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Protein

DNA polymerase delta subunit 4

Gene

Pold4

Organism
Mus musculus (Mouse)
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. Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system. 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. Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites. Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival.By similarity

GO - Biological processi

  • DNA biosynthetic process Source: GOC
  • DNA-dependent DNA replication Source: MGI
  • DNA repair Source: UniProtKB-KW
  • positive regulation of endothelial cell proliferation Source: MGI

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-110314 Recognition of DNA damage by PCNA-containing replication complex
R-MMU-174411 Polymerase switching on the C-strand of the telomere
R-MMU-174414 Processive synthesis on the C-strand of the telomere
R-MMU-174417 Telomere C-strand (Lagging Strand) Synthesis
R-MMU-174437 Removal of the Flap Intermediate from the C-strand
R-MMU-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-MMU-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-MMU-5651801 PCNA-Dependent Long Patch Base Excision Repair
R-MMU-5656169 Termination of translesion DNA synthesis
R-MMU-5685942 HDR through Homologous Recombination (HRR)
R-MMU-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER
R-MMU-5696400 Dual Incision in GG-NER
R-MMU-6782135 Dual incision in TC-NER
R-MMU-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-MMU-69091 Polymerase switching
R-MMU-69166 Removal of the Flap Intermediate
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1916995 Pold4

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001860521 – 107DNA polymerase delta subunit 4Add BLAST107

Post-translational modificationi

Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination in response to UV irradiation or treatment with an alkylating agent, leading to proteasomal degradation. This modification is mediated, at least in part, by RNF8.1 Publication
Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation. This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ9CWP8
PaxDbiQ9CWP8
PRIDEiQ9CWP8

PTM databases

PhosphoSitePlusiQ9CWP8

Expressioni

Inductioni

In response to DNA damage or genotoxic stress, such as UV irradiation or treatment with an alkylating agent, protein expression drastically drops.1 Publication

Gene expression databases

BgeeiENSMUSG00000024854 Expressed in 246 organ(s), highest expression level in ear
CleanExiMM_POLD4
ExpressionAtlasiQ9CWP8 baseline and differential
GenevisibleiQ9CWP8 MM

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. Within this complex, directly interacts with POLD1 and POLD2. Directly interacts with PCNA, as do POLD1 and POLD3; this interaction stimulates Pol-delta4 polymerase activity. As POLD1 and POLD2, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA, possibly by increasing initiation frequency. 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) that has a increased proofreading activity. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2.By similarity

Protein-protein interaction databases

ComplexPortaliCPX-2098 Delta DNA polymerase complex
CORUMiQ9CWP8
STRINGi10090.ENSMUSP00000025773

Family & Domainsi

Motif

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410J65P Eukaryota
ENOG410XUCX LUCA
GeneTreeiENSGT00390000005096
HOGENOMiHOG000031022
HOVERGENiHBG057838
InParanoidiQ9CWP8
KOiK03505
OMAiQTHPGDP
OrthoDBiEOG091G10DR
PhylomeDBiQ9CWP8
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

Sequencei

Sequence statusi: Complete.

Q9CWP8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGRKRFITDS YPVVKKREGP PGHSKGELAP ELGEDTQSLS QEETELELLR
60 70 80 90 100
QFDLAWQYGP CTGITRLQRW SRAEQMGLKP PLEVYQVLKA HPEDPHFQCS

LWHLYPL
Length:107
Mass (Da):12,403
Last modified:June 1, 2001 - v1
Checksum:i14A27054D4E7511E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK010477 mRNA Translation: BAB26970.1
BC028520 mRNA Translation: AAH28520.1
CCDSiCCDS29424.1
RefSeqiNP_081472.1, NM_027196.4
UniGeneiMm.32518

Genome annotation databases

EnsembliENSMUST00000025773; ENSMUSP00000025773; ENSMUSG00000024854
ENSMUST00000180621; ENSMUSP00000137813; ENSMUSG00000097508
GeneIDi69745
KEGGimmu:69745
UCSCiuc008fzm.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK010477 mRNA Translation: BAB26970.1
BC028520 mRNA Translation: AAH28520.1
CCDSiCCDS29424.1
RefSeqiNP_081472.1, NM_027196.4
UniGeneiMm.32518

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-2098 Delta DNA polymerase complex
CORUMiQ9CWP8
STRINGi10090.ENSMUSP00000025773

PTM databases

PhosphoSitePlusiQ9CWP8

Proteomic databases

MaxQBiQ9CWP8
PaxDbiQ9CWP8
PRIDEiQ9CWP8

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025773; ENSMUSP00000025773; ENSMUSG00000024854
ENSMUST00000180621; ENSMUSP00000137813; ENSMUSG00000097508
GeneIDi69745
KEGGimmu:69745
UCSCiuc008fzm.2 mouse

Organism-specific databases

CTDi57804
MGIiMGI:1916995 Pold4

Phylogenomic databases

eggNOGiENOG410J65P Eukaryota
ENOG410XUCX LUCA
GeneTreeiENSGT00390000005096
HOGENOMiHOG000031022
HOVERGENiHBG057838
InParanoidiQ9CWP8
KOiK03505
OMAiQTHPGDP
OrthoDBiEOG091G10DR
PhylomeDBiQ9CWP8
TreeFamiTF103004

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q9CWP8
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024854 Expressed in 246 organ(s), highest expression level in ear
CleanExiMM_POLD4
ExpressionAtlasiQ9CWP8 baseline and differential
GenevisibleiQ9CWP8 MM

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_MOUSE
AccessioniPrimary (citable) accession number: Q9CWP8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 122 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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