Free for academic non-profit institutions. Other users need a Commercial license

Aliases for POLD4 Gene

Aliases for POLD4 Gene

  • DNA Polymerase Delta 4, Accessory Subunit 2 3 5
  • Polymerase (DNA-Directed), Delta 4, Accessory Subunit 2 3
  • Polymerase (DNA) Delta 4, Accessory Subunit 2 3
  • DNA Polymerase Delta Smallest Subunit P12 2 3
  • POLDS 3 4
  • DNA Polymerase Delta Subunit P12 4
  • DNA Polymerase Delta Subunit 4 3
  • P12 3

External Ids for POLD4 Gene

Previous GeneCards Identifiers for POLD4 Gene

  • GC11M069752
  • GC11M068815
  • GC11M067369
  • GC11M066894
  • GC11M066875
  • GC11M067119
  • GC11M063448

Summaries for POLD4 Gene

Entrez Gene Summary for POLD4 Gene

  • This gene encodes the smallest subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein enhances the activity of DNA polymerase delta and plays a role in fork repair and stabilization through interactions with the DNA helicase Bloom syndrome protein. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

GeneCards Summary for POLD4 Gene

POLD4 (DNA Polymerase Delta 4, Accessory Subunit) is a Protein Coding gene. Among its related pathways are DNA Double-Strand Break Repair and Telomere C-strand (Lagging Strand) Synthesis. GO annotations related to this gene include DNA-directed DNA polymerase activity. An important paralog of this gene is ENSG00000256514.

UniProtKB/Swiss-Prot for POLD4 Gene

  • 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).

Gene Wiki entry for POLD4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for POLD4 Gene

Genomics for POLD4 Gene

Regulatory Elements for POLD4 Gene

Enhancers for POLD4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11G067383 1.4 Ensembl ENCODE dbSUPER 13.1 -25.8 -25828 0.8 HDGF ARNT WRNIP1 ZFP64 ARID4B SIN3A ZNF2 ZNF48 ZBTB7B ZNF121 RN7SKP239 POLD4 CARNS1 PPP1CA PTPRCAP RPS6KB2 ENSG00000255949 RAD9A PIR46028 ENSG00000275484
GH11G067380 1.1 Ensembl ENCODE dbSUPER 13.2 -24.4 -24447 1.4 HDGF CTCF SMAD5 CEBPB ZNF592 POLR2A IKZF1 RELB MLLT1 MYC CARNS1 SSH3 POLD4 PPP1CA PTPRCAP RPS6KB2 ENSG00000255949 ENSG00000275484 PIR46028
GH11G067251 1.2 ENCODE dbSUPER 11.8 +103.3 103277 3.5 HDGF PKNOX1 SIN3A ZNF2 YY1 GLIS2 FOS JUNB ZHX2 REST SSH3 ANKRD13D POLD4 RN7SKP239 ENSG00000256514 CLCF1 PPP1CA RPS6KB2 PTPRCAP ENSG00000255949
GH11G067316 1.1 ENCODE 12.4 +39.4 39402 2.3 HDGF CREB3L1 WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 ZNF143 GRK2 SSH3 POLD4 RN7SKP239 CLCF1 ENSG00000256514 RNU6-1238P TBC1D10C CARNS1 PPP1CA
GH11G067382 0.6 ENCODE dbSUPER 13.1 -25.3 -25283 0.0 GATAD2B POLD4 CARNS1 PPP1CA PTPRCAP RPS6KB2 ENSG00000255949 ENSG00000275484 PIR46028
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around POLD4 on UCSC Golden Path with GeneCards custom track

Genomic Location for POLD4 Gene

Chromosome:
11
Start:
67,350,765 bp from pter
End:
67,356,972 bp from pter
Size:
6,208 bases
Orientation:
Minus strand

Genomic View for POLD4 Gene

Genes around POLD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
POLD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for POLD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for POLD4 Gene

Proteins for POLD4 Gene

  • Protein details for POLD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9HCU8-DPOD4_HUMAN
    Recommended name:
    DNA polymerase delta subunit 4
    Protein Accession:
    Q9HCU8
    Secondary Accessions:
    • F5H506

    Protein attributes for POLD4 Gene

    Size:
    107 amino acids
    Molecular mass:
    12433 Da
    Quaternary structure:
    • 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).

