Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002242
UniProt IDP09884
Primary gene name(s)POLA1
Synonym gene name(s)POLA
Protein nameDNA polymerase alpha catalytic subunit
Protein functionPlays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex, composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58 is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses, PubMed:27019227. {ECO:0000269|PubMed:27019227, ECO:0000269|PubMed:9518481}.
Subcellular locationNucleus {ECO:0000269|PubMed:27019227}. Cytoplasm, cytosol {ECO:0000269|PubMed:27019227}. Note=In the cytosol, colocalizes with RNA:DNA hybrids with a speckled pattern. {ECO:0000269|PubMed:27019227}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P09884
Gene Ontology
(Biological Process)
Complete annatation
cell proliferation [GO:0008283];
DNA replication [GO:0006260];
DNA replication, synthesis of RNA primer [GO:0006269];
DNA replication initiation [GO:0006270];
DNA strand elongation involved in DNA replication [GO:0006271];
double-strand break repair via nonhomologous end joining [GO:0006303];
G1/S transition of mitotic cell cycle [GO:0000082];
lagging strand elongation [GO:0006273];
leading strand elongation [GO:0006272];
regulation of transcription involved in G1/S transition of mitotic cell cycle [GO:0000083];
telomere maintenance via recombination [GO:0000722];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
3'-5' exonuclease activity [GO:0008408];
4 iron, 4 sulfur cluster binding [GO:0051539];
chromatin binding [GO:0003682];
DNA binding [GO:0003677];
DNA-directed DNA polymerase activity [GO:0003887];
metal ion binding [GO:0046872];
nucleoside binding [GO:0001882];
nucleotide binding [GO:0000166];
protein kinase binding [GO:0019901]
Gene Ontology
(Cellular Component)
Complete annatation
alpha DNA polymerase:primase complex [GO:0005658];
cytoplasm [GO:0005737];
nuclear envelope [GO:0005635];
nuclear matrix [GO:0016363];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction111418
Phylogenetic treeP09884
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. CD31.91349500722447.02173013013008e-050.000352183667860661
AZA vs. DISU-0.2911546166810390.2580515993078610.839581352451412
AZA vs. IL70.5867673130057840.004497445783766650.20730886941503
AZA vs. SAHA0.2907422822305770.2413386195837030.612757007176138
DISU vs. CD3-2.216634640534364.32930972316115e-063.52927817338696e-05
DISU vs. IL70.8685369000081790.0007652765228303160.0227994932444012
DISU vs. SAHA0.5832383805261780.04841573167103710.274416506962843
DMSO vs. AZA0.01833293959557670.9161545410295761
DMSO vs. CD3-1.905613921456078.09878327252544e-050.00037254403053617
DMSO vs. DISU0.3078549576193870.2149066314869830.726641897354462
DMSO vs. IL70.5752333374346680.005916200824308880.158308817091567
DMSO vs. SAHA0.2657063298659170.2674747074746640.616377877117838
HIV vs. Mock in Activation0.01233304714632270.9906409556072660.999983755607037
HIV vs. Mock in Latency0.09032928878412310.5979921516121640.999834320637052
IL7 vs. CD3-1.318826267135350.009386036911132380.0282894889745048
SAHA vs. CD3-1.646766250330910.0007298964400640480.00273348393433529
SAHA vs. IL7-0.2985188143641080.2302336209232540.471141004759406
(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 0.235455 0.102065
(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
0.935 1.179 1.082 0.909 1.248
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00631 Clofarabine approved, investigational yes inhibitor
DB01073 Fludarabine approved yes inhibitor
DB00242 Cladribine approved, investigational yes inhibitor
DB01280 Nelarabine approved, investigational unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1K0P NMR - A=1347-1377.
1K18 NMR - A=1347-1377.
1N5G NMR - A=1345-1382.
4Q5V X-ray 2.5Å A/E=336-1257.
4QCL X-ray 2.2Å A=336-1257.
4Y97 X-ray 2.5Å B/D/F/H=1265-1444.
5EXR X-ray 3.6Å C/G=335-1462.
5IUD X-ray 3.3Å A/D/G/J=338-1255.

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)