Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ4TZRS)

• DOT Name: Centromere protein U (CENPU)
• Synonyms: CENP-U; Centromere protein of 50 kDa; CENP-50; Interphase centromere complex protein 24; KSHV latent nuclear antigen-interacting protein 1; MLF1-interacting protein; Polo-box-interacting protein 1
• Gene Name: CENPU
• Related Disease:
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Acute erythroid leukemia
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Polycythemia vera
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Lung adenocarcinoma
  Systemic lupus erythematosus
  Glioblastoma multiforme
  Glioma
• UniProt ID: CENPU_HUMAN
• PDB ID: 7PB8; 7PKN; 7QOO; 7R5S; 7R5V; 7XHN; 7XHO; 7YWX; 7YYH
• Pfam ID: PF13097
• Sequence:
  MAPRGRRRPRPHRSEGARRSKNTLERTHSMKDKAGQKCKPIDVFDFPDNSDVSSIGRLGE
  NEKDEETYETFDPPLHSTAIYADEEEFSKHCGLSLSSTPPGKEAKRSSDTSGNEASEIES
  VKISAKKPGRKLRPISDDSESIEESDTRRKVKSAEKISTQRHEVIRTTASSELSEKPAES
  VTSKKTGPLSAQPSVEKENLAIESQSKTQKKGKISHDKRKKSRSKAIGSDTSDIVHIWCP
  EGMKTSDIKELNIVLPEFEKTHLEHQQRIESKVCKAAIATFYVNVKEQFIKMLKESQMLT
  NLKRKNAKMISDIEKKRQRMIEVQDELLRLEPQLKQLQTKYDELKERKSSLRNAAYFLSN
  LKQLYQDYSDVQAQEPNVKETYDSSSLPALLFKARTLLGAESHLRNINHQLEKLLDQG
• Function: Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression.
• Tissue Specificity: Expressed at high levels in the testis, fetal liver, thymus, bone marrow and at lower levels in the lymph nodes, placenta, colon and spleen. Present in all cell lines examined, including B-cells, T-cells, epithelial cells and fibroblast cells. Expressed at high levels in glioblastoma cell lines.
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[7]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Altered Expression	[9]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[9]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[6]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[10]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[12]
Glioma	DIS5RPEH	Limited	Biomarker	[12]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Centromere protein U (CENPU) affects the response to substance of Fluorouracil.	[40]
Topotecan	DMP6G8T	Approved	Centromere protein U (CENPU) affects the response to substance of Topotecan.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Centromere protein U (CENPU).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Centromere protein U (CENPU).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centromere protein U (CENPU).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centromere protein U (CENPU).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Centromere protein U (CENPU).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Centromere protein U (CENPU).	[18]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Centromere protein U (CENPU).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Centromere protein U (CENPU).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centromere protein U (CENPU).	[21]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Centromere protein U (CENPU).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centromere protein U (CENPU).	[21]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Centromere protein U (CENPU).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Centromere protein U (CENPU).	[23]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Centromere protein U (CENPU).	[24]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Centromere protein U (CENPU).	[25]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Centromere protein U (CENPU).	[26]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Centromere protein U (CENPU).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Centromere protein U (CENPU).	[28]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Centromere protein U (CENPU).	[29]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Centromere protein U (CENPU).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Centromere protein U (CENPU).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Centromere protein U (CENPU).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centromere protein U (CENPU).	[33]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Centromere protein U (CENPU).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centromere protein U (CENPU).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Centromere protein U (CENPU).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Centromere protein U (CENPU).	[25]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centromere protein U (CENPU).	[38]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Centromere protein U (CENPU).	[39]

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 Centromere protein U (CENPU).	[34]

References

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