Details of Drug Off-Target (DOT)

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

• DOT Name: BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1)
• Synonyms: Deleted in bladder cancer protein 1
• Gene Name: BRINP1
• Related Disease:
  Urinary bladder cancer
  Urinary bladder neoplasm
  Acute lymphocytic leukaemia
  Aerodigestive tract cancer
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  Attention deficit hyperactivity disorder
  Autism spectrum disorder
  Bladder cancer
  Carcinoma
  Colorectal carcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Mental disorder
  Neuroblastoma
  Parkinson disease
  Sarcoma
  Schizophrenia
  Soft tissue sarcoma
  Tarsal-carpal coalition syndrome
  Transitional cell carcinoma
  Urothelial carcinoma
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Neurodevelopmental disorder
  Squamous cell carcinoma
  Stomach cancer
  Cervical cancer
  Cervical carcinoma
  Childhood kidney Wilms tumor
  Non-small-cell lung cancer
  Wilms tumor
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Myasthenia gravis
  Non-insulin dependent diabetes
• UniProt ID: BRNP1_HUMAN
• Pfam ID: PF19052 ; PF01823
• Sequence:
  MNWRFVELLYFLFIWGRISVQPSHQEPAGTDQHVSKEFDWLISDRGPFHHSRSYLSFVER
  HRQGFTTRYKIYREFARWKVRNTAIERRDLVRHPVPLMPEFQRSIRLLGRRPTTQQFIDT
  IIKKYGTHLLISATLGGEEALTMYMDKSRLDRKSGNATQSVEALHQLASSYFVDRDGTMR
  RLHEIQISTGAIKVTETRTGPLGCNSYDNLDSVSSVLLQSTESKLHLQGLQIIFPQYLQE
  KFVQSALSYIMCNGEGEYLCQNSQCRCQCAEEFPQCNCPITDIQIMEYTLANMAKSWAEA
  YKDLENSDEFKSFMKRLPSNHFLTIGSIHQHWGNDWDLQNRYKLLQSATEAQRQKIQRTA
  RKLFGLSVRCRHNPNHQLPRERTIQQWLARVQSLLYCNENGFWGTFLESQRSCVCHGSTT
  LCQRPIPCVIGGNNSCAMCSLANISLCGSCNKGYKLYRGRCEPQNVDSERSEQFISFETD
  LDFQDLELKYLLQKMDSRLYVHTTFISNEIRLDTFFDPRWRKRMSLTLKSNKNRMDFIHM
  VIGMSMRICQMRNSSLDPMFFVYVNPFSGSHSEGWNMPFGEFGYPRWEKIRLQNSQCYNW
  TLLLGNRWKTFFETVHIYLRSRTRLPTLLRNETGQGPVDLSDPSKRQFYIKISDVQVFGY
  SLRFNADLLRSAVQQVNQSYTQGGQFYSSSSVMLLLLDIRDRINRLAPPVAPGKPQLDLF
  SCMLKHRLKLTNSEIIRVNHALDLYNTEILKQSDQMTAKLC
• Function: Plays a role in neurogenesis and brain development. May suppress cell cycle progression in postmitotic neurons by inhibiting G1/S transition.
• Tissue Specificity: Highly expressed in brain. Weakly expressed in heart, lung, skeletal muscle, kidney, thymus, prostate, testis and small intestine.

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Urinary bladder cancer	DISDV4T7	Definitive	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[2]
Aerodigestive tract cancer	DIS3AOQ7	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[4]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Altered Expression	[6]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[9]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[11]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Mental disorder	DIS3J5R8	Strong	Biomarker	[6]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[12]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[13]
Sarcoma	DISZDG3U	Strong	Altered Expression	[14]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[6]
Soft tissue sarcoma	DISSN8XB	Strong	Altered Expression	[14]
Tarsal-carpal coalition syndrome	DISY90L2	Strong	Genetic Variation	[15]
Transitional cell carcinoma	DISWVVDR	Strong	Genetic Variation	[16]
Urothelial carcinoma	DISRTNTN	Strong	Genetic Variation	[16]
Colon cancer	DISVC52G	moderate	Biomarker	[8]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[17]
Neurodevelopmental disorder	DIS372XH	moderate	Genetic Variation	[18]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[7]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[10]
Cervical cancer	DISFSHPF	Disputed	Biomarker	[19]
Cervical carcinoma	DIST4S00	Disputed	Biomarker	[19]
Childhood kidney Wilms tumor	DIS0NMK3	Disputed	Genetic Variation	[19]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Biomarker	[20]
Wilms tumor	DISB6T16	Disputed	Genetic Variation	[19]
Breast cancer	DIS7DPX1	Limited	Biomarker	[21]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[21]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[22]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[26]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[28]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[29]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[30]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[28]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[31]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[32]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[34]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[37]

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 decreases the methylation of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of BMP/retinoic acid-inducible neural-specific protein 1 (BRINP1).	[36]

