Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - Q9HCU8 (DPOD4_HUMAN)

Protein

DNA polymerase delta subunit 4

Gene

POLD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity (PubMed:16510448, PubMed:19074196, PubMed:20334433). Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system (PubMed:24035200). Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb (PubMed:24310611). Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites (PubMed:19074196). Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival (PubMed:24022480).6 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processDNA damage, DNA excision, DNA repair, DNA replication

Enzyme and pathway databases

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 4
Alternative name(s):
DNA polymerase delta subunit p12
Gene namesi
Name:POLD4
Synonyms:POLDS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000175482.8
HGNCiHGNC:14106 POLD4
MIMi611525 gene
neXtProtiNX_Q9HCU8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1 – 16Missing : Complete loss of PCNA binding and of degradation after UV irradiation. 1 PublicationAdd BLAST16
Mutagenesisi4K → A: No effect on PCNA binding. 1 Publication1
Mutagenesisi4K → 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 Publication1
Mutagenesisi4K → R: No effect on ubiquitination. Loss of ubiquitination, when associated with R-15, R-25, R-74 and R-89. 1 Publication1
Mutagenesisi7I → A: Complete loss of PCNA binding; when associated with 10-AA-11. 1 Publication1
Mutagenesisi8T → A: Strongly increased stability following UV irradiation; when associated with A-9. 1 Publication1
Mutagenesisi8T → D: Complete loss of PCNA binding. 1 Publication1
Mutagenesisi9D → A: Strongly increased stability following UV irradiation; when associated with A-8. 1 Publication1
Mutagenesisi10 – 11SY → AA: Complete loss of PCNA binding; when associated with A-7. 1 Publication2
Mutagenesisi10S → 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 Publication1
Mutagenesisi15K → 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 Publications1
Mutagenesisi15K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-25, R-74 and R-89. 1 Publication1
Mutagenesisi16R → A: Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-17. 1 Publication1
Mutagenesisi17R → A: Increased stability following UV irradiation and no trough during S phase; when associated with A-15 and A-16. 1 Publication1
Mutagenesisi25K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-74 and R-89. 1 Publication1
Mutagenesisi74K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-89. 1 Publication1
Mutagenesisi89K → R: No effect on ubiquitination. Loss of ubiquitination; when associated with R-4, R-15, R-25 and R-74. 1 Publication1

Organism-specific databases

DisGeNETi57804
OpenTargetsiENSG00000175482
PharmGKBiPA33498

Chemistry databases

ChEMBLiCHEMBL2363042

Polymorphism and mutation databases

BioMutaiPOLD4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860511 – 107DNA polymerase delta subunit 4Add BLAST107

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation (PubMed:17317665, PubMed:16934752, PubMed:23233665, PubMed:23913683). This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)) (PubMed:23233665, PubMed:24022480). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage (PubMed:24022480).5 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9HCU8
MaxQBiQ9HCU8
PaxDbiQ9HCU8
PeptideAtlasiQ9HCU8
PRIDEiQ9HCU8
ProteomicsDBi81802

PTM databases

iPTMnetiQ9HCU8
PhosphoSitePlusiQ9HCU8

Expressioni

Developmental stagei

Expression is cell cycle-dependent, with highest levels in G2/M phase and a drastic drop in S phase (PubMed:22801543, PubMed:23913683). This trough may be mediated by DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2))-mediated proteasomal degradation (PubMed:23913683).2 Publications

Inductioni

In response to DNA damage, genotoxic stress and replication stress, following UV irradiation, ionizing radiation, treatment with methyl methanesulfonate, hydroxyurea, or with aphidicolin, protein expression drops to undetectable levels, due to proteasomal degradation (PubMed:17317665, PubMed:22801543, PubMed:23233665, PubMed:23913683, PubMed:24300032). This down-regulation is ATR-dependent (PubMed:17317665).5 Publications

Gene expression databases

BgeeiENSG00000175482 Expressed in 88 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_POLD4
ExpressionAtlasiQ9HCU8 baseline and differential
GenevisibleiQ9HCU8 HS

Organism-specific databases

HPAiHPA071529

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 a 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 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi121774, 9 interactors
ComplexPortaliCPX-2097 Delta DNA polymerase complex
CORUMiQ9HCU8
IntActiQ9HCU8, 7 interactors
STRINGi9606.ENSP00000311368

Structurei

3D structure databases

ProteinModelPortaliQ9HCU8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1 – 16PCNA-interaction protein motif (PIP box)2 PublicationsAdd BLAST16

Sequence similaritiesi

Belongs to the DNA polymerase delta subunit 4 family.Curated

Phylogenomic databases

eggNOGiENOG410J65P Eukaryota
ENOG410XUCX LUCA
GeneTreeiENSGT00390000005096
HOGENOMiHOG000031022
HOVERGENiHBG057838
InParanoidiQ9HCU8
KOiK03505
OMAiQTHPGDP
OrthoDBiEOG091G10DR
PhylomeDBiQ9HCU8
TreeFamiTF103004

