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    POLD1 DNA polymerase delta 1, catalytic subunit [ Homo sapiens (human) ]

    Gene ID: 5424, updated on 9-Dec-2024

    Summary

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    Official Symbol
    POLD1provided by HGNC
    Official Full Name
    DNA polymerase delta 1, catalytic subunitprovided by HGNC
    Primary source
    HGNC:HGNC:9175
    See related
    Ensembl:ENSG00000062822 MIM:174761; AllianceGenome:HGNC:9175
    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
    CDC2; MDPL; POLD; CRCS10; IMD120
    Summary
    This gene encodes the 125-kDa catalytic 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. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]
    Expression
    Broad expression in bone marrow (RPKM 7.5), testis (RPKM 4.7) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See POLD1 in Genome Data Viewer
    Location:
    19q13.33
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (50384323..50418018)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (53471875..53505574)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (50887580..50921275)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14983 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14984 Neighboring gene napsin A aspartic peptidase Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50879623-50880434 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10959 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10960 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10961 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50888337-50888838 Neighboring gene nuclear receptor subfamily 1 group H member 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50918101-50918885 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50918886-50919670 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10965 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10966 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:50921334-50921502 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14987 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50930914-50931487 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50931488-50932060 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10967 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10968 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50935955-50936713 Neighboring gene Spi-B transcription factor Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50937528-50938028 Neighboring gene myosin binding protein C2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50954383-50954951

    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. Pedigree analysis of a POLD1 germline mutation in urothelial carcinoma shows a close association between different mutation burdens and overall survival. Wang Y, et al. Cell Mol Immunol, 2021 Mar. PMID 32265515, Free PMC Article
    2. Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL). Elouej S, et al. Metabolism, 2017 Jun. PMID 28521875
    3. The catalytic subunit of DNA polymerase δ inhibits γTuRC activity and regulates Golgi-derived microtubules. Shen Y, et al. Nat Commun, 2017 Sep 15. PMID 28916777, Free PMC Article
    4. The catalytic subunit of DNA polymerase δ is a nucleocytoplasmic shuttling protein. Shen Y, et al. Exp Cell Res, 2019 Feb 15. PMID 30625304
    5. Human DNA polymerase delta requires an iron-sulfur cluster for high-fidelity DNA synthesis. Jozwiakowski SK, et al. Life Sci Alliance, 2019 Aug. PMID 31278166, Free PMC Article

    See all (250) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Discovery of recessive effect of human polymerase delta proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells.
      Title: Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells.
    2. DNA polymerase epsilon and delta variants drive mutagenesis in polypurine tracts in human tumors.
      Title: DNA polymerase ε and δ variants drive mutagenesis in polypurine tracts in human tumors.
    3. Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases epsilon and delta in glioma families.
      Title: Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families.
    4. POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma.
      Title: POLD1 Is Required for Cell Cycle Progression by Overcoming DNA Damage in Malignant Pleural Mesothelioma.
    5. Race, Prevalence of POLE and POLD1 Alterations, and Survival Among Patients With Endometrial Cancer.
      Title: Race, Prevalence of POLE and POLD1 Alterations, and Survival Among Patients With Endometrial Cancer.
    6. DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC.
      Title: DNA polymerase POLD1 promotes proliferation and metastasis of bladder cancer by stabilizing MYC.
    7. DNA Polymerase Delta Exhibits Altered Catalytic Properties on Lysine Acetylation.
      Title: DNA Polymerase Delta Exhibits Altered Catalytic Properties on Lysine Acetylation.
    8. Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity.
      Title: Functional landscapes of POLE and POLD1 mutations in checkpoint blockade-dependent antitumor immunity.
    9. POLE/POLD1 mutation and tumor immunotherapy.
      Title: POLE/POLD1 mutation and tumor immunotherapy.
    10. Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene.
      Title: Scrutinizing Deleterious Nonsynonymous SNPs and Their Effect on Human POLD1 Gene.
    Submit: New GeneRIF Correction See all GeneRIFs (83)

