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Overview

Uniprot IDP27008
Protein NamePoly [ADP-ribose] polymerase 1
Gene NameParp1
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
209 VKSEGKRKCDEVDGI
497 PGEVVVPKGKSAAPS
654 QDEEAVKKLAVKPGT
97 EAGGVAGKGQHGGGG

Function

Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (By similarity). Mediates glutamate, aspartate, serine, histidine or tyrosine 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 (By similarity). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (By similarity). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site. Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (By similarity). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), 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 PARP1 in order to limit the length of poly-ADP-ribose chains. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR and NFAT5. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (By similarity). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair. In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (By similarity). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II. Acts both as a positive and negative regulator of transcription elongation, depending on the context. Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing. Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9. Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (By similarity). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos. Also acts as a negative regulator of the cGAS-STING pathway. Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS. Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (By similarity). Plays a role in sister chromatid cohesion by mediating ADP-ribosylation of RSMC during S phase which promotes the interaction between RSMC and CDCA5/sororin, leading to enhanced interaction of CDCA5/sororin with the cohesin complex and promotion of sister chromatid cohesion (By similarity)

Protein Sequence

10 MAEATERLYR 20 VEYAKSGRAS 30 CKKCSESIPK 40 DSLRMAIMVQ 50 SPMFDGKVPH 60 WYHFSCFWKV 70 GHSIRQPDTE 80 VDGFSELRWD 90 DQQKVKKTAE 100 AGGVAGKGQH 110 GGGGKAEKTL 120 GDFAAEYAKS 130 NRSTCKGCME 140 KIEKGQMRLS 150 KKMLDPEKPQ 160 LGMIDRWYHP 170 TCFVKNRDEL 180 GFRPEYSASQ 190 LKGFSLLSAE 200 DKEALKKQLP 210 AVKSEGKRKC 220 DEVDGIDEVA 230 KKKSKKGKDK 240 ESSKLEKALK 250 AQNELVWNIK 260 DELKKACSTN 270 DLKELLIFNQ 280 QQVPSGESAI 290 LDRVADGMAF 300 GALLPCKECS 310 GQLVFKSDAY 320 YCTGDVTAWT 330 KCMVKTQNPS 340 RKEWVTPKEF 350 REISYLKKLK 360 IKKQDRLFPP 370 ESSAPAPPAP 380 PVSITSAPTA 390 VNSSAPADKP 400 LSNMKILTLG 410 KLSQNKDEAK 420 AMIEKLGGKL 430 TGSANKASLC 440 ISTKKEVEKM 450 SKKMEEVKAA 460 NVRVVCEDFL 470 QDVSASAKSL 480 QELLSAHSLS 490 SWGAEVKVEP 500 GEVVVPKGKS 510 AAPSKKSKGA 520 VKEEGVNKSE 530 KRMKLTLKGG 540 AAVDPDSGLE 550 HSAHVLEKGG 560 KVFSATLGLV 570 DIVKGTNSYY 580 KLQLLESDKE 590 SRYWIFRSWG 600 RVGTVIGSNK 610 LEQMPSKEDA 620 VEHFMKLYEE 630 KTGNAWHSKN 640 FTKYPKKFYP 650 LEIDYGQDEE 660 AVKKLAVKPG 670 TKSKLPKPVQ 680 ELVGMIFDVE 690 SMKKALVEYE 700 IDLQKMPLGK 710 LSRRQIQAAY 720 SILSEVQQAV 730 SQGSSESQIL 740 DLSNRFYTLI 750 PHDFGMKKPP 760 LLNNTDSVQA 770 KVEMLDNLLD 780 IEVAYSLLRG 790 GSDDSSKDPI 800 DVNYEKLKTD 810 IKVVDRDSEE 820 AEVIRKYVKN 830 THATTHNAYD 840 LEVIDIFKIE 850 REGESQRYKP 860 FRQLHNRRLL 870 WHGSRTTNFA 880 GILSQGLRIA 890 PPEAPVTGYM 900 FGKGIYFADM 910 VSKSANYCHT 920 SQGDPIGLIL 930 LGEVALGNMY 940 ELKHASHISK 950 LPKGKHSVKG 960 LGKTAPDPSA 970 SITLDGVEVP 980 LGTGIPSGVN 990 DTCLLYNEYI 1000 VYDIAQVNLK 1010 YLLKLKFNFK TSLW

