Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4VFHWN)

• DOT Name: BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3)
• Synonyms: DBCCR1-like protein 1
• Gene Name: BRINP3
• Related Disease:
  Acute myocardial infarction
  Arteriosclerosis
  Atherosclerosis
  Gastric cancer
  Neoplasm
  Periodontal disease
  Stomach cancer
  Ulcerative colitis
  Non-insulin dependent diabetes
  Cerebral infarction
  Coronary atherosclerosis
  Coronary heart disease
  Myocardial infarction
  Type-1/2 diabetes
• UniProt ID: BRNP3_HUMAN
• Pfam ID: PF19052 ; PF01823
• Sequence:
  MIWRSRAGAELFSLMALWEWIALSLHCWVLAVAAVSDQHATSPFDWLLSDKGPFHRSQEY
  TDFVDRSRQGFSTRYKIYREFGRWKVNNLAVERRNFLGSPLPLAPEFFRNIRLLGRRPTL
  QQITENLIKKYGTHFLLSATLGGEESLTIFVDKRKLSKRAEGSDSTTNSSSVTLETLHQL
  AASYFIDRDSTLRRLHHIQIASTAIKVTETRTGPLGCSNYDNLDSVSSVLVQSPENKIQL
  QGLQVLLPDYLQERFVQAALSYIACNSEGEFICKENDCWCHCGPKFPECNCPSMDIQAME
  ENLLRITETWKAYNSDFEESDEFKLFMKRLPMNYFLNTSTIMHLWTMDSNFQRRYEQLEN
  SMKQLFLKAQKIVHKLFSLSKRCHKQPLISLPRQRTSTYWLTRIQSFLYCNENGLLGSFS
  EETHSCTCPNDQVVCTAFLPCTVGDASACLTCAPDNRTRCGTCNTGYMLSQGLCKPEVAE
  STDHYIGFETDLQDLEMKYLLQKTDRRIEVHAIFISNDMRLNSWFDPSWRKRMLLTLKSN
  KYKSSLVHMILGLSLQICLTKNSTLEPVLAVYVNPFGGSHSESWFMPVNENSFPDWERTK
  LDLPLQCYNWTLTLGNKWKTFFETVHIYLRSRIKSNGPNGNESIYYEPLEFIDPSRNLGY
  MKINNIQVFGYSMHFDPEAIRDLILQLDYPYTQGSQDSALLQLLEIRDRVNKLSPPGQRR
  LDLFSCLLRHRLKLSTSEVVRIQSALQAFNAKLPNTMDYDTTKLCS
• Function: Inhibits neuronal cell proliferation by negative regulation of the cell cycle transition. Promotes pituitary gonadotrope cell proliferation, migration and invasion, when overexpressed. May play a role in cell pituitary tumor development.
• Tissue Specificity: Strongly expressed in oral keratinocytes compared to the weak expression in tongue squamous cell carcinoma (SCC). Expressed in endothelial and aortic smooth muscle cells. Overexpressed in gonadotropinomas compared to normal pituitarie tissues.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[2]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[2]
Gastric cancer	DISXGOUK	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Periodontal disease	DISJQHVN	Strong	Altered Expression	[4]
Stomach cancer	DISKIJSX	Strong	Biomarker	[3]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[5]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Altered Expression	[6]
Cerebral infarction	DISR1WNP	Limited	Biomarker	[7]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[8]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[8]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[8]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[7]

8 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 3 (BRINP3).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of BMP/retinoic acid-inducible neural-specific protein 3 (BRINP3).	[17]

1 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 3 (BRINP3).	[15]

References

• [1] Family with sequence similarity 5, member C (FAM5C) increases leukocyte adhesion molecules in vascular endothelial cells: implication in vascular inflammation.PLoS One. 2014 Sep 24;9(9):e107236. doi: 10.1371/journal.pone.0107236. eCollection 2014.
• [2] Genetic and functional association of FAM5C with myocardial infarction.BMC Med Genet. 2008 Apr 22;9:33. doi: 10.1186/1471-2350-9-33.
• [3] Hypermethylated FAM5C and MYLK in serum as diagnosis and pre-warning markers for gastric cancer.Dis Markers. 2012;32(3):195-202. doi: 10.3233/DMA-2011-0877.
• [4] FAM5C contributes to aggressive periodontitis.PLoS One. 2010 Apr 7;5(4):e10053. doi: 10.1371/journal.pone.0010053.
• [5] Mucosal transcriptomics implicates under expression of BRINP3 in the pathogenesis of ulcerative colitis.Inflamm Bowel Dis. 2014 Oct;20(10):1802-12. doi: 10.1097/MIB.0000000000000169.
• [6] Association of osteoglycin and FAM5C with bone turnover markers, bone mineral density, and vertebral fractures in postmenopausal women with type 2 diabetes mellitus.Bone. 2017 Feb;95:5-10. doi: 10.1016/j.bone.2016.11.007. Epub 2016 Nov 8.
• [7] The Expression of microRNA-223 and FAM5C in Cerebral Infarction Patients with Diabetes Mellitus.Cardiovasc Toxicol. 2017 Jan;17(1):42-48. doi: 10.1007/s12012-015-9354-7.
• [8] The relationships between FAM5C SNP (rs10920501) variability and metabolic syndrome and inflammation in women with coronary heart disease.Biol Res Nurs. 2013 Apr;15(2):160-6. doi: 10.1177/1099800411424487. Epub 2011 Oct 18.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.