Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT62KOXF)

• DOT Name: Actin-binding LIM protein 2 (ABLIM2)
• Synonyms: abLIM-2; Actin-binding LIM protein family member 2
• Gene Name: ABLIM2
• Related Disease: Chronic obstructive pulmonary disease
• UniProt ID: ABLM2_HUMAN
• PDB ID: 1V6G; 1WIG; 2L3X
• Pfam ID: PF16182 ; PF00412 ; PF02209
• Sequence:
  MSAVSQPQAAPSPLEKSPSTAILCNTCGNVCKGEVLRVQDKYFHIKCFVCKACGCDLAEG
  GFFVRQGEYICTLDYQRLYGTRCFSCDQFIEGEVVSALGKTYHPDCFVCAVCRLPFPPGD
  RVTFNGKECMCQKCSLPVSVGSSAHLSQGLRSCGGCGTEIKNGQALVALDKHWHLGCFKC
  KSCGKLLNAEYISKDGLPYCEADYHAKFGIRCDSCEKYITGRVLEAGEKHYHPSCALCVR
  CGQMFAEGEEMYLQGSSIWHPACRQAARTEDRNKETRTSSESIISVPASSTSGSPSRVIY
  AKLGGEILDYRDLAALPKSKAIYDIDRPDMISYSPYISHSAGDRQSYGEGDQDDRSYKQC
  RTSSPSSTGSVSLGRYTPTSRSPQHYSRPGSESGRSTPSLSVLSDSKPPPSTYQQAPRHF
  HVPDTGVKDNIYRKPPIYRQHAARRSDGEDGSLDQDNRKKSSWLMLKGDADTRTNSPDLD
  TQSLSHSSGTDRDPLQRMAGDSFHSRFPYSKSDPLPGHGKNGLDQRNANLAPCGADPDAS
  WGMREYKIYPYDSLIVTNRIRVKLPKDVDRTRLERHLSPEEFQEVFGMSIEEFDRLALWK
  RNDLKKKALLF
• Function: May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity.
• Tissue Specificity: Highly expressed in skeletal muscle.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway: DCC mediated attractive signaling (R-HSA-418885)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[1]

4 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 Actin-binding LIM protein 2 (ABLIM2).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Actin-binding LIM protein 2 (ABLIM2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Actin-binding LIM protein 2 (ABLIM2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Actin-binding LIM protein 2 (ABLIM2).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Actin-binding LIM protein 2 (ABLIM2).	[3]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Actin-binding LIM protein 2 (ABLIM2).	[5]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Actin-binding LIM protein 2 (ABLIM2).	[6]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Actin-binding LIM protein 2 (ABLIM2).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Actin-binding LIM protein 2 (ABLIM2).	[7]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Actin-binding LIM protein 2 (ABLIM2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Actin-binding LIM protein 2 (ABLIM2).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Actin-binding LIM protein 2 (ABLIM2).	[11]

References

• [1] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [2] 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.
• [3] 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.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] 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.
• [6] Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. Immunology. 2007 Jun;121(2):266-75. doi: 10.1111/j.1365-2567.2007.02574.x. Epub 2007 Mar 7.
• [7] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [8] 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.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [10] 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.
• [11] 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.