PARP2

Summary

PARP2 (poly(ADP-ribose) polymerase 2, HGNC:272) is a protein-coding gene on chromosome 14q11.2, encoding Poly [ADP-ribose] polymerase 2 (Q9UGN5). Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.

This gene encodes poly(ADP-ribosyl)transferase-like 2 protein, which contains a catalytic domain and is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. Two alternatively spliced transcript variants encoding distinct isoforms have been found.

Source: NCBI Gene 10038 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 96 total
• GTEx eGene: eQTL in 44 tissues, sQTL in 49 (q < 0.05)
• Drug target: yes — 5 curated mechanism-of-action drugs, 5 via a complex or family; 11 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 2 — Niraparib, Talazoparib
• Approved drugs acting on a complex or family including it: 3 — Olaparib, Rucaparib, Rucaparib Camsylate (PARP 1, 2 and 3)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_001042618
• Notable: 96 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:272
Approved symbol	PARP2
Name	poly(ADP-ribose) polymerase 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ARTD2
Ensembl gene	ENSG00000129484
Ensembl biotype	protein_coding
OMIM	607725
Entrez	10038

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 13 protein_coding, 11 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000429687

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 3, TSL 4: 2, TSL 5: 1

ENST00000429687, ENST00000250416, ENST00000527384, ENST00000527915, ENST00000528465, ENST00000529465, ENST00000530598, ENST00000532299, ENST00000534664, ENST00000539930, ENST00000555140, ENST00000859467, ENST00000859468, ENST00000925414, ENST00000925415, ENST00000925416, ENST00000965371, ENST00000965372, ENST00000986834, ENST00000986835, ENST00000986836, ENST00001054151, ENST00001054152, ENST00001054153, ENST00001054154, ENST00001054155, ENST00001054156, ENST00001067485, ENST00001127978, ENST00001134963

RefSeq mRNA: 2 — MANE Select: NM_001042618 NM_001042618, NM_005484

CCDS: CCDS41910, CCDS45077

Canonical transcript exons

ENST00000429687 — 16 exons

Exon	Start	End
ENSE00000652570	20345394	20345464
ENSE00000652572	20346863	20346913
ENSE00000652574	20350526	20350622
ENSE00000652577	20351047	20351122
ENSE00000652580	20354809	20354947
ENSE00000652588	20357051	20357149
ENSE00000652590	20357396	20357520
ENSE00001124500	20357638	20357904
ENSE00001633883	20344932	20345087
ENSE00002146831	20343635	20343687
ENSE00003461934	20356307	20356434
ENSE00003518738	20355897	20356031
ENSE00003626094	20352245	20352347
ENSE00003657630	20354085	20354247
ENSE00003664358	20355752	20355815
ENSE00003693946	20356590	20356689

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9618 / max 760.7416, expressed in 1783 samples.

Highest expression (Bgee): cerebellar hemisphere, cerebellar cortex, hemisphere of cerebellum, cerebellum, frontal lobe.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PARP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 49 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 93 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	0.0e+00	+1.62	14:20344308:C:A
Artery Tibial	sqtl	0.0e+00	-1.80	14:20344308:C:A
Cells Cultured fibroblasts	sqtl	0.0e+00	-1.77	14:20344308:C:A
Muscle Skeletal	sqtl	0.0e+00	+1.63	14:20344308:C:A
Nerve Tibial	sqtl	0.0e+00	+1.66	14:20344308:C:A
Skin Not Sun Exposed Suprapubic	sqtl	0.0e+00	+1.69	14:20344308:C:A
Skin Sun Exposed Lower leg	sqtl	0.0e+00	-1.77	14:20344308:C:A
Thyroid	sqtl	0.0e+00	-1.74	14:20348974:G:C
Esophagus Mucosa	sqtl	2.0e-296	-1.79	14:20344308:C:A
Lung	sqtl	1.3e-284	+1.69	14:20345513:A:G
Adipose Visceral Omentum	sqtl	6.6e-264	+1.61	14:20344308:C:A
Breast Mammary Tissue	sqtl	2.5e-261	-1.77	14:20344308:C:A
Esophagus Muscularis	sqtl	2.8e-260	-1.75	14:20344308:C:A
Colon Transverse	sqtl	3.2e-220	-1.82	14:20344308:C:A
Artery Aorta	sqtl	8.0e-218	+1.63	14:20344308:C:A
Colon Sigmoid	sqtl	4.9e-189	-1.74	14:20344308:C:A
Heart Atrial Appendage	sqtl	5.6e-179	+1.67	14:20344308:C:A
Testis	sqtl	1.6e-175	-1.83	14:20344308:C:A
Cells EBV-transformed lymphocytes	sqtl	9.8e-172	-1.81	14:20344308:C:A
Stomach	sqtl	3.8e-168	+1.68	14:20345513:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
138421	18.9618	1783