    Alternative splice isoforms for POLD4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for POLD4 Gene

Post-translational modifications for POLD4 Gene

  • 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).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for POLD4 Gene

No data available for DME Specific Peptides for POLD4 Gene

Domains & Families for POLD4 Gene

Gene Families for POLD4 Gene

Protein Domains for POLD4 Gene

Suggested Antigen Peptide Sequences for POLD4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9HCU8

UniProtKB/Swiss-Prot:

DPOD4_HUMAN :
  • Belongs to the DNA polymerase delta subunit 4 family.
Family:
  • Belongs to the DNA polymerase delta subunit 4 family.
genes like me logo Genes that share domains with POLD4: view

Function for POLD4 Gene

Molecular function for POLD4 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot Induction:
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).

Gene Ontology (GO) - Molecular Function for POLD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003887 DNA-directed DNA polymerase activity TAS --
GO:0005515 protein binding IPI 12403614
genes like me logo Genes that share ontologies with POLD4: view
genes like me logo Genes that share phenotypes with POLD4: view

Animal Model Products

CRISPR Products

miRNA for POLD4 Gene

miRTarBase miRNAs that target POLD4

Inhibitory RNA Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for POLD4 Gene

Localization for POLD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for POLD4 Gene

Nucleus. Note=Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation. {ECO:0000269 PubMed:22801543}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for POLD4 gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 5
extracellular 1

Gene Ontology (GO) - Cellular Components for POLD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS,IDA --
GO:0005654 nucleoplasm TAS --
GO:0005730 nucleolus IDA --
GO:0005739 mitochondrion IDA --
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with POLD4: view

Pathways & Interactions for POLD4 Gene

SuperPathways for POLD4 Gene

SuperPathway Contained pathways
1 Telomere C-strand (Lagging Strand) Synthesis
2 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
3 Mismatch repair
4 DNA Double-Strand Break Repair
5 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
genes like me logo Genes that share pathways with POLD4: view

Pathways by source for POLD4 Gene

Gene Ontology (GO) - Biological Process for POLD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000722 telomere maintenance via recombination TAS --
GO:0000723 telomere maintenance TAS --
GO:0000731 DNA synthesis involved in DNA repair IBA --
GO:0006260 DNA replication TAS 10751307
GO:0006261 DNA-dependent DNA replication IBA --
genes like me logo Genes that share ontologies with POLD4: view

No data available for SIGNOR curated interactions for POLD4 Gene

Drugs & Compounds for POLD4 Gene

(2) Drugs for POLD4 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clofarabine Approved, Investigational Pharma Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 159
Cytarabine Approved, Investigational Pharma 1117

(2) ApexBio Compounds for POLD4 Gene

Compound Action Cas Number
Clofarabine Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 123318-82-1
Cytarabine 147-94-4
genes like me logo Genes that share compounds with POLD4: view

Drug Products

Transcripts for POLD4 Gene

Unigene Clusters for POLD4 Gene

Polymerase (DNA-directed), delta 4, accessory subunit:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for POLD4 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c · 2d · 2e · 2f ^ 3a · 3b ^ 4 ^ 5a · 5b · 5c · 5d ^ 6a · 6b · 6c · 6d · 6e
SP1: - - - - - - - - - - -
SP2: - - - - - -
SP3: - - - - - - -
SP4: - - - - -
SP5: - - -
SP6: - - - - - - -
SP7: - - -
SP8: - - - - - -
SP9: - - -
SP10: - -
SP11:
SP12: - - -

Relevant External Links for POLD4 Gene

GeneLoc Exon Structure for
POLD4
ECgene alternative splicing isoforms for
POLD4

Expression for POLD4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for POLD4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for POLD4 Gene

