Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA2YKO6)

• DOT Name: Ribosome biogenesis protein NOP53 (NOP53)
• Synonyms: Glioma tumor suppressor candidate region gene 2 protein; Protein interacting with carboxyl terminus 1; PICT-1; p60
• Gene Name: NOP53
• Related Disease:
  Atypical endometrial hyperplasia
  Endometrial cancer
  Endometrial carcinoma
  Glioma
  Adult glioblastoma
  Alzheimer disease
  Brain neoplasm
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Choriocarcinoma
  Dilated cardiomyopathy 1A
  Gastric cancer
  Hepatocellular carcinoma
  Herpes simplex infection
  Invasive ductal breast carcinoma
  Listeriosis
  Lyme disease
  Major depressive disorder
  Neoplasm
  Periventricular leukomalacia
  Polycystic ovarian syndrome
  Prostate carcinoma
  Stomach cancer
  Advanced cancer
  Glioblastoma multiforme
  Neuroblastoma
  Squamous cell carcinoma
  Adenocarcinoma
  Prostate cancer
  Amyotrophic lateral sclerosis
  B-cell neoplasm
  Clear cell renal carcinoma
  Cystitis
  Hereditary hemochromatosis
  Renal cell carcinoma
• UniProt ID: NOP53_HUMAN
• PDB ID: 8FKZ; 8FL2; 8FL3; 8FL4; 8FL6; 8FL7; 8FLA; 8FLB; 8FLD; 8FLE; 8INE; 8INF; 8IPX; 8IPY; 8IR3
• Pfam ID: PF07767
• Sequence:
  MAAGGSGVGGKRSSKSDADSGFLGLRPTSVDPALRRRRRGPRNKKRGWRRLAQEPLGLEV
  DQFLEDVRLQERTSGGLLSEAPNEKLFFVDTGSKEKGLTKKRTKVQKKSLLLKKPLRVDL
  ILENTSKVPAPKDVLAHQVPNAKKLRRKEQLWEKLAKQGELPREVRRAQARLLNPSATRA
  KPGPQDTVERPFYDLWASDNPLDRPLVGQDEFFLEQTKKKGVKRPARLHTKPSQAPAVEV
  APAGASYNPSFEDHQTLLSAAHEVELQRQKEAEKLERQLALPATEQAATQESTFQELCEG
  LLEESDGEGEPGQGEGPEAGDAEVCPTPARLATTEKKTEQQRRREKAVHRLRVQQAALRA
  ARLRHQELFRLRGIKAQVALRLAELARRQRRRQARREAEADKPRRLGRLKYQAPDIDVQL
  SSELTDSLRTLKPEGNILRDRFKSFQRRNMIEPRERAKFKRKYKVKLVEKRAFREIQL
• Function: Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis. In ribosome biogenesis, may also play a role in rRNA transcription. Also functions as a nucleolar sensor that regulates the activation of p53/TP53 in response to ribosome biogenesis perturbation, DNA damage and other stress conditions. DNA damage or perturbation of ribosome biogenesis disrupt the interaction between NOP53 and RPL11 allowing RPL11 transport to the nucleoplasm where it can inhibit MDM2 and allow p53/TP53 activation. It may also positively regulate the function of p53/TP53 in cell cycle arrest and apoptosis through direct interaction, preventing its MDM2-dependent ubiquitin-mediated proteasomal degradation. Originally identified as a tumor suppressor, it may also play a role in cell proliferation and apoptosis by positively regulating the stability of PTEN, thereby antagonizing the PI3K-AKT/PKB signaling pathway. May also inhibit cell proliferation and increase apoptosis through its interaction with NF2. May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation. Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex. May also regulate cellular aerobic respiration. In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of RIGI.
• Tissue Specificity: Expressed at high levels in heart and pancreas, moderate levels in placenta, liver, skeletal muscle, and kidney, and low levels in brain and lung.

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atypical endometrial hyperplasia	DIS2POYG	Definitive	Altered Expression	[1]
Endometrial cancer	DISW0LMR	Definitive	Altered Expression	[1]
Endometrial carcinoma	DISXR5CY	Definitive	Altered Expression	[1]
Glioma	DIS5RPEH	Definitive	Biomarker	[2]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[4]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cervical cancer	DISFSHPF	Strong	Genetic Variation	[7]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Choriocarcinoma	DISDBVNL	Strong	Biomarker	[9]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[10]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[13]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[10]
Listeriosis	DISKMQBM	Strong	Biomarker	[14]
Lyme disease	DISO70G5	Strong	Genetic Variation	[15]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Periventricular leukomalacia	DIS152XL	Strong	Biomarker	[17]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[19]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[11]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[20]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[3]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[21]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[22]
Adenocarcinoma	DIS3IHTY	Disputed	Biomarker	[23]
Prostate cancer	DISF190Y	Disputed	Biomarker	[19]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[24]
B-cell neoplasm	DISVY326	Limited	Biomarker	[25]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[20]
Cystitis	DIS2D4B9	Limited	Biomarker	[26]
Hereditary hemochromatosis	DISVG5MT	Limited	Biomarker	[27]
Renal cell carcinoma	DISQZ2X8	Limited	Altered Expression	[20]

9 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 Ribosome biogenesis protein NOP53 (NOP53).	[28]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[29]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[30]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[33]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[36]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Ribosome biogenesis protein NOP53 (NOP53).	[37]

1 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 decreases the phosphorylation of Ribosome biogenesis protein NOP53 (NOP53).	[35]

References

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• [33] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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