Gene Ontology

Classification GO ID Description
Biological Process GO:1990966 ATP generation from poly-ADP-D-ribose
Biological Process GO:0006284 base-excision repair
Biological Process GO:0048148 behavioral response to cocaine
Biological Process GO:0016051 carbohydrate biosynthetic process
Biological Process GO:1904646 cellular response to amyloid-beta
Biological Process GO:0032869 cellular response to insulin stimulus
Biological Process GO:1990090 cellular response to nerve growth factor stimulus
Biological Process GO:0034599 cellular response to oxidative stress
Biological Process GO:0071451 cellular response to superoxide
Biological Process GO:0071560 cellular response to transforming growth factor beta stimulus
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0071294 cellular response to zinc ion
Biological Process GO:0046697 decidualization
Biological Process GO:0030592 DNA ADP-ribosylation
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006259 DNA metabolic process
Biological Process GO:0006281 DNA repair
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0071169 establishment of protein localization to chromatin
Biological Process GO:0045087 innate immune response
Biological Process GO:0032042 mitochondrial DNA metabolic process
Biological Process GO:0043504 mitochondrial DNA repair
Biological Process GO:0007005 mitochondrion organization
Biological Process GO:1904178 negative regulation of adipose tissue development
Biological Process GO:2001170 negative regulation of ATP biosynthetic process
Biological Process GO:0160049 negative regulation of cGAS/STING signaling pathway
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:0045824 negative regulation of innate immune response
Biological Process GO:0032700 negative regulation of interleukin-17 production
Biological Process GO:1904357 negative regulation of telomere maintenance via telomere lengthening
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0034244 negative regulation of transcription elongation by RNA polymerase II
Biological Process GO:0043123 positive regulation of canonical NF-kappaB signal transduction
Biological Process GO:0010613 positive regulation of cardiac muscle hypertrophy
Biological Process GO:0032786 positive regulation of DNA-templated transcription, elongation
Biological Process GO:1905168 positive regulation of double-strand break repair via homologous recombination
Biological Process GO:0033148 positive regulation of intracellular estrogen receptor signaling pathway
Biological Process GO:0051901 positive regulation of mitochondrial depolarization
Biological Process GO:1904762 positive regulation of myofibroblast differentiation
Biological Process GO:0060545 positive regulation of necroptotic process
Biological Process GO:1900182 positive regulation of protein localization to nucleus
Biological Process GO:0060391 positive regulation of SMAD protein signal transduction
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0070213 protein auto-ADP-ribosylation
Biological Process GO:0016540 protein autoprocessing
Biological Process GO:0071168 protein localization to chromatin
Biological Process GO:0070212 protein poly-ADP-ribosylation
Biological Process GO:1905051 regulation of base-excision repair
Biological Process GO:0045188 regulation of circadian sleep/wake cycle, non-REM sleep
Biological Process GO:0040009 regulation of growth rate
Biological Process GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
Biological Process GO:0032880 regulation of protein localization
Biological Process GO:1903516 regulation of single strand break repair
Biological Process GO:0071932 replication fork reversal
Biological Process GO:1904044 response to aldosterone
Biological Process GO:0045471 response to ethanol
Biological Process GO:0010332 response to gamma radiation
Biological Process GO:0023019 signal transduction involved in regulation of gene expression
Biological Process GO:0000012 single strand break repair
Biological Process GO:0000723 telomere maintenance
Biological Process GO:0007179 transforming growth factor beta receptor signaling pathway
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0001650 fibrillar center
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005635 nuclear envelope
Cellular Component GO:0043596 nuclear replication fork
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0032993 protein-DNA complex
Cellular Component GO:0090734 site of DNA damage
Cellular Component GO:0035861 site of double-strand break
Cellular Component GO:0005667 transcription regulator complex
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0003684 damaged DNA binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0008047 enzyme activator activity
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0042826 histone deacetylase binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0051287 NAD binding
Molecular Function GO:0140294 NAD DNA ADP-ribosyltransferase activity
Molecular Function GO:0003950 NAD+ poly-ADP-ribosyltransferase activity
Molecular Function GO:0140822 NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity
Molecular Function GO:0140816 NAD+-histone H2BS6 serine ADP-ribosyltransferase activity
Molecular Function GO:0140817 NAD+-histone H3S10 serine ADP-ribosyltransferase activity
Molecular Function GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity
Molecular Function GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity
Molecular Function GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity
Molecular Function GO:0140815 NAD+-protein-histidine ADP-ribosyltransferase activity
Molecular Function GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity
Molecular Function GO:0140808 NAD+-protein-tyrosine ADP-ribosyltransferase activity
Molecular Function GO:0044378 non-sequence-specific DNA binding, bending
Molecular Function GO:0030331 nuclear estrogen receptor binding
Molecular Function GO:0031491 nucleosome binding
Molecular Function GO:0016779 nucleotidyltransferase activity
Molecular Function GO:0016763 pentosyltransferase activity
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0070412 R-SMAD binding
Molecular Function GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
Molecular Function GO:1990165 single-strand break-containing DNA binding
Molecular Function GO:0140537 transcription regulator activator activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006915 apoptotic process

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.