Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002243
UniProt IDQ15054
Primary gene name(s)POLD3
Synonym gene name(s)KIAA0039
Protein nameDNA polymerase delta subunit 3
Protein functionAs a component of the trimeric and tetrameric DNA polymerase delta complexes, Pol-delta3 and Pol-delta4, respectively, plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA, PubMed:10219083, PubMed:10852724, PubMed:11595739, PubMed:16510448, PubMed:24035200. Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4, PubMed:19074196, PubMed:20334433. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated, PubMed:24035200. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair, NER synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites, PubMed:20227374. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication, BIR, PubMed:24310611. Involved in the translesion synthesis, TLS of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta, REV3L or eta, POLH. Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion, PubMed:19074196, PubMed:25628356, PubMed:27185888. Also involved in TLS, as a component of the POLZ complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the minimal DNA polymerase zeta complex, consisting of only REV3L and REV7, PubMed:24449906. {ECO:0000269|PubMed:10219083, ECO:0000269|PubMed:10852724, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:25628356, ECO:0000269|PubMed:27185888}.
Subcellular locationCytoplasm {ECO:0000250|UniProtKB:Q9EQ28}. Nucleus {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}. Note=Partially colocalizes with PCNA and POLD1 at S phase replication sites, PubMed:11595739. Recruited to DNA damage sites within 2 hours following UV irradiation, PubMed:20227374, PubMed:22801543. {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q15054
Gene Ontology
(Biological Process)
Complete annatation
DNA damage response, detection of DNA damage [GO:0042769];
DNA strand elongation involved in DNA replication [GO:0006271];
DNA synthesis involved in DNA repair [GO:0000731];
mismatch repair [GO:0006298];
nucleotide-excision repair, DNA gap filling [GO:0006297];
nucleotide-excision repair, DNA incision [GO:0033683];
nucleotide-excision repair, DNA incision, 5'-to lesion [GO:0006296];
telomere maintenance [GO:0000723];
telomere maintenance via recombination [GO:0000722];
transcription-coupled nucleotide-excision repair [GO:0006283];
translesion synthesis [GO:0019985]
Gene Ontology
(Molecular Function)
Complete annatation
DNA-directed DNA polymerase activity [GO:0003887]
Gene Ontology
(Cellular Component)
Complete annatation
delta DNA polymerase complex [GO:0043625];
mitochondrion [GO:0005739];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction115940
Phylogenetic treeQ15054
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.096921784796740.04576973075373010.092819157016259
AZA vs. DISU-0.003819417955121370.9881061077601830.998932793566471
AZA vs. IL70.1663400952103960.3970700193919540.999311006273513
AZA vs. SAHA-0.2890844036524540.2427529130388810.614607978826628
DISU vs. CD3-1.112713173378410.04714640089799050.103042605065435
DISU vs. IL70.1609536673301880.5264533270396510.840724509849313
DISU vs. SAHA-0.2840477626382210.3351490469426860.714633741719471
DMSO vs. AZA-0.02010959582845440.9069781193400211
DMSO vs. CD3-1.127516219323630.04234851842968980.0836059155731614
DMSO vs. DISU-0.0176126747844870.9432486296500680.992824680352116
DMSO vs. IL70.1931561116044460.3082761269016120.789757154213466
DMSO vs. SAHA-0.2755688830434480.2490148583889220.597310668594531
HIV vs. Mock in Activation-0.07444271210759370.9503203711682750.999983755607037
HIV vs. Mock in Latency0.1768769557218390.2958672427000570.999834320637052
IL7 vs. CD3-0.9231579494802850.1034447509674480.194730352144141
SAHA vs. CD3-1.41051833204520.01121237120035950.0282998357484229
SAHA vs. IL7-0.4581194452150910.06447774199440290.217387046035256
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.114492 0.466724
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.028 0.957 0.771 0.661 0.835
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1U76 X-ray 2.6Å B/D/F=452-466.
2N1G NMR - B=231-246.
3E0J X-ray 3.0Å B/D/F/H=1-144.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00230 Purine metabolism - Homo sapiens (human)
hsa00240 Pyrimidine metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa03030 DNA replication - Homo sapiens (human)
hsa03410 Base excision repair - Homo sapiens (human)
hsa03420 Nucleotide excision repair - Homo sapiens (human)
hsa03430 Mismatch repair - Homo sapiens (human)
hsa03440 Homologous recombination - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)