Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRE19ZS)

• DOT Name: MOB kinase activator 1B (MOB1B)
• Synonyms: Mob1 homolog 1A; Mob1A; Mob1B; Mps one binder kinase activator-like 1A
• Gene Name: MOB1B
• Related Disease: Neoplasm
• UniProt ID: MOB1B_HUMAN
• Pfam ID: PF03637
• Sequence:
  MSFLFGSRSSKTFKPKKNIPEGSHQYELLKHAEATLGSGNLRMAVMLPEGEDLNEWVAVN
  TVDFFNQINMLYGTITDFCTEESCPVMSAGPKYEYHWADGTNIKKPIKCSAPKYIDYLMT
  WVQDQLDDETLFPSKIGVPFPKNFMSVAKTILKRLFRVYAHIYHQHFDPVIQLQEEAHLN
  TSFKHFIFFVQEFNLIDRRELAPLQELIEKLTSKDR
• Function: Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38L.
• Tissue Specificity: Adrenal gland, bone marrow, brain, lung, placenta, prostate, salivary gland, skeletal muscle, testis, thymus, thyroid gland, uterus, colon with mucosa, fetal brain and fetal liver.
• KEGG Pathway:
  Hippo sig.ling pathway (hsa04390)
  Hippo sig.ling pathway - multiple species (hsa04392)
• Reactome Pathway: Signaling by Hippo (R-HSA-2028269)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of MOB kinase activator 1B (MOB1B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MOB kinase activator 1B (MOB1B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of MOB kinase activator 1B (MOB1B).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of MOB kinase activator 1B (MOB1B).	[5]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of MOB kinase activator 1B (MOB1B).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of MOB kinase activator 1B (MOB1B).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of MOB kinase activator 1B (MOB1B).	[10]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of MOB kinase activator 1B (MOB1B).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of MOB kinase activator 1B (MOB1B).	[6]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of MOB kinase activator 1B (MOB1B).	[9]

References

• [1] Cancer susceptibility and embryonic lethality in Mob1a/1b double-mutant mice.J Clin Invest. 2012 Dec;122(12):4505-18. doi: 10.1172/JCI63735. Epub 2012 Nov 12.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [10] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [11] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.