Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1S0CDX)

• DOT Name: FHF complex subunit HOOK-interacting protein 2B (FHIP2B)
• Synonyms: FHIP2B; Retinoic acid-induced protein 16
• Gene Name: FHIP2B
• UniProt ID: FHI2B_HUMAN
• Pfam ID: PF19314 ; PF19311 ; PF10257
• Sequence:
  MLSRLGALLQEAVGAREPSIDLLQAFVEHWKGITHYYIESTDESTPAKKTDIPWRLKQML
  DILVYEEQQQAAAGEAGPCLEYLLQHKILETLCTLGKAEYPPGMRQQVFQFFSKVLAQVQ
  HPLLHYLSVHRPVQKLLRLGGTASGSVTEKEEVQFTTVLCSKIQQDPELLAYILEGKKIV
  GRKKACGEPTALPKDTTSHGDKDCSHDGAPARPQLDGESCGAQALNSHMPAETEELDGGT
  TESNLITSLLGLCQSKKSRVALKAQENLLLLVSMASPAAATYLVQSSACCPAIVRHLCQL
  YRSMPVFLDPADIATLEGISWRLPSAPSDEASFPGKEALAAFLGWFDYCDHLITEAHTVV
  ADALAKAVAENFFVETLQPQLLHVSEQSILTSTALLTAMLRQLRSPALLREAVAFLLGTD
  RQPEAPGDNPHTLYAHLIGHCDHLSDEISITTLRLFEELLQKPHEGIIHSLVLRNLEGRP
  YVAWGSPEPESYEDTLDLEEDPYFTDSFLDSGFQTPAKPRLAPATSYDGKTAVTEIVNSF
  LCLVPEEAKTSAFLEETGYDTYVHDAYGLFQECSSRVASWGWPLTPTPLDPHEPERPFFE
  GHFLRVLFDRMSRILDQPYSLNLQVTSVLSRLALFPHPHIHEYLLDPYISLAPGCRSLFS
  VLVRVIGDLMQRIQRVPQFPGKLLLVRKQLTGQAPGEQLDHQTLLQGVVVLEEFCKELAA
  IAFVKFPPHDPRQNVSPAPEGQV
• Function: Able to activate MAPK/ERK and TGFB signaling pathways. May regulate the activity of genes involved in intestinal barrier function and immunoprotective inflammation. May play a role in cell proliferation.
• Tissue Specificity: Expressed in liver.

Molecular Interaction Atlas (MIA) of This DOT

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 FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[6]

2 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 FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of FHF complex subunit HOOK-interacting protein 2B (FHIP2B).	[7]

References

• [1] 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.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] 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.