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	96.49	gold quality
cerebellar cortex	UBERON:0002129	96.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.40	gold quality
cerebellum	UBERON:0002037	95.69	gold quality
right frontal lobe	UBERON:0002810	94.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.64	gold quality
ventricular zone	UBERON:0003053	93.59	gold quality
ganglionic eminence	UBERON:0004023	93.52	gold quality
prefrontal cortex	UBERON:0000451	93.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.20	gold quality
cortical plate	UBERON:0005343	92.99	gold quality
cerebellar vermis	UBERON:0004720	92.92	gold quality
left ovary	UBERON:0002119	92.84	gold quality
adenohypophysis	UBERON:0002196	92.76	gold quality
frontal cortex	UBERON:0001870	92.66	gold quality
neocortex	UBERON:0001950	92.59	gold quality
body of uterus	UBERON:0009853	92.50	gold quality
tibial nerve	UBERON:0001323	92.35	gold quality
cingulate cortex	UBERON:0003027	92.32	gold quality
right adrenal gland cortex	UBERON:0035827	92.24	gold quality
middle temporal gyrus	UBERON:0002771	92.22	gold quality
anterior cingulate cortex	UBERON:0009835	92.21	gold quality
primary visual cortex	UBERON:0002436	92.09	gold quality
right ovary	UBERON:0002118	92.04	gold quality
nucleus accumbens	UBERON:0001882	91.92	gold quality
body of pancreas	UBERON:0001150	91.91	gold quality
pituitary gland	UBERON:0000007	91.88	gold quality
right uterine tube	UBERON:0001302	91.82	gold quality
cerebral cortex	UBERON:0000956	91.67	gold quality
right adrenal gland	UBERON:0001233	91.67	gold quality
brain	UBERON:0000955	91.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.56	gold quality
left testis	UBERON:0004533	91.56	gold quality
central nervous system	UBERON:0001017	91.54	gold quality
left adrenal gland cortex	UBERON:0035825	91.53	gold quality
occipital lobe	UBERON:0002021	91.51	gold quality
caudate nucleus	UBERON:0001873	91.50	gold quality
left adrenal gland	UBERON:0001234	91.48	gold quality
putamen	UBERON:0001874	91.48	gold quality
right testis	UBERON:0004534	91.47	gold quality
mucosa of stomach	UBERON:0001199	91.40	gold quality
skin of leg	UBERON:0001511	91.33	gold quality
telencephalon	UBERON:0001893	91.33	gold quality
forebrain	UBERON:0001890	91.32	gold quality
amygdala	UBERON:0001876	91.30	gold quality
embryo	UBERON:0000922	91.28	gold quality
metanephros cortex	UBERON:0010533	91.20	gold quality
ovary	UBERON:0000992	91.19	gold quality
adrenal cortex	UBERON:0001235	91.19	gold quality
skin of abdomen	UBERON:0001416	91.18	gold quality
hypothalamus	UBERON:0001898	91.15	gold quality
testis	UBERON:0000473	90.96	gold quality
left lobe of thyroid gland	UBERON:0001120	90.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.78	gold quality
gastrocnemius	UBERON:0001388	90.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.71	gold quality
muscle of leg	UBERON:0001383	90.70	gold quality
adrenal gland	UBERON:0002369	90.62	gold quality
apex of heart	UBERON:0002098	90.61	gold quality
left uterine tube	UBERON:0001303	90.46	gold quality
thyroid gland	UBERON:0002046	90.45	gold quality
ectocervix	UBERON:0012249	90.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.23	gold quality
muscle organ	UBERON:0001630	90.17	gold quality
spinal cord	UBERON:0002240	90.14	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.12	gold quality
smooth muscle tissue	UBERON:0001135	90.05	gold quality
deltoid	UBERON:0001476	89.97	gold quality
body of stomach	UBERON:0001161	89.93	gold quality
endometrium epithelium	UBERON:0004811	89.90	gold quality
endocervix	UBERON:0000458	89.87	gold quality
right lobe of thyroid gland	UBERON:0001119	89.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.81	gold quality
lower esophagus	UBERON:0013473	89.80	gold quality
zone of skin	UBERON:0000014	89.66	gold quality
tibialis anterior	UBERON:0001385	89.63	gold quality
minor salivary gland	UBERON:0001830	89.60	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.60	gold quality
gluteal muscle	UBERON:0002000	89.53	gold quality
pancreas	UBERON:0001264	89.44	gold quality
rectum	UBERON:0001052	89.41	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.38	gold quality
type B pancreatic cell	CL:0000169	89.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.37	gold quality
pons	UBERON:0000988	89.33	gold quality
descending thoracic aorta	UBERON:0002345	89.19	gold quality
temporal lobe	UBERON:0001871	89.14	gold quality
spleen	UBERON:0002106	88.96	gold quality
quadriceps femoris	UBERON:0001377	88.95	gold quality
esophagus	UBERON:0001043	88.92	gold quality
right lobe of liver	UBERON:0001114	88.92	gold quality
Ammon’s horn	UBERON:0001954	88.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.78	gold quality
frontal pole	UBERON:0002795	88.73	gold quality
substantia nigra	UBERON:0002038	88.71	gold quality
vastus lateralis	UBERON:0001379	88.69	silver quality
right lung	UBERON:0002167	88.65	gold quality
sural nerve	UBERON:0015488	88.64	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	30.3	low
Postcentral gyrus	tissue	25.4
Tongue	tissue	25.3
Bone marrow	tissue	25.3	low
Retina	tissue	24.5
Testis	tissue	22.2	high
Ovary	tissue	20.3	not detected
Pituitary gland	tissue	20.2
Endometrium 1	tissue	19.6	low
Nucleus accumbens	tissue	18.2
Adrenal gland	tissue	17.0	medium
Epididymis	tissue	16.8	medium
Tonsil	tissue	16.7	medium
Skin 1	tissue	16.2	low
Liver	tissue	16.0	low
Breast	tissue	15.6	not detected
Heart muscle	tissue	15.1	not detected
Fallopian tube	tissue	14.9	low
Vagina	tissue	14.8	medium
Smooth muscle	tissue	14.8	not detected
Kidney	tissue	14.4	low
Locus coeruleus	tissue	14.4
Hippocampus	tissue	13.8	medium
Lymph node	tissue	13.5	medium
Rectum	tissue	13.2	low
Seminal vesicle	tissue	12.7	low
Lung	tissue	12.7	low
Stomach 1	tissue	12.6	not detected
Pancreas	tissue	12.6	not detected
Placenta	tissue	12.1	low
Duodenum	tissue	12.0	low
Small intestine	tissue	11.9	medium
Thyroid gland	tissue	11.7	low
Spleen	tissue	11.6	not detected
Prostate	tissue	11.2	low
Esophagus	tissue	11.1	medium
Salivary gland	tissue	11.1	not detected
Thymus	tissue	11.1
Cervix	tissue	11.0	medium
Corpus callosum	tissue	11.0
Caudate putamen	tissue	10.9
Colon	tissue	10.6	medium
Adipose tissue	tissue	10.4	not detected
Parathyroid gland	tissue	10.4	not detected
Periaqueductal gray	tissue	10.3
Appendix	tissue	10.1	not detected
Frontal cortex	tissue	9.8
Choroid plexus	tissue	9.5
Gallbladder	tissue	9.4	low
Spinal cord	tissue	9.3
Urinary bladder	tissue	8.7	medium
Substantia nigra	tissue	8.4
Pons	tissue	8.2
Medulla oblongata	tissue	8.0
Hypothalamus	tissue	7.6
Midbrain	tissue	7.5
Superior colliculi	tissue	7.5
Septum	tissue	7.2
Thalamus	tissue	6.9
Cerebellum	tissue	6.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Orbitofrontal gyrus, anterior (23.7), Inferior frontal gyrus, opercular (23.3), Postcentral gyrus, middle (22.0), Frontal eye field (21.8), Perirhinal gyrus (21.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PARP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

11 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-125B-2-3P	96.69	68.38	1210

Functional genomics

gnomAD constraint: pLI 3.29e-11, LOEUF 1.04, missense Z 0.85 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000429687 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 40)

