Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAP29SS)

• DOT Name: Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1)
• Synonyms: Terminal deoxynucleotidyltransferase-interacting factor 1; TdIF1; TdT-interacting factor 1
• Gene Name: DNTTIP1
• Related Disease:
  Adenocarcinoma
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
• UniProt ID: TDIF1_HUMAN
• PDB ID: 2MWI; 4D6K; 6Z2J; 6Z2K
• Pfam ID: PF18192 ; PF21229
• Sequence:
  MGATGDAEQPRGPSGAERGGLELGDAGAAGQLVLTNPWNIMIKHRQVQRRGRRSQMTTSF
  TDPAISMDLLRAVLQPSINEEIQTVFNKYMKFFQKAALNVRDNVGEEVDAEQLIQEACRS
  CLEQAKLLFSDGEKVIPRLTHELPGIKRGRQAEEECAHRGSPLPKKRKGRPPGHILSSDR
  AAAGMVWKPKSCEPIRREGPKWDPARLNESTTFVLGSRANKALGMGGTRGRIYIKHPHLF
  KYAADPQDKHWLAEQHHMRATGGKMAYLLIEEDIRDLAASDDYRGCLDLKLEELKSFVLP
  SWMVEKMRKYMETLRTENEHRAVEAPPQT
• Function: Increases DNTT terminal deoxynucleotidyltransferase activity (in vitro). Also acts as a transcriptional regulator, binding to the consensus sequence 5'-GNTGCATG-3' following an AT-tract. Associates with RAB20 promoter and positively regulates its transcription. Binds DNA and nucleosomes; may recruit HDAC1 complexes to nucleosomes or naked DNA.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Lung neoplasm	DISVARNB	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1) affects the response to substance of NAPQI.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Deoxynucleotidyltransferase terminal-interacting protein 1 (DNTTIP1).	[7]

References

• [1] TdIF1: a putative oncogene in NSCLC tumor progression.Signal Transduct Target Ther. 2018 Oct 19;3:28. doi: 10.1038/s41392-018-0030-9. eCollection 2018.
• [2] 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.
• [3] Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology. 2008 Oct;149(10):4809-20. doi: 10.1210/en.2008-0035. Epub 2008 Jun 12.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [7] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [8] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.