Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1G25B)

• DOT Name: Cytohesin-2 (CYTH2)
• Synonyms: ARF exchange factor; ARF nucleotide-binding site opener; Protein ARNO; PH, SEC7 and coiled-coil domain-containing protein 2
• Gene Name: CYTH2
• UniProt ID: CYH2_HUMAN
• PDB ID: 1PBV; 1R8M; 1R8Q; 1R8S; 1S9D; 4JMI; 4JMO; 4JWL; 4JXH; 4L5M; 4Z21
• Pfam ID: PF00169 ; PF01369
• Sequence:
  MEDGVYEPPDLTPEERMELENIRRRKQELLVEIQRLREELSEAMSEVEGLEANEGSKTLQ
  RNRKMAMGRKKFNMDPKKGIQFLVENELLQNTPEEIARFLYKGEGLNKTAIGDYLGEREE
  LNLAVLHAFVDLHEFTDLNLVQALRQFLWSFRLPGEAQKIDRMMEAFAQRYCLCNPGVFQ
  STDTCYVLSFAVIMLNTSLHNPNVRDKPGLERFVAMNRGINEGGDLPEELLRNLYDSIRN
  EPFKIPEDDGNDLTHTFFNPDREGWLLKLGGGRVKTWKRRWFILTDNCLYYFEYTTDKEP
  RGIIPLENLSIREVDDPRKPNCFELYIPNNKGQLIKACKTEADGRVVEGNHMVYRISAPT
  QEEKDEWIKSIQAAVSVDPFYEMLAARKKRISVKKKQEQP
• Function: Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Activates ARF factors through replacement of GDP with GTP. The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane. Involved in neurite growth.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Phospholipase D sig.ling pathway (hsa04072)
  Endocytosis (hsa04144)
  Pathogenic Escherichia coli infection (hsa05130)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
• Reactome Pathway: Intra-Golgi traffic (R-HSA-6811438)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Cytohesin-2 (CYTH2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cytohesin-2 (CYTH2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytohesin-2 (CYTH2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytohesin-2 (CYTH2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytohesin-2 (CYTH2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytohesin-2 (CYTH2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cytohesin-2 (CYTH2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytohesin-2 (CYTH2).	[8]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cytohesin-2 (CYTH2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytohesin-2 (CYTH2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cytohesin-2 (CYTH2).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cytohesin-2 (CYTH2).	[12]

References

• [1] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [2] 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.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.