• PARP-1 and PARP-2 act as positive regulators of genomic stability in eukaryotic cells by counteracting topoisomerase I-induced DNA damage (PMID:14699148)
• PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of surfactant protein B, a protein required for lung function (PMID:16461352)
• cells from old subjects show a constitutive expression level of both parp 1 and parp 2 genes reduced by a half (PMID:17518695)
• Determination of Poly (ADP-ribose) polymerase (PARP) homologues in human ejaculated sperm and its correlation with sperm maturation. (PMID:18339380)
• PARP-1-but not PARP-2-is required for proper expression of major genes involved in regulation of apoptosis (PMID:18587655)
• Results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions. (PMID:18644123)
• The histone subcode: poly(ADP-ribose) polymerase-1 (Parp-1) and Parp-2 control cell differentiation by regulating the transcriptional intermediary factor TIF1beta and the heterochromatin protein HP1alpha (PMID:18676401)
• The PARP-2 gene might be associated with azoospermia by meiotic arrest (PMID:19806447)
• In complex with its inhibitor, the crystal structure of PARP2 alpha-helix 5 that contains glutamate residue Glu335 is closer to the active site than in both PARP1 and PARP3 and suggests a mechanism for a weak bias toward PARP2. (PMID:20092359)
• PARP-1 (but not PARP-2) poly(ADP) ribosylates Snail1, both in vivo and in vitro, and interacts with Snail1, an association that is sensitive to PARP inhibitors. (PMID:21577210)
• these findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein-protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression. (PMID:23291187)
• the depletion of PARP-2 leads to lower HDL levels which represent a risk factor to cardiovascular diseases. (PMID:24365238)
• Nuclear Smad function is negatively regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG during the course of TGFB signaling. (PMID:25133494)
• Interaction of PARP-2 with AP site containing DNA (PMID:25724268)
• Identification of ADP-ribosylation sites in PARP2 and the determination of the extent ofpoly(ADP-ribosyl)ated residues in this protein was performed. (PMID:25800440)
• Data show that E7449 represents a dual Poly(ADP-ribose) Polymerase 1/2 and tankyrase 1/2 inhibitor which has the advantage of targeting Wnt/beta-catenin signaling addicted tumors. (PMID:26513298)
• The initial affinity between the PARP1, PARP2 and the DNA damaged site appears to influence both the size of the Poly(ADP-Ribose) synthesized and the time of residence of PARylated PARP1 and PARP2 on DNA damages. (PMID:26673720)
• Our data suggest for the first time that a SNP in PARP2, rs878156, may together with other genetic variants modulate cancer specific survival in breast cancer patients depending on chemotherapy (PMID:26674097)
• Our study differentiates the functions of PARP-2 domains from those of PARP-1, the other major DDR-PARP, and highlights the specialization of the multi-domain architectures of DDR-PARPs. (PMID:26704974)
• Studies indicate that poly(ADP-ribose) polymerase 2 (PARP2) is involved in the differentiation of several cell types, including erythrocytes, T cells and adipocytes. (PMID:27087568)
• Findings indicate that Increased poly(ADP-ribose) polymerase-2 (PARP-2) expression and loss of micrRNA miR-149 expression are involved in the pathogenesis of hepatocellular carcinomas (HCC) and are poor prognosis factors in patients with HCC. (PMID:27300349)
• data further suggest that ARTD2 would function in double strand break repair as a dimeric module, while in single strand break repair it would function as a monomer. (PMID:27708353)
• either PARP1 or PARP2 are sufficient for near-normal XRCC1 recruitment at oxidative single-strand breaks (PMID:27965414)
• PARP2 specifically limits the accumulation of the resection barrier factor 53BP1 at DNA damage sites, allowing efficient CtIP-dependent DNA end-resection (PMID:29036662)
• Report a requirement for PARP2 in stabilizing replication forks that encounter base excision repair (BER) intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to single stranded breaks or homologous recombination dysfunction, it is redundant with PARP1 in BER. (PMID:29467415)
• PARP2 is preferentially activated by poly(ADP-ribose) (PAR) and subsequently catalyzes branched PAR chain synthesis. (PMID:30104678)
• analysis of how ARTD2/PARP2 functions in DNA break recognition (PMID:30321391)
• The PARP2 plays under different physiological conditions, and reveal that PARP2 is tightly regulated by distinct pathways. (PMID:30880404)
• This study suggests that the functions of PARP1 and PARP2 overlap in DNA Base Excision Repair after a site cleavage and provides evidence for a role of PARP2 in the regulation of PARP1 activity. (PMID:31129062)
• PARP2 significantly higher expressed in primary prostate cancer (PC) tumors than in benign prostate, and even more so in castration-resistant PC. PARP-2, but not PARP-1, is a critical component in androgen receptor (AR)-mediated transcription through interacting with the pioneer factor FOXA1 and facilitating AR recruitment to genome-wide prostate-specific enhancer regions and regulation PC growth. (PMID:31266892)
• RPA directly binds activated PARP2 through poly(ADP-ribosyl)ation and can protect single-strand L1 integration intermediates from APOBEC3-mediated cytidine deamination in vitro. (PMID:31473101)
• HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation; as HPF1 forms a joint active site with PARP1 or PARP2, our data implicate HPF1 as an important determinant of the response to clinical PARP inhibitors (PMID:32028527)
• myeloid deletion of PARP2, but not PARP1, increases the population of immature myeloid cells in bone marrow, and impairs the expression of chemokines such as CCL3 through enhancing the transcriptional repression by beta-catenin. (PMID:32221289)
• Expression of poly-ADP-ribose polymerase (PARP) in endometrial adenocarcinoma: Prognostic potential. (PMID:32360251)
• Poly(ADP-Ribose) Polymerase Activity and Coronary Artery Disease in Type 2 Diabetes Mellitus: An Observational and Bidirectional Mendelian Randomization Study. (PMID:32757651)
• Progress and outlook in studying the substrate specificities of PARPs and related enzymes. (PMID:32785980)
• Bridging of DNA breaks activates PARP2-HPF1 to modify chromatin. (PMID:32939087)
• PARPs’ impact on base excision DNA repair. (PMID:33087277)
• Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1. (PMID:33141820)
• The Oncogenic Helicase ALC1 Regulates PARP Inhibitor Potency by Trapping PARP2 at DNA Breaks. (PMID:33275888)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	parp2	ENSDARG00000079202
mus_musculus	Parp2	ENSMUSG00000036023
rattus_norvegicus	Parp2	ENSRNOG00000008892
caenorhabditis_elegans		WBGENE00004050

Paralogs (2): PARP3 (ENSG00000041880), PARP1 (ENSG00000143799)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1341112) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 32 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal heart morphology	1
enlarged heart	1
liver hypoplasia	1
pale liver	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal thymus morphology	1
enlarged thymus	1
anemia	1
impaired hematopoiesis	1
increased mortality induced by gamma-irradiation	1
increased cellular sensitivity to gamma-irradiation induced cell death	1
abnormal skin morphology	1
abnormal eye morphology	1
prolonged QT interval	1
elevated level of mitotic sister chromatid exchange	1
spontaneous chromosome breakage	1
induced chromosome breakage	1
abnormal cell cycle checkpoint function	1
abnormal sinus arrhythmia	1
decreased circulating iron level	1
abnormal QT variability	1
increased spleen weight	1
decreased heart rate	1
cardiovascular system phenotype	1

+7 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cricetulus griseus	Q9R152	95.4%	Diamond
Bos taurus	P18493	88.9%	Diamond
Oncorhynchus masou	Q08824	87.4%	Diamond
Gallus gallus	P26446	80.0%	Diamond
Oryza sativa Japonica Group	Q7EYV7	80.0%	Diamond
Zea mays	Q9ZSV1	80.0%	Diamond
Xenopus laevis	P31669	77.0%	Diamond
Sarcophaga peregrina	Q11208	62.4%	Diamond
Arabidopsis thaliana	Q11207	62.3%	Diamond
Drosophila melanogaster	P35875	60.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORA79B	snoRNA	109616976
CCNB1IP1	protein-coding	57820
RPPH1	ncRNA	85495
TTC5	protein-coding	91875
KLHL33	protein-coding	123103
TEP1	protein-coding	7011
SNORD126	snoRNA	100113391

Protein

Protein identifiers

Poly [ADP-ribose] polymerase 2 — Q9UGN5 (reviewed: Q9UGN5)

Alternative names: ADP-ribosyltransferase diphtheria toxin-like 2, DNA ADP-ribosyltransferase PARP2, NAD(+) ADP-ribosyltransferase 2, Poly[ADP-ribose] synthase 2, Protein poly-ADP-ribosyltransferase PARP2

All UniProt accessions (4): E9PJ27, G3V167, Q9UGN5, H0YH02

UniProt curated annotations — full annotation on UniProt →

Function. Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2’-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1. Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site. PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains. Specifically mediates formation of branched poly-ADP-ribosylation. Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF. In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5’-terminal phosphates at DNA strand breaks termini in nicked duplex.

Subunit / interactions. Component of a base excision repair (BER) complex, containing at least XRCC1, PARP1, POLB and LRIG3. Homo- and heterodimer with PARP1. Interacts (via the PARP catalytic domain) with HPF1. Interacts with core nucleosomes.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed, mainly in actively dividing tissues. The highest levels are in the brain, heart, pancreas, skeletal muscle and testis; also detected in kidney, liver, lung, placenta, ovary and spleen; levels are low in leukocytes, colon, small intestine, prostate and thymus.

Post-translational modifications. Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP2-HPF1 complex from chromatin. Poly-ADP-ribosylated by PARP1. Acetylation reduces DNA binding and enzymatic activity. Proteolytically cleaved by caspase-8 (CASP8) in response to apoptosis, leading to its inactivation.

Activity regulation. ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. CHD1L promotes PARP2 removal from chromatin. ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination. PARPi molecules (niraparib, talazoparib, and, to a lesser extent, olaparib) also trap PARP2 at DNA damage sites.

Domain organisation. The N-terminal region (NTR) recognizes and binds poly-ADP-ribose chains produced by PARP1, leading to its recruitment to DNA damage sites. The N-terminal disordered region does not act as a key DNA-binding domain. The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage. The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins. The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition.

