UniProtKB - P49005 (DPOD2_HUMAN)
Protein
DNA polymerase delta subunit 2
Gene
POLD2
Organism
Homo sapiens (Human)
Status
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
- DNA binding Source: InterPro
- DNA-directed DNA polymerase activity Source: Reactome
GO - Biological processi
- DNA damage response, detection of DNA damage Source: Reactome
- DNA replication Source: ProtInc
- DNA strand elongation involved in DNA replication Source: GO_Central
- nucleotide-excision repair, DNA gap filling Source: Reactome
- nucleotide-excision repair, DNA incision Source: Reactome
- nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
- telomere maintenance Source: Reactome
- telomere maintenance via semi-conservative replication Source: Reactome
- transcription-coupled nucleotide-excision repair Source: Reactome
- translesion synthesis Source: Reactome
Keywordsi
Biological process | DNA damage, DNA excision, DNA repair, DNA replication |
Enzyme and pathway databases
Reactomei | R-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 2Alternative name(s): DNA polymerase delta subunit p50 |
Gene namesi | Name:POLD2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000106628.10 |
HGNCi | HGNC:9176 POLD2 |
MIMi | 600815 gene |
neXtProti | NX_P49005 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Note: Recruited to DNA damage sites within 2 hours following UV irradiation.1 Publication
Nucleus
- delta DNA polymerase complex Source: GO_Central
- nucleoplasm Source: HPA
- nucleus Source: ProtInc
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 217 | L → W: Loss of POLD3-binding in a yeast two-hybrid assay. 1 Publication | 1 | |
Mutagenesisi | 224 | G → W: Loss of POLD3-binding in a yeast two-hybrid assay. 1 Publication | 1 | |
Mutagenesisi | 231 | E → W: Loss of POLD3-binding in a yeast two-hybrid assay. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 5425 |
OpenTargetsi | ENSG00000106628 |
PharmGKBi | PA33497 |
Chemistry databases
ChEMBLi | CHEMBL2363042 |
Polymorphism and mutation databases
BioMutai | POLD2 |
DMDMi | 1352307 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000096166 | 1 – 469 | DNA polymerase delta subunit 2Add BLAST | 469 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 15 | PhosphoserineCombined sources | 1 | |
Modified residuei | 257 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P49005 |
jPOSTi | P49005 |
MaxQBi | P49005 |
PaxDbi | P49005 |
PeptideAtlasi | P49005 |
PRIDEi | P49005 |
ProteomicsDBi | 55954 |
PTM databases
iPTMneti | P49005 |
PhosphoSitePlusi | P49005 |
Expressioni
Developmental stagei
Expression is cell cycle-dependent, with highest levels in G2/M phase and lowest in S.1 Publication
Gene expression databases
Bgeei | ENSG00000106628 Expressed in 231 organ(s), highest expression level in heart left ventricle |
ExpressionAtlasi | P49005 baseline and differential |
Genevisiblei | P49005 HS |
Organism-specific databases
HPAi | HPA026745 |
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
Protein-protein interaction databases
BioGridi | 111421, 37 interactors |
ComplexPortali | CPX-2097 Delta DNA polymerase complex |
CORUMi | P49005 |
IntActi | P49005, 19 interactors |
MINTi | P49005 |
STRINGi | 9606.ENSP00000386105 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3E0J | X-ray | 3.00 | A/C/E/G | 1-469 | [»] | |
ProteinModelPortali | P49005 | |||||
SMRi | P49005 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P49005 |
Family & Domainsi
Sequence similaritiesi
Belongs to the DNA polymerase delta/II small subunit family.Curated
Phylogenomic databases
eggNOGi | KOG2732 Eukaryota COG1311 LUCA |
GeneTreei | ENSGT00390000006780 |
HOGENOMi | HOG000189057 |
HOVERGENi | HBG051396 |
InParanoidi | P49005 |
KOi | K02328 |
OrthoDBi | 736068at2759 |
PhylomeDBi | P49005 |
TreeFami | TF101073 |
Family and domain databases
InterProi | View protein in InterPro IPR007185 DNA_pol_alpha/epsilon_bsu IPR040663 DNA_pol_D_N IPR024826 DNA_pol_delta/II_ssu |
PANTHERi | PTHR10416 PTHR10416, 1 hit |
Pfami | View protein in Pfam PF18018 DNA_pol_D_N, 1 hit PF04042 DNA_pol_E_B, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All
