Details of Drug Off-Target (DOT)

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

• DOT Name: Atrophin-1 (ATN1)
• Synonyms: Dentatorubral-pallidoluysian atrophy protein
• Gene Name: ATN1
• Related Disease:
  Acute lymphocytic leukaemia
  Adult teratoma
  Advanced cancer
  Autoimmune disease
  Autoimmune thyroid disease
  Breast cancer
  Breast carcinoma
  Cardiac arrest
  Colon cancer
  Colorectal carcinoma
  Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
  Cryopyrin-associated periodic syndrome
  Dementia
  Dentatorubral-pallidoluysian atrophy
  Depression
  Glioblastoma multiforme
  Glioma
  Graft-versus-host disease
  Granulomatous disease, chronic, X-linked
  Hashimoto thyroiditis
  Hepatocellular carcinoma
  Hyperglycemia
  Influenza
  Intellectual disability
  Metastatic malignant neoplasm
  Neuroblastoma
  Non-small-cell lung cancer
  Pancreatic cancer
  Plasma cell myeloma
  Primary myelofibrosis
  Prostate carcinoma
  Prostate neoplasm
  Small lymphocytic lymphoma
  Spinocerebellar ataxia type 17
  Systemic lupus erythematosus
  Thyroiditis
  Uveal Melanoma
  Childhood acute lymphoblastic leukemia
  Colon carcinoma
  Nervous system inflammation
  Sjogren syndrome
  Adult T-cell leukemia/lymphoma
  Prostate cancer
  Crohn disease
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Melanoma
  Rheumatoid arthritis
• UniProt ID: ATN1_HUMAN
• Pfam ID: PF03154
• Sequence:
  MKTRQNKDSMSMRSGRKKEAPGPREELRSRGRASPGGVSTSSSDGKAEKSRQTAKKARVE
  EASTPKVNKQGRSEEISESESEETNAPKKTKTEQELPRPQSPSDLDSLDGRSLNDDGSSD
  PRDIDQDNRSTSPSIYSPGSVENDSDSSSGLSQGPARPYHPPPLFPPSPQPPDSTPRQPE
  ASFEPHPSVTPTGYHAPMEPPTSRMFQAPPGAPPPHPQLYPGGTGGVLSGPPMGPKGGGA
  ASSVGGPNGGKQHPPPTTPISVSSSGASGAPPTKPPTTPVGGGNLPSAPPPANFPHVTPN
  LPPPPALRPLNNASASPPGLGAQPLPGHLPSPHAMGQGMGGLPPGPEKGPTLAPSPHSLP
  PASSSAPAPPMRFPYSSSSSSSAAASSSSSSSSSSASPFPASQALPSYPHSFPPPTSLSV
  SNQPPKYTQPSLPSQAVWSQGPPPPPPYGRLLANSNAHPGPFPPSTGAQSTAHPPVSTHH
  HHHQQQQQQQQQQQQQQQQQQQHHGNSGPPPPGAFPHPLEGGSSHHAHPYAMSPSLGSLR
  PYPPGPAHLPPPHSQVSYSQAGPNGPPVSSSSNSSSSTSQGSYPCSHPSPSQGPQGAPYP
  FPPVPTVTTSSATLSTVIATVASSPAGYKTASPPGPPPYGKRAPSPGAYKTATPPGYKPG
  SPPSFRTGTPPGYRGTSPPAGPGTFKPGSPTVGPGPLPPAGPSGLPSLPPPPAAPASGPP
  LSATQIKQEPAEEYETPESPVPPARSPSPPPKVVDVPSHASQSARFNKHLDRGFNSCARS
  DLYFVPLEGSKLAKKRADLVEKVRREAEQRAREEKEREREREREKEREREKERELERSVK
  LAQEGRAPVECPSLGPVPHRPPFEPGSAVATVPPYLGPDTPALRTLSEYARPHVMSPGNR
  NHPFYVPLGAVDPGLLGYNVPALYSSDPAAREREREARERDLRDRLKPGFEVKPSELEPL
  HGVPGPGLDPFPRHGGLALQPGPPGLHPFPFHPSLGPLERERLALAAGPALRPDMSYAER
  LAAERQHAERVAALGNDPLARLQMLNVTPHHHQHSHIHSHLHLHQQDAIHAASASVHPLI
  DPLASGSHLTRIPYPAGTLPNPLLPHPLHENEVLRHQLFAAPYRDLPASLSAPMSAAHQL
  QAMHAQSAELQRLALEQQQWLHAHHPLHSVPLPAQEDYYSHLKKESDKPL
• Function: Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation. Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats.
• Tissue Specificity: Widely expressed in various tissues including heart, lung, kidney, ovary, testis, prostate, placenta, skeletal Low levels in the liver, thymus and leukocytes. In the adult brain, broadly expressed in amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus, and thalamus. High levels in fetal tissues, especially brain.
• Reactome Pathway: Regulation of PTEN gene transcription (R-HSA-8943724)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[1]