Similarity. Belongs to the ARTD/PARP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UGN5-1	1	yes
Q9UGN5-2	2

RefSeq proteins (2): NP_001036083, NP_005475 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004102	Poly(ADP-ribose)pol_reg_dom	Domain
IPR008893	WGR_domain	Domain
IPR012317	Poly(ADP-ribose)pol_cat_dom	Domain
IPR036616	Poly(ADP-ribose)pol_reg_dom_sf	Homologous_superfamily
IPR036930	WGR_dom_sf	Homologous_superfamily
IPR050800	ARTD/PARP	Family

Pfam: PF00644, PF02877, PF05406

Enzyme classification (BRENDA)

• EC 2.4.2.30 — NAD+ ADP-ribosyltransferase (BRENDA: 32 organisms, 193 substrates, 306 inhibitors, 42 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.002–0.251	25
(ADP-D-RIBOSYL)N-ACTIN	0.011–0.037	7
(ADP-D-RIBOSYL)N-SOYBEAN-TRYPSIN-INHIBITOR	0.03–0.429	6
(ADP-D-RIBOSYL)N-RHOA PROTEIN	0.017	1
N6-ETHENO-NAD+	0.0225	1

Catalyzed reactions (Rhea)

• L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + nicotinamide (RHEA:54424)
• L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + nicotinamide (RHEA:58224)
• L-seryl-[protein] + NAD(+) = O-(ADP-D-ribosyl)-L-seryl-[protein] + nicotinamide + H(+) (RHEA:58232)

UniProt features (103 total): helix 26, strand 25, mutagenesis site 21, sequence variant 6, binding site 4, modified residue 4, domain 3, turn 3, region of interest 2, sequence conflict 2, short sequence motif 2, chain 1, site 1, splice variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

30 structures by resolution:

PDB	Title	Method	Resolution (Å)
4ZZX	Structure of PARP2 catalytic domain bound to an isoindolinone inhibitor	X-RAY DIFFRACTION	1.65
5D5K	Crystal Structure NLS from human PARP-2 complexed with Importin alpha delta IBB	X-RAY DIFFRACTION	1.9
3KJD	Human poly(ADP-ribose) polymerase 2, catalytic fragment in complex with an inhibitor …	X-RAY DIFFRACTION	1.95
3KCZ	Human poly(ADP-ribose) polymerase 2, catalytic fragment in complex with an inhibitor …	X-RAY DIFFRACTION	2
7R59	PARP2 catalytic domain in complex with OUL245	X-RAY DIFFRACTION	2
4TVJ	HUMAN ARTD2 (PARP2) - CATALYTIC DOMAIN IN COMPLEX WITH OLAPARIB	X-RAY DIFFRACTION	2.1
8HKO	Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to Rucaparib	X-RAY DIFFRACTION	2.1
9IM8	Mutated ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to a pyrimidine …	X-RAY DIFFRACTION	2.1
9ZQB	Nucleosome with an SSB at SHL -2.8 in complex with human PARP2 and HPF1, Class 1	ELECTRON MICROSCOPY	2.1
4ZZY	Structure of human PARP2 catalytic domain bound to an isoindolinone inhibitor	X-RAY DIFFRACTION	2.2
6F1K	Structure of ARTD2/PARP2 WGR domain bound to double strand DNA without 5’phosphate	X-RAY DIFFRACTION	2.2
8HLJ	Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to Olaparib …	X-RAY DIFFRACTION	2.24
9ZQC	Nucleosome with an SSB at SHL -2.8 in complex with human PARP2 and HPF1, Class 2	ELECTRON MICROSCOPY	2.37
4PJV	Structure of PARP2 catalytic domain bound to inhibitor BMN 673	X-RAY DIFFRACTION	2.5
8HKN	Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to approved drug …	X-RAY DIFFRACTION	2.5
5DSY	Crystal structure of constitutively active PARP-2	X-RAY DIFFRACTION	2.7
8HLQ	Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to Niraparib …	X-RAY DIFFRACTION	2.7
6F5B	Structure of ARTD2/PARP2 WGR domain bound to double stranded DNA with 5’phosphate	X-RAY DIFFRACTION	2.8
7AEO	Human ARTD2 in complex with DNA oligonucleotides	X-RAY DIFFRACTION	2.8
8HKS	Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to …	X-RAY DIFFRACTION	2.8
6TX3	HPF1 bound to catalytic fragment of PARP2	X-RAY DIFFRACTION	2.96
6F5F	Structure of ARTD2/PARP2 WGR domain bound to double strand DNA with 5 nucleotide overhang …	X-RAY DIFFRACTION	2.98
8HE8	Human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to a …	X-RAY DIFFRACTION	3.05
8JNY	Mutated human ADP-ribosyltransferase 2 (PARP2) catalytic domain bound to a …	X-RAY DIFFRACTION	3.2
9ZQA	Nucleosome with an SSB at SHL -2.8 in complex with the WGR domain of human PARP2, Class 2	ELECTRON MICROSCOPY	3.28
9ZQ9	Nucleosome with an SSB at SHL -2.8 in complex with the WGR domain of human PARP2, Class 1	ELECTRON MICROSCOPY	3.3
6X0L	Bridging of double-strand DNA break activates PARP2/HPF1 to modify chromatin	ELECTRON MICROSCOPY	3.9
6X0M	Bridging of double-strand DNA break activates PARP2/HPF1 to modify chromatin	ELECTRON MICROSCOPY	6.3
6X0N	Bridging of double-strand DNA break activates PARP2/HPF1 to modify chromatin	ELECTRON MICROSCOPY	10
6USJ	Structure of two nucleosomes bridged by human PARP2	ELECTRON MICROSCOPY	10.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGN5-F1	82.82	0.64

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nucleoli

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2)

Position	Role
207–208	cleavage; by caspase-8
558	for poly [adp-ribose] polymerase activity

Ligand- & substrate-binding residues (4)

Position	Role
428–430	NAD(+)
437	NAD(+)
444	NAD(+)
470	NAD(+)

Post-translational modifications (4)

Type	Positions
N6-acetyllysine	37, 38
Phosphoserine	226, 232

Mutagenesis-validated functional residues (21)

Position	Phenotype
21–22	reduced localization to the nucleus. abolished localization to the nucleus; when associated with 37-a-a-38.
37–38	reduced localization to the nucleus. abolished localization to the nucleus; when associated with 21-a-a-22.
125–126	in parp2-qfrd mutant; induces conformational change that bridges nucleosomes by binding to linker dna ends and promotes interaction with …
127	decreased poly [adp-ribose] polymerase activity. impaired formation of a complex with damaged dna.
128	does not affect poly [adp-ribose] polymerase activity.
129	reduced recruitment to dna damage sites. abolished dna-induced adp-ribosyltransferase activity.
130	decreased poly [adp-ribose] polymerase activity.
132	decreased poly [adp-ribose] polymerase activity.
151	decreased poly [adp-ribose] polymerase activity. impaired formation of a complex with damaged dna.
153	abolished formation of a complex with core nucleosome and hpf1, leading to abolished ability to catalyze serine adp-ribosylation of …
154	abolished formation of a complex with core nucleosome and hpf1, leading to abolished ability to catalyze serine adp-ribosylation of …
159	decreased poly [adp-ribose] polymerase activity.
183	decreased poly [adp-ribose] polymerase activity. impaired formation of a complex with damaged dna.
201	reduced dna-induced adp-ribosyltransferase activity.
201	reduced recruitment to dna damage sites. decreased poly [adp-ribose] polymerase activity.
286	increased dna-induced adp-ribosyltransferase activity.
338	does not affect dna-induced adp-ribosyltransferase activity.
394	strongly reduced serine adp-ribosylation, caused by abolished interaction with hpf1.
428	abolished trapping at dna damage sites upon binding to parp inhibitors (parpi).
558	abolished poly [adp-ribose] polymerase activity without affecting localization to dna damage sites.
582–583	strongly reduced serine adp-ribosylation, caused by abolished interaction with hpf1.

