Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBZ080L)

• DOT Name: Centrosomal AT-AC splicing factor (CENATAC)
• Synonyms: Coiled-coil domain-containing protein 84
• Gene Name: CENATAC
• Related Disease: Mosaic variegated aneuploidy syndrome 4
• UniProt ID: CATAC_HUMAN
• Pfam ID: PF14968
• Sequence:
  MAPAQRCPLCRQTFFCGRGHVYSRKHQRQLKEALERLLPQVEAARKAIRAAQVERYVPEH
  ERCCWCLCCGCEVREHLSHGNLTVLYGGLLEHLASPEHKKATNKFWWENKAEVQMKEKFL
  VTPQDYARFKKSMVKGLDSYEEKEDKVIKEMAAQIREVEQSRQEVVRSVLEPQAVPDPEE
  GSSAPRSWKGMNSQVASSLQQPSNLDLPPAPELDWMETGPSLTFIGHQDIPGVGNIHSGA
  TPPWMIQDEEYIAGNQEIGPSYEEFLKEKEKQKLKKLPPDRVGANFDHSSRTSAGWLPSF
  GRVWNNGRRWQSRHQFKTEAAAMKKQSHTEKS
• Function: Component of the minor spliceosome that promotes splicing of a specific, rare minor intron subtype. Negative regulator of centrosome duplication. Constrains centriole number by modulating the degradation of the centrosome-duplication-associated protein SASS6 in an acetylation-dependent manner. SIRT1 deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly. The CENATAC acetylation level is restored in mitosis by NAT10, promoting SASS6 proteasome degradation by facilitating SASS6 binding to APC/C E3 ubiquitin-protein ligase complex/FZR1.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mosaic variegated aneuploidy syndrome 4	DISFPWZS	Limited	Autosomal recessive	[1]

7 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 Centrosomal AT-AC splicing factor (CENATAC).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Centrosomal AT-AC splicing factor (CENATAC).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Centrosomal AT-AC splicing factor (CENATAC).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Centrosomal AT-AC splicing factor (CENATAC).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Centrosomal AT-AC splicing factor (CENATAC).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Centrosomal AT-AC splicing factor (CENATAC).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Centrosomal AT-AC splicing factor (CENATAC).	[7]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] 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.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.