PARP1 poly(ADP-ribose) polymerase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PARP1provided by HGNC
Official Full Name: poly(ADP-ribose) polymerase 1provided by HGNC
Primary source: HGNC:HGNC:270
See related: Ensembl:ENSG00000143799 MIM:173870; AllianceGenome:HGNC:270
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PARP; PARS; PPOL; ADPRT; ARTD1; ADPRT1; PARP-1; ADPRT 1; pADPRT-1; Poly-PARP
Summary: This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lymph node (RPKM 71.4), appendix (RPKM 40.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q42.12

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (226360691..226408093, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (225548804..225596198, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (226548392..226595794, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PARP1 roles in DNA repair and DNA replication: The basi(c)s of PARP inhibitor efficacy and resistance.
Title: PARP1 roles in DNA repair and DNA replication: The basi(c)s of PARP inhibitor efficacy and resistance.
Blocking lipid synthesis induces DNA damage in prostate cancer and increases cell death caused by PARP inhibition.
Title: Blocking lipid synthesis induces DNA damage in prostate cancer and increases cell death caused by PARP inhibition.
FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells.
Title: FANCJ promotes PARP1 activity during DNA replication that is essential in BRCA1 deficient cells.
A Knockout of Poly(ADP-Ribose) Polymerase 1 in a Human Cell Line: An Influence on Base Excision Repair Reactions in Cellular Extracts.
Title: A Knockout of Poly(ADP-Ribose) Polymerase 1 in a Human Cell Line: An Influence on Base Excision Repair Reactions in Cellular Extracts.
PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/beta-catenin signalling pathway.
Title: PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway.
A review of poly(ADP-ribose)polymerase-1 (PARP1) role and its inhibitors bearing pyrazole or indazole core for cancer therapy.
Title: A review of poly(ADP-ribose)polymerase-1 (PARP1) role and its inhibitors bearing pyrazole or indazole core for cancer therapy.
Value of the NF-kappaB signalling pathway and the DNA repair gene PARP1 in predicting distant metastasis after breast cancer surgery.
Title: Value of the NF-κB signalling pathway and the DNA repair gene PARP1 in predicting distant metastasis after breast cancer surgery.
TKT-PARP1 axis induces radioresistance by promoting DNA double-strand break repair in hepatocellular carcinoma.
Title: TKT-PARP1 axis induces radioresistance by promoting DNA double-strand break repair in hepatocellular carcinoma.
Cancer-educated neutrophils promote lung cancer progression via PARP-1-ALOX5-mediated MMP-9 expression.
Title: Cancer-educated neutrophils promote lung cancer progression via PARP-1-ALOX5-mediated MMP-9 expression.
PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends.
Title: PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends.

Submit: New GeneRIF Correction See all GeneRIFs (925)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication is enhanced by PARP1 in monocyte derived macrophages	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	The mRNA expression levels for alpha-tubulin, TRADD, IFN-gamma R2, GAS1, MADD, NF-kappaB, I-kappa B, 14-3-3 protein, APaf1, PARP, IGF-1 receptor, RB1, Rb2/p130, ARC, and caspase 6 are upregulated in human neuronal cells after treatment with HIV-1 gp120	PubMed
	env	Contact of CD4+ T cells with HIV-1 infected or HIV-1 gp120-expressing cells induces PARP hydrolysis, which leads to the cleavage of 116 kDa PARP into two fragments	PubMed
Nef	nef	HIV-1 Nef enhances apoptosis in CD4+ T lymphoblastoid cell lines through mechanisms that include the cleavage of the caspase target poly(ADP-ribose) polymerase	PubMed
	nef	Expression of HIV-1 Nef in human brain micro vascular endothelial cells induces the cleavage of PARP protein, which is involved in DNA repair	PubMed
Tat	tat	HIV-1 Tat binds TOP2B (topoisomeraseIIb), XRCC6 (Ku70), and PARP1 during transactivation and viral replication	PubMed
	tat	HIV-1 clade B and C Tat induces cleavage of both PARP and CASP3 in primary glia	PubMed
	tat	HIV-1 Tat-induced PARP cleavage during mitotic arrest occurs downstream of Tat-induced cytochrome c release during mitotic arrest in CD4+ T-lymphocytes	PubMed
	tat	CB1 and CB2 endocannabinoid receptors are involved in HIV-1 Tat-induced cleavage of PARP1 and CASP3 in retinal cells	PubMed
	tat	The levels of PARP1 protein are reduced after Caco-2 cells exposure to HIV-1 Tat compared with control	PubMed
	tat	PARP1 negatively regulates HIV-1 transcription by directly competing with Tat-P-TEFb complex for binding to TAR RNA	PubMed
	tat	HIV-1 Tat induces the cleavage of PARP and activation of apoptosis through a p56lck dependent mechanism	PubMed
	tat	Treatment of primary human microvascular endothelial cells of lung origin with HIV-1 Tat caused cleavage of poly(A/DP)-ribose polymerase as a result of caspase activation	PubMed
	tat	The poly(A) site in the HIV-1 5'-LTR is occluded in a Tat-dependent manner, suggesting a role for Tat in regulating this nucleotide signal	PubMed
	tat	Poly(ADP-ribose) polymerase modifies HIV-1 Tat with poly(ADP-ribose), suggesting a role for this enzyme in the regulation of HIV-1 gene expression	PubMed
	tat	Purified recombinant HIV-1 Tat protein stimulates poly(ADP-ribose) polymerase in a dose dependent manner	PubMed
Vpr	vpr	Recruitment of PARP-1 by HIV-1 Vpr-glucocorticoid receptor (GR) complex prevents its nuclear localization, which is necessary for Vpr to suppress NF-kappaB	PubMed
	vpr	HIV-1 Vpr induces apoptosis and the cleavage of ADPRT in a manner that is signaled through the DNA damage signaling protein ataxia telangiectasia Rad3-related protein (ATR)	PubMed
Vpu	vpu	HIV-1 Vpu-induced cleavage of PARP is dependent on caspase activity in cells	PubMed
integrase	gag-pol	PARP has been described as a requirement for efficient HIV-1 integration, however a conflicting report indicates it is not essential for efficient lentivirus integration	PubMed
retropepsin	gag-pol	Inhibition of HIV-1 protease by saquinavir and leu3.a blocks PARP cleavage and protects cells from apoptosis and necrosis	PubMed
	gag-pol	Positional proteomics analysis identifies the cleavage of human poly (ADP-ribose) polymerase family, member 1 (PARP1) at amino acid residues 185-186 by the HIV-1 protease	PubMed
	gag-pol	HIV-1 protease directly cleaves and activates procaspase 8 in T cells, which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:196988 (e-PCR)
- UniSTS:155905