Adult teratoma	DISBY81U	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Autoimmune thyroid disease	DISIHC6A	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cardiac arrest	DIS9DIA4	Strong	Biomarker	[8]
Colon cancer	DISVC52G	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[10]
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies	DISP500B	Strong	Autosomal dominant	[11]
Cryopyrin-associated periodic syndrome	DISPXXOZ	Strong	Genetic Variation	[12]
Dementia	DISXL1WY	Strong	Genetic Variation	[13]
Dentatorubral-pallidoluysian atrophy	DISHWE0K	Strong	Autosomal dominant	[14]
Depression	DIS3XJ69	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[16]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Graft-versus-host disease	DIS0QADF	Strong	Biomarker	[18]
Granulomatous disease, chronic, X-linked	DISNTTS3	Strong	Biomarker	[19]
Hashimoto thyroiditis	DIS77CDF	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[20]
Hyperglycemia	DIS0BZB5	Strong	Biomarker	[21]
Influenza	DIS3PNU3	Strong	Biomarker	[22]
Intellectual disability	DISMBNXP	Strong	Biomarker	[11]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[23]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[26]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[27]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[28]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[29]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[30]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[31]
Spinocerebellar ataxia type 17	DISJXO7P	Strong	Genetic Variation	[32]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[33]
Thyroiditis	DISTCV24	Strong	Genetic Variation	[34]
Uveal Melanoma	DISA7ZGL	Strong	Biomarker	[35]
Childhood acute lymphoblastic leukemia	DISJ5D6U	moderate	Biomarker	[1]
Colon carcinoma	DISJYKUO	moderate	Biomarker	[9]
Nervous system inflammation	DISB3X5A	moderate	Biomarker	[36]
Sjogren syndrome	DISUBX7H	moderate	Biomarker	[37]
Adult T-cell leukemia/lymphoma	DIS882XU	Disputed	Biomarker	[38]
Prostate cancer	DISF190Y	Disputed	Biomarker	[29]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[39]
leukaemia	DISS7D1V	Limited	Biomarker	[40]
Leukemia	DISNAKFL	Limited	Biomarker	[40]
Lung cancer	DISCM4YA	Limited	Biomarker	[41]
Lung carcinoma	DISTR26C	Limited	Biomarker	[41]
Melanoma	DIS1RRCY	Limited	Biomarker	[42]
Rheumatoid arthritis	DISTSB4J	Limited	Genetic Variation	[43]

6 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 Atrophin-1 (ATN1).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Atrophin-1 (ATN1).	[45]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Atrophin-1 (ATN1).	[47]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Atrophin-1 (ATN1).	[48]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Atrophin-1 (ATN1).	[50]
UNC0379	DMD1E4J	Preclinical	UNC0379 decreases the expression of Atrophin-1 (ATN1).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the sumoylation of Atrophin-1 (ATN1).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Atrophin-1 (ATN1).	[49]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Atrophin-1 (ATN1).	[51]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Atrophin-1 (ATN1).	[51]

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