Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0NEJ4X)

• DOT Name: Histone H3-like centromeric protein A (CENPA)
• Synonyms: Centromere autoantigen A; Centromere protein A; CENP-A
• Gene Name: CENPA
• Related Disease:
  Cervical Intraepithelial neoplasia
  Colorectal carcinoma
  Colorectal neoplasm
  Estrogen-receptor positive breast cancer
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Scleroderma
  Seminoma
  Triple negative breast cancer
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Epithelial ovarian cancer
  Non-insulin dependent diabetes
  Systemic sclerosis
  Type-1/2 diabetes
• UniProt ID: CENPA_HUMAN
• PDB ID: 3AN2; 3NQJ; 3NQU; 3R45; 3WTP; 5CVD; 5Z23; 6BUZ; 6C0W; 6E0C; 6E0P; 6KDQ; 6KDS; 6L49; 6MUO; 6MUP; 6O1D; 6SE0; 6SE6; 6SEE; 6SEF; 6SEG; 6TEM; 7D20; 7PII; 7R5R; 7U46; 7U47; 7U4D; 7YWX; 7YYH
• Pfam ID: PF00125
• Sequence:
  MGPRRRSRKPEAPRRRSPSPTPTPGPSRRGPSLGASSHQHSRRRQGWLKEIRKLQKSTHL
  LIRKLPFSRLAREICVKFTRGVDFNWQAQALLALQEAAEAFLVHLFEDAYLLTLHAGRVT
  LFPKDVQLARRIRGLEEGLG
• Function: Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes. Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore. The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis.
• 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
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[3]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Biomarker	[4]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Scleroderma	DISVQ342	Strong	Biomarker	[10]
Seminoma	DIS3J8LJ	Strong	Biomarker	[11]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[12]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[13]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[13]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[14]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[15]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[16]
Systemic sclerosis	DISF44L6	Limited	Altered Expression	[17]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[16]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Histone H3-like centromeric protein A (CENPA) affects the response to substance of Vinblastine.	[48]

33 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 Histone H3-like centromeric protein A (CENPA).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Histone H3-like centromeric protein A (CENPA).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Histone H3-like centromeric protein A (CENPA).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Histone H3-like centromeric protein A (CENPA).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Histone H3-like centromeric protein A (CENPA).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histone H3-like centromeric protein A (CENPA).	[23]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Histone H3-like centromeric protein A (CENPA).	[24]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Histone H3-like centromeric protein A (CENPA).	[25]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histone H3-like centromeric protein A (CENPA).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Histone H3-like centromeric protein A (CENPA).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Histone H3-like centromeric protein A (CENPA).	[28]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Histone H3-like centromeric protein A (CENPA).	[28]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Histone H3-like centromeric protein A (CENPA).	[29]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Histone H3-like centromeric protein A (CENPA).	[30]
Menadione	DMSJDTY	Approved	Menadione decreases the expression of Histone H3-like centromeric protein A (CENPA).	[27]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Histone H3-like centromeric protein A (CENPA).	[31]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Histone H3-like centromeric protein A (CENPA).	[32]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Histone H3-like centromeric protein A (CENPA).	[33]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Histone H3-like centromeric protein A (CENPA).	[34]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Histone H3-like centromeric protein A (CENPA).	[35]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Histone H3-like centromeric protein A (CENPA).	[36]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Histone H3-like centromeric protein A (CENPA).	[37]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Histone H3-like centromeric protein A (CENPA).	[38]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Histone H3-like centromeric protein A (CENPA).	[25]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Histone H3-like centromeric protein A (CENPA).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Histone H3-like centromeric protein A (CENPA).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Histone H3-like centromeric protein A (CENPA).	[41]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Histone H3-like centromeric protein A (CENPA).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Histone H3-like centromeric protein A (CENPA).	[43]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Histone H3-like centromeric protein A (CENPA).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Histone H3-like centromeric protein A (CENPA).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Histone H3-like centromeric protein A (CENPA).	[46]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Histone H3-like centromeric protein A (CENPA).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
VX-680	DM93YKJ	Phase 2	VX-680 decreases the phosphorylation of Histone H3-like centromeric protein A (CENPA).	[39]

References

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