrid assay. 1 Publication1
Mutagenesisi224G → W: Loss of POLD3-binding in a yeast two-hybrid assay. 1 Publication1
Mutagenesisi231E → W: Loss of POLD3-binding in a yeast two-hybrid assay. 1 Publication1

Organism-specific databases

DisGeNETi5425.
OpenTargetsiENSG00000106628.
PharmGKBiPA33497.

Polymorphism and mutation databases

BioMutaiPOLD2.
DMDMi1352307.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000961661 – 469DNA polymerase delta subunit 2Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei15PhosphoserineCombined sources1
Modified residuei257PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49005.
MaxQBiP49005.
PaxDbiP49005.
PeptideAtlasiP49005.
PRIDEiP49005.

PTM databases

iPTMnetiP49005.
PhosphoSitePlusiP49005.

Expressioni

Developmental stagei

Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in S.1 Publication

Gene expression databases

BgeeiENSG00000106628.
CleanExiHS_POLD2.
ExpressionAtlasiP49005. baseline and differential.
GenevisibleiP49005. HS.

Organism-specific databases

HPAiHPA026745.

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 (PubMed:22801543, PubMed:17317665). Within Pol-delta4, directly interacts with POLD1, POLD3 and POLD4 (PubMed:11328591, PubMed:16510448). 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 (PubMed:22801543, PubMed:17317665). 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 (PubMed:12403614). Contrary to the other components of Pol-delta4, does not directly interact with PCNA (PubMed:12403614, PubMed:16510448). 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 (PubMed:15670210). Directly interacts with POLDIP2 and POLDIP3 (PubMed:12522211). Directly interacts with KCTD13/PDIP1; in the presence of PCNA, this interaction may stimulate DNA polymerase activity (PubMed:11593007). Component of the DNA polymerase zeta complex (POLZ), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (PubMed:24449906). Interacts with KCTD10 (By similarity).By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PCNAP120042EBI-372354,EBI-358311
POLD1P2834010EBI-372354,EBI-716569
POLD3Q150545EBI-372354,EBI-864956
POLD4Q9HCU83EBI-372354,EBI-864968
WRNIP1Q96S552EBI-372354,EBI-2513471

Protein-protein interaction databases

BioGridi111421. 31 interactors.
IntActiP49005. 17 interactors.
STRINGi9606.ENSP00000386105.

Structurei

Secondary structure

1469
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 7Combined sources6
Beta strandi13 – 16Combined sources4
Beta strandi32 – 34Combined sources3
Helixi37 – 39Combined sources3
Helixi55 – 72Combined sources18
Beta strandi82 – 84Combined sources3
Beta strandi91 – 100Combined sources10
Beta strandi132 – 136Combined sources5
Beta strandi141 – 147Combined sources7
Turni150 – 152Combined sources3
Beta strandi158 – 165Combined sources8
Beta strandi169 – 177Combined sources9
Beta strandi195 – 199Combined sources5
Helixi209 – 223Combined sources15
Helixi229 – 235Combined sources7
Beta strandi238 – 245Combined sources8
Helixi265 – 287Combined sources23
Beta strandi292 – 295Combined sources4
Beta strandi300 – 302Combined sources3
Beta strandi304 – 307Combined sources4
Helixi317 – 320Combined sources4
Beta strandi325 – 327Combined sources3
Beta strandi330 – 336Combined sources7
Beta strandi339 – 343Combined sources5
Helixi347 – 355Combined sources9
Helixi361 – 370Combined sources10
Beta strandi400 – 409Combined sources10
Beta strandi411 – 416Combined sources6
Beta strandi422 – 429Combined sources8
Helixi431 – 434Combined sources4
Beta strandi436 – 441Combined sources6
Turni442 – 445Combined sources4
Beta strandi449 – 454Combined sources6
Turni460 – 462Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3E0JX-ray3.00A/C/E/G1-469[»]
ProteinModelPortaliP49005.
SMRiP49005.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49005.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2732. Eukaryota.
COG1311. LUCA.
GeneTreeiENSGT00390000006780.
HOGENOMiHOG000189057.
HOVERGENiHBG051396.
InParanoidiP49005.
KOiK02328.
PhylomeDBiP49005.
TreeFamiTF101073.

