P18493

SS
Gene name
PARP1 (ADPRT)
Protein name
Poly [ADP-ribose] polymerase 1
Names
PARP-1 , EC 2.4.2.30 , ADP-ribosyltransferase diphtheria toxin-like 1 , ARTD1 , DNA ADP-ribosyltransferase PARP1 , EC 2.4.2.- , NAD, + ADP-ribosyltransferase 1 , ADPRT 1 , Poly[ADP-ribose] synthase 1 , Protein poly-ADP-ribosyltransferase PARP1 , EC 2.4.2.- [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus , Poly [ADP-ribose] polymerase 1, 89-kDa form; Poly [ADP-ribose] polymerase 1, processed N-terminus , Poly [ADP-ribose] polymerase 1, 24-kDa form]
Species
Bos taurus (Bovine)
KEGG Pathway
bta:286764
EC number
2.4.2.30: Pentosyltransferases
Protein Class

Descriptions

PARP2, also known as ARTD2, is an enzyme that becomes activated by DNA damage, specifically by 5′-phosphorylated DNA ends. It catalyzes poly-ADP-ribosylation, a post-translational modification involved in DNA repair processes. PARP2 plays a crucial role in DNA damage detection and repair, with its activity being essential for maintaining genomic stability and proper cellular function in response to genotoxic stress. In its inactive state, PARP2’s regulatory domain (RD) covers the active site, preventing substrate NAD+ binding. DNA damage recognition leads to RD unfolding and reorganization, enabling the enzyme to access and modify target macromolecules for ADP-ribosylation. The activation of PARP2 by DNA damage induces significant conformational changes in the enzyme, which relieve its autoinhibited state. This allows PARP2 to bind NAD+ and histone PARylation factor 1 (HPF1), altering its residue specificity during DNA repair.

Autoinhibitory domains (AIDs)

664-796 (RD domain) SS

Target domain

790-1016 (ART domain)

Relief mechanism

Ligand binding, Others

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

0 structures for P18493

Entry ID Method Resolution Chain Position Source
No available structures

No variants for P18493

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P18493

No associated diseases with P18493

4 regional properties for P18493

Type Name Position InterPro Accession
domain Forkhead-associated (FHA) domain 483 - 542 IPR000253
domain Kinesin motor domain 4 - 366 IPR001752
conserved_site Kinesin motor domain, conserved site 251 - 262 IPR019821
domain Kinesin-like KIF1-type 659 - 699 IPR022140

Functions

Description
EC Number 2.4.2.30 Pentosyltransferases
Subcellular Localization
  • Chromosome
  • Nucleus
  • Nucleus, nucleolus
  • Cytoplasm, cytosol
  • Localizes to sites of DNA damage
  • Recognizes (via PARP-type zinc-fingers) and binds DNA strand breaks
  • Also binds normal/undamaged chromatin
  • Auto poly-ADP-ribosylation promotes dissociation from chromatin
  • Extracted from chromatin by VCP/p97 following sumoylation and ubiquitination
  • Translocates from the nucleus to the cytosol following phosphorylation by PRKDC
  • Recruited to replication forks following interaction with CARM1
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
chromatin The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nuclear envelope The double lipid bilayer enclosing the nucleus and separating its contents from the rest of the cytoplasm; includes the intermembrane space, a gap of width 20-40 nm (also called the perinuclear space).
nuclear replication fork The Y-shaped region of a nuclear replicating DNA molecule, resulting from the separation of the DNA strands and in which the synthesis of new strands takes place. Also includes associated protein complexes.
nucleolus A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
site of DNA damage A region of a chromosome at which DNA damage has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix.
site of double-strand break A region of a chromosome at which a DNA double-strand break has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix.

13 GO annotations of molecular function

Name Definition
damaged DNA binding Binding to damaged DNA.
NAD binding Binding to nicotinamide adenine dinucleotide, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NAD+, or the reduced form, NADH.
NAD+ ADP-ribosyltransferase activity Catalysis of the reaction
NAD+- protein-aspartate ADP-ribosyltransferase activity Catalysis of the reaction
NAD+-protein ADP-ribosyltransferase activity Catalysis of the reaction
NAD+-protein-glutamate ADP-ribosyltransferase activity Catalysis of the reaction
NAD+-protein-histidine ADP-ribosyltransferase activity Catalysis of the reaction
NAD+-protein-serine ADP-ribosyltransferase activity Catalysis of the reaction
NAD+-protein-tyrosine ADP-ribosyltransferase activity Catalysis of the reaction
nucleosome binding Binding to a nucleosome, a complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures.
nucleotidyltransferase activity Catalysis of the transfer of a nucleotidyl group to a reactant.
protein homodimerization activity Binding to an identical protein to form a homodimer.
zinc ion binding Binding to a zinc ion (Zn).

