Details of Drug Off-Target (DOT)

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

• DOT Name: Centrosomal protein of 57 kDa (CEP57)
• Synonyms: Cep57; FGF2-interacting protein; Testis-specific protein 57; Translokin
• Gene Name: CEP57
• Related Disease:
  Mosaic variegated aneuploidy syndrome 2
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Mosaic variegated aneuploidy syndrome 1
  Neoplasm
  Retinoblastoma
  Mosaic variegated aneuploidy syndrome
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CEP57_HUMAN
• PDB ID: 4L0R
• Pfam ID: PF14073 ; PF06657
• Sequence:
  MAAASVSAASGSHLSNSFAEPSRSNGSMVRHSSSPYVVYPSDKPFLNSDLRRSPSKPTLA
  YPESNSRAIFSALKNLQDKIRRLELERIQAEESVKTLSRETIEYKKVLDEQIQERENSKN
  EESKHNQELTSQLLAAENKCNLLEKQLEYMRNMIKHAEMERTSVLEKQVSLERERQHDQT
  HVQSQLEKLDLLEQEYNKLTTMQALAEKKMQELEAKLHEEEQERKRMQAKAAELQTGLET
  NRLIFEDKATPCVPNARRIKKKKSKPPEKKSSRNYFGAQPHYRLCLGDMPFVAGKSTSPS
  HAVVANVQLVLHLMKQHSKALCNDRVINSIPLAKQVSSRGGKSKKLSVTPPSSNGINEEL
  SEVLQTLQDEFGQMSFDHQQLAKLIQESPTVELKDKLECELEALVGRMEAKANQITKVRK
  YQAQLEKQKLEKQKKELKATKKTLDEERNSSSRSGITGTTNKKDFMKLRPGEKRRKNLQL
  LKDMQSIQNSLQSSSLCWDY
• Function: Centrosomal protein which may be required for microtubule attachment to centrosomes. May act by forming ring-like structures around microtubules. Mediates nuclear translocation and mitogenic activity of the internalized growth factor FGF2, but that of FGF1.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway:
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mosaic variegated aneuploidy syndrome 2	DIS3IPQ6	Definitive	Autosomal recessive	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Mosaic variegated aneuploidy syndrome 1	DISOV0CG	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[7]
Mosaic variegated aneuploidy syndrome	DIS5QTMU	Supportive	Autosomal dominant	[8]
Prostate cancer	DISF190Y	Limited	Altered Expression	[9]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Centrosomal protein of 57 kDa (CEP57) affects the response to substance of Methotrexate.	[31]
Mitomycin	DMH0ZJE	Approved	Centrosomal protein of 57 kDa (CEP57) affects the response to substance of Mitomycin.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Centrosomal protein of 57 kDa (CEP57).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Centrosomal protein of 57 kDa (CEP57).	[26]

21 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 Centrosomal protein of 57 kDa (CEP57).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Centrosomal protein of 57 kDa (CEP57).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Centrosomal protein of 57 kDa (CEP57).	[16]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Centrosomal protein of 57 kDa (CEP57).	[17]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Centrosomal protein of 57 kDa (CEP57).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Centrosomal protein of 57 kDa (CEP57).	[20]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[21]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Centrosomal protein of 57 kDa (CEP57).	[22]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Centrosomal protein of 57 kDa (CEP57).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Centrosomal protein of 57 kDa (CEP57).	[24]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[21]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Centrosomal protein of 57 kDa (CEP57).	[25]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Centrosomal protein of 57 kDa (CEP57).	[27]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Centrosomal protein of 57 kDa (CEP57).	[29]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centrosomal protein of 57 kDa (CEP57).	[24]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Centrosomal protein of 57 kDa (CEP57).	[30]

References

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