P49005-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WWF6 | A0A087WWF6_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 504 | Annotation score: | ||
F8W8R3 | F8W8R3_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 455 | Annotation score: | ||
C9JHC7 | C9JHC7_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 257 | Annotation score: | ||
H7C1B3 | H7C1B3_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 83 | Annotation score: | ||
C9JLE1 | C9JLE1_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 220 | Annotation score: | ||
C9J8Z7 | C9J8Z7_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 155 | Annotation score: | ||
C9IZD2 | C9IZD2_HUMAN | DNA polymerase delta subunit 2 | POLD2 | 148 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 271 | A → T in BAG35221 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_014885 | 303 | N → S1 PublicationCorresponds to variant dbSNP:rs3087366Ensembl. | 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 |
CCDSi | CCDS5477.1 |
PIRi | I38950 |
RefSeqi | NP_001120690.1, NM_001127218.2 NP_001243808.1, NM_001256879.1 NP_006221.2, NM_006230.3 |
UniGenei | Hs.306791 Hs.740138 |
Genome annotation databases
Ensembli | ENST00000406581; ENSP00000386105; ENSG00000106628 ENST00000452185; ENSP00000395231; ENSG00000106628 |
GeneIDi | 5425 |
KEGGi | hsa:5425 |
UCSCi | uc010kxz.5 human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS5477.1 |
PIRi | I38950 |
RefSeqi | NP_001120690.1, NM_001127218.2 NP_001243808.1, NM_001256879.1 NP_006221.2, NM_006230.3 |
UniGenei | Hs.306791 Hs.740138 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3E0J | X-ray | 3.00 | A/C/E/G | 1-469 | [»] | |
ProteinModelPortali | P49005 | |||||
SMRi | P49005 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 111421, 37 interactors |
ComplexPortali | CPX-2097 Delta DNA polymerase complex |
CORUMi | P49005 |
IntActi | P49005, 19 interactors |
MINTi | P49005 |
STRINGi | 9606.ENSP00000386105 |
Chemistry databases
ChEMBLi | CHEMBL2363042 |
PTM databases
iPTMneti | P49005 |
PhosphoSitePlusi | P49005 |
Polymorphism and mutation databases
BioMutai | POLD2 |
DMDMi | 1352307 |
Proteomic databases
EPDi | P49005 |
jPOSTi | P49005 |
MaxQBi | P49005 |
PaxDbi | P49005 |
PeptideAtlasi | P49005 |
PRIDEi | P49005 |
ProteomicsDBi | 55954 |
Protocols and materials databases
DNASUi | 5425 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENST00000406581; ENSP00000386105; ENSG00000106628 ENST00000452185; ENSP00000395231; ENSG00000106628 |
GeneIDi | 5425 |
KEGGi | hsa:5425 |
UCSCi | uc010kxz.5 human |
Organism-specific databases
CTDi | 5425 |
DisGeNETi | 5425 |
EuPathDBi | HostDB:ENSG00000106628.10 |
GeneCardsi | POLD2 |
HGNCi | HGNC:9176 POLD2 |
HPAi | HPA026745 |
MIMi | 600815 gene |
neXtProti | NX_P49005 |
OpenTargetsi | ENSG00000106628 |
PharmGKBi | PA33497 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2732 Eukaryota COG1311 LUCA |
GeneTreei | ENSGT00390000006780 |
HOGENOMi | HOG000189057 |
HOVERGENi | HBG051396 |
InParanoidi | P49005 |
KOi | K02328 |
OrthoDBi | 736068at2759 |
PhylomeDBi | P49005 |
TreeFami | TF101073 |
Enzyme and pathway databases
Reactomei | R-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
ChiTaRSi | POLD2 human |
EvolutionaryTracei | P49005 |
GeneWikii | POLD2 |
GenomeRNAii | 5425 |
PROi | PR:P49005 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000106628 Expressed in 231 organ(s), highest expression level in heart left ventricle |
ExpressionAtlasi | P49005 baseline and differential |
Genevisiblei | P49005 HS |
Family and domain databases
InterProi | View protein in InterPro IPR007185 DNA_pol_alpha/epsilon_bsu IPR040663 DNA_pol_D_N IPR024826 DNA_pol_delta/II_ssu |
PANTHERi | PTHR10416 PTHR10416, 1 hit |
Pfami | View protein in Pfam PF18018 DNA_pol_D_N, 1 hit PF04042 DNA_pol_E_B, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | DPOD2_HUMAN | |
Accessioni | P49005Primary (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: | February 13, 2019 | |
This is version 179 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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 proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations