Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002093
UniProt IDP09874
Primary gene name(s)PARP1
Synonym gene name(s)ADPRT, PPOL
Protein namePoly [ADP-ribose] polymerase 1
Protein functionInvolved in the base excision repair, BER pathway, by catalyzing the poly(ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks, PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272. Mediates the poly(ADP-ribosylation of APLF and CHFR, PubMed:17396150. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1, Th1 cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production, PubMed:17177976. Required for PARP9 and DTX3L recruitment to DNA damage sites, PubMed:23230272. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites, PubMed:23230272. Mediates the poly(ADP-ribosylation of histones in a HPF1-dependent manner, PubMed:27067600. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5, PubMed:27257257. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming, PubMed:27257257. {ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27257257}.
Subcellular locationNucleus. Nucleus, nucleolus. Note=Localizes at sites of DNA damage.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P09874
Gene Ontology
(Biological Process)
Complete annatation
ATP generation from poly-ADP-D-ribose [GO:1990966];
cellular response to beta-amyloid [GO:1904646];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to insulin stimulus [GO:0032869];
cellular response to oxidative stress [GO:0034599];
cellular response to zinc ion [GO:0071294];
DNA damage response, detection of DNA damage [GO:0042769];
DNA ligation involved in DNA repair [GO:0051103];
DNA repair [GO:0006281];
double-strand break repair [GO:0006302];
double-strand break repair via homologous recombination [GO:0000724];
global genome nucleotide-excision repair [GO:0070911];
lagging strand elongation [GO:0006273];
macrophage differentiation [GO:0030225];
mitochondrial DNA metabolic process [GO:0032042];
mitochondrial DNA repair [GO:0043504];
mitochondrion organization [GO:0007005];
negative regulation of ATP biosynthetic process [GO:2001170];
negative regulation of telomere maintenance via telomere lengthening [GO:1904357];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
nucleotide-excision repair, DNA damage recognition [GO:0000715];
nucleotide-excision repair, DNA duplex unwinding [GO:0000717];
nucleotide-excision repair, DNA incision [GO:0033683];
nucleotide-excision repair, DNA incision, 3'-to lesion [GO:0006295];
nucleotide-excision repair, DNA incision, 5'-to lesion [GO:0006296];
nucleotide-excision repair, preincision complex assembly [GO:0006294];
nucleotide-excision repair, preincision complex stabilization [GO:0006293];
positive regulation of cardiac muscle hypertrophy [GO:0010613];
positive regulation of intracellular estrogen receptor signaling pathway [GO:0033148];
positive regulation of mitochondrial depolarization [GO:0051901];
positive regulation of myofibroblast differentiation [GO:1904762];
positive regulation of neuron death [GO:1901216];
positive regulation of SMAD protein import into nucleus [GO:0060391];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transcription regulatory region DNA binding [GO:2000679];
protein ADP-ribosylation [GO:0006471];
protein autoprocessing [GO:0016540];
protein modification process [GO:0036211];
protein poly-ADP-ribosylation [GO:0070212];
protein sumoylation [GO:0016925];
regulation of cellular protein localization [GO:1903827];
regulation of DNA methylation [GO:0044030];
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway [GO:1903376];
regulation of SMAD protein complex assembly [GO:0010990];
response to aldosterone [GO:1904044];
response to gamma radiation [GO:0010332];
signal transduction involved in regulation of gene expression [GO:0023019];
transcription from RNA polymerase II promoter [GO:0006366];
transforming growth factor beta receptor signaling pathway [GO:0007179]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
DNA ligase, ATP activity [GO:0003910];
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
NAD+ ADP-ribosyltransferase activity [GO:0003950];
NAD binding [GO:0051287];
poly(A RNA binding [GO:0044822];
protein kinase binding [GO:0019901];
protein N-terminus binding [GO:0047485];
transcription factor binding [GO:0008134];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
membrane [GO:0016020];
mitochondrion [GO:0005739];
nuclear chromosome, telomeric region [GO:0000784];
nuclear envelope [GO:0005635];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
protein complex [GO:0043234];
transcription factor complex [GO:0005667]
Protein-protein interaction106652
Phylogenetic treeP09874
