Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ZG99E)

• DOT Name: Integrator complex subunit 7 (INTS7)
• Synonyms: Int7
• Gene Name: INTS7
• Related Disease:
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Bipolar disorder
• UniProt ID: INT7_HUMAN
• PDB ID: 7CUN; 7PKS; 7YCX
• Sequence:
  MASNSTKSFLADAGYGEQELDANSALMELDKGLRSGKLGEQCEAVVRFPRLFQKYPFPIL
  INSAFLKLADVFRVGNNFLRLCVLKVTQQSEKHLEKILNVDEFVKRIFSVIHSNDPVARA
  ITLRMLGSLASIIPERKNAHHSIRQSLDSHDNVEVEAAVFAAANFSAQSKDFAVGICNKI
  SEMIQGLATPVDLKLKLIPILQHMHHDAILASSARQLLQQLVTSYPSTKMVIVSLHTFTL
  LAASSLVDTPKQIQLLLQYLKNDPRKAVKRLAIQDLKLLANKTPHTWSRENIQALCECAL
  QTPYDSLKLGMLSVLSTLSGTIAIKHYFSIVPGNVSSSPRSSDLVKLAQECCYHNNRGIA
  AHGVRVLTNITVSCQEKDLLALEQDAVFGLESLLVLCSQDDSPGAQATLKIALNCMVKLA
  KGRPHLSQSVVETLLTQLHSAQDAARILMCHCLAAIAMQLPVLGDGMLGDLMELYKVIGR
  SATDKQQELLVSLATVIFVASQKALSVESKAVIKQQLESVSNGWTVYRIARQASRMGNHD
  MAKELYQSLLTQVASEHFYFWLNSLKEFSHAEQCLTGLQEENYSSALSCIAESLKFYHKG
  IASLTAASTPLNPLSFQCEFVKLRIDLLQAFSQLICTCNSLKTSPPPAIATTIAMTLGND
  LQRCGRISNQMKQSMEEFRSLASRYGDLYQASFDADSATLRNVELQQQSCLLISHAIEAL
  ILDPESASFQEYGSTGTAHADSEYERRMMSVYNHVLEEVESLNRKYTPVSYMHTACLCNA
  IIALLKVPLSFQRYFFQKLQSTSIKLALSPSPRNPAEPIAVQNNQQLALKVEGVVQHGSK
  PGLFRKIQSVCLNVSSTLQSKSGQDYKIPIDNMTNEMEQRVEPHNDYFSTQFLLNFAILG
  THNITVESSVKDANGIVWKTGPRTTIFVKSLEDPYSQQIRLQQQQAQQPLQQQQQRNAYT
  RF
• 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). Plays a role in DNA damage response (DDR) signaling during the S phase. 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[3]

3 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 Integrator complex subunit 7 (INTS7).	[4]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Integrator complex subunit 7 (INTS7).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Integrator complex subunit 7 (INTS7).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Integrator complex subunit 7 (INTS7).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Integrator complex subunit 7 (INTS7).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Integrator complex subunit 7 (INTS7).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Integrator complex subunit 7 (INTS7).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Integrator complex subunit 7 (INTS7).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Integrator complex subunit 7 (INTS7).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Integrator complex subunit 7 (INTS7).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Integrator complex subunit 7 (INTS7).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Integrator complex subunit 7 (INTS7).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Integrator complex subunit 7 (INTS7).	[9]

References

• [1] Characterization of novel CD55 isoforms expression innormal and neoplastic tissues.Tissue Antigens. 2013 Jul;82(1):26-34. doi: 10.1111/tan.12138. Epub 2013 May 21.
• [2] Comparative Proteome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteogenomics.Cancer Genomics Proteomics. 2019 Jul-Aug;16(4):273-286. doi: 10.21873/cgp.20132.
• [3] Genome-wide association study of temperament in bipolar disorder reveals significant associations with three novel Loci.Biol Psychiatry. 2012 Aug 15;72(4):303-10. doi: 10.1016/j.biopsych.2012.01.018. Epub 2012 Feb 23.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [10] 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.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.