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-5696394	DNA Damage Recognition in GG-NER	curated
R-HSA-5696400	Dual Incision in GG-NER	curated
R-HSA-5696395	Formation of Incision Complex in GG-NER	curated
R-HSA-5685939	HDR through MMEJ (alt-NHEJ)	curated
R-HSA-110362	POLB-Dependent Long Patch Base Excision Repair	curated
R-HSA-73884	Base Excision Repair	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-110373	Resolution of AP sites via the multiple-nucleotide patch replacement pathway	—
R-HSA-73933	Resolution of Abasic Sites (AP sites)	—

MSigDB gene sets: 255 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, PID_TELOMERASE_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, KAUFFMANN_DNA_REPAIR_GENES, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, GOBP_DECIDUALIZATION, MODULE_118, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_DNA_MODIFICATION

GO Biological Process (8): DNA repair (GO:0006281), double-strand break repair (GO:0006302), DNA damage response (GO:0006974), DNA ADP-ribosylation (GO:0030592), decidualization (GO:0046697), protein poly-ADP-ribosylation (GO:0070212), protein auto-ADP-ribosylation (GO:0070213), DNA repair-dependent chromatin remodeling (GO:0140861)

GO Molecular Function (17): chromatin binding (GO:0003682), damaged DNA binding (GO:0003684), NAD+ poly-ADP-ribosyltransferase activity (GO:0003950), nucleotidyltransferase activity (GO:0016779), nucleosome binding (GO:0031491), poly-ADP-D-ribose binding (GO:0072572), NAD DNA ADP-ribosyltransferase activity (GO:0140294), NAD+-protein-serine ADP-ribosyltransferase activity (GO:0140805), NAD+-protein-aspartate ADP-ribosyltransferase activity (GO:0140806), NAD+-protein-glutamate ADP-ribosyltransferase activity (GO:0140807), poly-ADP-D-ribose modification-dependent protein binding (GO:0160004), NAD+-protein mono-ADP-ribosyltransferase activity (GO:1990404), DNA binding (GO:0003677), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), site of DNA damage (GO:0090734), chromosome (GO:0005694)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	3
DNA Repair	3
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Homology Directed Repair	1
Resolution of Abasic Sites (AP sites)	1
DNA Double-Strand Break Repair	1
Nucleotide Excision Repair	1
Base Excision Repair	1

GO top-level categories

30 GO namespaces:

Category	Terms
pentosyltransferase activity	3
NAD+-protein mono-ADP-ribosyltransferase activity	3
DNA damage response	2
post-translational protein modification	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membraneless organelle	2
DNA metabolic process	1
DNA repair	1
cellular response to stress	1
DNA modification	1
maternal placenta development	1
developmental process involved in reproduction	1
tissue development	1
animal gross anatomical part developmental process	1
chromatin remodeling	1
DNA binding	1
transferase activity, transferring phosphorus-containing groups	1
chromatin binding	1
protein-containing complex binding	1
carbohydrate derivative binding	1
ADP-D-ribose modification-dependent protein binding	1
catalytic activity, acting on a protein	1
nucleic acid binding	1
molecular_function	1
catalytic activity	1
transferase activity	1
intracellular membrane-bounded organelle	1
chromosome	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 21 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

21 experimentally-supported GO terms:

GO term	NS	Evidence
DNA ADP-ribosylation	BP	direct assay
DNA damage response	BP	direct assay
DNA repair	BP	direct assay
DNA repair-dependent chromatin remodeling	BP	direct assay
protein auto-ADP-ribosylation	BP	direct assay
protein poly-ADP-ribosylation	BP	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
site of DNA damage	CC	direct assay
NAD DNA ADP-ribosyltransferase activity	MF	direct assay
NAD+ poly-ADP-ribosyltransferase activity	MF	direct assay
NAD+-protein mono-ADP-ribosyltransferase activity	MF	direct assay
NAD+-protein-aspartate ADP-ribosyltransferase activity	MF	direct assay
NAD+-protein-glutamate ADP-ribosyltransferase activity	MF	direct assay
NAD+-protein-serine ADP-ribosyltransferase activity	MF	direct assay
chromatin binding	MF	direct assay
damaged DNA binding	MF	direct assay
nucleosome binding	MF	direct assay
poly-ADP-D-ribose binding	MF	direct assay
poly-ADP-D-ribose modification-dependent protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,597 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PARP2	XRCC1	P18887	889
PARP2	LIG3	P49916	871
PARP2	PARG	Q86W56	818
PARP2	POLB	P06746	814
PARP2	PARP10	Q53GL7	771
PARP2	HPF1	Q9NWY4	764
PARP2	TNKS2	Q9H2K2	747
PARP2	PARP16	Q8N5Y8	731
PARP2	TNKS	O95271	725
PARP2	BRCA1	P38398	724
PARP2	PARP15	Q460N3	702
PARP2	PARP14	Q460N5	689
PARP2	BRCA2	P51587	685
PARP2	BUB3	O43684	682
PARP2	ADPRS	Q9NX46	676

IntAct

Human interaction partners of PARP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 54 partners by confidence:

Partner	Interaction type	MIscore	Records
APLF	adp ribosylation reaction	0.690	1
HMGN2	adp ribosylation reaction	0.590	1
FKBP3	adp ribosylation reaction	0.560	2
STAC	adp ribosylation reaction	0.560	2
AGO1	adp ribosylation reaction	0.440	1
ANKS6	adp ribosylation reaction	0.440	1
CCDC107	adp ribosylation reaction	0.440	1
CCDC33	adp ribosylation reaction	0.440	1
CD58	adp ribosylation reaction	0.440	1
CDCA7	adp ribosylation reaction	0.440	1
CERT1	adp ribosylation reaction	0.440	1
CHRDL1	adp ribosylation reaction	0.440	1
CT55	adp ribosylation reaction	0.440	1
CTNNB1	adp ribosylation reaction	0.440	1
DDX20	adp ribosylation reaction	0.440	1
DFFB	adp ribosylation reaction	0.440	1
DIDO1	adp ribosylation reaction	0.440	1
DIPK1A	adp ribosylation reaction	0.440	1
ERC1	adp ribosylation reaction	0.440	1
FAM168B	adp ribosylation reaction	0.440	1
FHIP2A	adp ribosylation reaction	0.440	1
GNAQ	adp ribosylation reaction	0.440	1
GRAMD1C	adp ribosylation reaction	0.440	1
H1-4	adp ribosylation reaction	0.440	1
HABP2	adp ribosylation reaction	0.440	1
HAUS6	adp ribosylation reaction	0.440	1
IFNA16	adp ribosylation reaction	0.440	1
IL21	adp ribosylation reaction	0.440	1
ING5	adp ribosylation reaction	0.440	1
KDELR2	adp ribosylation reaction	0.440	1

BioGRID (931 interactions; top human partners by supporting records in a sample of 600 records): HIST1H3A (Proximity Label-MS; 4 records), APLF (Affinity Capture-MS; 3 records), C4orf27 (Affinity Capture-Western; 3 records), H2AFY2 (Affinity Capture-MS; 3 records), HIST1H2BA (Affinity Capture-MS; 3 records), HIST1H4A (Affinity Capture-MS; 3 records), PARP1 (Affinity Capture-Western; 3 records), POLB (Affinity Capture-MS; 3 records), RNF146 (Affinity Capture-MS; 3 records), RPA2 (Affinity Capture-MS; 3 records), RPA4 (Affinity Capture-MS; 3 records), SPIN2B (Affinity Capture-MS; 3 records), BRCA2 (Synthetic Lethality; 2 records), CD44 (Affinity Capture-MS; 2 records), CDX1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
veliparib	down-regulates	PARP2	“chemical inhibition”
1038915-60-4	down-regulates	PARP2	“chemical inhibition”
olaparib	down-regulates	PARP2	“chemical inhibition”
A-966492	down-regulates	PARP2	“chemical inhibition”