Family and domain databases

InterProiIPR007185. DNA_pol_alpha/epsilon_bsu.
IPR024826. DNA_pol_delta/II_ssu.
[Graphical view]
PANTHERiPTHR10416. PTHR10416. 1 hit.
PfamiPF04042. DNA_pol_E_B. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P49005-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFSEQAAQRA HTLLSPPSAN NATFARVPVA TYTNSSQPFR LGERSFSRQY
60 70 80 90 100
AHIYATRLIQ MRPFLENRAQ QHWGSGVGVK KLCELQPEEK CCVVGTLFKA
110 120 130 140 150
MPLQPSILRE VSEEHNLLPQ PPRSKYIHPD DELVLEDELQ RIKLKGTIDV
160 170 180 190 200
SKLVTGTVLA VFGSVRDDGK FLVEDYCFAD LAPQKPAPPL DTDRFVLLVS
210 220 230 240 250
GLGLGGGGGE SLLGTQLLVD VVTGQLGDEG EQCSAAHVSR VILAGNLLSH
260 270 280 290 300
STQSRDSINK 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 QTVLLVTVPD FSATQTACLV NLRSLACQPI
460
SFSGFGAEDD DLGGLGLGP
Length:469
Mass (Da):51,289
Last modified:February 1, 1996 - v1
Checksum:i389EF730999755AC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti271A → T in BAG35221 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014885303N → S.1 PublicationCorresponds to variant rs3087366dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U21090 mRNA. Translation: AAC50216.1.
AF239710 Genomic DNA. Translation: AAG09763.1.
AY116646 Genomic DNA. Translation: AAM51148.1.
AK292347 mRNA. Translation: BAF85036.1.
AK312294 mRNA. Translation: BAG35221.1.
CH236960 Genomic DNA. Translation: EAL23767.1.
CH471128 Genomic DNA. Translation: EAW61118.1.
BC000459 mRNA. Translation: AAH00459.1.
CCDSiCCDS5477.1.
PIRiI38950.
RefSeqiNP_001120690.1. NM_001127218.2.
NP_001243808.1. NM_001256879.1.
NP_006221.2. NM_006230.3.
UniGeneiHs.306791.
Hs.740138.

Genome annotation databases

EnsembliENST00000406581; ENSP00000386105; ENSG00000106628.
ENST00000452185; ENSP00000395231; ENSG00000106628.
GeneIDi5425.
KEGGihsa:5425.
UCSCiuc010kxz.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U21090 mRNA. Translation: AAC50216.1.
AF239710 Genomic DNA. Translation: AAG09763.1.
AY116646 Genomic DNA. Translation: AAM51148.1.
AK292347 mRNA. Translation: BAF85036.1.
AK312294 mRNA. Translation: BAG35221.1.
CH236960 Genomic DNA. Translation: EAL23767.1.
CH471128 Genomic DNA. Translation: EAW61118.1.
BC000459 mRNA. Translation: AAH00459.1.
CCDSiCCDS5477.1.
PIRiI38950.
RefSeqiNP_001120690.1. NM_001127218.2.
NP_001243808.1. NM_001256879.1.
NP_006221.2. NM_006230.3.
UniGeneiHs.306791.
Hs.740138.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3E0JX-ray3.00A/C/E/G1-469[»]
ProteinModelPortaliP49005.
SMRiP49005.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111421. 31 interactors.
IntActiP49005. 17 interactors.
STRINGi9606.ENSP00000386105.

PTM databases

iPTMnetiP49005.
PhosphoSitePlusiP49005.

Polymorphism and mutation databases

BioMutaiPOLD2.
DMDMi1352307.

Proteomic databases

EPDiP49005.
MaxQBiP49005.
PaxDbiP49005.
PeptideAtlasiP49005.
PRIDEiP49005.

Protocols and materials databases

DNASUi5425.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000406581; ENSP00000386105; ENSG00000106628.
ENST00000452185; ENSP00000395231; ENSG00000106628.
GeneIDi5425.
KEGGihsa:5425.
UCSCiuc010kxz.5. human.

Organism-specific databases

CTDi5425.
DisGeNETi5425.
GeneCardsiPOLD2.
HGNCiHGNC:9176. POLD2.
HPAiHPA026745.
MIMi600815. gene.
neXtProtiNX_P49005.
OpenTargetsiENSG00000106628.
PharmGKBiPA33497.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2732. Eukaryota.
COG1311. LUCA.
GeneTreeiENSGT00390000006780.
HOGENOMiHOG000189057.
HOVERGENiHBG051396.
InParanoidiP49005.
KOiK02328.
PhylomeDBiP49005.
TreeFamiTF101073.

Enzyme and pathway databases

BioCyciZFISH:HS02933-MONOMER.
ReactomeiR-HSA-110314. Recognition of DNA damage by PCNA-containing replication complex.
R-HSA-174411. Polymerase switching on the C-strand of the telomere.
R-HSA-174414. Processive synthesis on the C-strand of the telomere.
R-HSA-174417. Telomere C-strand (Lagging Strand) Synthesis.
R-HSA-174437. Removal of the Flap Intermediate from the C-strand.
R-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-HSA-5656169. Termination of translesion DNA synthesis.
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5696397. Gap-filling DNA repair synthesis and ligation in GG-NER.
R-HSA-5696400. Dual Incision in GG-NER.
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-69091. Polymerase switching.
R-HSA-69166. Removal of the Flap Intermediate.
R-HSA-69183. Processive synthesis on the lagging strand.

Miscellaneous databases

ChiTaRSiPOLD2. human.
EvolutionaryTraceiP49005.
GeneWikiiPOLD2.
GenomeRNAii5425.
PROiP49005.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106628.
CleanExiHS_POLD2.
ExpressionAtlasiP49005. baseline and differential.
GenevisibleiP49005. HS.

Family and domain databases

InterProiIPR007185. DNA_pol_alpha/epsilon_bsu.
IPR024826. DNA_pol_delta/II_ssu.
[Graphical view]
PANTHERiPTHR10416. PTHR10416. 1 hit.
PfamiPF04042. DNA_pol_E_B. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDPOD2_HUMAN
AccessioniPrimary (citable) accession number: P49005
Secondary accession number(s): A4D2J4, B2R5S4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 164 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.