Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLSLV5A)

• DOT Name: Ankyrin repeat family A protein 2 (ANKRA2)
• Synonyms: RFXANK-like protein 2
• Gene Name: ANKRA2
• Related Disease:
  3-M syndrome
  MHC class II deficiency
• UniProt ID: ANRA2_HUMAN
• PDB ID: 3SO8; 3V2O; 3V2X; 3V31; 4LG6; 4QQI; 8CXG; 8CXH; 8CXI
• Pfam ID: PF00023 ; PF12796
• Sequence:
  MDTSTNLDIGAQLIVEECPSTYSLTGMPDIKIEHPLDPNSEEGSAQGVAMGMKFILPNRF
  DMNVCSRFVKSLNEEDSKNIQDQVNSDLEVASVLFKAECNIHTSPSPGIQVRHVYTPSTT
  KHFSPIKQSTTLTNKHRGNEVSTTPLLANSLSVHQLAAQGEMLYLATRIEQENVINHTDE
  EGFTPLMWAAAHGQIAVVEFLLQNGADPQLLGKGRESALSLACSKGYTDIVKMLLDCGVD
  VNEYDWNGGTPLLYAVHGNHVKCVKMLLESGADPTIETDSGYNSMDLAVALGYRSVQQVI
  ESHLLKLLQNIKE
• Function: May regulate the interaction between the 3M complex and the histone deacetylases HDAC4 and HDAC5. May also regulate LRP2/megalin.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
3-M syndrome	DISGKJY3	Strong	Biomarker	[1]
MHC class II deficiency	DISWMI0G	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[11]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ankyrin repeat family A protein 2 (ANKRA2).	[13]

References

• [1] Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein CCDC8.Structure. 2015 Apr 7;23(4):700-12. doi: 10.1016/j.str.2015.02.001. Epub 2015 Mar 5.
• [2] Evolutionary conservation and characterization of the bare lymphocyte syndrome transcription factor RFX-B and its paralogue ANKRA2.Immunogenetics. 2005 Feb;56(11):788-97. doi: 10.1007/s00251-004-0738-2. Epub 2005 Jan 18.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [9] Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells. Eur J Pharmacol. 2014 Jun 5;732:60-7.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.