References

• [1] Detection of bladder cancer using novel DNA methylation biomarkers in urine sediments.Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1483-91. doi: 10.1158/1055-9965.EPI-11-0067. Epub 2011 May 17.
• [2] Downregulation of DBC1 expression in acute lymphoblastic leukaemia is mediated by aberrant methylation of its promoter.Br J Haematol. 2006 Jul;134(2):137-44. doi: 10.1111/j.1365-2141.2006.06131.x.
• [3] Deleted in Breast Cancer 1 as a Novel Prognostic Biomarker for Digestive System Cancers: A Meta-Analysis.J Cancer. 2019 Mar 3;10(7):1633-1641. doi: 10.7150/jca.26935. eCollection 2019.
• [4] Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.Diabetes. 2015 Jan;64(1):12-22. doi: 10.2337/db14-0192. Epub 2014 Jul 22.
• [5] Low expression but infrequent genomic loss of the putative tumour suppressor DBCCR1 in astrocytoma.Oncol Rep. 2005 Feb;13(2):335-40.
• [6] Decreased parvalbumin and somatostatin neurons in medial prefrontal cortex in BRINP1-KO mice.Neurosci Lett. 2018 Sep 14;683:82-88. doi: 10.1016/j.neulet.2018.06.050. Epub 2018 Jun 28.
• [7] The Expression of SIRT1 and DBC1 in Laryngeal and Hypopharyngeal Carcinomas.PLoS One. 2013 Jun 21;8(6):e66975. doi: 10.1371/journal.pone.0066975. Print 2013.
• [8] DBC1 regulates Wnt/-catenin-mediated expression of MACC1, a key regulator of cancer progression, in colon cancer.Cell Death Dis. 2018 Aug 6;9(8):831. doi: 10.1038/s41419-018-0899-9.
• [9] The overexpression of DBC1 in esophageal squamous cell carcinoma correlates with poor prognosis.Histol Histopathol. 2012 Jan;27(1):49-58. doi: 10.14670/HH-27.49.
• [10] High-definition CpG methylation of novel genes in gastric carcinogenesis identified by next-generation sequencing.Mod Pathol. 2016 Feb;29(2):182-93. doi: 10.1038/modpathol.2015.144. Epub 2016 Jan 15.
• [11] Identification of DBCCR1 as a suppressor in the development of lung cancer that is associated with increased DNA methyltransferase 1.Oncotarget. 2017 May 16;8(20):32821-32832. doi: 10.18632/oncotarget.15826.
• [12] CCAR2/DBC1 and Hsp60 Positively Regulate Expression of Survivin in Neuroblastoma Cells.Int J Mol Sci. 2019 Jan 1;20(1):131. doi: 10.3390/ijms20010131.
• [13] Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease.Ann Hum Genet. 2010 Mar;74(2):97-109. doi: 10.1111/j.1469-1809.2009.00560.x. Epub 2010 Jan 8.
• [14] Expression of SIRT1 and DBC1 is associated with poor prognosis of soft tissue sarcomas.PLoS One. 2013 Sep 3;8(9):e74738. doi: 10.1371/journal.pone.0074738. eCollection 2013.
• [15] Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer.Oncogene. 2001 Jan 25;20(4):531-7. doi: 10.1038/sj.onc.1204122.
• [16] Loss of heterozygosity at 9q32-33 (DBC1 locus) in primary non-invasive papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma of the bladder and their associated normal urothelium.J Pathol. 2008 Jul;215(3):263-72. doi: 10.1002/path.2353.
• [17] Overexpression of DBC1, correlated with poor prognosis, is a potential therapeutic target for hepatocellular carcinoma.Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):511-517. doi: 10.1016/j.bbrc.2017.10.134. Epub 2017 Oct 26.
• [18] Neurodevelopmental MACPFs: The vertebrate astrotactins and BRINPs.Semin Cell Dev Biol. 2017 Dec;72:171-181. doi: 10.1016/j.semcdb.2017.05.005. Epub 2017 May 12.
• [19] Methylation in the promoter regions of WT1, NKX6-1 and DBC1 genes in cervical cancer tissues of Uygur women in Xinjiang.Genet Mol Biol. 2018 Jan-Mar;41(1):9-17. doi: 10.1590/1678-4685-GMB-2016-0146.
• [20] Frequent silencing of DBC1 is by genetic or epigenetic mechanisms in non-small cell lung cancers.Hum Mol Genet. 2005 Apr 15;14(8):997-1007. doi: 10.1093/hmg/ddi092. Epub 2005 Mar 3.
• [21] The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ER and enhances ER target gene expression in breast cancer cells.Nucleic Acids Res. 2019 Mar 18;47(5):2322-2335. doi: 10.1093/nar/gky1306.
• [22] DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.Oncogene. 2018 Mar;37(10):1326-1339. doi: 10.1038/s41388-017-0047-5. Epub 2017 Dec 18.
• [23] DBC1 is a suppressor of B cell activation by negatively regulating alternative NF-B transcriptional activity.J Immunol. 2014 Dec 1;193(11):5515-24. doi: 10.4049/jimmunol.1401798. Epub 2014 Oct 31.
• [24] Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes.Clin Epigenetics. 2016 Nov 24;8:125. doi: 10.1186/s13148-016-0293-3. eCollection 2016.
• [25] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [26] 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.
• [27] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [28] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [29] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [30] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [31] 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.
• [32] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [33] 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.
• [34] 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.
• [35] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [36] 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.
• [37] 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.