Protein complexes (CORUM) (6)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

6 complexes by size:

Complex	Subunits	Members
★ DNA base excision repair complex	5	LIG3, PARP1, PARP2, POLB, XRCC1
★ PARP1-PARP2 complex	2	PARP1, PARP2
★ PARP2-SMAD2 complex	2	SMAD2, PARP2
★ PARP2-SMAD3 complex	2	PARP2, SMAD3
★ PARP2-SMAD4 complex	2	PARP2, SMAD4
★ HPF1-PARP2-nucleosome complex	2	HPF1, PARP2

Disease & clinical

Genetic variants

Variant evidence for PARP2: 96 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

96 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	3
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 1,131):

Position(s)	Effect	Δscore	Sites
14:20345098	donor_gain	1.0000
14:20346861–20346862	acceptor_loss	1.0000	6
14:20346914–20346915	donor_loss	1.0000	4
14:20350508	acceptor_gain	1.0000
14:20350516	acceptor_gain	1.0000
14:20350523	acceptor_gain	1.0000
14:20350623–20350624	donor_loss	1.0000	5
14:20352348–20352349	donor_loss	1.0000	5
14:20354077	acceptor_gain	1.0000
14:20354082	acceptor_gain	1.0000

AlphaMissense

1,134 missense substitutions predicted likely pathogenic (of 3,773 scored), across 287 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M456	9	0.853	0.985
F457	8	0.986	0.999
H428	8	0.983	0.995
H394	8	0.972	0.993
D465	8	0.966	0.991
F463	8	0.950	0.981
S470	8	0.933	0.997
F577	8	0.923	0.992
D95	8	0.912	0.959
N129	8	0.906	0.990
H390	8	0.851	0.970
F313	8	0.835	0.985
H311	8	0.765	0.925
W427	7	0.989	0.999
E558	7	0.988	0.996
W151	7	0.975	0.992
K469	7	0.972	0.998
F176	7	0.967	0.989
W188	7	0.966	0.991
F405	7	0.960	0.983

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.00011
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000151
Kidney Chromophobe (TCGA)	unfavorable	0.000568

Disease associations

OMIM: gene MIM:607725 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST005312_33	Menopause (age at onset)	2e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004704	age at menopause

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3390820 (PROTEIN FAMILY), CHEMBL5169089 (PROTEIN-PROTEIN INTERACTION), CHEMBL5366 (SINGLE PROTEIN), CHEMBL6177907 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PARP2 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

5 curated-mechanism drugs:

Drug	Modality	Max phase
NIRAPARIB	Small molecule	4
TALAZOPARIB	Small molecule	4
PAMIPARIB	Small molecule	3
2X-121	Small molecule	2
SENAPARIB	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes PARP2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
OLAPARIB	PARP 1, 2 and 3	3	4
RUCAPARIB	PARP 1, 2 and 3	3	4
RUCAPARIB CAMSYLATE	PARP 1, 2 and 3	3	4
VELIPARIB	PARP 1, 2 and 3	3	3
E-7016	PARP 1, 2 and 3	3	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,525 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1094636	NIRAPARIB	4	6,831
CHEMBL3137320	TALAZOPARIB	4	5,879
CHEMBL521686	OLAPARIB	4	13,785
CHEMBL1173055	RUCAPARIB	4	7,408
CHEMBL4112930	PAMIPARIB	3	2,251
CHEMBL5095220	SARUPARIB	3	393
CHEMBL506871	VELIPARIB	3	5,697
CHEMBL3644587	2X-121	2	275
CHEMBL5095043	ATAMPARIB	1	267
CHEMBL5095223	AZD-9574	1	147
CHEMBL4297461	CEP-9722	1	592

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Poly ADP-ribosylating PARPs and poly(ADP-ribose) glycohydrolase

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
pamiparib	Inhibition	9.05	pIC50
olaparib	Inhibition	9.0	pIC50
niraparib	Binding	8.68	pIC50
PARP1 inhibitor (S)-G9	Inhibition	7.59	pIC50
compound 5 [Tomassi et al., 2020]	Inhibition	7.42	pIC50
compound 10b [PMID: 26222319]	Inhibition	6.9	pKd
AZ1366	Inhibition	6.63	pIC50
saruparib	Inhibition	5.82	pIC50
MC2050	Inhibition	5.74	pIC50
palacaparib	Inhibition	4.03	pIC50

Binding affinities (BindingDB)

1335 measured of 1553 human assays (1558 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Veliparib	IC50	0.061 nM
US20250215013, Example 113	IC50	0.13 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 196	IC50	0.15 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 197	IC50	0.15 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 199	IC50	0.16 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL6146942	IC50	0.17 nM
CHEMBL5417456	IC50	0.19 nM
4-[[4-fluoro-3-[5-methyl-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	IC50	0.2 nM	US-9255106: Substituted [1,2,4]triazolo[4,3-a]pyrazines as PARP-1 inhibitors
US20250215013, Example 166	IC50	0.21 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL6141678	IC50	0.23 nM
US20250215013, Example 144	IC50	0.23 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 181	IC50	0.23 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL6141851	IC50	0.24 nM
US20250215013, Example 180	IC50	0.24 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 185	IC50	0.24 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL5176874	IC50	0.25 nM
CHEMBL5416841	IC50	0.25 nM
US20250215013, Example 53	IC50	0.25 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 112	IC50	0.26 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 165	IC50	0.26 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL6149121	IC50	0.28 nM
CHEMBL6149501	IC50	0.28 nM
US20250215013, Example 178	IC50	0.28 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 183	IC50	0.28 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
N-methyl-5-[(1S,6R)-5-((6-oxo-5H,7H,8H,9H-cyclopenta[c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl]pyridine-2-carboxamide and N-methyl-5-[(1R,6S)-5-((6-oxo-5H,7H,8H,9H-cyclopenta[c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl]pyridine-2-carboxamide	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
US20250221987, Example 16-2	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
N-methyl-5-((1S,6R)-5-((6-oxo-6,8,9,10-tetrahydro-5H-pyrano[2,3-c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide and N-methyl-5-((1R,6S)-5-((6-oxo-6,8,9,10-tetrahydro-5H-pyrano[2,3-c][1,5]naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
US20250221987, Example 46-2	IC50	0.3 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
CHEMBL6168775	IC50	0.32 nM
US20250215013, Example 177	IC50	0.32 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
US20250215013, Example 182	IC50	0.32 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
N-(1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)piperidin-4-yl)-5-(4-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)piperazin-1-yl)picolinamide	IC50	0.32 nM	US-20250222116: PARP-1 DEGRADATION AGENT AND USE THEREOF
US20250215013, Example 167	IC50	0.33 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL5180001	IC50	0.34 nM
5-[[(3R)-1-[(7-ethyl-6-oxo-5H-1,5-naphthyridin-3-yl)methyl]pyrrolidin-3-yl]amino]-N-methylpyridine-2-carboxamide	IC50	0.36 nM	US-20250034168: NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVE PARP INHIBITOR AND USE THEREOF
US20250215013, Example 43	IC50	0.39 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL4800042	IC50	0.4 nM
CHEMBL5206717	IC50	0.4 nM
CHEMBL5420649	IC50	0.4 nM
5-[4-[(3,6-difluoro-4-oxo-2,3,3a,5,5a,6,7,8,9,9a-decahydro-1H-pyrazolo[1,5-a]quinoxalin-7-yl)methyl]piperazin-1-yl]-6-fluoro-N-methylpyridine-2-carboxamide	IC50	0.4 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
N-cyclopropyl-5-((1S,6R)-5-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide and N-cyclopropyl-5-((1R,6S)-5-((7-ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-2,5-diazabicyclo[4.2.0]octan-2-yl)picolinamide	IC50	0.4 nM	US-20250221987: PIPERAZINO RING-CONTAINING DERIVATIVE, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
CHEMBL5182785	IC50	0.41 nM
CHEMBL6102151	IC50	0.41 nM
6-fluoro-5-[4-[(6-fluoro-4-oxo-5H-furo[3,2-c]quinolin-7-yl)methyl]piperazin-1-yl]-N-methylpyridine-2-carboxamide	IC50	0.41 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL6147580	IC50	0.42 nM
5-[4-[(3-chloro-6-fluoro-4-oxo-6H-pyrazolo[1,5-a]quinoxalin-7-yl)methyl]piperazin-1-yl]-6-fluoro-N-methylpyridine-2-carboxamide	IC50	0.42 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF
CHEMBL5618198	IC50	0.43 nM
CHEMBL5619354	IC50	0.43 nM
CHEMBL5619750	IC50	0.43 nM
US20250215013, Example 59	IC50	0.43 nM	US-20250215013: SUBSTITUTED TRICYCLIC COMPOUNDS AS PARP INHIBITORS AND THE USE THEREOF

