Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1KKMYZ)

• DOT Name: Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2)
• Synonyms: BAI-associated protein 2; BAI1-associated protein 2; Protein BAP2; Fas ligand-associated factor 3; FLAF3; Insulin receptor substrate p53/p58; IRS-58; IRSp53/58; Insulin receptor substrate protein of 53 kDa; IRSp53; Insulin receptor substrate p53
• Gene Name: BAIAP2
• Related Disease:
  Neoplasm
  Anxiety
  Attention deficit hyperactivity disorder
  Autism spectrum disorder
  Cognitive impairment
  Gout
  Major depressive disorder
  Mental disorder
  Mood disorder
  Schizophrenia
• UniProt ID: BAIP2_HUMAN
• PDB ID: 1WDZ; 1Y2O; 2YKT; 3RNJ; 4JS0; 6BCR; 6BCY; 6BD1; 6BD2; 6BQT; 6ZEG; 6ZEI
• Pfam ID: PF08397 ; PF07653
• Sequence:
  MSLSRSEEMHRLTENVYKTIMEQFNPSLRNFIAMGKNYEKALAGVTYAAKGYFDALVKMG
  ELASESQGSKELGDVLFQMAEVHRQIQNQLEEMLKSFHNELLTQLEQKVELDSRYLSAAL
  KKYQTEQRSKGDALDKCQAELKKLRKKSQGSKNPQKYSDKELQYIDAISNKQGELENYVS
  DGYKTALTEERRRFCFLVEKQCAVAKNSAAYHSKGKELLAQKLPLWQQACADPSKIPERA
  VQLMQQVASNGATLPSALSASKSNLVISDPIPGAKPLPVPPELAPFVGRMSAQESTPIMN
  GVTGPDGEDYSPWADRKAAQPKSLSPPQSQSKLSDSYSNTLPVRKSVTPKNSYATTENKT
  LPRSSSMAAGLERNGRMRVKAIFSHAAGDNSTLLSFKEGDLITLLVPEARDGWHYGESEK
  TKMRGWFPFSYTRVLDSDGSDRLHMSLQQGKSSSTGNLLDKDDLAIPPPDYGAASRAFPA
  QTASGFKQRPYSVAVPAFSQGLDDYGARSMSRNPFAHVQLKPTVTNDRCDLSAQGPEGRE
  HGDGSARTLAGR
• Function: Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions.
• Tissue Specificity: Isoform 1 and isoform 4 are expressed almost exclusively in brain. Isoform 4 is barely detectable in placenta, prostate and testis. A short isoform is ubiquitous, with the highest expression in liver, prostate, testis and placenta.
• KEGG Pathway:
  Adherens junction (hsa04520)
  Regulation of actin cytoskeleton (hsa04810)
  Pathogenic Escherichia coli infection (hsa05130)
  Yersinia infection (hsa05135)
• Reactome Pathway:
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC3 GTPase cycle (R-HSA-9013423)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Genetic Variation	[2]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[3]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[4]
Cognitive impairment	DISH2ERD	Strong	Biomarker	[4]
Gout	DISHC0U7	Strong	Genetic Variation	[5]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Mental disorder	DIS3J5R8	Strong	Biomarker	[4]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[6]

5 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 Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[18]

11 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 Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[12]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[20]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2).	[21]

References

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• [3] Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults.Psychiatry Res Neuroimaging. 2017 Nov 30;269:54-61. doi: 10.1016/j.pscychresns.2017.09.004. Epub 2017 Sep 12.
• [4] IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders.Neuropharmacology. 2016 Jan;100:27-39. doi: 10.1016/j.neuropharm.2015.06.019. Epub 2015 Aug 12.
• [5] Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response. Clin Pharmacol Ther. 2015 May;97(5):518-25.
• [6] DNA methylation as a putative mechanism for reduced dendritic spine density in the superior temporal gyrus of subjects with schizophrenia.Transl Psychiatry. 2017 Feb 14;7(2):e1032. doi: 10.1038/tp.2016.297.
• [7] 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.
• [8] 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.
• [9] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [13] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [18] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [19] 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.
• [20] 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.
• [21] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.