Human Gene POLD1 (uc002psc.5)
  Description: Homo sapiens polymerase (DNA directed), delta 1, catalytic subunit (POLD1), transcript variant 1, mRNA.
RefSeq Summary (NM_001256849): 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].
Transcript (Including UTRs)
   Position: hg19 chr19:50,887,580-50,921,275 Size: 33,696 Total Exon Count: 27 Strand: +
Coding Region
   Position: hg19 chr19:50,902,109-50,921,204 Size: 19,096 Coding Exon Count: 26 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:50,887,580-50,921,275)mRNA (may differ from genome)Protein (1107 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCHPRDLynxMalacardsMGI
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: DPOD1_HUMAN
DESCRIPTION: RecName: Full=DNA polymerase delta catalytic subunit; EC=2.7.7.7; AltName: Full=DNA polymerase subunit delta p125;
FUNCTION: Possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single stranded DNA in the 3'- to 5'-direction. Required with its accessory proteins (proliferating cell nuclear antigen (PCNA) and replication factor C (RFC) or activator 1) for leading strand synthesis. Also involved in completing Okazaki fragments initiated by the DNA polymerase alpha/primase complex.
CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
COFACTOR: Binds 1 4Fe-4S cluster (By similarity).
SUBUNIT: Heterotetramer composed of subunits of 125 kDa, 50 kDa, 66 kDa and 12 kDa. The 125 kDa subunit contains the polymerase active site and most likely the active site for the 3'-5' exonuclease activity. Interacts with WRNIP1. Interacts with POLD4 and PCNA.
INTERACTION: P12004:PCNA; NbExp=2; IntAct=EBI-716569, EBI-358311; P49005:POLD2; NbExp=9; IntAct=EBI-716569, EBI-372354; Q9HCU8:POLD4; NbExp=10; IntAct=EBI-716569, EBI-864968;
SUBCELLULAR LOCATION: Nucleus.
DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes (By similarity).
MISCELLANEOUS: In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.
SIMILARITY: Belongs to the DNA polymerase type-B family.
SIMILARITY: Contains 1 CysA-type zinc finger.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/pold1/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): POLD1
CDC HuGE Published Literature: POLD1

-  MalaCards Disease Associations
  MalaCards Gene Search: POLD1
Diseases sorted by gene-association score: mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome* (1380), colorectal cancer 10* (904), polymerase proofreading-related adenomatous polyposis* (247), colorectal cancer susceptibility 10* (100), corneal endothelial dystrophy, autosomal recessive (6), lynch syndrome (5), hereditary colorectal cancer (5), familial colorectal cancer (5), colorectal cancer (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 21.91 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 223.31 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -29.2072-0.406 Picture PostScript Text
3' UTR -14.9271-0.210 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR006172 - DNA-dir_DNA_pol_B
IPR017964 - DNA-dir_DNA_pol_B_CS
IPR006133 - DNA-dir_DNA_pol_B_exonuc
IPR006134 - DNA-dir_DNA_pol_B_multi_dom
IPR004578 - DNA-dir_DNA_pol_B_pol2
IPR023211 - DNA_pol_palm_dom
IPR012337 - RNaseH-like_dom
IPR025687 - Znf-C4pol

Pfam Domains:
PF00136 - DNA polymerase family B
PF03104 - DNA polymerase family B, exonuclease domain
PF14260 - C4-type zinc-finger of DNA polymerase delta

SCOP Domains:
53098 - Ribonuclease H-like
56672 - DNA/RNA polymerases

ModBase Predicted Comparative 3D Structure on P28340
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene DetailsGene Details Gene DetailsGene DetailsGene Details
Gene SorterGene Sorter Gene SorterGene SorterGene Sorter
 RGDEnsemblFlyBaseWormBaseSGD
 Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence
 AlignmentAlignmentAlignmentAlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003684 damaged DNA binding
GO:0003887 DNA-directed DNA polymerase activity
GO:0004518 nuclease activity
GO:0004527 exonuclease activity
GO:0005515 protein binding
GO:0008296 3'-5'-exodeoxyribonuclease activity
GO:0016740 transferase activity
GO:0016779 nucleotidyltransferase activity
GO:0016787 hydrolase activity
GO:0046872 metal ion binding
GO:0051536 iron-sulfur cluster binding
GO:0051539 4 iron, 4 sulfur cluster binding