ChEMBL bioactivities

1104 potent at pChembl≥5 of 1178 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	CHEMBL5222013
10.00	IC50	0.1	nM	OLAPARIB
10.00	IC50	0.1	nM	CHEMBL5397373
9.96	IC50	0.11	nM	PAMIPARIB
9.96	IC50	0.11	nM	OLAPARIB
9.89	IC50	0.13	nM	OLAPARIB
9.70	IC50	0.2	nM	CHEMBL3984980
9.70	IC50	0.2	nM	TALAZOPARIB
9.66	IC50	0.22	nM	CHEMBL3907010
9.66	IC50	0.22	nM	CHEMBL5423934
9.62	IC50	0.24	nM	CHEMBL5421335
9.59	IC50	0.26	nM	CHEMBL5423161
9.57	Kd	0.27	nM	OLAPARIB
9.55	Kd	0.28	nM	OLAPARIB
9.54	IC50	0.29	nM	CHEMBL5439635
9.52	IC50	0.3	nM	CHEMBL3933450
9.52	IC50	0.3	nM	CHEMBL3926240
9.52	IC50	0.3	nM	CHEMBL3922789
9.52	IC50	0.3	nM	CHEMBL3929889
9.52	IC50	0.3	nM	CHEMBL3975917
9.52	IC50	0.3	nM	TALAZOPARIB
9.52	IC50	0.3	nM	PAMIPARIB
9.52	IC50	0.3	nM	CHEMBL5420649
9.52	IC50	0.3	nM	OLAPARIB
9.49	IC50	0.32	nM	CHEMBL5182405
9.48	IC50	0.33	nM	CHEMBL5419831
9.48	IC50	0.33	nM	CHEMBL5416806
9.42	IC50	0.38	nM	CHEMBL5432851
9.40	IC50	0.4	nM	CHEMBL4107982
9.40	IC50	0.3981	nM	OLAPARIB
9.40	IC50	0.4	nM	OLAPARIB
9.40	IC50	0.4	nM	RUCAPARIB
9.36	IC50	0.44	nM	CHEMBL5432860
9.35	IC50	0.45	nM	OLAPARIB
9.31	IC50	0.49	nM	CHEMBL2323226
9.31	IC50	0.49	nM	CHEMBL5394020
9.30	IC50	0.5	nM	CHEMBL3955609
9.30	IC50	0.5	nM	PAMIPARIB
9.30	IC50	0.5	nM	CHEMBL3901232
9.30	IC50	0.5	nM	OLAPARIB
9.30	IC50	0.5	nM	RUCAPARIB
9.30	Kd	0.5	nM	OLAPARIB
9.24	IC50	0.58	nM	TALAZOPARIB
9.22	IC50	0.6	nM	CHEMBL3972156
9.22	IC50	0.6	nM	TALAZOPARIB
9.21	IC50	0.62	nM	CHEMBL5423072
9.19	IC50	0.6457	nM	CHEMBL4529965
9.19	IC50	0.64	nM	CHEMBL5080271
9.15	IC50	0.7	nM	CHEMBL3914932
9.15	IC50	0.7	nM	CHEMBL3901034

