Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMBE0NS)

• DOT Name: MOB kinase activator 2 (MOB2)
• Synonyms: HCCA2; Mob2 homolog; Mps one binder kinase activator-like 2
• Gene Name: MOB2
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Familial prostate carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Periventricular nodular heterotopia
  Prostate cancer, hereditary, 1
  Prostate carcinoma
  Non-insulin dependent diabetes
• UniProt ID: MOB2_HUMAN
• Pfam ID: PF03637
• Sequence:
  MDWLMGKSKAKPNGKKPAAEERKAYLEPEHTKARITDFQFKELVVLPREIDLNEWLASNT
  TTFFHHINLQYSTISEFCTGETCQTMAVCNTQYYWYDERGKKVKCTAPQYVDFVMSSVQK
  LVTDEDVFPTKYGREFPSSFESLVRKICRHLFHVLAHIYWAHFKETLALELHGHLNTLYV
  HFILFAREFNLLDPKETAIMDDLTEVLCSGAGGVHSGGSGDGAGSGGPGAQNHVKER
• Function: Stimulates the autophosphorylation and kinase activity of STK38 and STK38L.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[1]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Periventricular nodular heterotopia	DISU3ZRI	Strong	Genetic Variation	[3]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[4]

5 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 MOB kinase activator 2 (MOB2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of MOB kinase activator 2 (MOB2).	[6]
Aspirin	DM672AH	Approved	Aspirin increases the expression of MOB kinase activator 2 (MOB2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of MOB kinase activator 2 (MOB2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of MOB kinase activator 2 (MOB2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of MOB kinase activator 2 (MOB2).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant affects the methylation of MOB kinase activator 2 (MOB2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of MOB kinase activator 2 (MOB2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of MOB kinase activator 2 (MOB2).	[8]

References

• [1] Identification and characterization of a novel human hepatocellular carcinoma-associated gene.Br J Cancer. 2001 Oct 19;85(8):1162-7. doi: 10.1054/bjoc.2001.2059.
• [2] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [3] Mob2 Insufficiency Disrupts Neuronal Migration in the Developing Cortex.Front Cell Neurosci. 2018 Mar 12;12:57. doi: 10.3389/fncel.2018.00057. eCollection 2018.
• [4] Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians.Diabetes. 2013 Aug;62(8):2984-91. doi: 10.2337/db12-1767. Epub 2013 Apr 29.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.