Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEADE76)

• DOT Name: ATM interactor (ATMIN)
• Synonyms: ATM/ATR-substrate CHK2-interacting zinc finger protein; ASCIZ; Zinc finger protein 822
• Gene Name: ATMIN
• Related Disease:
  Adult lymphoma
  B-cell neoplasm
  Lung adenocarcinoma
  Lymphoma
  Neoplasm
  Pediatric lymphoma
  Adult glioblastoma
  Glioblastoma multiforme
  Autosomal recessive polycystic kidney disease
  Pneumocystis pneumonia
• UniProt ID: ATMIN_HUMAN
• Sequence:
  MAASEAAAAAGSAALAAGARAVPAATTGAAAAASGPWVPPGPRLRGSRPRPAGATQQPAV
  PAPPAGELIQPSVSELSRAVRTNILCTVRGCGKILPNSPALNMHLVKSHRLQDGIVNPTI
  RKDLKTGPKFYCCPIEGCPRGPERPFSQFSLVKQHFMKMHAEKKHKCSKCSNSYGTEWDL
  KRHAEDCGKTFRCTCGCPYASRTALQSHIYRTGHEIPAEHRDPPSKKRKMENCAQNQKLS
  NKTIESLNNQPIPRPDTQELEASEIKLEPSFEDSCGSNTDKQTLTTPPRYPQKLLLPKPK
  VALVKLPVMQFSVMPVFVPTADSSAQPVVLGVDQGSATGAVHLMPLSVGTLILGLDSEAC
  SLKESLPLFKIANPIAGEPISTGVQVNFGKSPSNPLQELGNTCQKNSISSINVQTDLSYA
  SQNFIPSAQWATADSSVSSCSQTDLSFDSQVSLPISVHTQTFLPSSKVTSSIAAQTDAFM
  DTCFQSGGVSRETQTSGIESPTDDHVQMDQAGMCGDIFESVHSSYNVATGNIISNSLVAE
  TVTHSLLPQNEPKTLNQDIEKSAPIINFSAQNSMLPSQNMTDNQTQTIDLLSDLENILSS
  NLPAQTLDHRSLLSDTNPGPDTQLPSGPAQNPGIDFDIEEFFSASNIQTQTEESELSTMT
  TEPVLESLDIETQTDFLLADTSAQSYGCRGNSNFLGLEMFDTQTQTDLNFFLDSSPHLPL
  GSILKHSSFSVSTDSSDTETQTEGVSTAKNIPALESKVQLNSTETQTMSSGFETLGSLFF
  TSNETQTAMDDFLLADLAWNTMESQFSSVETQTSAEPHTVSNF
• Function: Transcription factor. Plays a crucial role in cell survival and RAD51 foci formation in response to methylating DNA damage. Involved in regulating the activity of ATM in the absence of DNA damage. May play a role in stabilizing ATM. Binds to the DYNLL1 promoter and activates its transcription.
• Tissue Specificity: Ubiquitously expressed in normal tissues and cancer cell lines with highest levels in placenta and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[1]
B-cell neoplasm	DISVY326	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[3]
Lymphoma	DISN6V4S	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[4]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[4]
Autosomal recessive polycystic kidney disease	DISPUS40	Limited	Altered Expression	[5]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of ATM interactor (ATMIN).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of ATM interactor (ATMIN).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATM interactor (ATMIN).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ATM interactor (ATMIN).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATM interactor (ATMIN).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of ATM interactor (ATMIN).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of ATM interactor (ATMIN).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of ATM interactor (ATMIN).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ATM interactor (ATMIN).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of ATM interactor (ATMIN).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ATM interactor (ATMIN).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ATM interactor (ATMIN).	[16]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of ATM interactor (ATMIN).	[17]

References

• [1] The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma.Cell Rep. 2016 Feb 16;14(6):1488-1499. doi: 10.1016/j.celrep.2016.01.012. Epub 2016 Jan 28.
• [2] Dynein light chain regulates adaptive and innate B cell development by distinctive genetic mechanisms.PLoS Genet. 2017 Sep 18;13(9):e1007010. doi: 10.1371/journal.pgen.1007010. eCollection 2017 Sep.
• [3] ATMIN Is a Tumor Suppressor Gene in Lung Adenocarcinoma.Cancer Res. 2019 Oct 15;79(20):5159-5166. doi: 10.1158/0008-5472.CAN-19-0647. Epub 2019 Sep 3.
• [4] Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation.Elife. 2016 Mar 17;5:e08711. doi: 10.7554/eLife.08711.
• [5] Atmin modulates Pkhd1 expression and may mediate Autosomal Recessive Polycystic Kidney Disease (ARPKD) through altered non-canonical Wnt/Planar Cell Polarity (PCP) signalling.Biochim Biophys Acta Mol Basis Dis. 2019 Feb 1;1865(2):378-390. doi: 10.1016/j.bbadis.2018.11.003. Epub 2018 Nov 7.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] 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.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.