Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWKP0JC)

• DOT Name: Heat shock factor 2-binding protein (HSF2BP)
• Gene Name: HSF2BP
• Related Disease:
  Cardiovascular disease
  Eosinophilic esophagitis
  Chronic obstructive pulmonary disease
  Premature ovarian failure 19
• UniProt ID: HSF2B_HUMAN
• PDB ID: 7BDX; 7LDG; 8A50; 8A51
• Sequence:
  MGEAGAAEEACRHMGTKEEFVKVRKKDLERLTTEVMQIRDFLPRILNGEVLESFQKLKIV
  EKNLERKEQELEQLKMDCEHFKARLETVQADNIREKKEKLALRQQLNEAKQQLLQQAEYC
  TEMGAAACTLLWGVSSSEEVVKAILGGDKALKFFSITGQTMESFVKSLDGDVQELDSDES
  QFVFALAGIVTNVAAIACGREFLVNSSRVLLDTILQLLGDLKPGQCTKLKVLMLMSLYNV
  SINLKGLKYISESPGFIPLLWWLLSDPDAEVCLHVLRLVQSVVLEPEVFSKSASEFRSSL
  PLQRILAMSKSRNPRLQTAAQELLEDLRTLEHNV
• Function: Meiotic recombination factor component of recombination bridges involved in meiotic double-strand break repair. Modulates the localization of recombinases DMC1:RAD51 to meiotic double-strand break (DSB) sites through the interaction with BRCA2 and its recruitment during meiotic recombination. Indispensable for the DSB repair, homologous synapsis, and crossover formation that are needed for progression past metaphase I, is essential for spermatogenesis and male fertility. Required for proper recombinase recruitment in female meiosis. Inhibits BNC1 transcriptional activity during spermatogenesis, probably by sequestering it in the cytoplasm. May be involved in modulating HSF2 activation in testis.
• Tissue Specificity: Testis specific. Overexpressed in some tumors .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Eosinophilic esophagitis	DISR8WSB	Strong	Genetic Variation	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[3]
Premature ovarian failure 19	DIS60A1W	Limited	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Heat shock factor 2-binding protein (HSF2BP).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heat shock factor 2-binding protein (HSF2BP).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Heat shock factor 2-binding protein (HSF2BP).	[7]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Heat shock factor 2-binding protein (HSF2BP).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Heat shock factor 2-binding protein (HSF2BP).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Heat shock factor 2-binding protein (HSF2BP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Heat shock factor 2-binding protein (HSF2BP).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Heat shock factor 2-binding protein (HSF2BP).	[12]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.Nat Genet. 2014 Aug;46(8):895-900. doi: 10.1038/ng.3033. Epub 2014 Jul 13.
• [3] Genetic overlap of chronic obstructive pulmonary disease and cardiovascular disease-related traits: a large-scale genome-wide cross-trait analysis.Respir Res. 2019 Apr 2;20(1):64. doi: 10.1186/s12931-019-1036-8.
• [4] A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. Elife. 2020 Aug 26;9:e56996. doi: 10.7554/eLife.56996.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [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] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.