Biological Process:
GO:0000723 telomere maintenance
GO:0000731 DNA synthesis involved in DNA repair
GO:0006260 DNA replication
GO:0006281 DNA repair
GO:0006283 transcription-coupled nucleotide-excision repair
GO:0006287 base-excision repair, gap-filling
GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion
GO:0006297 nucleotide-excision repair, DNA gap filling
GO:0006974 cellular response to DNA damage stimulus
GO:0009411 response to UV
GO:0019985 translesion synthesis
GO:0032201 telomere maintenance via semi-conservative replication
GO:0033683 nucleotide-excision repair, DNA incision
GO:0034644 cellular response to UV
GO:0042769 DNA damage response, detection of DNA damage
GO:0045004 DNA replication proofreading
GO:0055089 fatty acid homeostasis

Cellular Component:
GO:0000109 nucleotide-excision repair complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005829 cytosol
GO:0016020 membrane
GO:0016235 aggresome
GO:0043625 delta DNA polymerase complex
GO:0000784 nuclear chromosome, telomeric region


-  Descriptions from all associated GenBank mRNAs
  AB209560 - Homo sapiens mRNA for polymerase (DNA directed), delta 1, catalytic subunit 125kDa variant protein.
M80397 - Human DNA polymerase delta catalytic subunit mRNA, complete cds.
M81735 - Human DNA polymerase delta mRNA, complete cds.
BC008800 - Homo sapiens polymerase (DNA directed), delta 1, catalytic subunit 125kDa, mRNA (cDNA clone MGC:3951 IMAGE:3634655), complete cds.
DQ895953 - Synthetic construct Homo sapiens clone IMAGE:100010413; FLH188923.01L; RZPDo839H0763D polymerase (DNA directed), delta 1, catalytic subunit 125kDa (POLD1) gene, encodes complete protein.
EU176381 - Synthetic construct Homo sapiens clone IMAGE:100006478; FLH188930.01X; RZPDo839G12251D polymerase (DNA directed), delta 1, catalytic subunit 125kDa (POLD1) gene, encodes complete protein.
CU679117 - Synthetic construct Homo sapiens gateway clone IMAGE:100020563 5' read POLD1 mRNA.
KJ897353 - Synthetic construct Homo sapiens clone ccsbBroadEn_06747 POLD1 gene, encodes complete protein.
DQ234348 - Homo sapiens DNA-directed polymerase delta 1 mRNA, complete cds, alternatively spliced.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00230 - Purine metabolism
hsa00240 - Pyrimidine metabolism
hsa01100 - Metabolic pathways
hsa03030 - DNA replication
hsa03410 - Base excision repair
hsa03420 - Nucleotide excision repair
hsa03430 - Mismatch repair
hsa03440 - Homologous recombination

Reactome (by CSHL, EBI, and GO)

Protein P28340 (Reactome details) participates in the following event(s):

