Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTALDF8Q)

• DOT Name: MAU2 chromatid cohesion factor homolog (MAU2)
• Synonyms: MAU-2; Cohesin loading complex subunit SCC4 homolog
• Gene Name: MAU2
• Related Disease:
  Advanced cancer
  Bladder cancer
  Colorectal carcinoma
  Fibrosarcoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  Hypercalcaemia
  Melanoma
  Neoplasm
  Oral cancer
  Oral cavity squamous cell carcinoma
  Pancreatic adenocarcinoma
  Prostate carcinoma
  Schizophrenia
  Squamous cell carcinoma
  Bipolar disorder
  Cornelia de Lange syndrome
  Methicillin-resistant staphylococci infection
• UniProt ID: SCC4_HUMAN
• Pfam ID: PF10345
• Sequence:
  MAAQAAAAAQAAAAQAAQAEAADSWYLALLGFAEHFRTSSPPKIRLCVHCLQAVFPFKPP
  QRIEARTHLQLGSVLYHHTKNSEQARSHLEKAWLISQQIPQFEDVKFEAASLLSELYCQE
  NSVDAAKPLLRKAIQISQQTPYWHCRLLFQLAQLHTLEKDLVSACDLLGVGAEYARVVGS
  EYTRALFLLSKGMLLLMERKLQEVHPLLTLCGQIVENWQGNPIQKESLRVFFLVLQVTHY
  LDAGQVKSVKPCLKQLQQCIQTISTLHDDEILPSNPADLFHWLPKEHMCVLVYLVTVMHS
  MQAGYLEKAQKYTDKALMQLEKLKMLDCSPILSSFQVILLEHIIMCRLVTGHKATALQEI
  SQVCQLCQQSPRLFSNHAAQLHTLLGLYCVSVNCMDNAEAQFTTALRLTNHQELWAFIVT
  NLASVYIREGNRHQEVLYSLLERINPDHSFPVSSHCLRAAAFYVRGLFSFFQGRYNEAKR
  FLRETLKMSNAEDLNRLTACSLVLLGHIFYVLGNHRESNNMVVPAMQLASKIPDMSVQLW
  SSALLRDLNKACGNAMDAHEAAQMHQNFSQQLLQDHIEACSLPEHNLITWTDGPPPVQFQ
  AQNGPNTSLASLL
• Function: Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with NIPBL/SCC2 which mediates the loading of the cohesin complex onto chromatin. Plays a role in sister chromatid cohesion and normal progression through prometaphase.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway: Cohesin Loading onto Chromatin (R-HSA-2470946)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[3]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[2]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[4]
Melanoma	DIS1RRCY	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Oral cancer	DISLD42D	Strong	Altered Expression	[7]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Biomarker	[8]
Pancreatic adenocarcinoma	DISKHX7S	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[10]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[11]
Bipolar disorder	DISAM7J2	moderate	Genetic Variation	[12]
Cornelia de Lange syndrome	DISEQSXO	moderate	Genetic Variation	[13]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[14]

5 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 MAU2 chromatid cohesion factor homolog (MAU2).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of MAU2 chromatid cohesion factor homolog (MAU2).	[16]
Selenium	DM25CGV	Approved	Selenium decreases the expression of MAU2 chromatid cohesion factor homolog (MAU2).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of MAU2 chromatid cohesion factor homolog (MAU2).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of MAU2 chromatid cohesion factor homolog (MAU2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of MAU2 chromatid cohesion factor homolog (MAU2).	[18]

References

• [1] Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF-/STAT3 signalling axis in oral squamous cell carcinoma models.IUBMB Life. 2019 Oct;71(10):1595-1610. doi: 10.1002/iub.2104. Epub 2019 Jun 28.
• [2] Replication of an adenoviral vector controlled by the human telomerase reverse transcriptase promoter causes tumor-selective tumor lysis.Cancer Res. 2003 Nov 15;63(22):7936-41.
• [3] Allele-specific imbalance mapping at human orthologs of mouse susceptibility to colon cancer (Scc) loci.Int J Cancer. 2015 Nov 15;137(10):2323-31. doi: 10.1002/ijc.29599. Epub 2015 May 29.
• [4] Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation.Biochem Biophys Res Commun. 2000 Mar 16;269(2):532-6. doi: 10.1006/bbrc.2000.2314.
• [5] Histamine inhibits the production of interferon-induced protein of 10 kDa in human squamous cell carcinoma and melanoma.J Invest Dermatol. 2002 Dec;119(6):1411-9. doi: 10.1046/j.1523-1747.2002.19627.x.
• [6] Platycodin D, a triterpenoid saponin from Platycodon grandiflorum, suppresses the growth and invasion of human oral squamous cell carcinoma cells via the NF-B pathway.J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21934. Epub 2017 May 26.
• [7] Promoter methylation of MGMT in oral carcinoma: A population-based study and meta-analysis.Arch Oral Biol. 2017 Aug;80:197-208. doi: 10.1016/j.archoralbio.2017.04.006. Epub 2017 Apr 23.
• [8] NVP-BEZ235 Attenuated Cell Proliferation and Migration in the Squamous Cell Carcinoma of Oral Cavities and p70S6K Inhibition Mimics its Effect.Int J Mol Sci. 2018 Nov 10;19(11):3546. doi: 10.3390/ijms19113546.
• [9] Survival and prognostic factors in patients with pancreatic squamous cell carcinoma.Eur J Surg Oncol. 2019 Sep;45(9):1700-1705. doi: 10.1016/j.ejso.2019.05.011. Epub 2019 May 15.
• [10] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [11] Management of Non-melanoma Skin Cancer in Transplant Recipients.Clin Oncol (R Coll Radiol). 2019 Nov;31(11):779-788. doi: 10.1016/j.clon.2019.08.005. Epub 2019 Sep 26.
• [12] Genome-wide association study reveals two new risk loci for bipolar disorder.Nat Commun. 2014 Mar 11;5:3339. doi: 10.1038/ncomms4339.
• [13] Isolated NIBPL missense mutations that cause Cornelia de Lange syndrome alter MAU2 interaction.Eur J Hum Genet. 2012 Mar;20(3):271-6. doi: 10.1038/ejhg.2011.175. Epub 2011 Sep 21.
• [14] Differences between methicillin-resistant Staphylococcus aureus bacteremic isolates harboring type IV and type V staphylococcal cassette chromosome mec genes based on prior patient healthcare exposure.Eur J Clin Microbiol Infect Dis. 2010 Dec;29(12):1539-46. doi: 10.1007/s10096-010-1038-4. Epub 2010 Sep 18.
• [15] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [16] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [17] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [18] 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.
• [19] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.