Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT56VFRL)

• DOT Name: Deoxyribonuclease-1-like 2 (DNASE1L2)
• Synonyms: EC 3.1.21.-; DNase I homolog protein DHP1; Deoxyribonuclease I-like 2; DNase I-like 2
• Gene Name: DNASE1L2
• Related Disease:
  Prostate cancer
  Prostate neoplasm
• UniProt ID: DNSL2_HUMAN
• EC Number: 3.1.21.-
• Pfam ID: PF03372
• Sequence:
  MGGPRALLAALWALEAAGTAALRIGAFNIQSFGDSKVSDPACGSIIAKILAGYDLALVQE
  VRDPDLSAVSALMEQINSVSEHEYSFVSSQPLGRDQYKEMYLFVYRKDAVSVVDTYLYPD
  PEDVFSREPFVVKFSAPGTGERAPPLPSRRALTPPPLPAAAQNLVLIPLHAAPHQAVAEI
  DALYDVYLDVIDKWGTDDMLFLGDFNADCSYVRAQDWAAIRLRSSEVFKWLIPDSADTTV
  GNSDCAYDRIVACGARLRRSLKPQSATVHDFQEEFGLDQTQALAISDHFPVEVTLKFHR
• Function: Divalent cation-dependent acid DNA endonuclease involved in the breakdown of the nucleus during corneocyte formation of epidermal keratinocytes. May play an immune role by eliminating harmful DNA released into the extracellular environment by damaged epidermal cells.
• Tissue Specificity: Preferentially expressed in the skin and up-regulated during keratinocytes differentiation. Highly abundant (at protein level) in the stratum granulosum.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Deoxyribonuclease-1-like 2 (DNASE1L2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Deoxyribonuclease-1-like 2 (DNASE1L2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Deoxyribonuclease-1-like 2 (DNASE1L2).	[3]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Deoxyribonuclease-1-like 2 (DNASE1L2).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Deoxyribonuclease-1-like 2 (DNASE1L2).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Deoxyribonuclease-1-like 2 (DNASE1L2).	[7]

References

• [1] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [4] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [5] 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.
• [6] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.