PubChem BioAssay actives

847 with measured affinity, of 1591 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[3-[3-(5-bromofuran-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	2012695: Inhibition of PARP2 (unknown origin) using histone as substrate by ELISA	ic50	<0.0001	uM
(2R)-14-fluoro-2-methyl-6,9,10,19-tetrazapentacyclo[14.2.1.02,6.08,18.012,17]nonadeca-1(18),8,12(17),13,15-pentaen-11-one	1949554: Inhibition of PARP-2 (unknown origin)	ic50	0.0001	uM
ethyl N-[6-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]phenyl]-1H-benzimidazol-2-yl]carbamate	2115914: Inhibition of PARP2 (unknown origin)	ic50	0.0001	uM
1-[[3-[4-(cyclopentylmethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0001	uM
Olaparib	1896631: Inhibition of PARP-2 (unknown origin)	ic50	0.0001	uM
Talazoparib	1909173: Inhibition of PARP2 (unknown origin) using NAD as substrate incubated for 1 min	ic50	0.0002	uM
1-[[3-[4-(1-cyclopentylethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0002	uM
1-[[3-[4-(cyclohexylmethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0002	uM
3,3-dimethyl-16-(2-piperidin-1-ylethyl)-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0002	uM
4-[[4-fluoro-3-[5-methyl-3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	1638269: Inhibition of recombinant human PARP2 using histone as substrate after 1 hr in presence of NAD+ by ELISA	ic50	0.0002	uM
2-[[1-(2-chloroacetyl)-3,4-dihydro-2H-quinolin-6-yl]oxy]-N-[10-[4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]-10-oxodecyl]acetamide	1908537: Inhibition of PARP2 (unknown origin)	ic50	0.0003	uM
4-[[4-fluoro-3-[(5R)-5-methyl-3-(1,3-thiazol-2-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl]phenyl]methyl]-2H-phthalazin-1-one	2019974: Inhibition of PARP2 (unknown origin) by ELISA assay	ic50	0.0003	uM
1-[[3-(4-cyclohexyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
1-[[3-[4-(1-cyclohexylethyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
1-[[3-[4-(2,2-dimethylpropyl)-3-oxopiperazine-1-carbonyl]-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
1-[[3-(4-cyclopentyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0003	uM
16-[2-(dimethylamino)ethyl]-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0003	uM
16-[2-(diethylamino)ethyl]-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0003	uM
16-[2-(dimethylamino)ethyl]-11-fluoro-3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0003	uM
1-[[4-fluoro-3-[4-(2-methylpropyl)-3-oxopiperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0004	uM
1-[[3-(4-butan-2-yl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0004	uM
Rucaparib	1909171: Inhibition of PARP2 (unknown origin)	ic50	0.0004	uM
1-[[3-(4-butyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0005	uM
5-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-5-azatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-trien-2-one	728422: Inhibition of PARP1/PARP2 in human SKOV3 cells assessed as reduction in H2O2-induced PARylation incubated for 4 hrs prior to H2O2 treatment	ic50	0.0005	uM
1-[[4-fluoro-3-[(3R)-3-methyl-4-(2-methylpropanoyl)piperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	1830903: Inhibition of recombinant human PARP2 using NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0006	uM
3,3-dimethyl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0006	uM
2-[2-[[4-[(Z)-(7-carbamoyl-3-oxo-1-benzofuran-2-ylidene)methyl]benzoyl]amino]ethyl]-1H-benzimidazole-4-carboxamide	1508854: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay	ic50	0.0006	uM
1-[[4-fluoro-3-(3-oxo-4-phenylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0006	uM
3-fluoro-7,8,17-triazatetracyclo[12.2.1.05,16.09,15]heptadeca-1,3,5(16),8,14-pentaen-6-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0007	uM
11-fluoro-3-propan-2-yl-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0007	uM
1-[[4-fluoro-3-(3-oxo-4-prop-2-enylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0007	uM
11-fluoro-6,7,16-triazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0008	uM
3-propan-2-yl-3,6,7,16-tetrazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0008	uM
1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0008	uM
1-[[4-fluoro-3-[4-(2-methoxyethyl)-3-oxopiperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0008	uM
1-[[3-(4-benzyl-3-oxopiperazine-1-carbonyl)-4-fluorophenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0008	uM
4-[[3-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazine-1-carbonyl]-4-fluorophenyl]methyl]-2H-phthalazin-1-one	1758282: Inhibition of PARP2 (unknown origin) using biotin-NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0009	uM
2-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazine-1-carbonyl]-1-benzofuran-7-carboxamide	1758282: Inhibition of PARP2 (unknown origin) using biotin-NAD+ as substrate incubated for 1 hr by ELISA	ic50	0.0009	uM
sodium 1-[[4-fluoro-3-(3-oxo-4-pentan-3-ylpiperazine-1-carbonyl)phenyl]methyl]quinazolin-3-ide-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0009	uM
1-[[4-fluoro-3-[4-(3-methylbutyl)-3-oxopiperazine-1-carbonyl]phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0009	uM
1-[[4-fluoro-3-(3-oxo-4-pentylpiperazine-1-carbonyl)phenyl]methyl]quinazoline-2,4-dione	2019976: Inhibition of human recombinant PARP2 expressed in Escherichia coli BL21(DE3) incubated for 1 hr by ELISA assay	ic50	0.0009	uM
11-(1,3-dihydroisoindol-2-ylmethyl)-2,3,10,12-tetrazatricyclo[7.3.1.05,13]trideca-1,5(13),6,8,11-pentaen-4-one	1424648: Inhibition of recombinant human PARP2 using DNase I-activated herring sperm DNA and [3H]nicotinamide after 2 mins by scintillation counting method	ic50	0.0010	uM
3-(2-amino-2-methylpropanoyl)-3,6,7,16-tetrazatetracyclo[11.2.1.05,15.09,14]hexadeca-1(15),5,9(14),10,12-pentaen-8-one	1683889: Inhibition of PARP-2 (unknown origin) pre-incubated for 30 mins before addition of activated DNA and NAD by chemiluminescent assay	ic50	0.0010	uM
(3S)-1-(2-cyclopropylethyl)-N-[5-[(2,4-dioxoquinazolin-1-yl)methyl]-2-fluoro-3-pyridinyl]pyrrolidine-3-carboxamide	1486468: Inhibition of recombinant human PARP-2 expressed in Escherichia coli BL21 (DE3) using sheared DNA as substrate in presence of biotinylated NAD after 1 hr by ELISA	ic50	0.0010	uM
2-(4-piperidin-4-ylphenyl)-1H-benzimidazole-4-carboxamide	475222: Inhibition of PARP2 by top count scintillation counting	ki	0.0010	uM
2-[4-[[4-[(2-aminophenyl)carbamoyl]phenyl]methylamino]phenyl]-1H-benzimidazole-4-carboxamide	2108844: Inhibition of PARP2 (unknown origin) using histone/NAD+ as substrates by NAD/NADH-Glo assay	ic50	0.0010	uM
2-(3-pyrazin-2-ylpropanoyl)-2,11-diazatricyclo[7.3.1.05,13]trideca-5(13),6,8-trien-10-one	455968: Inhibition of PARP2	ic50	0.0010	uM
2-(2-pyridin-3-ylacetyl)-2,11-diazatricyclo[7.3.1.05,13]trideca-5(13),6,8-trien-10-one	455968: Inhibition of PARP2	ic50	0.0010	uM
2-(4-pyridin-4-ylphenyl)-1H-benzimidazole-4-carboxamide	475222: Inhibition of PARP2 by top count scintillation counting	ki	0.0010	uM
2-[4-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]piperazin-1-yl]pyridine-3-carbonitrile	1265290: Inhibition of human PARP2 (2 to 583 residues) expressed in Baculovirus infected Sf9 insect cells using activated DNA as substrate after 1 hr by streptavidin-horseradish peroxidase-based luminescence assay	ic50	0.0010	uM

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
veliparib	affects binding, decreases activity	4
bisphenol A	decreases expression, increases expression, affects cotreatment, increases methylation	3
Valproic Acid	affects expression, decreases expression, decreases methylation	3
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects binding, decreases activity	2
Cisplatin	increases expression	2
FR900359	decreases phosphorylation	1
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
cypermethrin	increases expression	1
3-aminobenzamide	affects binding	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
deguelin	increases expression	1
tanespimycin	increases expression	1
CPG-oligonucleotide	decreases expression	1
K 7174	decreases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
pyrachlostrobin	increases expression	1
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide	increases expression	1
rucaparib	decreases activity	1
olaparib	affects binding, decreases activity	1
STA 9090	increases expression	1
XAV939	decreases activity	1
niraparib	affects binding, decreases activity	1
(+)-JQ1 compound	decreases expression	1
talazoparib	decreases activity	1
Resveratrol	affects cotreatment, increases expression	1

ChEMBL screening assays

241 unique, capped per target: 233 binding, 5 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1115416	Binding	Inhibition of PARP in hydrogen peroxide-induced human HeLa cells assessed as inhibition DNA-damage-induced PARylation	Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. — *J Med Chem*
CHEMBL3429724	Functional	Inhibition of PARP activity in tumor of immunocompromised mouse xenografted with human MDA-MB-436 cells harboring BRCA1 mutant assessed as incorporation of [3H]NAD in PAR chains in response to nicked DNA at 50 to 100 mg/kg, po measured afte	Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. — *J Med Chem*
CHEMBL4345423	ADMET	Inhibition of human recombinant N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 cells assessed as reduction in auto-PARylation using histone as substrate measured after 45 mins in presence of biotinylat	Design and Discovery of an Orally Efficacious Spiroindolinone-Based Tankyrase Inhibitor for the Treatment of Colon Cancer. — *J Med Chem*

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3DG	Abcam HEK293T PARP2 KO	Transformed cell line	Female
CVCL_C0BR	Abcam U2OS PARP2 KO	Cancer cell line	Female
CVCL_D7WL	Ubigene A-549 PARP2 KO	Cancer cell line	Male
CVCL_E1IX	HyCyte A-549 KO-hPARP2	Cancer cell line	Male
CVCL_KT90	HeLa SilenciX PARP2	Cancer cell line	Female
CVCL_RR04	MCF10A PARP2 (-/-)	Spontaneously immortalized cell line	Female
CVCL_TC15	HAP1 PARP2 (-) 1	Cancer cell line	Male
CVCL_TC16	HAP1 PARP2 (-) 2	Cancer cell line	Male
CVCL_XR37	HAP1 PARP2 (-) 3	Cancer cell line	Male
CVCL_XR38	HAP1 PARP2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PARP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.