Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5H4M62)

• DOT Name: Abl interactor 1 (ABI1)
• Synonyms: Abelson interactor 1; Abi-1; Abl-binding protein 4; AblBP4; Eps8 SH3 domain-binding protein; Eps8-binding protein; Nap1-binding protein; Nap1BP; Spectrin SH3 domain-binding protein 1; e3B1
• Gene Name: ABI1
• Related Disease:
  Carcinoma
  Acute monocytic leukemia
  Adult acute monocytic leukemia
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon polyp
  Colorectal carcinoma
  Epithelial ovarian cancer
  Gastric cancer
  Metastatic malignant neoplasm
  Obstructive sleep apnea
  Osteoporosis
  Ovarian cancer
  Ovarian neoplasm
  Primary myelofibrosis
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Stomach cancer
  Hepatocellular carcinoma
  Neoplasm
  Acute leukaemia
  Acute myelogenous leukaemia
  Adenocarcinoma
  Benign neoplasm
  Esophageal squamous cell carcinoma
  leukaemia
  Leukemia
• UniProt ID: ABI1_HUMAN
• PDB ID: 7LXE
• Pfam ID: PF07815 ; PF00018
• Sequence:
  MAELQMLLEEEIPSGKRALIESYQNLTRVADYCENNYIQATDKRKALEETKAYTTQSLAS
  VAYQINALANNVLQLLDIQASQLRRMESSINHISQTVDIHKEKVARREIGILTTNKNTSR
  THKIIAPANMERPVRYIRKPIDYTVLDDVGHGVKWLKAKHGNNQPARTGTLSRTNPPTQK
  PPSPPMSGRGTLGRNTPYKTLEPVKPPTVPNDYMTSPARLGSQHSPGRTASLNQRPRTHS
  GSSGGSGSRENSGSSSIGIPIAVPTPSPPTIGPENISVPPPSGAPPAPPLAPLLPVSTVI
  AAPGSAPGSQYGTMTRQISRHNSTTSSTSSGGYRRTPSVTAQFSAQPHVNGGPLYSQNSI
  SIAPPPPPMPQLTPQIPLTGFVARVQENIADSPTPPPPPPPDDIPMFDDSPPPPPPPPVD
  YEDEEAAVVQYNDPYADGDPAWAPKNYIEKVVAIYDYTKDKDDELSFMEGAIIYVIKKND
  DGWYEGVCNRVTGLFPGNYVESIMHYTD
• Function: May act in negative regulation of cell growth and transformation by interacting with nonreceptor tyrosine kinases ABL1 and/or ABL2. May play a role in regulation of EGF-induced Erk pathway activation. Involved in cytoskeletal reorganization and EGFR signaling. Together with EPS8 participates in transduction of signals from Ras to Rac. In vitro, a trimeric complex of ABI1, EPS8 and SOS1 exhibits Rac specific guanine nucleotide exchange factor (GEF) activity and ABI1 seems to act as an adapter in the complex. Regulates ABL1/c-Abl-mediated phosphorylation of ENAH. Recruits WASF1 to lamellipodia and there seems to regulate WASF1 protein level. In brain, seems to regulate the dendritic outgrowth and branching as well as to determine the shape and number of synaptic contacts of developing neurons.
• Tissue Specificity: Widely expressed, with highest expression in brain.
• KEGG Pathway:
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  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

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Altered Expression	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Genetic Variation	[2]
Adult acute monocytic leukemia	DISG6BLX	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[5]
Colon polyp	DIS7V594	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Obstructive sleep apnea	DIS0SVD1	Strong	Altered Expression	[10]
Osteoporosis	DISF2JE0	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[11]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[12]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[12]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[13]
Neoplasm	DISZKGEW	moderate	Biomarker	[12]
Acute leukaemia	DISDQFDI	Limited	Altered Expression	[14]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[14]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[1]
Benign neoplasm	DISDUXAD	Limited	Altered Expression	[15]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Altered Expression	[1]
leukaemia	DISS7D1V	Limited	Altered Expression	[16]
Leukemia	DISNAKFL	Limited	Altered Expression	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Abl interactor 1 (ABI1).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Abl interactor 1 (ABI1).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Abl interactor 1 (ABI1).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Abl interactor 1 (ABI1).	[20]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Abl interactor 1 (ABI1).	[21]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Abl interactor 1 (ABI1).	[22]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Abl interactor 1 (ABI1).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Abl interactor 1 (ABI1).	[24]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Abl interactor 1 (ABI1).	[28]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Abl interactor 1 (ABI1).	[29]

