UniProt Accession

 PARP1_HUMAN; P09874; B1ANJ4; Q8IUZ9 

Genbank Protein ID

 M18112; J03473; M32721; M29786; M29545; M29766; M29767; M29768; M29769; M29770; M29771; M29772; M29773; M29774; M29775; M29776; M29777; M29778; M29779; M29780; M29781; M29783; M29784; M29785; M29544; M29782; AF524947; AL359704; AL359742; AL359742; AL359704; CH471098; BC037545; X56140; X56141; X16674; M60436; M17081 

Genbank Nucleotide ID

 AAA60137.1; AAB59447.1; AAA60155.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAA51663.1; AAM75364.1; CAH70215.1; CAH70215.1; CAI12102.1; CAI12102.1; EAW69783.1; AAH37545.1; CAA39606.1; CAA39606.1; CAA34663.1; AAA60000.1; AAA51599.1 

Protein Name

 Poly [ADP-ribose] polymerase 1 

Protein Synonyms/Alias

 PARP-1; ADP-ribosyltransferase diphtheria toxin-like 1; ARTD1; NAD(+) ADP-ribosyltransferase 1; ADPRT 1; Poly[ADP-ribose] synthase 1 

Gene Name

 PARP1 

Gene Synonyms/Alias

 ADPRT; PPOL 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
7	*MAESSDKLYRVEYA	ubiquitination	[1, 2]
84	LRWDDQQKVKKTAEA	acetylation	[2]
97	EAGGVTGKGQDGIGS	acetylation	[2, 3, 4]
97	EAGGVTGKGQDGIGS	ubiquitination	[1, 2, 5]
105	GQDGIGSKAEKTLGD	acetylation	[3, 6]
108	GIGSKAEKTLGDFAA	acetylation	[2, 4]
108	GIGSKAEKTLGDFAA	ubiquitination	[7, 8]
119	DFAAEYAKSNRSTCK	ubiquitination	[1, 5, 7, 8, 9, 10]
131	TCKGCMEKIEKGQVR	acetylation	[3]
148	KKMVDPEKPQLGMID	acetylation	[2, 4]
165	YHPGCFVKNREELGF	ubiquitination	[1, 7, 8, 9, 11]
196	TEDKEALKKQLPGVK	acetylation	[2]
203	KKQLPGVKSEGKRKG	sumoylation	[12, 13]
209	VKSEGKRKGDEVDGV	ubiquitination	[2, 5]
221	DGVDEVAKKKSKKEK	ubiquitination	[5]
239	SKLEKALKAQNDLIW	ubiquitination	[7, 8]
249	NDLIWNIKDELKKVC	ubiquitination	[1, 10]
254	NIKDELKKVCSTNDL	ubiquitination	[1, 9]
269	KELLIFNKQQVPSGE	ubiquitination	[1, 2, 5, 7, 8, 9, 10, 11, 14]
320	GDVTAWTKCMVKTQT	ubiquitination	[7, 8]
331	KTQTPNRKEWVTPKE	ubiquitination	[1]
337	RKEWVTPKEFREISY	ubiquitination	[1, 7, 8, 9]
394	DKPLSNMKILTLGKL	ubiquitination	[7, 8, 9]
400	MKILTLGKLSRNKDE	ubiquitination	[1, 7, 8, 9]
414	EVKAMIEKLGGKLTG	ubiquitination	[1, 9]
418	MIEKLGGKLTGTANK	acetylation	[2]
447	NKKMEEVKEANIRVV	ubiquitination	[1]
486	SPWGAEVKAEPVEVV	sumoylation	[12, 15, 16, 17]
498	EVVAPRGKSGAALSK	acetylation	[18]
505	KSGAALSKKSKGQVK	acetylation	[18]
508	AALSKKSKGQVKEEG	acetylation	[18]
521	EGINKSEKRMKLTLK	acetylation	[2, 18]
524	NKSEKRMKLTLKGGA	acetylation	[18]
528	KRMKLTLKGGAAVDP	ubiquitination	[2, 7, 8, 10]
548	HSAHVLEKGGKVFSA	acetylation	[2, 3, 4]
548	HSAHVLEKGGKVFSA	ubiquitination	[5, 7, 8, 10, 19]
551	HVLEKGGKVFSATLG	ubiquitination	[1, 2, 7, 8]
564	LGLVDIVKGTNSYYK	ubiquitination	[7, 8]
579	LQLLEDDKENRYWIF	acetylation	[2, 4]
579	LQLLEDDKENRYWIF	ubiquitination	[7, 8, 9]
600	GTVIGSNKLEQMPSK	acetylation	[2, 3, 4]
