Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002244
UniProt IDQ9HCU8
Primary gene name(s)POLD4
Synonym gene name(s)POLDS
Protein nameDNA polymerase delta subunit 4
Protein functionAs 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. {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611}.
Subcellular locationNucleus {ECO:0000269|PubMed:22801543}. Note=Partially recruited to DNA damage sites within 2 hours following UV irradiation, before degradation. {ECO:0000269|PubMed:22801543}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9HCU8
Gene Ontology
(Biological Process)
Complete annatation
DNA damage response, detection of DNA damage [GO:0042769];
DNA-dependent DNA replication [GO:0006261];
DNA replication [GO:0006260];
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];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction121774
Phylogenetic treeQ9HCU8
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. CD3-1.329108453064958.03792063545083e-050.000396944756938123
AZA vs. DISU-0.4740948214361260.06390081210613430.556725447722039
AZA vs. IL7-0.3546967141794680.06762331715581390.741943239707313
AZA vs. SAHA-0.2221244238766120.3655586658270150.732937529344751
DISU vs. CD30.8422876295754430.02527860626036370.0622731999948885
DISU vs. IL70.1094918734579210.6679578921386110.907625828565631
DISU vs. SAHA0.2546244922655380.3900157286961430.75512937399532
DMSO vs. AZA-0.03460280946236470.8378944909815081
DMSO vs. CD31.282095738543289.42918678775717e-050.000427477276429617
DMSO vs. DISU0.4371945762768670.07671210001986140.516786476217841
DMSO vs. IL7-0.3124678507674160.08518356375679070.546491570583801
DMSO vs. SAHA-0.1923821841871940.4170220968534640.757404196394138
HIV vs. Mock in Activation-0.07220932368767390.9086279286915160.999983755607037
HIV vs. Mock in Latency-0.08883482466962450.5926658781223870.999834320637052
IL7 vs. CD30.9801356422779540.002745521319052480.0100787245109786
SAHA vs. CD31.083339874490250.00258667599350770.00808570985732443
SAHA vs. IL70.1303510384735130.5943704479599390.793074114250216
(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) TRUE
(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 -0.325563 0.0100693
(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
unknown unknown unknown unknown unknown
(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

not found

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)