    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

    Associated conditions

    Description Tests
    Colorectal cancer, susceptibility to, 10
    MedGen: C2675481 OMIM: 612591 GeneReviews: Not available
    		Compare labs
    Mandibular hypoplasia-deafness-progeroid syndrome
    MedGen: C3715192 OMIM: 615381 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-06-05)

    ClinGen Genome Curation Page
    Haploinsufficency

    Little evidence for dosage pathogenicity (Last evaluated 2020-06-05)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3'-5'-DNA exonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 4 iron, 4 sulfur cluster binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-directed DNA polymerase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-directed DNA polymerase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables chromatin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables damaged DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables enzyme binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA replication proofreading IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA synthesis involved in DNA repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA synthesis involved in DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    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 base-excision repair, gap-filling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in base-excision repair, gap-filling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to UV IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in error-free translesion synthesis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fatty acid homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in nucleotide-excision repair, DNA gap filling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in nucleotide-excision repair, DNA gap filling IC
    Inferred by Curator
    more info
    		 PubMed 
    involved_in nucleotide-excision repair, DNA gap filling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to UV TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in aggresome IDA
    Inferred from Direct Assay
    more info
    		  
    colocalizes_with chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    part_of delta DNA polymerase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of delta DNA polymerase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of delta DNA polymerase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    part_of nucleotide-excision repair complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    DNA polymerase delta catalytic subunit
    Names
    3'-5' exodeoxyribonuclease
    CDC2 homolog
    DNA polymerase subunit delta p125
    polymerase (DNA directed), delta 1, catalytic subunit 125kDa
    polymerase (DNA) delta 1, catalytic subunit
    NP_001243778.1
    NP_001295561.1
    NP_002682.2
    XP_005259065.1
    XP_011525340.1
    XP_016882371.1
    XP_047294902.1
    XP_047294903.1
    XP_047294904.1
    XP_047294905.1
    XP_047294906.1
    XP_054177207.1
    XP_054177208.1
    XP_054177209.1
    XP_054177210.1
    XP_054177211.1
    XP_054177212.1
    XP_054177213.1
    XP_054177214.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_033800.1 RefSeqGene

      Range
      5001..38696
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_785

    mRNA and Protein(s)

    1. NM_001256849.1 → NP_001243778.1  DNA polymerase delta catalytic subunit isoform 1

      See identical proteins and their annotated locations for NP_001243778.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) contains an alternate exon in the 5' UTR and uses an alternate splice site in the 3' coding region, compared to variant 4. The encoded isoform (1) is shorter than isoform 2.
      Source sequence(s)
      AA236879, BC008800, CD101690
      Consensus CDS
      CCDS12795.1
      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6
      Related
      ENSP00000473052.1, ENST00000599857.7
      Conserved Domains (1) summary
      PTZ00166
      Location:81 → 1100
      PTZ00166; DNA polymerase delta catalytic subunit; Provisional

    2. NM_001308632.1 → NP_001295561.1  DNA polymerase delta catalytic subunit isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) encodes the longer isoform (2).
      Source sequence(s)
      AC008655, AC020909, DQ234348
      Consensus CDS
      CCDS82381.1
      UniProtKB/TrEMBL
      M0R2B7, Q308M6
      Related
      ENSP00000472445.1, ENST00000595904.6
      Conserved Domains (4) summary
      cd05777
      Location:304 → 533
      DNA_polB_delta_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase delta, a family-B DNA polymerase
      cd05533
      Location:579 → 1000
      POLBc_delta; DNA polymerase type-B delta subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. Presently, no direct data is available regarding ...
      PTZ00166
      Location:81 → 1126
      PTZ00166; DNA polymerase delta catalytic subunit; Provisional
      pfam14260
      Location:1038 → 1108
      zf-C4pol; C4-type zinc-finger of DNA polymerase delta