This gene is overexpressed in Breast (31.8) and Plasma (21.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for POLD4 Gene



Protein tissue co-expression partners for POLD4 Gene

NURSA nuclear receptor signaling pathways regulating expression of POLD4 Gene:

POLD4

SOURCE GeneReport for Unigene cluster for POLD4 Gene:

Hs.523829

Evidence on tissue expression from TISSUES for POLD4 Gene

  • Kidney(2.3)
  • Nervous system(2.3)
  • Lung(2.2)
  • Muscle(2.1)
genes like me logo Genes that share expression patterns with POLD4: view

Primer Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for POLD4 Gene

Orthologs for POLD4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for POLD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia POLD4 34 35
  • 99.69 (n)
dog
(Canis familiaris)
Mammalia POLD4 34 35
  • 90.03 (n)
cow
(Bos Taurus)
Mammalia POLD4 34 35
  • 88.16 (n)
mouse
(Mus musculus)
Mammalia Pold4 34 16 35
  • 85.67 (n)
rat
(Rattus norvegicus)
Mammalia Pold4 34
  • 85.36 (n)
oppossum
(Monodelphis domestica)
Mammalia POLD4 35
  • 39 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii POLD4 35
  • 38 (a)
OneToOne
Species where no ortholog for POLD4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for POLD4 Gene

ENSEMBL:
Gene Tree for POLD4 (if available)
TreeFam:
Gene Tree for POLD4 (if available)

Paralogs for POLD4 Gene

Paralogs for POLD4 Gene

genes like me logo Genes that share paralogs with POLD4: view

Variants for POLD4 Gene

Sequence variations from dbSNP and Humsavar for POLD4 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs1001090983 -- 67,353,217(+) TTTCC(C/T)TTTCC intron-variant
rs1001544985 -- 67,353,022(+) CAAAC(-/T)TGCCT intron-variant, nc-transcript-variant, reference, frameshift-variant
rs1002167751 -- 67,353,693(+) GGGCG(G/T)TGCCT intron-variant, upstream-variant-2KB
rs1002259222 -- 67,353,108(+) CGAGG(C/T)TGGCT intron-variant
rs1002357075 -- 67,353,737(+) GGCGG(A/G)GGACC intron-variant, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for POLD4 Gene

Variant ID Type Subtype PubMed ID
nsv367 CNV insertion 18451855
nsv468603 CNV loss 19166990
nsv555253 CNV loss 21841781

Variation tolerance for POLD4 Gene

Residual Variation Intolerance Score: 54.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.39; 8.69% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for POLD4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
POLD4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for POLD4 Gene

Disorders for POLD4 Gene

Relevant External Links for POLD4

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
POLD4

No disorders were found for POLD4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for POLD4 Gene

Publications for POLD4 Gene

  1. Identification of a fourth subunit of mammalian DNA polymerase delta. (PMID: 10751307) Liu L. … Lee M.Y.W.T. (J. Biol. Chem. 2000) 2 3 4 64
  2. The tail that wags the dog: p12, the smallest subunit of DNA polymerase I', is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression. (PMID: 24300032) Lee M.Y. … Lee E.Y. (Cell Cycle 2014) 3 4 64
  3. A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase I' in response to DNA damage and during the S phase. (PMID: 23913683) Zhang S. … Lee M.Y. (J. Biol. Chem. 2013) 3 4 64
  4. Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase I'. (PMID: 24035200) Lin S.H. … Lee M.Y. (DNA Repair (Amst.) 2013) 3 4 64
  5. Identification of RNF8 as a ubiquitin ligase involved in targeting the p12 subunit of DNA polymerase I' for degradation in response to DNA damage. (PMID: 23233665) Zhang S. … Lee M.Y. (J. Biol. Chem. 2013) 3 4 64

Products for POLD4 Gene

Sources for POLD4 Gene

Content
Loading form....