4 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 increases the methylation of Abl interactor 1 (ABI1).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Abl interactor 1 (ABI1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Abl interactor 1 (ABI1).	[27]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Abl interactor 1 (ABI1).	[26]

References

• [1] E3B1/ABI-1 isoforms are down-regulated in cancers of human gastrointestinal tract.Dis Markers. 2012;32(4):273-9. doi: 10.3233/DMA-2011-0881.
• [2] Is t(10;11)(p11.2;q23) involving MLL and ABI-1 genes associated with congenital acute monocytic leukemia?.Cancer Genet Cytogenet. 2002 Nov;139(1):57-9. doi: 10.1016/s0165-4608(02)00616-7.
• [3] Abl interactor 1: A novel biomarker for osteoporosis in Chinese elderly men.J Proteomics. 2019 Sep 15;207:103440. doi: 10.1016/j.jprot.2019.103440. Epub 2019 Jul 17.
• [4] Expression of Abl interactor 1 and its prognostic significance in breast cancer: a tissue-array-based investigation.Breast Cancer Res Treat. 2011 Sep;129(2):373-86. doi: 10.1007/s10549-010-1241-0. Epub 2010 Nov 3.
• [5] Abelson interactor protein-1 positively regulates breast cancer cell proliferation, migration, and invasion.Mol Cancer Res. 2007 Oct;5(10):1031-9. doi: 10.1158/1541-7786.MCR-06-0391.
• [6] Expression of Abelson interactor 1 (Abi1) correlates with inflammation, KRAS mutation and adenomatous change during colonic carcinogenesis.PLoS One. 2012;7(7):e40671. doi: 10.1371/journal.pone.0040671. Epub 2012 Jul 10.
• [7] Expression and Y435-phosphorylation of Abelson interactor 1 (Abi1) promotes tumour cell adhesion, extracellular matrix degradation and invasion by colorectal carcinoma cells.Mol Cancer. 2014 Jun 9;13:145. doi: 10.1186/1476-4598-13-145.
• [8] Inhibitory short peptides targeting EPS8/ABI1/SOS1 tri-complex suppress invasion and metastasis of ovarian cancer cells.BMC Cancer. 2019 Sep 5;19(1):878. doi: 10.1186/s12885-019-6087-1.
• [9] Downregulation of ABI1 expression affects the progression and prognosis of human gastric carcinoma.Med Oncol. 2010 Sep;27(3):632-9. doi: 10.1007/s12032-009-9260-6. Epub 2009 Jun 25.
• [10] 8-isoprostanes and resistin as markers of vascular damage in non-hypersomnolent obstructive sleep apnoea patients.Clin Physiol Funct Imaging. 2017 Nov;37(6):695-702. doi: 10.1111/cpf.12361. Epub 2016 Jun 3.
• [11] Bone marrow-specific loss of ABI1 induces myeloproliferative neoplasm with features resembling human myelofibrosis.Blood. 2018 Nov 8;132(19):2053-2066. doi: 10.1182/blood-2018-05-848408. Epub 2018 Sep 13.
• [12] Abi1 loss drives prostate tumorigenesis through activation of EMT and non-canonical WNT signaling.Cell Commun Signal. 2019 Sep 18;17(1):120. doi: 10.1186/s12964-019-0410-y.
• [13] Oncogenic function and prognostic significance of Abelson interactor 1 in hepatocellular carcinoma.Int J Oncol. 2017 May;50(5):1889-1898. doi: 10.3892/ijo.2017.3920. Epub 2017 Mar 20.
• [14] t(10;11)-acute leukemias with MLL-AF10 and MLL-ABI1 chimeric transcripts: specific expression patterns of ABI1 gene in leukemia and solid tumor cell lines.Genes Chromosomes Cancer. 2001 Sep;32(1):1-10. doi: 10.1002/gcc.1160.
• [15] Upregulation of Abelson interactor protein 1 predicts tumor progression and poor outcome in epithelial ovarian cancer.Hum Pathol. 2015 Sep;46(9):1331-40. doi: 10.1016/j.humpath.2015.05.015. Epub 2015 May 30.
• [16] Low expression of Abelson interactor-1 is linked to acquired drug resistance in Bcr-Abl-induced leukemia.Leukemia. 2014 Nov;28(11):2165-77. doi: 10.1038/leu.2014.120. Epub 2014 Apr 4.
• [17] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [18] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] 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.
• [21] 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.
• [22] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [23] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [24] Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [29] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.