UniProtKB - Q9HCU8 (DPOD4_HUMAN)
DNA polymerase delta subunit 4
POLD4
Functioni
GO - Biological processi
- base-excision repair, gap-filling Source: Reactome
- DNA damage response, detection of DNA damage Source: Reactome
- DNA-dependent DNA replication Source: GO_Central
- DNA synthesis involved in DNA repair Source: GO_Central
- mismatch repair Source: Reactome
- 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
PathwayCommonsi | Q9HCU8 |
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 4Alternative name(s): DNA polymerase delta subunit p12 |
Gene namesi | Name:POLD4 Synonyms:POLDS |
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
HGNCi | HGNC:14106, POLD4 |
MIMi | 611525, gene |
neXtProti | NX_Q9HCU8 |
VEuPathDBi | HostDB:ENSG00000175482.8 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Note: Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation.1 Publication
Nucleus
- delta DNA polymerase complex Source: GO_Central
- nucleoplasm Source: Reactome
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 16 | Missing : Complete loss of PCNA binding and of degradation after UV irradiation. 1 PublicationAdd BLAST | 16 | |
Mutagenesisi | 4 | K → A: No effect on PCNA binding. 1 Publication | 1 | |
Mutagenesisi | 4 | K → Q: No effect on PCNA binding, nor on degradation after UV irradiation; when associated with Y-10. No effect on PCNA binding, but normal degradation after UV irradiation; when associated with Y-10 and A-15. 1 Publication | 1 | |
Mutagenesisi | 4 | K → R: No effect on ubiquitination. Loss of ubiquitination, when associated with R-15, R-25, R-74 and R-89. 1 Publication | 1 | |
Mutagenesisi | 7 | I → A: Complete loss of PCNA binding; when associated with 10-AA-11. 1 Publication | 1 | |
Mutagenesisi | 8 | T → A: Strongly increased stability following UV irradiation; when associated with A-9. 1 Publication | 1 | |
Mutagenesisi | 8 | T → D: Complete loss of PCNA binding. 1 Publication | 1 | |
Mutagenesisi | 9 | D → A: Strongly increased stability following UV irradiation; when associated with A-8. 1 Publication | 1 | |
Mutagenesisi | 10 – 11 | SY → AA: Complete loss of PCNA binding; when associated with A-7. 1 Publication | 2 | |
Mutagenesisi | 10 | S → Y: No effect on PCNA binding, nor on degradation after UV irradiation; when associated with Q-4. No effect on PCNA binding, but normal degradation after UV irradiation with Q-4 and A-15. 1 Publication | 1 | |
Mutagenesisi | 15 | K → A: Decreased PCNA binding. No effect on PCNA binding, but normal degradation after UV irradiation; when associated with Q-4 and Y-10. Increased stability following UV irradiation and no trough during S phase; when associated with A-16 and A-17. 2 Publications | 1 | |
Mutagenesisi | 15 | K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-25, R-74 and R-89. 1 Publication | 1 | |
Mutagenesisi | 16 | R → A: Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-17. 1 Publication | 1 | |
Mutagenesisi | 17 | R → A: Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-16. 1 Publication | 1 | |
Mutagenesisi | 25 | K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-74 and R-89. 1 Publication | 1 | |
Mutagenesisi | 74 | K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-89. 1 Publication | 1 | |
Mutagenesisi | 89 | K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-74. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 57804 |
OpenTargetsi | ENSG00000175482 |
PharmGKBi | PA33498 |
Miscellaneous databases
Pharosi | Q9HCU8, Tbio |
Chemistry databases
ChEMBLi | CHEMBL2363042 |
Genetic variation databases
BioMutai | POLD4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186051 | 1 – 107 | DNA polymerase delta subunit 4Add BLAST | 107 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationProteomic databases
EPDi | Q9HCU8 |
jPOSTi | Q9HCU8 |
MassIVEi | Q9HCU8 |
MaxQBi | Q9HCU8 |
PaxDbi | Q9HCU8 |
PeptideAtlasi | Q9HCU8 |
PRIDEi | Q9HCU8 |
ProteomicsDBi | 26732 81802 [Q9HCU8-1] |
PTM databases
iPTMneti | Q9HCU8 |
PhosphoSitePlusi | Q9HCU8 |
Expressioni
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSG00000175482, Expressed in mucosa of transverse colon and 112 other tissues |
ExpressionAtlasi | Q9HCU8, baseline and differential |
Genevisiblei | Q9HCU8, HS |
Organism-specific databases
HPAi | ENSG00000175482, Low tissue specificity |
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:16510448, PubMed:17317665, PubMed:22801543). Within this complex, directly interacts with POLD1 and POLD2 (PubMed:12403614, PubMed:16510448). Directly interacts with PCNA, as do POLD1 and POLD3; this interaction stimulates Pol-delta4 polymerase activity (PubMed:24022480). As POLD1 and POLD2, 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). Upon genotoxic stress induced by DNA damaging agents or by replication stress, POLD4 is proteolytically degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) which has an increased proofreading activity (PubMed:22801543, PubMed:17317665). The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2 (PubMed:12522211).
