Details of Drug Off-Target (DOT)

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

• DOT Name: Ataxin-1-like (ATXN1L)
• Synonyms: Brother of ataxin-1; Brother of ATXN1
• Gene Name: ATXN1L
• Related Disease:
  Autosomal dominant cerebellar ataxia type II
  Spinocerebellar ataxia type 2
  Spinocerebellar ataxia type 5
  Spinocerebellar ataxia type 6
  Advanced cancer
  Spinocerebellar ataxia type 1
• UniProt ID: ATX1L_HUMAN
• Pfam ID: PF12547 ; PF08517
• Sequence:
  MKPVHERSQECLPPKKRDLPVTSEDMGRTTSCSTNHTPSSDASEWSRGVVVAGQSQAGAR
  VSLGGDGAEAITGLTVDQYGMLYKVAVPPATFSPTGLPSVVNMSPLPPTFNVASSLIQHP
  GIHYPPLHYAQLPSTSLQFIGSPYSLPYAVPPNFLPSPLLSPSANLATSHLPHFVPYASL
  LAEGATPPPQAPSPAHSFNKAPSATSPSGQLPHHSSTQPLDLAPGRMPIYYQMSRLPAGY
  TLHETPPAGASPVLTPQESQSALEAAAANGGQRPRERNLVRRESEALDSPNSKGEGQGLV
  PVVECVVDGQLFSGSQTPRVEVAAPAHRGTPDTDLEVQRVVGALASQDYRVVAAQRKEEP
  SPLNLSHHTPDHQGEGRGSARNPAELAEKSQARGFYPQSHQEPVKHRPLPKAMVVANGNL
  VPTGTDSGLLPVGSEILVASSLDVQARATFPDKEPTPPPITSSHLPSHFMKGAIIQLATG
  ELKRVEDLQTQDFVRSAEVSGGLKIDSSTVVDIQESQWPGFVMLHFVVGEQQSKVSIEVP
  PEHPFFVYGQGWSSCSPGRTTQLFSLPCHRLQVGDVCISISLQSLNSNSVSQASCAPPSQ
  LGPPRERPERTVLGSRELCDSEGKSQPAGEGSRVVEPSQPESGAQACWPAPSFQRYSMQG
  EEARAALLRPSFIPQEVKLSIEGRSNAGK
• Function: Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression. Can suppress ATXN1 cytotoxicity in spinocerebellar ataxia type 1 (SCA1). In concert with CIC and ATXN1, involved in brain development.
• Tissue Specificity: Expressed in cerebellum and cerebral cortex.
• KEGG Pathway:
  Notch sig.ling pathway (hsa04330)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Definitive	Therapeutic	[1]
Spinocerebellar ataxia type 2	DISF7WDI	Definitive	Therapeutic	[1]
Spinocerebellar ataxia type 5	DISPYXJ0	Definitive	Therapeutic	[1]
Spinocerebellar ataxia type 6	DISH7224	Definitive	Therapeutic	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Spinocerebellar ataxia type 1	DISF7BO2	Limited	Biomarker	[3]

2 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 Ataxin-1-like (ATXN1L).	[4]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ataxin-1-like (ATXN1L).	[6]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ataxin-1-like (ATXN1L).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Ataxin-1-like (ATXN1L).	[5]

References

• [1] Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat Genet. 2007 Mar;39(3):373-9. doi: 10.1038/ng1977. Epub 2007 Feb 18.
• [2] Transcriptomic analysis of CIC and ATXN1L reveal a functional relationship exploited by cancer.Oncogene. 2019 Jan;38(2):273-290. doi: 10.1038/s41388-018-0427-5. Epub 2018 Aug 9.
• [3] RNAi or overexpression: alternative therapies for Spinocerebellar Ataxia Type 1.Neurobiol Dis. 2013 Aug;56:6-13. doi: 10.1016/j.nbd.2013.04.003. Epub 2013 Apr 10.
• [4] 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.
• [5] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [6] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.