Details of Drug Off-Target (DOT)

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

• DOT Name: ABI gene family member 3 (ABI3)
• Synonyms: New molecule including SH3; Nesh
• Gene Name: ABI3
• Related Disease:
  Alzheimer disease
  Advanced cancer
  Carcinoma
  Colon carcinoma
  Familial Alzheimer disease
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Thyroid tumor
  Thyroid gland carcinoma
  Thyroid gland follicular carcinoma
  Lewy body dementia
• UniProt ID: ABI3_HUMAN
• Pfam ID: PF07815 ; PF14604
• Sequence:
  MAELQQLQEFEIPTGREALRGNHSALLRVADYCEDNYVQATDKRKALEETMAFTTQALAS
  VAYQVGNLAGHTLRMLDLQGAALRQVEARVSTLGQMVNMHMEKVARREIGTLATVQRLPP
  GQKVIAPENLPPLTPYCRRPLNFGCLDDIGHGIKDLSTQLSRTGTLSRKSIKAPATPASA
  TLGRPPRIPEPVHLPVVPDGRLSAASSAFSLASAGSAEGVGGAPTPKGQAAPPAPPLPSS
  LDPPPPPAAVEVFQRPPTLEELSPPPPDEELPLPLDLPPPPPLDGDELGLPPPPPGFGPD
  EPSWVPASYLEKVVTLYPYTSQKDNELSFSEGTVICVTRRYSDGWCEGVSSEGTGFFPGN
  YVEPSC
• Function: May inhibit tumor metastasis. In vitro, reduces cell motility.
• Tissue Specificity: Expressed in heart, lung, liver, pancreas, kidney, placenta and at low levels in brain and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Thyroid tumor	DISLVKMD	Strong	Altered Expression	[2]
Thyroid gland carcinoma	DISMNGZ0	moderate	Posttranslational Modification	[6]
Thyroid gland follicular carcinoma	DISFK2QT	moderate	Posttranslational Modification	[6]
Lewy body dementia	DISAE66J	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of ABI gene family member 3 (ABI3).	[8]
Rifampicin	DM5DSFZ	Approved	Rifampicin decreases the expression of ABI gene family member 3 (ABI3).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of ABI gene family member 3 (ABI3).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ABI gene family member 3 (ABI3).	[11]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of ABI gene family member 3 (ABI3).	[12]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion decreases the expression of ABI gene family member 3 (ABI3).	[12]

References

• [1] Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease.Transl Psychiatry. 2019 Jan 31;9(1):55. doi: 10.1038/s41398-019-0394-9.
• [2] ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence.BMC Cancer. 2011 Jan 11;11:11. doi: 10.1186/1471-2407-11-11.
• [3] Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.Nat Genet. 2017 Sep;49(9):1373-1384. doi: 10.1038/ng.3916. Epub 2017 Jul 17.
• [4] Cancer-associated loss of TARSH gene expression in human primary lung cancer.J Cancer Res Clin Oncol. 2006 Jan;132(1):28-34. doi: 10.1007/s00432-005-0032-1. Epub 2005 Oct 4.
• [5] Forced expression of NESH suppresses motility and metastatic dissemination of malignant cells.Cancer Res. 2002 Apr 15;62(8):2215-9.
• [6] Transcriptional regulation of the potential tumor suppressor ABI3 gene in thyroid carcinomas: interplay between methylation and NKX2-1 availability.Oncotarget. 2016 May 3;7(18):25960-70. doi: 10.18632/oncotarget.8416.
• [7] ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans.Mol Neurodegener. 2018 Oct 11;13(1):53. doi: 10.1186/s13024-018-0289-x.
• [8] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [9] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [10] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.