Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC54EPO)

• DOT Name: Adrenocortical dysplasia protein homolog (ACD)
• Synonyms: POT1 and TIN2-interacting protein
• Gene Name: ACD
• Related Disease:
  Late infantile neuronal ceroid lipofuscinosis
  Advanced cancer
  Amyotrophic lateral sclerosis
  Angle-closure glaucoma
  Cardiovascular disease
  Charcot marie tooth disease
  Dyskeratosis congenita
  Dyskeratosis congenita, autosomal dominant 6
  Dyskeratosis congenita, X-linked
  Familial atypical multiple mole melanoma syndrome
  Hepatitis C virus infection
  Malaria
  Melanoma
  Myocardial infarction
  Neoplasm
  Pancytopenia
  Primary angle-closure glaucoma
  Psoriasis
  Corneal dystrophy
  leukaemia
  Leukemia
  Pulmonary disease
  Hoyeraal-Hreidarsson syndrome
  Obsolete hereditary isolated aplastic anemia
  Chromosomal disorder
  Clear cell renal carcinoma
  Fabry disease
  Glucocorticoid deficiency 1
  Granular corneal dystrophy type II
  High blood pressure
  Non-insulin dependent diabetes
  Renal cell carcinoma
  Vitelliform macular dystrophy
  X-linked adrenal hypoplasia congenita
• UniProt ID: ACD_HUMAN
• PDB ID: 2I46; 5H65; 5I2X; 5I2Y; 5UN7; 5XYF; 7QXA; 7QXB; 7QXS; 7S1T; 7TRE; 8SOJ; 8SOK
• Pfam ID: PF10341
• Sequence:
  MAGSGRLVLRPWIRELILGSETPSSPRAGQLLEVLQDAEAAVAGPSHAPDTSDVGATLLV
  SDGTHSVRCLVTREALDTSDWEEKEFGFRGTEGRLLLLQDCGVHVQVAEGGAPAEFYLQV
  DRFSLLPTEQPRLRVPGCNQDLDVQKKLYDCLEEHLSESTSSNAGLSLSQLLDEMREDQE
  HQGALVCLAESCLTLEGPCTAPPVTHWAASRCKATGEAVYTVPSSMLCISENDQLILSSL
  GPCQRTQGPELPPPDPALQDLSLTLIASPPSSPSSSGTPALPGHMSSEESGTSISLLPAL
  SLAAPDPGQRSSSQPSPAICSAPATLTPRSPHASRTPSSPLQSCTPSLSPRSHVPSPHQA
  LVTRPQKPSLEFKEFVGLPCKNRPPFPRTGATRGAQEPCSVWEPPKRHRDGSAFQYEYEP
  PCTSLCARVQAVRLPPQLMAWALHFLMDAQPGSEPTPM
• Function: Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by recruiting telomerase to telomeres and increasing its processivity. May play a role in organogenesis.
• Reactome Pathway:
  Cleavage of the damaged pyrimidine (R-HSA-110329)
  Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330)
  Cleavage of the damaged purine (R-HSA-110331)
  Meiotic synapsis (R-HSA-1221632)
  Packaging Of Telomere Ends (R-HSA-171306)
  Telomere Extension By Telomerase (R-HSA-171319)
  Polymerase switching on the C-strand of the telomere (R-HSA-174411)
  Processive synthesis on the C-strand of the telomere (R-HSA-174414)
  Telomere C-strand (Lagging Strand) Synthesis (R-HSA-174417)
  Telomere C-strand synthesis initiation (R-HSA-174430)
  Removal of the Flap Intermediate from the C-strand (R-HSA-174437)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  Inhibition of DNA recombination at telomere (R-HSA-9670095)
  Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328)

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Late infantile neuronal ceroid lipofuscinosis	DISI3RIL	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[3]
Angle-closure glaucoma	DISZ95KY	Strong	Biomarker	[4]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[5]
Charcot marie tooth disease	DIS3BT2L	Strong	Biomarker	[3]
Dyskeratosis congenita	DISSXV0K	Strong	Biomarker	[6]
Dyskeratosis congenita, autosomal dominant 6	DIS7JDC9	Strong	Autosomal dominant	[7]
Dyskeratosis congenita, X-linked	DISJ3Y69	Strong	Genetic Variation	[8]
Familial atypical multiple mole melanoma syndrome	DIS2YEKP	Strong	SusceptibilityMutation	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[10]
Malaria	DISQ9Y50	Strong	Biomarker	[11]
Melanoma	DIS1RRCY	Strong	Genetic Variation	[12]
Myocardial infarction	DIS655KI	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Pancytopenia	DISVKEHV	Strong	Genetic Variation	[7]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Biomarker	[4]
Psoriasis	DIS59VMN	Strong	Biomarker	[14]
Corneal dystrophy	DISRDPA6	moderate	Genetic Variation	[15]
leukaemia	DISS7D1V	moderate	Biomarker	[16]
Leukemia	DISNAKFL	moderate	Biomarker	[16]
Pulmonary disease	DIS6060I	moderate	Biomarker	[17]
Hoyeraal-Hreidarsson syndrome	DISAUR8F	Supportive	Autosomal dominant	[8]
Obsolete hereditary isolated aplastic anemia	DIS2B0NW	Supportive	Autosomal dominant	[7]
Chromosomal disorder	DISM5BB5	Limited	Biomarker	[18]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[19]
Fabry disease	DISUUQJF	Limited	Genetic Variation	[20]
Glucocorticoid deficiency 1	DISCTX0T	Limited	Genetic Variation	[21]
Granular corneal dystrophy type II	DISAEE20	Limited	Biomarker	[22]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[23]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[19]
Vitelliform macular dystrophy	DISEFYYN	Limited	Biomarker	[25]
X-linked adrenal hypoplasia congenita	DISNMXY8	Limited	Genetic Variation	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adrenocortical dysplasia protein homolog (ACD).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Adrenocortical dysplasia protein homolog (ACD).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Adrenocortical dysplasia protein homolog (ACD).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Adrenocortical dysplasia protein homolog (ACD).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adrenocortical dysplasia protein homolog (ACD).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Adrenocortical dysplasia protein homolog (ACD).	[32]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Adrenocortical dysplasia protein homolog (ACD).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adrenocortical dysplasia protein homolog (ACD).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adrenocortical dysplasia protein homolog (ACD).	[36]

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 increases the phosphorylation of Adrenocortical dysplasia protein homolog (ACD).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Adrenocortical dysplasia protein homolog (ACD).	[35]

References

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