Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006233
UniProt IDP12004
Primary gene name(s)PCNA
Synonym gene name(s)unknown
Protein nameProliferating cell nuclear antigen
Protein functionAuxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic, AP endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response, DDR by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways, PubMed:24939902. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion, TLS polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion. {ECO:0000269|PubMed:18719106, ECO:0000269|PubMed:19443450, ECO:0000269|PubMed:24939902}.
Subcellular locationNucleus {ECO:0000269|PubMed:24115439, ECO:0000269|PubMed:24939902}. Note=Colocalizes with CREBBP, EP300 and POLD1 to sites of DNA damage, PubMed:24939902. Forms nuclear foci representing sites of ongoing DNA replication and vary in morphology and number during S phase. Together with APEX2, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents. {ECO:0000269|PubMed:24939902}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P12004
Gene Ontology
(Biological Process)
Complete annatation
cell proliferation [GO:0008283];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to UV [GO:0034644];
DNA damage response, detection of DNA damage [GO:0042769];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
DNA strand elongation involved in DNA replication [GO:0006271];
epithelial cell differentiation [GO:0030855];
error-free translesion synthesis [GO:0070987];
error-prone translesion synthesis [GO:0042276];
estrous cycle [GO:0044849];
G1/S transition of mitotic cell cycle [GO:0000082];
heart development [GO:0007507];
leading strand elongation [GO:0006272];
liver regeneration [GO:0097421];
mismatch repair [GO:0006298];
mitotic telomere maintenance via semi-conservative replication [GO:1902990];
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];
positive regulation of deoxyribonuclease activity [GO:0032077];
positive regulation of DNA repair [GO:0045739];
positive regulation of DNA replication [GO:0045740];
protein sumoylation [GO:0016925];
regulation of transcription involved in G1/S transition of mitotic cell cycle [GO:0000083];
replication fork processing [GO:0031297];
response to cadmium ion [GO:0046686];
response to dexamethasone [GO:0071548];
response to estradiol [GO:0032355];
response to L-glutamate [GO:1902065];
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
chromatin binding [GO:0003682];
damaged DNA binding [GO:0003684];
dinucleotide insertion or deletion binding [GO:0032139];
DNA polymerase binding [GO:0070182];
DNA polymerase processivity factor activity [GO:0030337];
enzyme binding [GO:0019899];
histone acetyltransferase binding [GO:0035035];
identical protein binding [GO:0042802];
MutLalpha complex binding [GO:0032405];
purine-specific mismatch base pair DNA N-glycosylase activity [GO:0000701];
receptor tyrosine kinase binding [GO:0030971]
Gene Ontology
(Cellular Component)
Complete annatation
centrosome [GO:0005813];
cytoplasm [GO:0005737];
DNA replication factor C complex [GO:0005663];
extracellular exosome [GO:0070062];
nuclear chromosome, telomeric region [GO:0000784];
nuclear replication fork [GO:0043596];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PCNA complex [GO:0043626];
PCNA-p21 complex [GO:0070557];
replisome [GO:0030894]
Protein-protein interaction111142
Phylogenetic treeP12004
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD31.779483738561590.0124727082084730.0314625369235323
AZA vs. DISU-0.3000863127585310.2354800496131590.820480344639691
AZA vs. IL70.4313839756447310.07654141299121770.773641548161711
AZA vs. SAHA-0.9393744322991610.0001346713119513290.0047165157732814
DISU vs. CD3-2.092812331755410.003388052958609670.0117378787170954
DISU vs. IL70.7221990495027250.004714577810307820.0728946261439901
DISU vs. SAHA-0.6372712629308160.029355567504280.204078474640339
DMSO vs. AZA-0.3769465389365540.02465885786064861
DMSO vs. CD3-2.168763620203990.0027731548746690.00830238040279979
DMSO vs. DISU-0.07882084798477410.746554736667840.969482258605607
DMSO vs. IL70.8154475040429620.001049415887035440.0581615606509533
DMSO vs. SAHA-0.5681554580285920.01639316446525830.124276348921483
HIV vs. Mock in Activation-0.1969932787482370.8905026650797450.999983755607037
HIV vs. Mock in Latency-0.1110714138192440.6339525433845220.999834320637052
IL7 vs. CD3-1.340918926906920.06031817970940740.12789083172878
SAHA vs. CD3-2.743333193919490.0001596634672383910.000722995327909422
SAHA vs. IL7-1.372856945483133.83333861320168e-082.97854362141248e-06
(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
2.1 0.001188115 1.4 0.02848839 1.6 0.120907557
(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) unknown
(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 0.76304 0.000305467
(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
0.105 0.004

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
1.044 0.979 0.94 0.923 0.971
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
0.63 <0.0001 0.17 0.0002 -0.17 0.0184 DNA recombination; repair and maintenance (4hpi)
(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
1AXC X-ray 2.6Å A/C/E=1-261.
1U76 X-ray 2.6Å A/C/E=1-261.
1U7B X-ray 1.8Å A=1-261.
1UL1 X-ray 2.9Å A/B/C=1-261.
1VYJ X-ray 2.8Å A/C/E/G/I/K=1-261.
1VYM X-ray 2.3Å A/B/C=1-261.
1W60 X-ray 3.1Å A/B=1-261.
2ZVK X-ray 2.7Å A/B/C=1-261.
2ZVL X-ray 2.5Å A/B/C/D/E/F=1-261.
2ZVM X-ray 2.3Å A/B/C=1-261.
3JA9 EM 22.0Å A/B/C=1-261.
3P87 X-ray 2.9Å A/B/C/D/E/F=1-261.
3TBL X-ray 2.9Å A/B/C=1-261.
3VKX X-ray 2.1Å A=1-261.
3WGW X-ray 2.8Å A/B=1-261.
4D2G X-ray 2.6Å A/B/C=1-261.
4RJF X-ray 2.0Å A/C/E=1-261.
4ZTD X-ray 2.2Å A/B/C=2-254.
5E0T X-ray 2.6Å A/B/C=1-261.
5E0U X-ray 1.9Å A/B/C=1-261.
5E0V X-ray 2.0Å A/B=1-261.
5IY4 X-ray 2.9Å A/C/E=1-261.

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

HIV Partner Interaction Type PubMed
Tat upregulates 23364796
Tat interacts with 15050687

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
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)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
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