Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL6QEJT)

• DOT Name: F-BAR domain only protein 2 (FCHO2)
• Gene Name: FCHO2
• UniProt ID: FCHO2_HUMAN
• PDB ID: 2V0O; 7OG1; 7OHO; 7OHZ; 7OI5; 7OIQ; 7OIT
• Pfam ID: PF00611 ; PF10291
• Sequence:
  MVMAYFVENFWGEKNSGFDVLYHNMKHGQISTKELADFVRERATIEEAYSRSMTKLAKSA
  SNYSQLGTFAPVWDVFKTSTEKLANCHLDLVRKLQELIKEVQKYGEEQVKSHKKTKEEVA
  GTLEAVQTIQSITQALQKSKENYNAKCVEQERLKKEGATQREIEKAAVKSKKATDTYKLY
  VEKYALAKADFEQKMTETAQKFQDIEETHLIHIKEIIGSLSNAIKEIHLQIGQVHEEFIN
  NMANTTVESLIQKFAESKGTGKERPGLIEFEECDTASAVEGIKPRKRKTFALPGIIKKEK
  DAESVECPDADSLNIPDVDEEGYSIKPETNQNDTKENHFYSSSDSDSEDEEPKKYRIEIK
  PMHPNNSHHTMASLDELKVSIGNITLSPAISRHSPVQMNRNLSNEELTKSKPSAPPNEKG
  TSDLLAWDPLFGPSLDSSSSSSLTSSSSARPTTPLSVGTIVPPPRPASRPKLTSGKLSGI
  NEIPRPFSPPVTSNTSPPPAAPLARAESSSSISSSASLSAANTPTVGVSRGPSPVSLGNQ
  DTLPVAVALTESVNAYFKGADPTKCIVKITGDMTMSFPSGIIKVFTSNPTPAVLCFRVKN
  ISRLEQILPNAQLVFSDPSQCDSNTKDFWMNMQAVTVYLKKLSEQNPAASYYNVDVLKYQ
  VSSNGIQSTPLNLATYWKCSASTTDLRVDYKYNPEAMVAPSVLSNIQVVVPVDGGVTNMQ
  SLPPAIWNAEQMKAFWKLSSISEKSENGGSGSLRAKFDLSEGPSKPTTLAVQFLSEGSTL
  SGVDFELVGTGYRLSLIKKRFATGRYLADC
• Function: Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2-dependent endocytosis of the transferrin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor.
• Reactome Pathway:
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)

Molecular Interaction Atlas (MIA) of This DOT

7 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 F-BAR domain only protein 2 (FCHO2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of F-BAR domain only protein 2 (FCHO2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of F-BAR domain only protein 2 (FCHO2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of F-BAR domain only protein 2 (FCHO2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of F-BAR domain only protein 2 (FCHO2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of F-BAR domain only protein 2 (FCHO2).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of F-BAR domain only protein 2 (FCHO2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of F-BAR domain only protein 2 (FCHO2).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of F-BAR domain only protein 2 (FCHO2).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of F-BAR domain only protein 2 (FCHO2).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.