Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA3NG8M)

• DOT Name: FYN-binding protein 2 (FYB2)
• Synonyms: Activation-dependent, raft-recruited ADAP-like phosphoprotein
• Gene Name: FYB2
• UniProt ID: FYB2_HUMAN
• Pfam ID: PF14603
• Sequence:
  MEGEGVRNFKELRAKFQNLDAPPLPGPIKFPAGVSPKGDIGGTQSTQILANGKPLSSNHK
  QRTPYCSSSESQPLQPQKIKLAQKSEIPKCSNSPGPLGKSTVCSATSSQKASLLLEVTQS
  NVEIITKEKVMVANSFRNKLWNWEKVSSQKSEMSSALLLANYGSKAIHLEGQKGMGLTPE
  EPRKKLETKGAQTLPSQKHVVAPKILHNVSEDPSFVISQHIRKSWENPPPERSPASSPCQ
  PIYECELASQAPEKQPDVRHHHLPKTKPLPSIDSLGPPPPKPSRPPIVNLQAFQRQPAAV
  PKTQGEVTVEEGSLSPERLFNAEFEEPHNYEATISYLRHSGNSINLCTAKEIADPTYEVG
  IEELQKPGKNFPYPEPSAKHEDKKMKEKQPCELKPKNTEKEPYSNHVFKVDACEGTPEKI
  QMTNVHTGRRNMLAGKQEAMIDIIQTNPCPEGPKLARHSQGHCGHLEVLESTKETPDLGV
  SKTSSISEEIYDDVEYSRKEVPKLNYSSSLASSSEENRELYEDVYKTKNNYPKIDLDGKE
  ALKRLQQFFKKEKDRFKIKKTKSKENLSAFSILLPDLELKSQEVIIYDDVDLSEKESKDE
  DKLKMWKPKFLTPKEKKEKNGAEESESFSPRNFFKTKKQNLEKNRMKREEKLFRERFKYD
  KEIIVINTAVACSNNSRNGIFDLPISPGEELEVIDTTEQNLVICRNSKGKYGYVLIEHLD
  FKHQSWSP
• Function: Adapter protein that plays a role in T-cell receptor (TCR)-mediated activation of signaling pathways. Required for T-cell activation and integrin-mediated T-cell adhesion in response to TCR stimulation.
• Tissue Specificity: Expressed in T-cells (at protein level). Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

9 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 FYN-binding protein 2 (FYB2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of FYN-binding protein 2 (FYB2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of FYN-binding protein 2 (FYB2).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of FYN-binding protein 2 (FYB2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of FYN-binding protein 2 (FYB2).	[5]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of FYN-binding protein 2 (FYB2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of FYN-binding protein 2 (FYB2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of FYN-binding protein 2 (FYB2).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of FYN-binding protein 2 (FYB2).	[10]

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 increases the methylation of FYN-binding protein 2 (FYB2).	[9]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [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] 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.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.