7 PublicationsBinary interactionsi
Hide detailsQ9HCU8
With | #Exp. | IntAct |
---|---|---|
PCNA [P12004] | 4 | EBI-864968,EBI-358311 |
POLD1 [P28340] | 12 | EBI-864968,EBI-716569 |
POLD2 [P49005] | 5 | EBI-864968,EBI-372354 |
WRNIP1 [Q96S55] | 2 | EBI-864968,EBI-2513471 |
Protein-protein interaction databases
BioGRIDi | 121774, 9 interactors |
ComplexPortali | CPX-2097, Delta DNA polymerase complex |
CORUMi | Q9HCU8 |
IntActi | Q9HCU8, 8 interactors |
STRINGi | 9606.ENSP00000311368 |
Miscellaneous databases
RNActi | Q9HCU8, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9HCU8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1 – 16 | PCNA-interaction protein motif (PIP box)2 PublicationsAdd BLAST | 16 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502SC9I, Eukaryota |
GeneTreei | ENSGT00390000005096 |
HOGENOMi | CLU_132157_0_0_1 |
InParanoidi | Q9HCU8 |
OMAi | WEYGPCT |
PhylomeDBi | Q9HCU8 |
TreeFami | TF103004 |
Family and domain databases
InterProi | View protein in InterPro IPR007218, DNA_pol_delta_4 |
PANTHERi | PTHR14303, PTHR14303, 1 hit |
Pfami | View protein in Pfam PF04081, DNA_pol_delta_4, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGRKRLITDS YPVVKRREGP AGHSKGELAP ELGEEPQPRD EEEAELELLR
60 70 80 90 100
QFDLAWQYGP CTGITRLQRW CRAKQMGLEP PPEVWQVLKT HPGDPRFQCS
LWHLYPL
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE9PL15 | E9PL15_HUMAN | DNA polymerase delta subunit 4 | POLD4 | 32 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_022269 | 39 | R → P1 PublicationCorresponds to variant dbSNP:rs28364240Ensembl. | 1 | |
Natural variantiVAR_057526 | 59 | G → R. Corresponds to variant dbSNP:rs34136263Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_046864 | 63 – 107 | GITRL…HLYPL → VSGISIPYEAPRKTSCP in isoform 2. 1 PublicationAdd BLAST | 45 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF179890 mRNA Translation: AAG08966.1 AY928482 Genomic DNA Translation: AAX09676.1 AP003419 Genomic DNA No translation available. BG403692 mRNA No translation available. |
CCDSi | CCDS58149.1 [Q9HCU8-2] CCDS8158.1 [Q9HCU8-1] |
RefSeqi | NP_001243799.1, NM_001256870.1 [Q9HCU8-2] NP_066996.3, NM_021173.4 [Q9HCU8-1] |
Genome annotation databases
Ensembli | ENST00000312419; ENSP00000311368; ENSG00000175482 [Q9HCU8-1] ENST00000539074; ENSP00000444780; ENSG00000175482 [Q9HCU8-2] |
GeneIDi | 57804 |
KEGGi | hsa:57804 |
UCSCi | uc001okm.5, human [Q9HCU8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF179890 mRNA Translation: AAG08966.1 AY928482 Genomic DNA Translation: AAX09676.1 AP003419 Genomic DNA No translation available. BG403692 mRNA No translation available. |
CCDSi | CCDS58149.1 [Q9HCU8-2] CCDS8158.1 [Q9HCU8-1] |
RefSeqi | NP_001243799.1, NM_001256870.1 [Q9HCU8-2] NP_066996.3, NM_021173.4 [Q9HCU8-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6HVO | X-ray | 2.10 | D/E/F | 1-19 | [»] | |