SHGC-79808 (e-PCR)
- UniSTS:96027

G67245 (e-PCR)
- UniSTS:186403

G67248 (e-PCR)
- UniSTS:186404

G67249 (e-PCR)
- UniSTS:186405

G67251 (e-PCR)
- UniSTS:186406

G67244 (e-PCR)
- UniSTS:186407

G67246 (e-PCR)
- UniSTS:186408

G67247 (e-PCR)
- UniSTS:186409

G67250 (e-PCR)
- UniSTS:186410

G67252 (e-PCR)
- UniSTS:186411

RH70493 (e-PCR)
- UniSTS:3628

G67253 (e-PCR)
- UniSTS:186412

SHGC-76463 (e-PCR)
- UniSTS:2642

RH11161 (e-PCR)
- UniSTS:91506

SHGC-144766 (e-PCR)
- UniSTS:172404

SHGC-30345 (e-PCR)
- UniSTS:34448

G07110 (e-PCR)
- UniSTS:82324

ADPRT_3241 (e-PCR)
- UniSTS:462018

SHGC-76015 (e-PCR)
- UniSTS:23752

D1S2048E (e-PCR)
- UniSTS:151523

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables NAD DNA ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD binding	IEA Inferred from Electronic Annotation more info
enables NAD+ ADP-ribosyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables NAD+ ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+ ADP-ribosyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables NAD+ ADP-ribosyltransferase activity	TAS Traceable Author Statement more info
enables NAD+- protein-aspartate ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables NAD+-histone H2BS6 serine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-histone H3S10 serine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein ADP-ribosyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables NAD+-protein ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein-glutamate ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein-histidine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein-serine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+-protein-tyrosine ADP-ribosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables R-SMAD binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	HDA more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables damaged DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables histone deacetylase binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables nuclear estrogen receptor binding	IEA Inferred from Electronic Annotation more info
enables nucleosome binding	IDA Inferred from Direct Assay more info	PubMed
enables nucleotidyltransferase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription regulator activator activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ATP generation from poly-ADP-D-ribose	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA repair	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA repair	TAS Traceable Author Statement more info	PubMed
involved_in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in carbohydrate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in cellular response to UV	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to amyloid-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to nerve growth factor stimulus	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to zinc ion	IEA Inferred from Electronic Annotation more info
involved_in decidualization	ISS Inferred from Sequence or Structural Similarity more info
involved_in double-strand break repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
involved_in double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in macrophage differentiation	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within mitochondrial DNA metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrial DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of ATP biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of adipose tissue development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cGAS/STING signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of telomere maintenance via telomere lengthening	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info
involved_in negative regulation of transcription elongation by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription, elongation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of SMAD protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cardiac muscle hypertrophy	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of intracellular estrogen receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mitochondrial depolarization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of myofibroblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of necroptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein localization to nucleus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of single strand break repair	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in protein auto-ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autoprocessing	IEA Inferred from Electronic Annotation more info
involved_in protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein modification process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein poly-ADP-ribosylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein poly-ADP-ribosylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of base-excision repair	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of catalytic activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of circadian sleep/wake cycle, non-REM sleep	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in replication fork reversal	IDA Inferred from Direct Assay more info	PubMed
involved_in response to aldosterone	IEA Inferred from Electronic Annotation more info
involved_in response to gamma radiation	IEA Inferred from Electronic Annotation more info
involved_in signal transduction involved in regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in telomere maintenance	TAS Traceable Author Statement more info	PubMed
involved_in transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in transforming growth factor beta receptor signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome, telomeric region	HDA more info	PubMed
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
is_active_in nuclear replication fork	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleolus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-DNA complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in site of DNA damage	IDA Inferred from Direct Assay more info	PubMed
located_in site of DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: poly [ADP-ribose] polymerase 1

Names: ADP-ribosyltransferase (NAD+; poly (ADP-ribose) polymerase); ADP-ribosyltransferase NAD(+); ADP-ribosyltransferase diphtheria toxin-like 1; DNA ADP-ribosyltransferase PARP1; NAD(+) ADP-ribosyltransferase 1; poly (ADP-ribose) polymerase family, member 1; poly(ADP-ribose) synthetase; poly(ADP-ribosyl)transferase; poly[ADP-ribose] synthase 1; protein poly-ADP-ribosyltransferase PARP1

NP_001609.2

EC 2.4.2.30

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.