Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1H0J0)

• DOT Name: BAI1-associated protein 3 (BAIAP3)
• Synonyms: BAP3; Brain-specific angiogenesis inhibitor I-associated protein 3
• Gene Name: BAIAP3
• Related Disease:
  Psoriasis
  Anxiety
  Anxiety disorder
• UniProt ID: BAIP3_HUMAN
• Pfam ID: PF00168 ; PF06292
• Sequence:
  MRPRGAAFAAGPPGDLHLGTAIGFAGAIWRSRSPAMSTLLDIKSSVLRQVQVCPSFRRRT
  EQDPGSASADPQEPATGAWKPGDGVEFFAHMRLMLKKGEGRQGLPCLEVPLRSGSPAPPE
  PVDPSLGLRALAPEEVEMLYEEALYTVLYRAGTMGPDQVDDEEALLSYLQQVFGTSLEEH
  TEAIERVRKAKAPTYALKVSVMRAKNLLAKDPNGFSDPYCMLGILPASDATREPRAQKEQ
  RFGFRKGSKRGGPLPAKCIQVTEVKSSTLNPVWKEHFLFEIEDVSTDQLHLDIWDHDDDV
  SLVEACRKLNEVIGLKGMGRYFKQIVKSARANGTAGPTEDHTDDFLGCLNIPVREVPVAG
  VDRWFKLEPRSSASRVQGHCHLVLKLITTQRDTAMSQRGRSGFLSHLLLLSHLLRLEHSA
  EEPNSSSWRGELSTPAATILCLHGAQSNLSPLQLAVLHWQVSSRHHQTCTLDYSYLLGLL
  EDMQAHWEEAPSLPQEQEESLADSLSAFSEFGLQLLRQLRDYFPATNSTAVHRLELLLKC
  LGKLQLFQPSFEICPFESELNMDIAAALKRGNREWYDRILNDKSPREQPGPQRLPGLVVL
  ADAVYDDLQFCYSVYASLFHSILNVDVFTLTFRQLERLVAEEAWVLTEELSPKMTLEVAS
  GLFELYLTLADLQRFWDSIPGRDSRSLALAGIHAPFLPAVKLWFQVLRDQAKWRLQGAVD
  MDTLEPVDASSRHSSSAATAGLCLSHIQELWVRLAWPDPAQAQGLGTQLGQDVCEATLFY
  TELLRKKVDTQPGAAGEAVSEALCVVLNNVELVRKAAGQALKGLAWPEGATGPEGVLPRP
  LLSCTQALDDDLQREAHTVTAHLTSKMVGDIRKYVQHISLSPDSIQNDEAVAPLMKYLDE
  KLALLNASLVKGNLSRVLEALWELLLQAILQALGANRDVSADFYSRFHFTLEALVSFFHA
  EGQGLPLESLRDGSYKRLKEELRLHKCSTRECIEQFYLDKLKQRTLEQNRFGRLSVRCHY
  EAAEQRLAVEVLHAADLLPLDANGLSDPFVIVELGPPHLFPLVRSQRTQVKTRTLHPVYD
  ELFYFSVPAEACRRRAACVLFTVMDHDWLSTNDFAGEAALGLGGVTGVARPQVGGGARAG
  QPVTLHLCRPRAQVRSALRRLEGRTSKEAQEFVKKLKELEKCMEADP
• Function: Functions in endosome to Golgi retrograde transport. In response to calcium influx, may interact with SNARE fusion receptors and membrane phospholipids to mediate endosome fusion with the trans-Golgi network. By promoting the recycling of secretory vesicle transmembrane proteins, it indirectly controls dense-core secretory vesicle biogenesis, maturation and their ability to mediate the constitutive and regulated secretion of neurotransmitters and hormones. May regulate behavior and food intake by controlling calcium-stimulated exocytosis of neurotransmitters including NPY and serotonin and hormones like insulin. Proposed to play a role in hypothalamic neuronal firing by modulating gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmission.
• Tissue Specificity: Predominantly expressed in brain . Also expressed in nonneural tissues such as breast and testes epithelium .
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Psoriasis	DIS59VMN	Strong	Altered Expression	[1]
Anxiety	DISIJDBA	Limited	Genetic Variation	[2]
Anxiety disorder	DISBI2BT	Limited	Genetic Variation	[2]

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 BAI1-associated protein 3 (BAIAP3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of BAI1-associated protein 3 (BAIAP3).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of BAI1-associated protein 3 (BAIAP3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of BAI1-associated protein 3 (BAIAP3).	[4]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of BAI1-associated protein 3 (BAIAP3).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BAI1-associated protein 3 (BAIAP3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BAI1-associated protein 3 (BAIAP3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of BAI1-associated protein 3 (BAIAP3).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of BAI1-associated protein 3 (BAIAP3).	[11]

References

• [1] Proteomic plasma profile of psoriatic patients.J Pharm Biomed Anal. 2018 Jun 5;155:185-193. doi: 10.1016/j.jpba.2018.03.068. Epub 2018 Apr 4.
• [2] Genetic markers of a Munc13 protein family member, BAIAP3, are gender specifically associated with anxiety and benzodiazepine abuse in mice and humans.Mol Med. 2013 Jul 24;19(1):135-48. doi: 10.2119/molmed.2013.00033.
• [3] 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.
• [4] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [5] Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.