Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8SRY1C)

• DOT Name: Annexin A11 (ANXA11)
• Synonyms: 56 kDa autoantigen; Annexin XI; Annexin-11; Calcyclin-associated annexin 50; CAP-50
• Gene Name: ANXA11
• Related Disease:
  Amyotrophic lateral sclerosis type 23
  Amyotrophic lateral sclerosis
  Inclusion body myopathy and brain white matter abnormalities
• UniProt ID: ANX11_HUMAN
• Pfam ID: PF00191
• Sequence:
  MSYPGYPPPPGGYPPAAPGGGPWGGAAYPPPPSMPPIGLDNVATYAGQFNQDYLSGMAAN
  MSGTFGGANMPNLYPGAPGAGYPPVPPGGFGQPPSAQQPVPPYGMYPPPGGNPPSRMPSY
  PPYPGAPVPGQPMPPPGQQPPGAYPGQPPVTYPGQPPVPLPGQQQPVPSYPGYPGSGTVT
  PAVPPTQFGSRGTITDAPGFDPLRDAEVLRKAMKGFGTDEQAIIDCLGSRSNKQRQQILL
  SFKTAYGKDLIKDLKSELSGNFEKTILALMKTPVLFDIYEIKEAIKGVGTDEACLIEILA
  SRSNEHIRELNRAYKAEFKKTLEEAIRSDTSGHFQRLLISLSQGNRDESTNVDMSLAQRD
  AQELYAAGENRLGTDESKFNAVLCSRSRAHLVAVFNEYQRMTGRDIEKSICREMSGDLEE
  GMLAVVKCLKNTPAFFAERLNKAMRGAGTKDRTLIRIMVSRSETDLLDIRSEYKRMYGKS
  LYHDISGDTSGDYRKILLKICGGND
• Function: Binds specifically to calcyclin in a calcium-dependent manner. Required for midbody formation and completion of the terminal phase of cytokinesis.
• KEGG Pathway: Amyotrophic lateral sclerosis (hsa05014)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 23	DISY3OI7	Definitive	Autosomal dominant	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[2]
Inclusion body myopathy and brain white matter abnormalities	DIS0A4GC	Limited	Autosomal dominant	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Annexin A11 (ANXA11) affects the response to substance of Methotrexate.	[19]

14 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 Annexin A11 (ANXA11).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Annexin A11 (ANXA11).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Annexin A11 (ANXA11).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Annexin A11 (ANXA11).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Annexin A11 (ANXA11).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Annexin A11 (ANXA11).	[9]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Annexin A11 (ANXA11).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Annexin A11 (ANXA11).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Annexin A11 (ANXA11).	[12]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Annexin A11 (ANXA11).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Annexin A11 (ANXA11).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Annexin A11 (ANXA11).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Annexin A11 (ANXA11).	[17]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Annexin A11 (ANXA11).	[18]

2 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 affects the methylation of Annexin A11 (ANXA11).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Annexin A11 (ANXA11).	[15]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis. Sci Transl Med. 2017 May 3;9(388):eaad9157. doi: 10.1126/scitranslmed.aad9157.
• [3] GABBR2 mutations determine phenotype in rett syndrome and epileptic encephalopathy. Ann Neurol. 2017 Sep;82(3):466-478. doi: 10.1002/ana.25032.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] 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.
• [6] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [13] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [14] 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.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [18] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.