R-HSA-69074 Formation of Processive Complex
R-HSA-174448 Formation of Processive Complex on the C-strand of the telomere
R-HSA-176702 Disassociation of Processive Complex and Completed Telomere End
R-HSA-69116 Formation of Okazaki fragments
R-HSA-174445 RPA binds to the Flap on the C-strand
R-HSA-174438 Formation of the Flap Intermediate on the C-strand
R-HSA-174456 Joining of adjacent Okazaki fragments of the C-strand
R-HSA-174446 Removal of remaining Flap from the C-strand
R-HSA-174444 Formation of C-strand Okazaki fragments
R-HSA-174441 Removal of RNA primer and dissociation of RPA and Dna2 from the C-strand
R-HSA-5653838 POLD,POLE binds deISGylated PCNA after TLS
R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA
R-HSA-5358579 DNA polymerase delta polymerizes DNA across single stranded gap
R-HSA-69127 Formation of the Flap Intermediate
R-HSA-69152 Removal of remaining Flap
R-HSA-69144 Removal of RNA primer and dissociation of RPA and Dna2
R-HSA-174451 Recruitment of Dna2 endonuclease to the C strand
R-HSA-110364 PCNA:POLD,POLE:RPA:RFC and FEN1 bind APEX1
R-HSA-5651992 PCNA-containing replication complex binds damaged dsDNA
R-HSA-5651809 LIG1, APEX1 and PCNA:POLD,POLE:RPA:RFC dissociate from repaired DNA
R-HSA-5653840 POLD,POLE complete replication of damaged DNA after TLS
R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site
R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site
R-HSA-69140 RPA binds to the Flap
R-HSA-110368 POLD,POLE-mediated DNA strand displacement synthesis
R-HSA-110371 LIG1 binds APEX1 and PCNA at SSB
R-HSA-110363 FEN1 bound to PCNA and APEX1 cleaves flap ssDNA
R-HSA-5651805 LIG1 bound to APEX1 and PCNA ligates SSB
R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA
R-HSA-69142 Recruitment of Dna2 endonuclease
R-HSA-5693593 D-loop extension by DNA polymerases
R-HSA-5690997 Ligation of newly synthesized repair patch to incised DNA in GG-NER
R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER
R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER
R-HSA-5691001 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in GG-NER
R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER
R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER
R-HSA-69091 Polymerase switching
R-HSA-174411 Polymerase switching on the C-strand of the telomere
R-HSA-174417 Telomere C-strand (Lagging Strand) Synthesis
R-HSA-2564830 Cytosolic iron-sulfur cluster assembly
R-HSA-69183 Processive synthesis on the lagging strand
R-HSA-174437 Removal of the Flap Intermediate from the C-strand
R-HSA-174414 Processive synthesis on the C-strand of the telomere
R-HSA-5656169 Termination of translesion DNA synthesis
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex
R-HSA-69109 Leading Strand Synthesis
R-HSA-69186 Lagging Strand Synthesis
R-HSA-180786 Extension of Telomeres
R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-1430728 Metabolism
R-HSA-69166 Removal of the Flap Intermediate
R-HSA-5651801 PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5696400 Dual Incision in GG-NER
R-HSA-6782135 Dual incision in TC-NER
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template
R-HSA-73893 DNA Damage Bypass
R-HSA-69190 DNA strand elongation
R-HSA-157579 Telomere Maintenance
R-HSA-5358508 Mismatch Repair
R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-73894 DNA Repair
R-HSA-69239 Synthesis of DNA
R-HSA-73886 Chromosome Maintenance
R-HSA-5685942 HDR through Homologous Recombination (HRR)
R-HSA-73933 Resolution of Abasic Sites (AP sites)
R-HSA-5696397 Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-5696398 Nucleotide Excision Repair
R-HSA-69242 S Phase
R-HSA-69306 DNA Replication
R-HSA-1640170 Cell Cycle
R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)
R-HSA-73884 Base Excision Repair
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-5693538 Homology Directed Repair
R-HSA-5693532 DNA Double-Strand Break Repair

-  Other Names for This Gene
  Alternate Gene Symbols: DPOD1_HUMAN, NM_001256849, NP_002682, P28340, POLD, Q8NER3, Q96H98, uc002psc.4
UCSC ID: uc002psc.5
RefSeq Accession: NM_001256849
Protein: P28340 (aka DPOD1_HUMAN)
CCDS: CCDS12795.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001256849.1
exon count: 27CDS single in 3' UTR: no RNA size: 3467
ORF size: 3324CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6742.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.