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. CD30.1035437616357830.7524397197599180.828458722786287
AZA vs. DISU-0.2910370074261990.2494816096986940.831029075563411
AZA vs. IL70.08078302484623370.6737497428450380.999311006273513
AZA vs. SAHA0.2806069015011420.2500165872612330.620064171828862
DISU vs. CD3-0.4065916282567550.2631911363605790.391256724802699
DISU vs. IL70.3624500601655040.1500258839740770.503128970709518
DISU vs. SAHA0.5730525994833430.05003704716392780.27961006222008
DMSO vs. AZA-0.01084622184999910.948240055127681
DMSO vs. CD3-0.1259155351658930.6939952725312030.775244078687668
DMSO vs. DISU0.2782568365220270.2535852743820370.771886382169071
DMSO vs. IL70.09890833277036710.5813493685949770.907460167501459
DMSO vs. SAHA0.2850277873023270.2272643275201370.573129911467257
HIV vs. Mock in Activation0.1740077175063060.7794857425972070.999983755607037
HIV vs. Mock in Latency-0.05293692528124640.7478167378645230.999834320637052
IL7 vs. CD3-0.01566562190060140.9610925582776040.976687380653043
SAHA vs. CD30.1525874488376570.6686034579516050.754101289384986
SAHA vs. IL70.1968497636301440.4198398950893510.663382240940972
(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
1.6 0.000173628 1.2 0.059723698 1.7 0.033118855
(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 0.951521 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
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
1.033 0.906 0.861 0.827 0.779
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
0.73 0.0241 0.37 0.9845 0.1 0.4943 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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02498 Carba-Nicotinamide-Adenine-Dinucleotide experimental unknown unknown
DB03072 2-{3-[4-(4-Fluorophenyl)-3,6-Dihydro-1(2h)-Pyridinyl]Propyl}-8-Methyl-4(3h)-Quinazolinone experimental unknown unknown
DB03073 3-Methoxybenzamide experimental unknown unknown
DB03509 2-(4-Chlorophenyl)-5-Quinoxalinecarboxamide experimental unknown unknown
DB03722 3,4-Dihydro-5-Methyl-Isoquinolinone experimental unknown unknown
DB02701 Nicotinamide approved unknown binder
DB07096 6-AMINO-BENZO[DE]ISOQUINOLINE-1,3-DIONE experimental unknown unknown
DB07232 Veliparib investigational unknown unknown
DB07330 trans-4-(7-carbamoyl-1H-benzimidazol-2-yl)-1-propylpiperidinium experimental unknown unknown
DB04010 2-(3&,39;-Methoxyphenyl) Benzimidazole-4-Carboxamide experimental unknown unknown
DB07787 5-FLUORO-1-[4-(4-PHENYL-3,6-DIHYDROPYRIDIN-1(2H)-YL)BUTYL]QUINAZOLINE-2,4(1H,3H)-DIONE experimental unknown unknown
DB02690 NU1025 experimental unknown unknown
DB09074 Olaparib approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1UK0 X-ray 3.0Å A/B=662-1011.
1UK1 X-ray 3.0Å A/B=662-1011.
1WOK X-ray 3.0Å A/B/C/D=662-1011.
2COK NMR - A=387-486.
2CR9 NMR - A=518-643.
2CS2 NMR - A=103-223.
2DMJ NMR - A=1-93.
2JVN NMR - A=233-358.
2L30 NMR - A=1-108.
2L31 NMR - A=103-214.
2N8A NMR - A=1-214.
2RCW X-ray 2.8Å A=662-1011.
2RD6 X-ray 2.3Å A=662-1011.
2RIQ X-ray 1.7Å A=216-366.
3GJW X-ray 2.3Å A=662-1011.
3GN7 X-ray 2.5Å A=662-1011.
3L3L X-ray 2.5Å A=662-1011.
3L3M X-ray 2.5Å A=662-1011.
3OD8 X-ray 2.4Å A/B/C/D/E/F/G/H=2-96.
3ODA X-ray 2.6Å A/B/C/D/E/F/G/H=2-96.
3ODC X-ray 2.8Å A/B=105-206.
3ODE X-ray 2.9Å A/B=105-206.
4AV1 X-ray 3.1Å A/B/C/D=5-202.
4DQY X-ray 3.2Å A/D=1-96# B/E=216-366# C/F=518-1014.
4GV7 X-ray 2.8Å A/B/C/D=662-1011.
4HHY X-ray 2.3Å A/B/C/D=660-1011.
4HHZ X-ray 2.7Å A/B/C/D=660-1011.
4L6S X-ray 2.2Å A/B=662-1011.
4OPX X-ray 3.3Å A/D=1-97# A/D=207-366# C/F=518-1014.
4OQA X-ray 3.6Å A/D=1-97# A/D=207-366# C/F=518-1014.
4OQB X-ray 3.3Å A/D=1-97# A/D=207-366# C/F=518-1014.
4PJT X-ray 2.3Å A/B/C/D=662-1011.
4R5W X-ray 2.8Å A/B=662-1011.
4R6E X-ray 2.2Å A/B/C/D=662-1011.
4RV6 X-ray 3.1Å A/B/C/D=662-1011.
4UND X-ray 2.2Å A/B=662-1011.
4UXB X-ray 3.2Å A/B=662-1011.
4XHU X-ray 2.0Å A/C=661-1014.
4ZZZ X-ray 1.9Å A/B=655-1014.
5A00 X-ray 2.7Å A=655-1014.
5DS3 X-ray 2.6Å A=788-1012.
5HA9 X-ray 4.0Å A/B=662-1011.

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

HIV Partner Interaction Type PubMed
Tat stimulates 10405328
Tat modified by 10405328
Vpr recruits 16429131
Envelope surface glycoprotein gp120 induces cleavage of 9548463
HIV-1 virus replication enhanced by expression of human gene 26379653
Vpu induces cleavage of 25352594
Tat interacts with 22216281
Tat regulates 8491200
Tat induces cleavage of 10799874
retropepsin cleaves 15781132
retropepsin induces cleavage of 12404116
Nef induces cleavage of 11123279
Tat regulated by 15498776
Envelope surface glycoprotein gp120 upregulates 15103018
Vpr induces cleavage of 15650754
integrase requires 11070027

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03410 Base excision repair - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)