Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWSXW4O)

• DOT Name: Protein mono-ADP-ribosyltransferase PARP6 (PARP6)
• Synonyms: EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 17; ARTD17; Poly polymerase 6; PARP-6
• Gene Name: PARP6
• Related Disease:
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Neoplasm
  Colorectal adenocarcinoma
• UniProt ID: PARP6_HUMAN
• EC Number: 2.4.2.-
• Pfam ID: PF00644
• Sequence:
  MDIKGQFWNDDDSEGDNESEEFLYGVQGSCAADLYRHPQLDADIEAVKEIYSENSVSIRE
  YGTIDDVDIDLHINISFLDEEVSTAWKVLRTEPIVLRLRFSLSQYLDGPEPSIEVFQPSN
  KEGFGLGLQLKKILGMFTSQQWKHLSNDFLKTQQEKRHSWFKASGTIKKFRAGLSIFSPI
  PKSPSFPIIQDSMLKGKLGVPELRVGRLMNRSISCTMKNPKVEVFGYPPSPQAGLLCPQH
  VGLPPPARTSPLVSGHCKNIPTLEYGFLVQIMKYAEQRIPTLNEYCVVCDEQHVFQNGSM
  LKPAVCTRELCVFSFYTLGVMSGAAEEVATGAEVVDLLVAMCRAALESPRKSIIFEPYPS
  VVDPTDPKTLAFNPKKKNYERLQKALDSVMSIREMTQGSYLEIKKQMDKLDPLAHPLLQW
  IISSNRSHIVKLPLSRLKFMHTSHQFLLLSSPPAKEARFRTAKKLYGSTFAFHGSHIENW
  HSILRNGLVNASYTKLQLHGAAYGKGIYLSPISSISFGYSGMGKGQHRMPSKDELVQRYN
  RMNTIPQTRSIQSRFLQSRNLNCIALCEVITSKDLQKHGNIWVCPVSDHVCTRFFFVYED
  GQVGDANINTQDPKIQKEIMRVIGTQVYTN
• Function: Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.
• Reactome Pathway:
  Maturation of nucleoprotein (R-HSA-9683610)
  Maturation of nucleoprotein (R-HSA-9694631)
  Nicotinamide salvaging (R-HSA-197264)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Colorectal adenocarcinoma	DISPQOUB	Limited	Altered Expression	[4]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein mono-ADP-ribosyltransferase PARP6 (PARP6).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein mono-ADP-ribosyltransferase PARP6 (PARP6).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein mono-ADP-ribosyltransferase PARP6 (PARP6).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein mono-ADP-ribosyltransferase PARP6 (PARP6).	[7]

References

• [1] PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell proliferation, is involved in colorectal cancer development.Int J Oncol. 2012 Dec;41(6):2079-86. doi: 10.3892/ijo.2012.1652. Epub 2012 Oct 4.
• [2] Pharmacological Inhibition of PARP6 Triggers Multipolar Spindle Formation and Elicits Therapeutic Effects in Breast Cancer.Cancer Res. 2018 Dec 1;78(23):6691-6702. doi: 10.1158/0008-5472.CAN-18-1362. Epub 2018 Oct 8.
• [3] PARP6 acts as a tumor suppressor via downregulating Survivin expression in colorectal cancer.Oncotarget. 2016 Apr 5;7(14):18812-24. doi: 10.18632/oncotarget.7712.
• [4] Knockdown of PARP6 or survivin promotes cell apoptosis and inhibits cell invasion of colorectal adenocarcinoma cells.Oncol Rep. 2017 Apr;37(4):2245-2251. doi: 10.3892/or.2017.5441. Epub 2017 Feb 14.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.