Family and domain databases

InterProiView protein in InterPro
IPR007218 DNA_pol_delta_4
PANTHERiPTHR14303 PTHR14303, 1 hit
PfamiView protein in Pfam
PF04081 DNA_pol_delta_4, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9HCU8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MGRKRLITDS YPVVKRREGP AGHSKGELAP ELGEEPQPRD EEEAELELLR 
        60         70         80         90        100
QFDLAWQYGP CTGITRLQRW CRAKQMGLEP PPEVWQVLKT HPGDPRFQCS 

LWHLYPL
Length:107
Mass (Da):12,433
Last modified:March 1, 2001 - v1
Checksum:i6F412738E4D9A19C
GO
Isoform 2 (identifier: Q9HCU8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     63-107: GITRLQRWCRAKQMGLEPPPEVWQVLKTHPGDPRFQCSLWHLYPL → VSGISIPYEAPRKTSCP

Note: No experimental confirmation available.
Show »
Length:79
Mass (Da):8,868
Checksum:iC8CD845791BE8759
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PL15E9PL15_HUMAN
DNA polymerase delta subunit 4
POLD4
32Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02226939R → P1 PublicationCorresponds to variant dbSNP:rs28364240Ensembl.1
Natural variantiVAR_05752659G → R. Corresponds to variant dbSNP:rs34136263Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04686463 – 107GITRL…HLYPL → VSGISIPYEAPRKTSCP in isoform 2. 1 PublicationAdd BLAST45

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.
CCDSiCCDS58149.1 [Q9HCU8-2]
CCDS8158.1 [Q9HCU8-1]
RefSeqiNP_001243799.1, NM_001256870.1 [Q9HCU8-2]
NP_066996.3, NM_021173.4 [Q9HCU8-1]
UniGeneiHs.523829

Genome annotation databases

EnsembliENST00000312419; ENSP00000311368; ENSG00000175482 [Q9HCU8-1]
ENST00000539074; ENSP00000444780; ENSG00000175482 [Q9HCU8-2]
GeneIDi57804
KEGGihsa:57804
UCSCiuc001okm.5 human [Q9HCU8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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.
CCDSiCCDS58149.1 [Q9HCU8-2]
CCDS8158.1 [Q9HCU8-1]
RefSeqiNP_001243799.1, NM_001256870.1 [Q9HCU8-2]
NP_066996.3, NM_021173.4 [Q9HCU8-1]
UniGeneiHs.523829

3D structure databases

ProteinModelPortaliQ9HCU8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121774, 9 interactors
ComplexPortaliCPX-2097 Delta DNA polymerase complex
CORUMiQ9HCU8
IntActiQ9HCU8, 7 interactors
STRINGi9606.ENSP00000311368

Chemistry databases

ChEMBLiCHEMBL2363042

PTM databases

iPTMnetiQ9HCU8
PhosphoSitePlusiQ9HCU8

Polymorphism and mutation databases

BioMutaiPOLD4

Proteomic databases

EPDiQ9HCU8
MaxQBiQ9HCU8
PaxDbiQ9HCU8
PeptideAtlasiQ9HCU8
PRIDEiQ9HCU8
ProteomicsDBi81802

Protocols and materials databases

DNASUi57804
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312419; ENSP00000311368; ENSG00000175482 [Q9HCU8-1]
ENST00000539074; ENSP00000444780; ENSG00000175482 [Q9HCU8-2]
GeneIDi57804
KEGGihsa:57804
UCSCiuc001okm.5 human [Q9HCU8-1]

Organism-specific databases

CTDi57804
DisGeNETi57804
EuPathDBiHostDB:ENSG00000175482.8
GeneCardsiPOLD4
HGNCiHGNC:14106 POLD4
HPAiHPA071529
MIMi611525 gene
neXtProtiNX_Q9HCU8
OpenTargetsiENSG00000175482
PharmGKBiPA33498
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J65P Eukaryota
ENOG410XUCX LUCA
GeneTreeiENSGT00390000005096
HOGENOMiHOG000031022
HOVERGENiHBG057838
InParanoidiQ9HCU8
KOiK03505
OMAiQTHPGDP
OrthoDBiEOG091G10DR
PhylomeDBiQ9HCU8
TreeFamiTF103004

Enzyme and pathway databases

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

GeneWikiiPOLD4
GenomeRNAii57804
PROiPR:Q9HCU8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000175482 Expressed in 88 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_POLD4
ExpressionAtlasiQ9HCU8 baseline and differential
GenevisibleiQ9HCU8 HS

Family and domain databases

InterProiView protein in InterPro
IPR007218 DNA_pol_delta_4
PANTHERiPTHR14303 PTHR14303, 1 hit
PfamiView protein in Pfam
PF04081 DNA_pol_delta_4, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDPOD4_HUMAN
AccessioniPrimary (citable) accession number: Q9HCU8
Secondary accession number(s): F5H506
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: March 1, 2001
Last modified: November 7, 2018
This is version 142 of the entry and version 1 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again