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    POLD4 DNA polymerase delta 4, accessory subunit [ Homo sapiens (human) ]

    Gene ID: 57804, updated on 5-Mar-2024

    Summary

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    Official Symbol
    POLD4provided by HGNC
    Official Full Name
    DNA polymerase delta 4, accessory subunitprovided by HGNC
    Primary source
    HGNC:HGNC:14106
    See related
    Ensembl:ENSG00000175482 MIM:611525; AllianceGenome:HGNC:14106
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    p12; POLDS
    Summary
    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]
    Expression
    Ubiquitous expression in lymph node (RPKM 33.7), small intestine (RPKM 29.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See POLD4 in Genome Data Viewer
    Location:
    11q13.2
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (67350765..67353596, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (67344877..67347708, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (67118236..67121067, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3622 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67057124-67058048 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67058049-67058971 Neighboring gene ankyrin repeat domain 13D Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67070151-67070668 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67070669-67071188 Neighboring gene slingshot protein phosphatase 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5086 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5085 Neighboring gene uncharacterized LOC100130987 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3624 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67119697-67120279 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67120280-67120861 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5087 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3625 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5088 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5089 Neighboring gene RN7SK pseudogene 239 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67134979-67135478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3626 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3627 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3628 Neighboring gene cardiotrophin like cytokine factor 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit. Khandagale P, et al. Life Sci Alliance, 2019 Apr. PMID 30885984, Free PMC Article
    2. The tail that wags the dog: p12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression. Lee MY, et al. Cell Cycle, 2014. PMID 24300032, Free PMC Article
    3. Regulation of DNA polymerase POLD4 influences genomic instability in lung cancer. Huang QM, et al. Cancer Res, 2010 Nov 1. PMID 20861182
    4. Roles of POLD4, smallest subunit of DNA polymerase delta, in nuclear structures and genomic stability of human cells. Huang QM, et al. Biochem Biophys Res Commun, 2010 Jan 1. PMID 19931513
    5. A novel DNA damage response: rapid degradation of the p12 subunit of dna polymerase delta. Zhang S, et al. J Biol Chem, 2007 May 25. PMID 17317665

    See all (33) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation.
      Title: POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation.
    2. Expression Profile, Molecular Association, and Clinical Significance of POLD4 in Glioblastoma.
      Title: Expression Profile, Molecular Association, and Clinical Significance of POLD4 in Glioblastoma.
    3. Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway.
      Title: Circular RNA circ_0026359 Enhances Cisplatin Resistance in Gastric Cancer via Targeting miR-1200/POLD4 Pathway.
    4. The role in cellular processes (DNA replication, DNA repair, homologous recombination) and cell cycle regulation of 2 forms of human DNA polymerase delta: delta3 and delta4 was reviewed. (REVIEW)
      Title: Two forms of human DNA polymerase δ: Who does what and why?
    5. Human Poldelta is a pentameric complex with a dimeric p12 subunit. RKR-mediated dimerization plays a vital role in p12 binding to PCNA and Poldelta5 architecture, and the phenomenon appears to be conserved throughout evolution.
      Title: Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit.
    6. the p12/Pol delta is a target as a nuclear substrate of mu-calpain in a calcium-triggered apoptosis and appears to be a potential marker in the study of the chemotherapy of cancer therapies.
      Title: Proteolysis of the human DNA polymerase delta smallest subunit p12 by μ-calpain in calcium-triggered apoptotic HeLa cells.
    7. A parallel study of Pol delta4 and Pol delta3 in Okazaki fragment processing provides evidence for a role of Pol delta3 in DNA replication
      Title: The tail that wags the dog: p12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression.
    8. Findings provide evidence for the novel concept that Pol delta3 has a role in lagging strand synthesis, and that both forms of Pol delta3 and 4 may participate in DNA replication in higher eukaryotic cells.
      Title: Dynamics of enzymatic interactions during short flap human Okazaki fragment processing by two forms of human DNA polymerase δ.
    9. ubiquitination of p12 through CRL4(Cdt2) and subsequent degradation form one mechanism by which a cell responds to DNA damage to inhibit fork progression.
      Title: Degradation of p12 subunit by CRL4Cdt2 E3 ligase inhibits fork progression after DNA damage.
    10. Data indicate that CRL4(Cdt2) regulates the degradation of the p12 subunit of Pol delta4.
      Title: A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA polymerase δ in response to DNA damage and during the S phase.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Potential readthrough

    Included gene: CLCF1

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to DNA-directed DNA polymerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA synthesis involved in DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA-templated DNA replication IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA-templated DNA replication IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of delta DNA polymerase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of delta DNA polymerase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    DNA polymerase delta subunit 4
    Names
    DNA polymerase delta smallest subunit p12
    polymerase (DNA) delta 4, accessory subunit
    polymerase (DNA-directed), delta 4, accessory subunit

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001256870.2 → NP_001243799.1  DNA polymerase delta subunit 4 isoform 2

      See identical proteins and their annotated locations for NP_001243799.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AP003419, BG403692, BG576821
      Consensus CDS
      CCDS58149.1
      UniProtKB/Swiss-Prot
      Q9HCU8
      Related
      ENSP00000444780.1, ENST00000539074.1

    2. NM_021173.5 → NP_066996.3  DNA polymerase delta subunit 4 isoform 1

      See identical proteins and their annotated locations for NP_066996.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AF179890, AP003419, BC070250
      Consensus CDS
      CCDS8158.1
      UniProtKB/Swiss-Prot
      F5H506, Q9HCU8
      UniProtKB/TrEMBL
      Q6NSD7
      Related
      ENSP00000311368.3, ENST00000312419.8
      Conserved Domains (1) summary
      pfam04081
      Location:50 → 94
      DNA_pol_delta_4; DNA polymerase delta, subunit 4

    RNA

    1. NR_046411.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP003419, BC001334, BG576821

    2. NR_046412.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate splice site in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP003419, BG576821, BP263644

    3. NR_046413.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in the 5' region, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.
      Source sequence(s)
      AP003419, BM697399
      Related
      ENST00000529704.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      67350765..67353596 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      67344877..67347708 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HCU8.1 GenPept UniProtKB/Swiss-Prot:Q9HCU8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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