16 GO annotations of biological process

Name Definition
apoptotic process A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
ATP generation from poly-ADP-D-ribose The process of generating ATP in the nucleus from poly-ADP-D-ribose. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming.
decidualization The cellular and vascular changes occurring in the endometrium of the pregnant uterus just after the onset of blastocyst implantation. This process involves the proliferation and differentiation of the fibroblast-like endometrial stromal cells into large, polyploid decidual cells that eventually form the maternal component of the placenta.
DNA ADP-ribosylation The covalent attachment of an ADP-ribosyl group to a residue in double-stranded DNA.
DNA damage response Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
double-strand break repair The repair of double-strand breaks in DNA via homologous and nonhomologous mechanisms to reform a continuous DNA helix.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
negative regulation of innate immune response Any process that stops, prevents, or reduces the frequency, rate or extent of the innate immune response.
negative regulation of transcription by RNA polymerase II Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
positive regulation of cardiac muscle hypertrophy Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division.
positive regulation of double-strand break repair via homologous recombination Any process that activates or increases the frequency, rate or extent of double-strand break repair via homologous recombination.
positive regulation of necroptotic process Any process that increases the rate, frequency or extent of a necroptotic process, a necrotic cell death process that results from the activation of endogenous cellular processes, such as signaling involving death domain receptors or Toll-like receptors.
protein auto-ADP-ribosylation The ADP-ribosylation by a protein of one or more of its own amino acid residues, or residues on an identical protein.
protein poly-ADP-ribosylation The transfer of multiple ADP-ribose residues from NAD to a protein amino acid, forming a poly(ADP-ribose) chain.
regulation of circadian sleep/wake cycle, non-REM sleep Any process that modulates the frequency, rate or extent of non-rapid eye movement sleep.
replication fork reversal Replication fork processing that involves the unwinding of blocked forks to form four-stranded structures resembling Holliday junctions, which are subsequently resolved.

14 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P26446 PARP1 Poly [ADP-ribose] polymerase 1 Gallus gallus (Chicken) SS
P35875 Parp Poly [ADP-ribose] polymerase Drosophila melanogaster (Fruit fly) SS
Q9UGN5 PARP2 Poly [ADP-ribose] polymerase 2 Homo sapiens (Human) EV
Q9Y6F1 PARP3 Protein mono-ADP-ribosyltransferase PARP3 Homo sapiens (Human) PR
P09874 PARP1 Poly [ADP-ribose] polymerase 1 Homo sapiens (Human) SS
O50017 PARP2 Poly [ADP-ribose] polymerase 2 Zea mays (Maize) SS
O88554 Parp2 Poly [ADP-ribose] polymerase 2 Mus musculus (Mouse) SS
P11103 Parp1 Poly [ADP-ribose] polymerase 1 Mus musculus (Mouse) SS
P27008 Parp1 Poly [ADP-ribose] polymerase 1 Rattus norvegicus (Rat) SS
Q0JMY1 PARP2-B Poly [ADP-ribose] polymerase 2-B Oryza sativa subsp. japonica (Rice) SS
Q5Z8Q9 PARP2-A Poly [ADP-ribose] polymerase 2-A Oryza sativa subsp. japonica (Rice) SS
Q11207 PARP2 Poly [ADP-ribose] polymerase 2 Arabidopsis thaliana (Mouse-ear cress) SS
Q9ZP54 PARP1 Poly [ADP-ribose] polymerase 1 Arabidopsis thaliana (Mouse-ear cress) SS
Q5RHR0 parp1 Poly [ADP-ribose] polymerase 1 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MAESSDKLYR VEYAKSGRAS CKKCKESIPK DSIRMAFMVE SPMFDGKIPH WYHLSCFWKV
70 80 90 100 110 120
GFSIWHPDVE VEGFSELRWD DQQTIKKMAE TGGRTDVSGK GQDGVGSKTE KTLIDFGAGY
130 140 150 160 170 180
AKSNRSTCKS CMEKIDKGQV RLSKKVVYPD KPQLGMVDCW YHPKCFVQKR EELGFRPEFS
190 200 210 220 230 240
ATHLMGFSVL TAEDQETLKK QLPAIKGERK RKGDEVDGID EVTKKKSKKE KDKEIKLEKA
250 260 270 280 290 300
LKAQNDLIWN VKDELKKACS TNDLKELLIF NKQEVPSGES AILDRVADGM VFGALLPCEE
310 320 330 340 350 360
CSGQLVFKGD AYYCTGDVTA WTKCMVKTQT PNRKEWVTPK EFREISYFKK LKIKKQDRIF
370 380 390 400 410 420
PPESSTPVGA AAPPSAASAP AAVHSGPPDK PLSNMKILTL GKLSQNKDEV KATIEKLGGK
430 440 450 460 470 480
LTGTANKASL CISTKKEVDK LNKKMEEVKE ANIRVVSEDF LQDISASTKS LQELLSTHLL
490 500 510 520 530 540
SPWGAEVKVE PVEAVGPKGK SGAAPSKKSK GPVKEEGTNK SEKRMKLTLK GGAAVDPDSG
550 560 570 580 590 600
LEHNAHVLEK GGKVFSATLG LVDIVKGTNS YYKLQLLEDD KESRYWIFRS WGRVGTVIGS
610 620 630 640 650 660
NKLEQMPSKE DAIEHFMKLY EEKTGNAWHS KNFTKHPKKF YPLEIDYGQD EEAVKKLTVN
670 680 690 700 710 720
PGTKSKLPKP VQNLIKMIFD VESMKKAMVE YEIDLQKMPL GKLSKRQIQA AYSILSEVQQ
730 740 750 760 770 780
ALSQGSSDSH ILDLSNRFYT LIPHDFGMKK PPLLNNANSV QAKVEMLDNL LDIEVAYSLL
790 800 810 820 830 840
RGGSDDSSKD PIDVNYEKLK TDIKVVDKDS EEAEIIRKYV KNTHATTHNA YDLEVVDIFK
850 860 870 880 890 900
IEREGESQRY KPFKQLHNRR LLWHGSRTTN FAGILSQGLR IAPPEAPVTG YMFGKGIYFA
910 920 930 940 950 960
DMVSKSANYC HTSQGDPIGL ILLGEAALGN MYELKHARHI SKLPKGKHSV KGLGKTTPDP
970 980 990 1000 1010
SASITVDGVE VPLGTGISSG VNDTCLLYNE YIVYDIAQVH LKYLLKLKFN FKTSLW