Details of Drug Off-Target (DOT)

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

• DOT Name: MOB-like protein phocein (MOB4)
• Synonyms: 2C4D; Class II mMOB1; Mob1 homolog 3; Mob3; Mps one binder kinase activator-like 3; Preimplantation protein 3
• Gene Name: MOB4
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Intrahepatic cholangiocarcinoma
  Neoplasm
  Obesity
  Renal fibrosis
  Schizophrenia
  Pancreatic cancer
  Colorectal carcinoma
• UniProt ID: PHOCN_HUMAN
• PDB ID: 5YF4; 7K36
• Pfam ID: PF03637
• Sequence:
  MVMAEGTAVLRRNRPGTKAQDFYNWPDESFDEMDSTLAVQQYIQQNIRADCSNIDKILEP
  PEGQDEGVWKYEHLRQFCLELNGLAVKLQSECHPDTCTQMTATEQWIFLCAAHKTPKECP
  AIDYTRHTLDGAACLLNSNKYFPSRVSIKESSVAKLGSVCRRIYRIFSHAYFHHRQIFDE
  YENETFLCHRFTKFVMKYNLMSKDNLIVPILEEEVQNSVSGESEA
• Function: May play a role in membrane trafficking, specifically in membrane budding reactions.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Altered Expression	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Lung neoplasm	DISVARNB	Definitive	Altered Expression	[1]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[1]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Renal fibrosis	DISMHI3I	Strong	Altered Expression	[5]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[6]
Pancreatic cancer	DISJC981	moderate	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[8]

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 MOB-like protein phocein (MOB4).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of MOB-like protein phocein (MOB4).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MOB-like protein phocein (MOB4).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of MOB-like protein phocein (MOB4).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of MOB-like protein phocein (MOB4).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of MOB-like protein phocein (MOB4).	[14]

References

• [1] Human MOB1 expression in non-small-cell lung cancer.Clin Lung Cancer. 2007 Jan;8(4):273-6. doi: 10.3816/CLC.2007.n.006.
• [2] Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma.Oncology. 2017;93(1):67-74. doi: 10.1159/000463390. Epub 2017 Apr 28.
• [3] Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.Nat Commun. 2017 Sep 25;8(1):695. doi: 10.1038/s41467-017-00795-y.
• [4] Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM.Genomics. 1997 May 1;41(3):332-44. doi: 10.1006/geno.1997.4672.
• [5] Kindlin-2 Inhibits the Hippo Signaling Pathway by Promoting Degradation of MOB1.Cell Rep. 2019 Dec 10;29(11):3664-3677.e5. doi: 10.1016/j.celrep.2019.11.035.
• [6] Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
• [7] The MST4-MOB4 complex disrupts the MST1-MOB1 complex in the Hippo-YAP pathway and plays a pro-oncogenic role in pancreatic cancer.J Biol Chem. 2018 Sep 14;293(37):14455-14469. doi: 10.1074/jbc.RA118.003279. Epub 2018 Aug 2.
• [8] Mob-1, a Ras target gene, is overexpressed in colorectal cancer.Oncogene. 1997 Apr 3;14(13):1607-10. doi: 10.1038/sj.onc.1200957.
• [9] 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.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.