Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQF0HNR)

• DOT Name: Ataxin-1 (ATXN1)
• Synonyms: Spinocerebellar ataxia type 1 protein
• Gene Name: ATXN1
• Related Disease:
  Acute myelogenous leukaemia
  Nervous system disease
  Non-insulin dependent diabetes
  Acute myocardial infarction
  Advanced cancer
  Alzheimer disease
  Atrial fibrillation
  Attention deficit hyperactivity disorder
  Autosomal dominant cerebellar ataxia type II
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac failure
  Cerebellar degeneration
  Congestive heart failure
  Friedreich's ataxia
  Gastric cancer
  Intellectual disability
  Lung adenocarcinoma
  Pathologic nystagmus
  Plasma cell myeloma
  Restless legs syndrome
  Retinopathy
  Spinocerebellar ataxia
  Spinocerebellar ataxia type 1
  Spinocerebellar ataxia type 3
  Spinocerebellar ataxia type 6
  Stomach cancer
  Triple negative breast cancer
  Amyotrophic lateral sclerosis
  Dystonia
  Familial atrial fibrillation
  Kennedy disease
  leukaemia
  Leukemia
  Cerebellar ataxia
  Cervical cancer
  Cervical carcinoma
  Dentatorubral-pallidoluysian atrophy
  Huntington disease
  Mental disorder
  Myocardial infarction
  Prostate cancer
  Prostate carcinoma
  Sleep disorder
  Spinocerebellar ataxia type 5
  Systemic lupus erythematosus
• UniProt ID: ATX1_HUMAN
• PDB ID: 1OA8; 2M41; 4APT; 4AQP; 4J2J; 4J2L; 6QIU
• Pfam ID: PF12547 ; PF08517
• Sequence:
  MKSNQERSNECLPPKKREIPATSRSSEEKAPTLPSDNHRVEGTAWLPGNPGGRGHGGGRH
  GPAGTSVELGLQQGIGLHKALSTGLDYSPPSAPRSVPVATTLPAAYATPQPGTPVSPVQY
  AHLPHTFQFIGSSQYSGTYASFIPSQLIPPTANPVTSAVASAAGATTPSQRSQLEAYSTL
  LANMGSLSQTPGHKAEQQQQQQQQQQQQHQHQQQQQQQQQQQQQQHLSRAPGLITPGSPP
  PAQQNQYVHISSSPQNTGRTASPPAIPVHLHPHQTMIPHTLTLGPPSQVVMQYADSGSHF
  VPREATKKAESSRLQQAIQAKEVLNGEMEKSRRYGAPSSADLGLGKAGGKSVPHPYESRH
  VVVHPSPSDYSSRDPSGVRASVMVLPNSNTPAADLEVQQATHREASPSTLNDKSGLHLGK
  PGHRSYALSPHTVIQTTHSASEPLPVGLPATAFYAGTQPPVIGYLSGQQQAITYAGSLPQ
  HLVIPGTQPLLIPVGSTDMEASGAAPAIVTSSPQFAAVPHTFVTTALPKSENFNPEALVT
  QAAYPAMVQAQIHLPVVQSVASPAAAPPTLPPYFMKGSIIQLANGELKKVEDLKTEDFIQ
  SAEISNDLKIDSSTVERIEDSHSPGVAVIQFAVGEHRAQVSVEVLVEYPFFVFGQGWSSC
  CPERTSQLFDLPCSKLSVGDVCISLTLKNLKNGSVKKGQPVDPASVLLKHSKADGLAGSR
  HRYAEQENGINQGSAQMLSENGELKFPEKMGLPAAPFLTKIEPSKPAATRKRRWSAPESR
  KLEKSEDEPPLTLPKPSLIPQEVKICIEGRSNVGK
• 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. Binds RNA in vitro. May be involved in RNA metabolism. In concert with CIC and ATXN1L, involved in brain development.
• Tissue Specificity: Widely expressed throughout the body.
• KEGG Pathway:
  Notch sig.ling pathway (hsa04330)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[7]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Altered Expression	[8]
Autosomal dominant cerebellar ataxia type II	DIS0PM39	Strong	Altered Expression	[9]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[10]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[11]
Cardiac failure	DISDC067	Strong	Biomarker	[12]
Cerebellar degeneration	DISPBCM3	Strong	Biomarker	[13]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[12]
Friedreich's ataxia	DIS5DV35	Strong	Genetic Variation	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[16]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[17]
Pathologic nystagmus	DIS1QSPO	Strong	Biomarker	[18]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[19]
Restless legs syndrome	DISNWY00	Strong	Biomarker	[20]
Retinopathy	DISB4B0F	Strong	Biomarker	[21]
Spinocerebellar ataxia	DISYMHUK	Strong	Genetic Variation	[22]
Spinocerebellar ataxia type 1	DISF7BO2	Strong	Autosomal dominant	[23]
Spinocerebellar ataxia type 3	DISQBQID	Strong	Biomarker	[24]
Spinocerebellar ataxia type 6	DISH7224	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[26]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[27]
Dystonia	DISJLFGW	moderate	Genetic Variation	[28]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[7]
Kennedy disease	DISXZVM1	moderate	Biomarker	[29]
leukaemia	DISS7D1V	moderate	Biomarker	[1]
Leukemia	DISNAKFL	moderate	Biomarker	[1]
Cerebellar ataxia	DIS9IRAV	Limited	Biomarker	[30]
Cervical cancer	DISFSHPF	Limited	Biomarker	[10]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[10]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Limited	Genetic Variation	[31]
Huntington disease	DISQPLA4	Limited	Biomarker	[32]
Mental disorder	DIS3J5R8	Limited	Biomarker	[33]
Myocardial infarction	DIS655KI	Limited	Biomarker	[34]
Prostate cancer	DISF190Y	Limited	Biomarker	[35]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[35]
Sleep disorder	DIS3JP1U	Limited	Biomarker	[36]
Spinocerebellar ataxia type 5	DISPYXJ0	Limited	Biomarker	[25]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[37]

27 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 (ATXN1).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ataxin-1 (ATXN1).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ataxin-1 (ATXN1).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ataxin-1 (ATXN1).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ataxin-1 (ATXN1).	[42]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ataxin-1 (ATXN1).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ataxin-1 (ATXN1).	[44]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Ataxin-1 (ATXN1).	[46]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ataxin-1 (ATXN1).	[47]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Ataxin-1 (ATXN1).	[48]
Marinol	DM70IK5	Approved	Marinol increases the expression of Ataxin-1 (ATXN1).	[49]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ataxin-1 (ATXN1).	[50]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ataxin-1 (ATXN1).	[51]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Ataxin-1 (ATXN1).	[53]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Ataxin-1 (ATXN1).	[43]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Ataxin-1 (ATXN1).	[43]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Ataxin-1 (ATXN1).	[54]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Ataxin-1 (ATXN1).	[54]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Ataxin-1 (ATXN1).	[54]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Ataxin-1 (ATXN1).	[54]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Ataxin-1 (ATXN1).	[43]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Ataxin-1 (ATXN1).	[43]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ataxin-1 (ATXN1).	[55]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Ataxin-1 (ATXN1).	[56]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ataxin-1 (ATXN1).	[57]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Ataxin-1 (ATXN1).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ataxin-1 (ATXN1).	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ataxin-1 (ATXN1).	[45]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Ataxin-1 (ATXN1).	[52]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Ataxin-1 (ATXN1).	[59]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Ataxin-1 (ATXN1).	[52]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Buthionine sulfoximine	DMJ46CB	Investigative	Buthionine sulfoximine affects the localization of Ataxin-1 (ATXN1).	[61]

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