Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA6LOLR)

• DOT Name: Mitochondrial inner membrane protease subunit 1 (IMMP1L)
• Synonyms: EC 3.4.21.-; IMP1-like protein
• Gene Name: IMMP1L
• Related Disease:
  Advanced cancer
  Breast carcinoma
  Mycoses
  Breast cancer
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Epithelial neoplasm
  Epithelial ovarian cancer
  Lung cancer
  Lung carcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Urinary tract infection
  Choriocarcinoma
  Metastatic malignant neoplasm
  Conjunctivitis
  Cystitis
  Melanoma
  Toxoplasmosis
• UniProt ID: IMP1L_HUMAN
• EC Number: 3.4.21.-
• Pfam ID: PF10502
• Sequence:
  MLRGVLGKTFRLVGYTIQYGCIAHCAFEYVGGVVMCSGPSMEPTIQNSDIVFAENLSRHF
  YGIQRGDIVIAKSPSDPKSNICKRVIGLEGDKILTTSPSDFFKSHSYVPMGHVWLEGDNL
  QNSTDSRCYGPIPYGLIRGRIFFKIWPLSDFGFLRASPNGHRFSDD
• Function: Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO.
• KEGG Pathway: Protein export (hsa03060)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[2]
Mycoses	DIS9K7PB	Definitive	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Lung cancer	DISCM4YA	Strong	Altered Expression	[9]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Urinary tract infection	DISMT6UV	Strong	Biomarker	[10]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[11]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Altered Expression	[1]
Conjunctivitis	DISGOZ4P	Limited	Biomarker	[12]
Cystitis	DIS2D4B9	Limited	Biomarker	[12]
Melanoma	DIS1RRCY	Limited	Altered Expression	[13]
Toxoplasmosis	DISYP8FH	Limited	Biomarker	[14]

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 Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[15]

8 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 Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[19]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Mitochondrial inner membrane protease subunit 1 (IMMP1L).	[23]

References

• [1] IMP1 KH1 and KH2 domains create a structural platform with unique RNA recognition and re-modelling properties.Nucleic Acids Res. 2019 May 7;47(8):4334-4348. doi: 10.1093/nar/gkz136.
• [2] IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p.Breast Cancer Res. 2018 Apr 18;20(1):32. doi: 10.1186/s13058-018-0959-1.
• [3] Molecular and epidemiological analysis of IMP-1 metallo--lactamase-producing Klebsiella pneumoniae in a tertiary care hospital in Japan.J Infect Chemother. 2019 Apr;25(4):240-246. doi: 10.1016/j.jiac.2018.11.012. Epub 2019 Jan 2.
• [4] IMP3 promotes TNBC stem cell property through miRNA-34a regulation.Eur Rev Med Pharmacol Sci. 2018 May;22(9):2688-2696. doi: 10.26355/eurrev_201805_14965.
• [5] IMP-1 displays cross-talk with K-Ras and modulates colon cancer cell survival through the novel proapoptotic protein CYFIP2.Cancer Res. 2011 Mar 15;71(6):2172-82. doi: 10.1158/0008-5472.CAN-10-3295. Epub 2011 Jan 20.
• [6] IMP1 3' UTR shortening enhances metastatic burden in colorectal cancer.Carcinogenesis. 2019 Jun 10;40(4):569-579. doi: 10.1093/carcin/bgy153.
• [7] Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon.Mol Cancer Res. 2015 Nov;13(11):1478-86. doi: 10.1158/1541-7786.MCR-15-0224. Epub 2015 Jul 20.
• [8] Humoral autoimmune responses to insulin-like growth factor II mRNA-binding proteins IMP1 and p62/IMP2 in ovarian cancer.J Immunol Res. 2014;2014:326593. doi: 10.1155/2014/326593. Epub 2014 Apr 27.
• [9] A Novel IMP1 Inhibitor, BTYNB, Targets c-Myc and Inhibits Melanoma and Ovarian Cancer Cell Proliferation.Transl Oncol. 2017 Oct;10(5):818-827. doi: 10.1016/j.tranon.2017.07.008. Epub 2017 Aug 29.
• [10] Detection of VIM-1 and IMP-1 genes in Klebsiella pneumoniae and relationship with biofilm formation.Microb Pathog. 2018 Feb;115:25-30. doi: 10.1016/j.micpath.2017.12.036. Epub 2017 Dec 14.
• [11] IMP1 promotes choriocarcinoma cell migration and invasion through the novel effectors RSK2 and PPME1.Gynecol Oncol. 2013 Oct;131(1):182-90. doi: 10.1016/j.ygyno.2013.07.106. Epub 2013 Aug 1.
• [12] Analysis of IMP-1 type metallo--lactamase-producing Acinetobacter radioresistens isolated from companion animals.J Infect Chemother. 2017 Sep;23(9):655-657. doi: 10.1016/j.jiac.2017.03.011. Epub 2017 Apr 10.
• [13] Protein kinase C- is upregulated by IMP1 in melanoma and is linked to poor survival.Melanoma Res. 2019 Oct;29(5):539-543. doi: 10.1097/CMR.0000000000000558.
• [14] Toxoplasma gondii immune mapped protein-1 (TgIMP1) is a novel vaccine candidate against toxoplasmosis.Vaccine. 2012 Mar 16;30(13):2282-7. doi: 10.1016/j.vaccine.2012.01.073. Epub 2012 Feb 3.
• [15] 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.
• [16] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [17] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [18] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [21] 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.
• [22] 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.
• [23] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.