Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO356QQ)

• DOT Name: Integrator complex subunit 10 (INTS10)
• Synonyms: Int10
• Gene Name: INTS10
• Related Disease:
  Breast carcinoma
  Hepatitis B virus infection
• UniProt ID: INT10_HUMAN
• Pfam ID: PF21045
• Sequence:
  MSAQGDCEFLVQRARELVPQDLWAAKAWLITARSLYPADFNIQYEMYTIERNAERTATAG
  RLLYDMFVNFPDQPVVWREISIITSALRNDSQDKQTQFLRSLFETLPGRVQCEMLLKVTE
  QCFNTLERSEMLLLLLRRFPETVVQHGVGLGEALLEAETIEEQESPVNCFRKLFVCDVLP
  LIINNHDVRLPANLLYKYLNKAAEFYINYVTRSTQIENQHQGAQDTSDLMSPSKRSSQKY
  IIEGLTEKSSQIVDPWERLFKILNVVGMRCEWQMDKGRRSYGDILHRMKDLCRYMNNFDS
  EAHAKYKNQVVYSTMLVFFKNAFQYVNSIQPSLFQGPNAPSQVPLVLLEDVSNVYGDVEI
  DRNKHIHKKRKLAEGREKTMSSDDEDCSAKGRNRHIVVNKAELANSTEVLESFKLARESW
  ELLYSLEFLDKEFTRICLAWKTDTWLWLRIFLTDMIIYQGQYKKAIASLHHLAALQGSIS
  QPQITGQGTLEHQRALIQLATCHFALGEYRMTCEKVLDLMCYMVLPIQDGGKSQEEPSKV
  KPKFRKGSDLKLLPCTSKAIMPYCLHLMLACFKLRAFTDNRDDMALGHVIVLLQQEWPRG
  ENLFLKAVNKICQQGNFQYENFFNYVTNIDMLEEFAYLRTQEGGKIHLELLPNQGMLIKH
  HTVTRGITKGVKEDFRLAMERQVSRCGENLMVVLHRFCINEKILLLQTLT
• Function: Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). May be not involved in the recruitment of cytoplasmic dynein to the nuclear envelope by different components of the INT complex.
• Reactome Pathway: RNA polymerase II transcribes snRNA genes (R-HSA-6807505)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Integrator complex subunit 10 (INTS10).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Integrator complex subunit 10 (INTS10).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Integrator complex subunit 10 (INTS10).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrator complex subunit 10 (INTS10).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Integrator complex subunit 10 (INTS10).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Integrator complex subunit 10 (INTS10).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Integrator complex subunit 10 (INTS10).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Integrator complex subunit 10 (INTS10).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Integrator complex subunit 10 (INTS10).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Integrator complex subunit 10 (INTS10).	[11]

References

• [1] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [2] Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese.Nat Commun. 2016 May 31;7:11664. doi: 10.1038/ncomms11664.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.