Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYB8ZMT)

• DOT Name: AP-4 complex accessory subunit RUSC1 (RUSC1)
• Synonyms: New molecule containing SH3 at the carboxy-terminus; Nesca; RUN and SH3 domain-containing protein 1
• Gene Name: RUSC1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: RUSC1_HUMAN
• PDB ID: 4GIW
• Pfam ID: PF02759 ; PF14604
• Sequence:
  MLSPQRALLCNLNHIHLQHVSLGLHLSRRPELQEGPLSTPPPPGDTGGKESRGPCSGTLV
  DANSNSPAVPCRCCQEHGPGLENRQDPSQEEEGAASPSDPGCSSSLSSCSDLSPDESPVS
  VYLRDLPGDEDAHPQPSIIPLEQGSPLASAGPGTCSPDSFCCSPDSCSGASSSPDPGLDS
  NCNALTTCQDVPSPGLEEEDERAEQDLPTSELLEADDGKIDAGKTEPSWKINPIWKIDTE
  KTKAEWKTTENNNTGWKNNGNVNSSWKSEPEKFDSGWKTNTRITDSGSKTDAGKIDGGWR
  SDVSEEPVPHRTITSFHELAQKRKRGPGLPLVPQAKKDRSDWLIVFSPDTELPPSGSPGG
  SSAPPREVTTFKELRSRSRAPAPPVPPRDPPVGWALVPPRPPPPPVPPRRKKNRPGLQPI
  AEGQSEEGRAVSPAAGEEAPAAKEPGAQAGLEVRSSWSFAGVPGAQRLWMAEAQSGTGQL
  QEQKKGLLIAVSVSVDKIISHFGAARNLVQKAQLGDSRLSPDVGHLVLTTLCPALHALVA
  DGLKPFRKDLITGQRRSSPWSVVEASVKPGSSTRSLGTLYSQVSRLAPLSSSRSRFHAFI
  LGLLNTKQLELWFSSLQEDAGLLSLLYLPTGFFSLARGGCPSLSTELLLLLQPLSVLTFH
  LDLLFEHHHHLPLGPPQAPAPPGPPPALQQTMQAMLHFGGRLAQSLRGTSKEAASDPSDS
  PNLPTPGSWWEQLTQASRVYASGGTEGFPLSRWAPGRHGTAAEEGAQERPLPTDEMAPGR
  GLWLGRLFGVPGGPAENENGALKSRRPSSWLPPTVSVLALVKRGAPPEMPSPQELEASAP
  RMVQTHRAVRALCDHTAARPDQLSFRRGEVLRVITTVDEDWLRCGRDGMEGLVPVGYTSL
  VL
• Function: Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network. Signaling adapter which plays a role in neuronal differentiation. Involved in regulation of NGF-dependent neurite outgrowth. May play a role in neuronal vesicular trafficking, specifically involving pre-synaptic membrane proteins. Seems to be involved in signaling pathways that are regulated by the prolonged activation of MAPK. Can regulate the polyubiquitination of IKBKG and thus may be involved in regulation of the NF-kappa-B pathway.
• Tissue Specificity: Predominantly expressed in brain.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	moderate	Biomarker	[1]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Disputed	Altered Expression	[2]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of AP-4 complex accessory subunit RUSC1 (RUSC1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of AP-4 complex accessory subunit RUSC1 (RUSC1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of AP-4 complex accessory subunit RUSC1 (RUSC1).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of AP-4 complex accessory subunit RUSC1 (RUSC1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of AP-4 complex accessory subunit RUSC1 (RUSC1).	[7]

References

• [1] Long noncoding RNA RUSC1ASN promotes cell proliferation and metastasis through Wnt/catenin signaling in human breast cancer.Mol Med Rep. 2019 Feb;19(2):861-868. doi: 10.3892/mmr.2018.9763. Epub 2018 Dec 14.
• [2] Long noncoding RNA RUSC1-AS-N indicates poor prognosis and increases cell viability in hepatocellular carcinoma.Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):388-396. doi: 10.26355/eurrev_201801_14185.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.