Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN02KUV)

• DOT Name: Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP)
• Synonyms: APBB1-interacting protein 1; Proline-rich EVH1 ligand 1; PREL-1; Proline-rich protein 73; Rap1-GTP-interacting adapter molecule; RIAM; Retinoic acid-responsive proline-rich protein 1; RARP-1
• Gene Name: APBB1IP
• Related Disease:
  Epithelial ovarian cancer
  High blood pressure
  Melanoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Severe combined immunodeficiency
  Autoimmune disease
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: AB1IP_HUMAN
• PDB ID: 2MWN; 3ZDL
• Pfam ID: PF00169 ; PF00788
• Sequence:
  MGESSEDIDQMFSTLLGEMDLLTQSLGVDTLPPPDPNPPRAEFNYSVGFKDLNESLNALE
  DQDLDALMADLVADISEAEQRTIQAQKESLQNQHHSASLQASIFSGAASLGYGTNVAATG
  ISQYEDDLPPPPADPVLDLPLPPPPPEPLSQEEEEAQAKADKIKLALEKLKEAKVKKLVV
  KVHMNDNSTKSLMVDERQLARDVLDNLFEKTHCDCNVDWCLYEIYPELQIERFFEDHENV
  VEVLSDWTRDTENKILFLEKEEKYAVFKNPQNFYLDNRGKKESKETNEKMNAKNKESLLE
  ESFCGTSIIVPELEGALYLKEDGKKSWKRRYFLLRASGIYYVPKGKTKTSRDLACFIQFE
  NVNIYYGTQHKMKYKAPTDYCFVLKHPQIQKESQYIKYLCCDDTRTLNQWVMGIRIAKYG
  KTLYDNYQRAVAKAGLASRWTNLGTVNAAAPAQPSTGPKTGTTQPNGQIPQATHSVSAVL
  QEAQRHAETSKDKKPALGNHHDPAVPRAPHAPKSSLPPPPPVRRSSDTSGSPATPLKAKG
  TGGGGLPAPPDDFLPPPPPPPPLDDPELPPPPPDFMEPPPDFVPPPPPSYAGIAGSELPP
  PPPPPPAPAPAPVPDSARPPPAVAKRPPVPPKRQENPGHPGGAGGGEQDFMSDLMKALQK
  KRGNVS
• Function: Appears to function in the signal transduction from Ras activation to actin cytoskeletal remodeling. Suppresses insulin-induced promoter activities through AP1 and SRE. Mediates Rap1-induced adhesion.
• Tissue Specificity: Widely expressed with high expression in thymus, spleen, lymph node, bone marrow and peripheral leukocytes.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Platelet activation (hsa04611)
• Reactome Pathway:
  GRB2 (R-HSA-354194)
  p130Cas linkage to MAPK signaling for integrins (R-HSA-372708)
  MAP2K and MAPK activation (R-HSA-5674135)
  Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946)
  Signaling by high-kinase activity BRAF mutants (R-HSA-6802948)
  Signaling by BRAF and RAF1 fusions (R-HSA-6802952)
  Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955)
  Signaling downstream of RAS mutants (R-HSA-9649948)
  Signaling by RAF1 mutants (R-HSA-9656223)
  Integrin signaling (R-HSA-354192)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[1]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[3]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Limited	Biomarker	[4]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[4]

11 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 Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[15]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP).	[14]

References

• [1] Luteolin promotes the sensitivity of cisplatin in ovarian cancer by decreasing PRPA1-medicated autophagy.Cell Mol Biol (Noisy-le-grand). 2018 May 15;64(6):17-22.
• [2] Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker.Hypertension. 2012 Jun;59(6):1204-11. doi: 10.1161/HYP.0b013e31825b30f8. Epub 2012 May 7.
• [3] Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells.J Biol Chem. 2011 May 27;286(21):18492-504. doi: 10.1074/jbc.M110.189811. Epub 2011 Mar 26.
• [4] Cutting Edge: Loss of T Cell RIAM Precludes Conjugate Formation with APC and Prevents Immune-Mediated Diabetes.J Immunol. 2017 May 1;198(9):3410-3415. doi: 10.4049/jimmunol.1601743. Epub 2017 Mar 27.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] 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.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] 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.
• [10] 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.
• [11] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] 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.
• [15] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [16] 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.