    3. NM_002691.4 → NP_002682.2  DNA polymerase delta catalytic subunit isoform 1

      See identical proteins and their annotated locations for NP_002682.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate exon in the 5' UTR and uses an alternate splice site in the 3' coding region, compared to variant 4. The encoded isoform (1) is shorter than isoform 2.
      Source sequence(s)
      AB209560, CD101690, M81735
      Consensus CDS
      CCDS12795.1
      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6
      Related
      ENSP00000406046.1, ENST00000440232.7
      Conserved Domains (1) summary
      PTZ00166
      Location:81 → 1100
      PTZ00166; DNA polymerase delta catalytic subunit; Provisional

    RNA

    1. NR_046402.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate first exon and lacks an internal exon in the 3' region, compared to variant 4. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 4, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA236879, AB209560, CD101690
      Related
      ENST00000600859.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      50384323..50418018
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047438947.1 → XP_047294903.1  DNA polymerase delta catalytic subunit isoform X1

      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6

    2. XM_047438949.1 → XP_047294905.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    3. XM_047438946.1 → XP_047294902.1  DNA polymerase delta catalytic subunit isoform X1

      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6
      Related
      ENSP00000510052.1, ENST00000687454.1

    4. XM_047438948.1 → XP_047294904.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    5. XM_017026882.3 → XP_016882371.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705
      Related
      ENSP00000481858.2, ENST00000613923.6
      Conserved Domains (4) summary
      cd05777
      Location:304 → 533
      DNA_polB_delta_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase delta, a family-B DNA polymerase
      cd05533
      Location:579 → 950
      POLBc_delta; DNA polymerase type-B delta subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. Presently, no direct data is available regarding ...
      PTZ00166
      Location:81 → 1076
      PTZ00166; DNA polymerase delta catalytic subunit; Provisional
      pfam14260
      Location:988 → 1058
      zf-C4pol; C4-type zinc-finger of DNA polymerase delta

    6. XM_005259008.5 → XP_005259065.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705
      Conserved Domains (4) summary
      cd05777
      Location:304 → 533
      DNA_polB_delta_exo; DEDDy 3'-5' exonuclease domain of eukaryotic DNA polymerase delta, a family-B DNA polymerase
      cd05533
      Location:579 → 950
      POLBc_delta; DNA polymerase type-B delta subfamily catalytic domain. Three DNA-dependent DNA polymerases type B (alpha, delta, and epsilon) have been identified as essential for nuclear DNA replication in eukaryotes. Presently, no direct data is available regarding ...
      PTZ00166
      Location:81 → 1076
      PTZ00166; DNA polymerase delta catalytic subunit; Provisional
      pfam14260
      Location:988 → 1058
      zf-C4pol; C4-type zinc-finger of DNA polymerase delta

    7. XM_011527038.2 → XP_011525340.1  DNA polymerase delta catalytic subunit isoform X1

      See identical proteins and their annotated locations for XP_011525340.1

      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6
      Related
      ENSP00000472600.2, ENST00000601098.6
      Conserved Domains (1) summary
      PTZ00166
      Location:81 → 1100
      PTZ00166; DNA polymerase delta catalytic subunit; Provisional

    8. XM_047438950.1 → XP_047294906.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    RNA

    1. XR_935835.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      53471875..53505574
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321233.1 → XP_054177208.1  DNA polymerase delta catalytic subunit isoform X1

      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6

    2. XM_054321238.1 → XP_054177213.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    3. XM_054321232.1 → XP_054177207.1  DNA polymerase delta catalytic subunit isoform X1

      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6

    4. XM_054321236.1 → XP_054177211.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    5. XM_054321237.1 → XP_054177212.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    6. XM_054321235.1 → XP_054177210.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    7. XM_054321234.1 → XP_054177209.1  DNA polymerase delta catalytic subunit isoform X1

      UniProtKB/Swiss-Prot
      P28340, Q8NER3, Q96H98
      UniProtKB/TrEMBL
      Q308M6

    8. XM_054321239.1 → XP_054177214.1  DNA polymerase delta catalytic subunit isoform X2

      UniProtKB/TrEMBL
      A0A087WYJ2, A0A2R8Y705

    RNA

    1. XR_008485165.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P28340.2 GenPept UniProtKB/Swiss-Prot:P28340

    Gene LinkOut

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