6S1M | electron microscopy | 4.27 | D | 2-107 | [»] | |
6S1N | electron microscopy | 4.86 | D | 2-107 | [»] | |
6S1O | electron microscopy | 8.10 | D | 2-107 | [»] | |
6TNY | electron microscopy | 3.08 | D | 2-107 | [»] | |
6TNZ | electron microscopy | 4.05 | D | 2-107 | [»] | |
SMRi | Q9HCU8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121774, 9 interactors |
ComplexPortali | CPX-2097, Delta DNA polymerase complex |
CORUMi | Q9HCU8 |
IntActi | Q9HCU8, 8 interactors |
STRINGi | 9606.ENSP00000311368 |
Chemistry databases
ChEMBLi | CHEMBL2363042 |
PTM databases
iPTMneti | Q9HCU8 |
PhosphoSitePlusi | Q9HCU8 |
Genetic variation databases
BioMutai | POLD4 |
Proteomic databases
EPDi | Q9HCU8 |
jPOSTi | Q9HCU8 |
MassIVEi | Q9HCU8 |
MaxQBi | Q9HCU8 |
PaxDbi | Q9HCU8 |
PeptideAtlasi | Q9HCU8 |
PRIDEi | Q9HCU8 |
ProteomicsDBi | 26732 81802 [Q9HCU8-1] |
Protocols and materials databases
Antibodypediai | 30343, 53 antibodies |
DNASUi | 57804 |
Genome annotation databases
Ensembli | ENST00000312419; ENSP00000311368; ENSG00000175482 [Q9HCU8-1] ENST00000539074; ENSP00000444780; ENSG00000175482 [Q9HCU8-2] |
GeneIDi | 57804 |
KEGGi | hsa:57804 |
UCSCi | uc001okm.5, human [Q9HCU8-1] |
Organism-specific databases
CTDi | 57804 |
DisGeNETi | 57804 |
GeneCardsi | POLD4 |
HGNCi | HGNC:14106, POLD4 |
HPAi | ENSG00000175482, Low tissue specificity |
MIMi | 611525, gene |
neXtProti | NX_Q9HCU8 |
OpenTargetsi | ENSG00000175482 |
PharmGKBi | PA33498 |
VEuPathDBi | HostDB:ENSG00000175482.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SC9I, Eukaryota |
GeneTreei | ENSGT00390000005096 |
HOGENOMi | CLU_132157_0_0_1 |
InParanoidi | Q9HCU8 |
OMAi | WEYGPCT |
PhylomeDBi | Q9HCU8 |
TreeFami | TF103004 |
Enzyme and pathway databases
PathwayCommonsi | Q9HCU8 |
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
BioGRID-ORCSi | 57804, 18 hits in 1000 CRISPR screens |
ChiTaRSi | POLD4, human |
GeneWikii | POLD4 |
GenomeRNAii | 57804 |
Pharosi | Q9HCU8, Tbio |
PROi | PR:Q9HCU8 |
RNActi | Q9HCU8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000175482, Expressed in mucosa of transverse colon and 112 other tissues |
ExpressionAtlasi | Q9HCU8, baseline and differential |
Genevisiblei | Q9HCU8, HS |
Family and domain databases
InterProi | View protein in InterPro IPR007218, DNA_pol_delta_4 |
PANTHERi | PTHR14303, PTHR14303, 1 hit |
Pfami | View protein in Pfam PF04081, DNA_pol_delta_4, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DPOD4_HUMAN | |
Accessioni | Q9HCU8Primary (citable) accession number: Q9HCU8 Secondary accession number(s): F5H506 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 26, 2001 |
Last sequence update: | March 1, 2001 | |
Last modified: | April 7, 2021 | |
This is version 158 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, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families