600	GTVIGSNKLEQMPSK	ubiquitination	[7, 8]
621	FMKLYEEKTGNAWHS	acetylation	[2, 3, 4, 6]
629	TGNAWHSKNFTKYPK	acetylation	[2]
633	WHSKNFTKYPKKFYP	acetylation	[6]
637	NFTKYPKKFYPLEID	ubiquitination	[7, 8]
653	GQDEEAVKKLTVNPG	ubiquitination	[5]
667	GTKSKLPKPVQDLIK	ubiquitination	[7, 8]
683	IFDVESMKKAMVEYE	acetylation	[2]
683	IFDVESMKKAMVEYE	ubiquitination	[5, 7, 8]
700	LQKMPLGKLSKRQIQ	ubiquitination	[9]
748	PHDFGMKKPPLLNNA	ubiquitination	[1]
787	GGSDDSSKDPIDVNY	acetylation	[4]
787	GGSDDSSKDPIDVNY	ubiquitination	[1, 5]
796	PIDVNYEKLKTDIKV	ubiquitination	[5]
852	CQRYKPFKQLHNRRL	acetylation	[2]
949	PKGKHSVKGLGKTTP	ubiquitination	[5]
1006	LKYLLKLKFNFKTSL	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [7] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [8] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [9] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [10] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [11] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [12] PARP-1 transcriptional activity is regulated by sumoylation upon heat shock.
 Martin N, Schwamborn K, Schreiber V, Werner A, Guillier C, Zhang XD, Bischof O, Seeler JS, Dejean A.
 EMBO J. 2009 Nov 18;28(22):3534-48. [PMID: 19779455]
 [13] Targeted identification of SUMOylation sites in human proteins using affinity enrichment and paralog-specific reporter ions.
 Lamoliatte F, Bonneil E, Durette C, Caron-Lizotte O, Wildemann D, Zerweck J, Wenschuh H, Thibault P.
 Mol Cell Proteomics. 2013 Jun 7;. [PMID: 23750026]
 [14] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [15] Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function.
 Messner S, Schuermann D, Altmeyer M, Kassner I, Schmidt D, Schär P, Müller S, Hottiger MO.
 FASEB J. 2009 Nov;23(11):3978-89. [PMID: 19622798]
 [16] Differential regulation of HIC1 target genes by CtBP and NuRD, via an acetylation/SUMOylation switch, in quiescent versus proliferating cells.
 Van Rechem C, Boulay G, Pinte S, Stankovic-Valentin N, Guérardel C, Leprince D.
 Mol Cell Biol. 2010 Aug;30(16):4045-59. [PMID: 20547755]
 [17] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
 [18] Acetylation of poly(ADP-ribose) polymerase-1 by p300/CREB-binding protein regulates coactivation of NF-kappaB-dependent transcription.
 Hassa PO, Haenni SS, Buerki C, Meier NI, Lane WS, Owen H, Gersbach M, Imhof R, Hottiger MO.
 J Biol Chem. 2005 Dec 9;280(49):40450-64. [PMID: 16204234]
 [19] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048] 

Functional Description

 Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP- ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Required for PARP9 and DTX3L recruitement 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. 

