Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDTPGW0)

• DOT Name: BRD4-interacting chromatin-remodeling complex-associated protein (BICRA)
• Synonyms: Glioma tumor suppressor candidate region gene 1 protein
• Gene Name: BICRA
• Related Disease:
  Brain neoplasm
  Lung cancer
  Lung carcinoma
  Advanced cancer
  Colorectal carcinoma
  Immunodeficiency 31B
  Major depressive disorder
  Metastatic prostate carcinoma
  Mood disorder
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Coffin-Siris syndrome 12
  Meningioma
  Glioma
• UniProt ID: BICRA_HUMAN
• Pfam ID: PF15249
• Sequence:
  MDDEDGRCLLDVICDPQALNDFLHGSEKLDSDDLLDNPGEAQSAFYEGPGLHVQEASGNH
  LNPEPNQPAPSVDLDFLEDDILGSPATGGGGGGSGGADQPCDILQQSLQEANITEQTLEA
  EAELDLGPFQLPTLQPADGGAGPTGAGGAAAVAAGPQALFPGSTDLLGLQGPPTVLTHQA
  LVPPQDVVNKALSVQPFLQPVGLGNVTLQPIPGLQGLPNGSPGGATAATLGLAPIQVVGQ
  PVMALNTPTSQLLAKQVPVSGYLASAAGPSEPVTLASAGVSPQGAGLVIQKNLSAAVATT
  LNGNSVFGGAGAASAPTGTPSGQPLAVAPGLGSSPLVPAPNVILHRTPTPIQPKPAGVLP
  PKLYQLTPKPFAPAGATLTIQGEPGALPQQPKAPQNLTFMAAGKAGQNVVLSGFPAPALQ
  ANVFKQPPATTTGAAPPQPPGALSKPMSVHLLNQGSSIVIPAQHMLPGQNQFLLPGAPAV
  QLPQQLSALPANVGGQILAAAAPHTGGQLIANPILTNQNLAGPLSLGPVLAPHSGAHSAH
  ILSAAPIQVGQPALFQMPVSLAAGSLPTQSQPAPAGPAATTVLQGVTLPPSAVAMLNTPD
  GLVQPATPAAATGEAAPVLTVQPAPQAPPAVSTPLPLGLQQPQAQQPPQAPTPQAAAPPQ
  ATTPQPSPGLASSPEKIVLGQPPSATPTAILTQDSLQMFLPQERSQQPLSAEGPHLSVPA
  SVIVSAPPPAQDPAPATPVAKGAGLGPQAPDSQASPAPAPQIPAAAPLKGPGPSSSPSLP
  HQAPLGDSPHLPSPHPTRPPSRPPSRPQSVSRPPSEPPLHPCPPPQAPPTLPGIFVIQNQ
  LGVPPPASNPAPTAPGPPQPPLRPQSQPPEGPLPPAPHLPPSSTSSAVASSSETSSRLPA
  PTPSDFQLQFPPSQGPHKSPTPPPTLHLVPEPAAPPPPPPRTFQMVTTPFPALPQPKALL
  ERFHQVPSGIILQNKAGGAPAAPQTSTSLGPLTSPAASVLVSGQAPSGTPTAPSHAPAPA
  PMAATGLPPLLPAENKAFASNLPTLNVAKAASSGPGKPSGLQYESKLSGLKKPPTLQPSK
  EACFLEHLHKHQGSVLHPDYKTAFPSFEDALHRLLPYHVYQGALPSPSDYHKVDEEFETV
  STQLLKRTQAMLNKYRLLLLEESRRVSPSAEMVMIDRMFIQEEKTTLALDKQLAKEKPDE
  YVSSSRSLGLPIAASSEGHRLPGHGPLSSSAPGASTQPPPHLPTKLVIRHGGAGGSPSVT
  WARASSSLSSSSSSSSAASSLDADEDGPMPSRNRPPIKTYEARSRIGLKLKIKQEAGLSK
  VVHNTALDPVHQPPPPPATLKVAEPPPRPPPPPPPTGQMNGTVDHPPPAAPERKPLGTAP
  HCPRLPLRKTYRENVGGPGAPEGTPAGRARGGSPAPLPAKVDEATSGLIRELAAVEDELY
  QRMLKGPPPEPAASAAQGTGDPDWEAPGLPPAKRRKSESPDVDQASFSSDSPQDDTLTEH
  LQSAIDSILNLQQAPGRTPAPSYPHAASAGTPASPPPLHRPEAYPPSSHNGGLGARTLTR
• Function: Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. May play a role in BRD4-mediated gene transcription.
• Tissue Specificity: Expressed at moderate levels in heart, brain, placenta, skeletal muscle, and pancreas, and at lower levels in lung, liver and kidney.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Brain neoplasm	DISY3EKS	Definitive	Genetic Variation	[1]
Lung cancer	DISCM4YA	Definitive	Genetic Variation	[1]
Lung carcinoma	DISTR26C	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Immunodeficiency 31B	DISY5F50	Strong	Genetic Variation	[4]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[5]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[6]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Coffin-Siris syndrome 12	DISMEAB6	Moderate	Autosomal dominant	[7]
Meningioma	DISPT4TG	moderate	Genetic Variation	[8]
Glioma	DIS5RPEH	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[11]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[13]
Marinol	DM70IK5	Approved	Marinol increases the expression of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of BRD4-interacting chromatin-remodeling complex-associated protein (BICRA).	[15]

References

• [1] GLTSCR1, ATM, PPP1R13L and CD3EAP Genetic Variants and Lung Cancer Risk in a Chinese Population.Curr Med Sci. 2018 Aug;38(4):734-740. doi: 10.1007/s11596-018-1938-6. Epub 2018 Aug 20.
• [2] High levels of glioma tumor suppressor candidate region gene 1 predicts a poor prognosis for prostate cancer.Oncol Lett. 2018 Nov;16(5):6749-6755. doi: 10.3892/ol.2018.9490. Epub 2018 Sep 24.
• [3] GLTSCR1 Negatively Regulates BRD4-Dependent Transcription Elongation and Inhibits CRC Metastasis.Adv Sci (Weinh). 2019 Oct 16;6(23):1901114. doi: 10.1002/advs.201901114. eCollection 2019 Dec.
• [4] Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.PLoS One. 2011;6(12):e28632. doi: 10.1371/journal.pone.0028632. Epub 2011 Dec 12.
• [5] Analysis of 23andMe antidepressant efficacy survey data: implication of circadian rhythm and neuroplasticity in bupropion response.Transl Psychiatry. 2016 Sep 13;6(9):e889. doi: 10.1038/tp.2016.171.
• [6] Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1-like form SWI/SNF chromatin remodeling subcomplexes.J Biol Chem. 2018 Mar 16;293(11):3892-3903. doi: 10.1074/jbc.RA117.001065. Epub 2018 Jan 26.
• [7] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [8] DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma.Neuro Oncol. 2010 Jan;12(1):37-48. doi: 10.1093/neuonc/nop012. Epub 2009 Dec 10.
• [9] ERCC1 and ERCC2 polymorphisms and adult glioma.Neuro Oncol. 2005 Oct;7(4):495-507. doi: 10.1215/S1152851705000037.
• [10] 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.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [13] 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.
• [14] 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.
• [15] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [16] 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.
• [17] 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.