Sequence Annotation

 DOMAIN 385 476 BRCT.
 DOMAIN 662 779 PARP alpha-helical.
 DOMAIN 788 1014 PARP catalytic.
 DNA_BIND 2 372
 ZN_FING 9 93 PARP-type 1.
 ZN_FING 113 203 PARP-type 2.
 REGION 373 524 Automodification domain.
 MOTIF 207 209 Nuclear localization signal.
 MOTIF 221 226 Nuclear localization signal.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 41 41 Phosphoserine.
 MOD_RES 97 97 N6-acetyllysine.
 MOD_RES 105 105 N6-acetyllysine.
 MOD_RES 131 131 N6-acetyllysine.
 MOD_RES 179 179 Phosphoserine.
 MOD_RES 368 368 Phosphothreonine.
 MOD_RES 407 407 PolyADP-ribosyl glutamic acid
 MOD_RES 413 413 PolyADP-ribosyl glutamic acid
 MOD_RES 435 435 PolyADP-ribosyl glutamic acid
 MOD_RES 437 437 PolyADP-ribosyl glutamic acid
 MOD_RES 444 444 PolyADP-ribosyl glutamic acid
 MOD_RES 445 445 PolyADP-ribosyl glutamic acid
 MOD_RES 448 448 PolyADP-ribosyl glutamic acid
 MOD_RES 456 456 PolyADP-ribosyl glutamic acid
 MOD_RES 471 471 PolyADP-ribosyl glutamic acid
 MOD_RES 484 484 PolyADP-ribosyl glutamic acid
 MOD_RES 488 488 PolyADP-ribosyl glutamic acid
 MOD_RES 491 491 PolyADP-ribosyl glutamic acid
 MOD_RES 513 513 PolyADP-ribosyl glutamic acid
 MOD_RES 514 514 PolyADP-ribosyl glutamic acid
 MOD_RES 520 520 PolyADP-ribosyl glutamic acid
 MOD_RES 600 600 N6-acetyllysine.
 MOD_RES 621 621 N6-acetyllysine.
 MOD_RES 782 782 Phosphoserine.  

Keyword

 3D-structure; Acetylation; ADP-ribosylation; Complete proteome; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; Glycosyltransferase; Metal-binding; NAD; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; S-nitrosylation; Transcription; Transcription regulation; Transferase; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1014 AA 

Protein Sequence

Gene Ontology

 GO:0005635; C:nuclear envelope; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005667; C:transcription factor complex; IDA:BHF-UCL.
 GO:0003677; F:DNA binding; TAS:ProtInc.
 GO:0051287; F:NAD binding; IEA:Compara.
 GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006284; P:base-excision repair; IEA:Compara.
 GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
 GO:0042769; P:DNA damage response, detection of DNA damage; IEA:Compara.
 GO:0006302; P:double-strand break repair; IMP:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:Reactome.
 GO:0016540; P:protein autoprocessing; IEA:Compara.
 GO:0070212; P:protein poly-ADP-ribosylation; IDA:UniProtKB.
 GO:0040009; P:regulation of growth rate; IEA:Compara.
 GO:0000723; P:telomere maintenance; IEA:Compara.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. 

Interpro

 IPR001357; BRCT_dom.
 IPR008288; NAD_ADPRT.
 IPR012982; PADR1.
 IPR012317; Poly(ADP-ribose)pol_cat_dom.
 IPR004102; Poly(ADP-ribose)pol_reg_dom.
 IPR008893; WGR_domain.
 IPR001510; Znf_PARP. 

Pfam

 PF00533; BRCT
 PF08063; PADR1
 PF00644; PARP
 PF02877; PARP_reg
 PF05406; WGR
 PF00645; zf-PARP 

SMART

 SM00292; BRCT
 SM00773; WGR 

PROSITE

 PS50172; BRCT
 PS51060; PARP_ALPHA_HD
 PS51059; PARP_CATALYTIC
 PS00347; PARP_ZN_FINGER_1
 PS50064; PARP_ZN_FINGER_2 

PRINTS